Exercise induces cortical plasticity after neonatal spinal cord injury in the rat

PubMed Central

Kao, T; Shumsky, JS; Murray, M; Moxon, KA

2009-01-01

Exercise-induced cortical plasticity is associated with improved functional outcome after brain or nerve injury. Exercise also improves functional outcomes after spinal cord injury, but its effects on cortical plasticity are not known. The goal of this investigation was to study the effect of moderate exercise (treadmill locomotion, 3 min/day, 5days/week) on the somatotopic organization of forelimb and hindlimb somatosensory cortex (SI) after neonatal thoracic transection. We used adult rats spinalized as neonates because some of these animals develop weight-supported stepping and, therefore, the relationship between cortical plasticity and stepping could also be examined. Acute, single-neuron mapping was used to determine the percentage of cortical cells responding to cutaneous forelimb stimulation in normal, spinalized, and exercised spinalized rats. Multiple single neuron recording from arrays of chronically implanted microwires examined the magnitude of response of these cells in normal and exercised spinalized rats. Our results show that exercise not only increased the percentage of responding cells in the hindlimb SI, but also increased the magnitude of the response of these cells. This increase in response magnitude was correlated with behavioral outcome measures. In the forelimb SI, neonatal transection reduced the percentage of responding cells to forelimb stimulation but exercise reversed this loss. This restoration in the percentage of responding cells after exercise was accompanied by an increase in their response magnitude. Therefore, the increase in responsiveness of hindlimb SI to forelimb stimulation after neonatal transection and exercise may be due, in part, to the effect of exercise on the forelimb SI. PMID:19515923

Cycling exercise and fetal spinal cord transplantation act synergistically on atrophied muscle following chronic spinal cord injury in rats.

PubMed

Peterson, C A; Murphy, R J; Dupont-Versteegden, E E; Houlé, J D

2000-01-01

The potential of two interventions, alone or in combination, to restore chronic spinal cord transection-induced changes in skeletal muscles of adult Sprague-Dawley rats was studied. Hind limb skeletal muscles were examined in the following groups of animals: rats with a complete spinal cord transection (Tx) for 8 weeks; Tx with a 4-week delay before initiation of a 4-week motor-assisted cycling exercise (Ex) program; Tx with a 4-week delay before transplantation (Tp) of fetal spinal cord tissue into the lesion cavity; Tx with a 4-week delay before Tp and Ex; and uninjured control animals. Muscle mass, muscle to body mass ratios, and mean myofiber cross-sectional areas were significantly reduced 8 weeks after transection. Whereas transplantation of fetal spinal cord tissue did not reverse this atrophy and exercise alone had only a modest effect in restoring lost muscle mass, the combination of exercise and transplantation significantly increased muscle mass, muscle to body mass ratios, and mean myofiber cross-sectional areas in both soleus and plantaris muscles. Spinal cord injury (SCI) also caused changes in myosin heavy chain (MyHC) expression toward faster isoforms in both soleus and plantaris and increased soleus myofiber succinate dehydrogenase (SDH) activity. Combined exercise and transplantation led to a change in the expression of the fastest MyHC isoform in soleus but had no effect in the plantaris. Exercise alone and in combination with transplantation reduced SDH activity to control levels in the soleus. These results suggest a synergistic action of exercise and transplantation of fetal spinal cord tissue on skeletal muscle properties following SCI, even after an extended post-injury period before intervention.

Tail Nerve Electrical Stimulation and Electro-Acupuncture Can Protect Spinal Motor Neurons and Alleviate Muscle Atrophy after Spinal Cord Transection in Rats

PubMed Central

Zhang, Yu-Ting; Jin, Hui; Wang, Jun-Hua; Wen, Lan-Yu; Yang, Yang; Ruan, Jing-Wen; Zhang, Shu-Xin; Ling, Eng-Ang

2017-01-01

Spinal cord injury (SCI) often results in death of spinal neurons and atrophy of muscles which they govern. Thus, following SCI, reorganizing the lumbar spinal sensorimotor pathways is crucial to alleviate muscle atrophy. Tail nerve electrical stimulation (TANES) has been shown to activate the central pattern generator (CPG) and improve the locomotion recovery of spinal contused rats. Electroacupuncture (EA) is a traditional Chinese medical practice which has been proven to have a neural protective effect. Here, we examined the effects of TANES and EA on lumbar motor neurons and hindlimb muscle in spinal transected rats, respectively. From the third day postsurgery, rats in the TANES group were treated 5 times a week and those in the EA group were treated once every other day. Four weeks later, both TANES and EA showed a significant impact in promoting survival of lumbar motor neurons and expression of choline acetyltransferase (ChAT) and ameliorating atrophy of hindlimb muscle after SCI. Meanwhile, the expression of neurotrophin-3 (NT-3) in the same spinal cord segment was significantly increased. These findings suggest that TANES and EA can augment the expression of NT-3 in the lumbar spinal cord that appears to protect the motor neurons as well as alleviate muscle atrophy. PMID:28744378

Axon regeneration can facilitate or suppress hindlimb function after olfactory ensheathing glia transplantation.

PubMed

Takeoka, Aya; Jindrich, Devin L; Muñoz-Quiles, Cintia; Zhong, Hui; van den Brand, Rubia; Pham, Daniel L; Ziegler, Matthias D; Ramón-Cueto, Almudena; Roy, Roland R; Edgerton, V Reggie; Phelps, Patricia E

2011-03-16

Reports based primarily on anatomical evidence suggest that olfactory ensheathing glia (OEG) transplantation promotes axon regeneration across a complete spinal cord transection in adult rats. Based on functional, electrophysiological, and anatomical assessments, we found that OEG promoted axon regeneration across a complete spinal cord transection and that this regeneration altered motor responses over time. At 7 months after transection, 70% of OEG-treated rats showed motor-evoked potentials in hindlimb muscles after transcranial electric stimulation. Furthermore, a complete spinal cord retransection performed 8 months after injury demonstrated that this axon regeneration suppressed locomotor performance and decreased the hypersensitive hindlimb withdrawal response to mechanical stimulation. OEG transplantation alone promoted reorganization of lumbosacral locomotor networks and, when combined with long-term training, enhanced some stepping measures. These novel findings demonstrate that OEG promote regeneration of mature axons across a complete transection and reorganization of spinal circuitry, both of which contribute to sensorimotor function.

Axon Regeneration Can Facilitate or Suppress Hindlimb Function after Olfactory Ensheathing Glia Transplantation

PubMed Central

Takeoka, Aya; Jindrich, Devin L.; Muñoz-Quiles, Cintia; Zhong, Hui; van den Brand, Rubia; Pham, Daniel L.; Ziegler, Matthias D.; Ramón-Cueto, Almudena; Roy, Roland R.; Edgerton, V. Reggie

2011-01-01

Reports based primarily on anatomical evidence suggest that olfactory ensheathing glia (OEG) transplantation promotes axon regeneration across a complete spinal cord transection in adult rats. Based on functional, electrophysiological, and anatomical assessments, we found that OEG promoted axon regeneration across a complete spinal cord transection and that this regeneration altered motor responses over time. At 7 months after transection, 70% of OEG-treated rats showed motor-evoked potentials in hindlimb muscles after transcranial electric stimulation. Furthermore, a complete spinal cord retransection performed 8 months after injury demonstrated that this axon regeneration suppressed locomotor performance and decreased the hypersensitive hindlimb withdrawal response to mechanical stimulation. OEG transplantation alone promoted reorganization of lumbosacral locomotor networks and, when combined with long-term training, enhanced some stepping measures. These novel findings demonstrate that OEG promote regeneration of mature axons across a complete transection and reorganization of spinal circuitry, both of which contribute to sensorimotor function. PMID:21411671

Role of spared pathways in locomotor recovery after body-weight-supported treadmill training in contused rats.

PubMed

Singh, Anita; Balasubramanian, Sriram; Murray, Marion; Lemay, Michel; Houle, John

2011-12-01

Body-weight-supported treadmill training (BWSTT)-related locomotor recovery has been shown in spinalized animals. Only a few animal studies have demonstrated locomotor recovery after BWSTT in an incomplete spinal cord injury (SCI) model, such as contusion injury. The contribution of spared descending pathways after BWSTT to behavioral recovery is unclear. Our goal was to evaluate locomotor recovery in contused rats after BWSTT, and to study the role of spared pathways in spinal plasticity after BWSTT. Forty-eight rats received a contusion, a transection, or a contusion followed at 9 weeks by a second transection injury. Half of the animals in the three injury groups were given BWSTT for up to 8 weeks. Kinematics and the Basso-Beattie-Bresnahan (BBB) test assessed behavioral improvements. Changes in Hoffmann-reflex (H-reflex) rate depression property, soleus muscle mass, and sprouting of primary afferent fibers were also evaluated. BWSTT-contused animals showed accelerated locomotor recovery, improved H-reflex properties, reduced muscle atrophy, and decreased sprouting of small caliber afferent fibers. BBB scores were not improved by BWSTT. Untrained contused rats that received a transection exhibited a decrease in kinematic parameters immediately after the transection; in contrast, trained contused rats did not show an immediate decrease in kinematic parameters after transection. This suggests that BWSTT with spared descending pathways leads to neuroplasticity at the lumbar spinal level that is capable of maintaining locomotor activity. Discontinuing training after the transection in the trained contused rats abolished the improved kinematics within 2 weeks and led to a reversal of the improved H-reflex response, increased muscle atrophy, and an increase in primary afferent fiber sprouting. Thus continued training may be required for maintenance of the recovery. Transected animals had no effect of BWSTT, indicating that in the absence of spared pathways this training paradigm did not improve function.

Full spinal cord regeneration after total transection is not possible due to entropy change.

PubMed

Zielinski, P; Sokal, P

2016-09-01

Transected spinal cord regeneration is a main challenge of regenerative medicine. The mainstream of research is focused on the promotion of spinal axons growth, which is strongly inhibited in mammals. Assuming that the inhibition of the axonal growth may be ever overcome, the complexity of neural reconnections may be the second serious stand to overcome. Peripheral nerve axons regeneration seem to form a random pattern of their targets reconnections. The hypothesis is that due to the laws of entropy or irreversible information loss the full spinal cord restoration after the transection is not possible. The hypothesis is discussed based on several assumptions. Simplifying the dissertation spinal cord is represented by 2millions of pyramidal axons. After the transection each of these axons has to make a growth and reconnect with exactly matching targets below the transection, in the same number. Axons are guided by neurotrophic factors and afterwards reconnected with neuroplasticity mechanisms. Assuming random reconnections, there are 2,000,000! permutations [Formula: see text] , therefore the chance of ideally random but correct reconnection of pyramidal axons with adequate targets is 1/2,000,000!. Apart from pyramidal axons, there are other axons, like extrapyramidal, sensory and associative. Empirical data and analysis of neurotrophic factors and organogenesis mechanisms may seem to slightly contradict the hypothesis, but strictly adhering to the second law of thermodynamics and entropy laws the full restoration of the transected cord may never be possible. Copyright © 2016 Elsevier Ltd. All rights reserved.

Electrical field distribution within the injured cat spinal cord: injury potentials and field distribution.

PubMed

Khan, T; Myklebust, J; Swiontek, T; Sayers, S; Dauzvardis, M

1994-12-01

This study investigated the spontaneous injury potentials measured after contusion or transection injury to the cat spinal cord. In addition, the distribution of electrical field potentials on the surface and within the spinal cord were measured following applied electrical fields after transection and contusion injuries. After transection of the spinal cord, the injury potentials were -19.8 +/- 2.6 mV; after contusion of the spinal cord, the injury potentials were -9.5 +/- 2.2 mV. These potentials returned to control values within 2.5-4h after injury. The electrical field distribution measured on the dorsal surface, as well as within the spinal cord, after the application of a 10 microA current, showed little difference between contusion and transection injuries. Scalar potential fields were measured using two configurations of stimulating electrodes: dorsal to dorsal (D-D), in which both electrodes were placed epidurally on the dorsal surface of the spinal cord, and ventral to dorsal (V-D), in which one electrode was placed dorsally and one ventrally. As reported in normal uninjured cats, the total current in the midsagittal plane for the D-D configuration was largely confined to the dorsal portion of the spinal cord; with the V-D configuration, the current distribution was uniform throughout the spinal cord. In the injured spinal cord, the equipotential lines midway between the stimulating electrodes have a wider separation than in the uninjured spinal cord. Because the magnitude of the electrical field E is equal to the current density J multiplied by the resistivity r, this suggests that either the current density is reduced or that the resistivity is reduced.

Spinal cord regeneration in Xenopus tadpoles proceeds through activation of Sox2-positive cells

PubMed Central

2012-01-01

Background In contrast to mammals, amphibians, such as adult urodeles (for example, newts) and anuran larvae (for example, Xenopus) can regenerate their spinal cord after injury. However, the cellular and molecular mechanisms involved in this process are still poorly understood. Results Here, we report that tail amputation results in a global increase of Sox2 levels and proliferation of Sox2+ cells. Overexpression of a dominant negative form of Sox2 diminished proliferation of spinal cord resident cells affecting tail regeneration after amputation, suggesting that spinal cord regeneration is crucial for the whole process. After spinal cord transection, Sox2+ cells are found in the ablation gap forming aggregates. Furthermore, Sox2 levels correlated with regenerative capabilities during metamorphosis, observing a decrease in Sox2 levels at non-regenerative stages. Conclusions Sox2+ cells contribute to the regeneration of spinal cord after tail amputation and transection. Sox2 levels decreases during metamorphosis concomitantly with the lost of regenerative capabilities. Our results lead to a working hypothesis in which spinal cord damage activates proliferation and/or migration of Sox2+ cells, thus allowing regeneration of the spinal cord after tail amputation or reconstitution of the ependymal epithelium after spinal cord transection. PMID:22537391

Baclofen or nNOS inhibitor affect molecular and behavioral alterations evoked by traumatic spinal cord injury in rat spinal cord.

PubMed

Kisucká, Alexandra; Hricová, Ľudmila; Pavel, Jaroslav; Strosznajder, Joanna B; Chalimoniuk, Malgorzata; Langfort, Jozef; Gálik, Ján; Maršala, Martin; Radoňak, Jozef; Lukáčová, Nadežda

2015-06-01

The loss of descending control after spinal cord injury (SCI) and incessant stimulation of Ia monosynaptic pathway, carrying proprioceptive impulses from the muscles and tendons into the spinal cord, evoke exaggerated α-motoneuron activity leading to increased reflex response. Previous results from our laboratory have shown that Ia monosynaptic pathway is nitrergic. The aim of this study was to find out whether nitric oxide produced by neuronal nitric oxide synthase (nNOS) plays a role in setting the excitability of α-motoneurons after thoracic spinal cord transection. We tested the hypothesis that the inhibition of nNOS in α-motoneurons after SCI could have a neuroprotective effect on reflex response. Rats underwent spinal cord transection at Th10 level followed by 7, 10, and 14 days of survival. The animals were treated with Baclofen (a gamma aminobutyric acid B receptor agonist, 3 μg/two times per day/intrathecally) applied for 3 days from the seventh day after transection; N-nitro-l-arginine (NNLA) (nNOS blocator) applied for the first 3 days after injury (20 mg/kg per day, intramuscularly); NNLA and Baclofen; or NNLA (60 mg/kg/day, single dose) applied on the 10th day after transection. We detected the changes in the level of nNOS protein, nNOS messenger RNA, and nNOS immunoreactivity. To investigate the reflex response to heat-induced stimulus, tail-flick test was monitored in treated animals up to 16 days after SCI. Our data indicate that Baclofen therapy is more effective than the combined treatment with NNLA and Baclofen therapy. The single dose of NNLA (60 mg/kg) applied on the 10th day after SCI or Baclofen therapy reduced nNOS expression in α-motoneurons and suppressed symptoms of increased reflex activity. The results clearly show that increased nNOS expression in α-motoneurons after SCI may be pharmacologically modifiable with Baclofen or bolus dose of nNOS blocker. Copyright © 2015. Published by Elsevier Inc.

Polyethylene glycol-induced motor recovery after total spinal transection in rats.

PubMed

Ren, Shuai; Liu, Ze-Han; Wu, Qiong; Fu, Kuang; Wu, Jun; Hou, Li-Ting; Li, Ming; Zhao, Xin; Miao, Qing; Zhao, Yun-Long; Wang, Sheng-Yu; Xue, Yan; Xue, Zhen; Guo, Ya-Shan; Canavero, Sergio; Ren, Xiao-Ping

2017-08-01

Despite more than a century of research, spinal paralysis remains untreatable via biological means. A new understanding of spinal cord physiology and the introduction of membrane fusogens have provided new hope that a biological cure may soon become available. However, proof is needed from adequately powered animal studies. Two groups of rats (n=9, study group, n=6 controls) were submitted to complete transection of the dorsal cord at T10. The animals were randomized to receive either saline or polyethylene glycol (PEG) in situ. After 4 weeks, the treated group had recovered ambulation vs none in the control group (BBB scores; P=.0145). One control died. All animals were studied with somatosensory-evoked potentials (SSEP) and diffusion tensor imaging (DTI). SSEP recovered postoperatively only in PEG-treated rats. At study end, DTI showed disappearance of the transection gap in the treated animals vs an enduring gap in controls (fractional anisotropy/FA at level: P=.0008). We show for the first time in an adequately powered study that the paralysis attendant to a complete transection of the spinal cord can be reversed. This opens the path to a severance-reapposition cure of spinal paralysis, in which the injured segment is excised and the two stumps approximated after vertebrectomy/diskectomies. © 2017 John Wiley & Sons Ltd.

Evidence that spinal segmental nitric oxide mediates tachyphylaxis to peripheral local anesthetic nerve block.

PubMed

Wang, C; Sholas, M G; Berde, C B; DiCanzio, J; Zurakowski, D; Wilder, R T

2001-09-01

Tachyphylaxis to sciatic nerve blockade in rats correlates with hyperalgesia. Spinal inhibition of nitric oxide synthase with N(G)nitro-L-arginine methyl ester (L-NAME) has been shown to prevent hyperalgesia. Given systemically, L-NAME also prevents tachyphylaxis. The action of L-NAME in preventing tachyphylaxis therefore may be mediated at spinal sites. We compared systemic versus intrathecal potency of L-NAME in modulating tachyphylaxis to sciatic nerve block. Rats were prepared with intrathecal catheters. Three sequential sciatic nerve blocks were placed. Duration of block of thermal nocifensive, proprioceptive and motor responses was recorded. We compared spinal versus systemic dose-response to L-NAME, and examined effects of intrathecal arginine on tachyphylaxis. An additional group of rats underwent testing after T10 spinal cord transection. In these rats duration of sciatic nerve block was assessed by determining the heat-induced flexion withdrawal reflex. L-NAME was 25-fold more potent in preventing tachyphylaxis given intrathecally than intraperitoneally. Intrathecal arginine augmented tachyphylaxis. Spinalized rats exhibited tachyphylaxis to sciatic block. The increased potency of intrathecal versus systemic L-NAME suggests a spinal site of action in inhibiting tachyphylaxis. Descending pathways are not necessary for the development of tachyphylaxis since it occurs even after T10 spinal cord transection. Thus tachyphylaxis, like hyperalgesia, is mediated at least in part by a spinal site of action.

L-Dopa effect on frequency-dependent depression of the H-reflex in adult rats with complete spinal cord transection.

PubMed

Liu, Hao; Skinner, Robert D; Arfaj, Ahmad; Yates, Charlotte; Reese, Nancy B; Williams, Keith; Garcia-Rill, Edgar

2010-10-30

This study investigated whether l-dopa (DOPA), locomotor-like passive exercise (Ex) using a motorized bicycle exercise trainer (MBET), or their combination in adult rats with complete spinal cord transection (Tx) preserves and restores low frequency-dependent depression (FDD) of the H-reflex. Adult Sprague-Dawley rats (n=56) transected at T8-9 had one of five treatments beginning 7 days after transection: Tx (transection only), Tx+Ex, Tx+DOPA, Tx+Ex+DOPA, and control (Ctl, no treatment) groups. After 30 days of treatment, FDD of the H-reflex was tested. Stimulation of the tibial nerve at 0.2, 1, 5, and 10Hz evoked an H-reflex that was recorded from plantar muscles of the hind paw. No significant differences were found at the stimulation rate of 1Hz. However, at 5Hz, FDD of the H-reflex in the Tx+Ex, Tx+DOPA and Ctl groups was significantly different from the Tx group (p<0.01). At 10Hz, all of the treatment groups were significantly different from the Tx group (p<0.01). No significant difference was identified between the Ctl and any of the treatment groups. These results suggest that DOPA significantly preserved and restored FDD after transection as effectively as exercise alone or exercise in combination with DOPA. Thus, there was no additive benefit when DOPA was combined with exercise. Copyright © 2010 Elsevier Inc. All rights reserved.

Central vs. peripheral neuraxial sympathetic control of porcine ventricular electrophysiology

PubMed Central

Yamakawa, Kentaro; Howard-Quijano, Kimberly; Zhou, Wei; Rajendran, Pradeep; Yagishita, Daigo; Vaseghi, Marmar; Ajijola, Olujimi A.; Armour, J. Andrew; Shivkumar, Kalyanam; Ardell, Jeffrey L.

2015-01-01

Sympathoexcitation is associated with ventricular arrhythmogenesis. The aim of this study was to determine the role of thoracic dorsal root afferent neural inputs to the spinal cord in modulating ventricular sympathetic control of normal heart electrophysiology. We hypothesize that dorsal root afferent input tonically modulates basal and evoked efferent sympathetic control of the heart. A 56-electrode sock placed on the epicardial ventricle in anesthetized Yorkshire pigs (n = 17) recorded electrophysiological function, as well as activation recovery interval (ARI) and dispersion in ARI, at baseline conditions and during stellate ganglion electrical stimulation. Measures were compared between intact states and sequential unilateral T1–T4 dorsal root transection (DRTx), ipsilateral ventral root transection (VRTx), and contralateral dorsal and ventral root transections (DVRTx). Left or right DRTx decreased global basal ARI [Lt.DRTx: 369 ± 12 to 319 ± 13 ms (P < 0.01) and Rt.DRTx: 388 ± 19 to 356 ± 15 ms (P < 0.01)]. Subsequent unilateral VRTx followed by contralateral DRx+VRTx induced no further change. In intact states, left and right stellate ganglion stimulation shortened ARIs (6 ± 2% vs. 17 ± 3%), while increasing dispersion (+139% vs. +88%). There was no difference in magnitude of ARI or dispersion change with stellate stimulation following spinal root transections. Interruption of thoracic spinal afferent signaling results in enhanced basal cardiac sympathoexcitability without diminishing the sympathetic response to stellate ganglion stimulation. This suggests spinal dorsal root transection releases spinal cord-mediated tonic inhibitory control of efferent sympathetic tone, while maintaining intrathoracic cardiocentric neural networks. PMID:26661096

Electronic bypass of spinal lesions: activation of lower motor neurons directly driven by cortical neural signals.

PubMed

Li, Yan; Alam, Monzurul; Guo, Shanshan; Ting, K H; He, Jufang

2014-07-03

Lower motor neurons in the spinal cord lose supraspinal inputs after complete spinal cord injury, leading to a loss of volitional control below the injury site. Extensive locomotor training with spinal cord stimulation can restore locomotion function after spinal cord injury in humans and animals. However, this locomotion is non-voluntary, meaning that subjects cannot control stimulation via their natural "intent". A recent study demonstrated an advanced system that triggers a stimulator using forelimb stepping electromyographic patterns to restore quadrupedal walking in rats with spinal cord transection. However, this indirect source of "intent" may mean that other non-stepping forelimb activities may false-trigger the spinal stimulator and thus produce unwanted hindlimb movements. We hypothesized that there are distinguishable neural activities in the primary motor cortex during treadmill walking, even after low-thoracic spinal transection in adult guinea pigs. We developed an electronic spinal bridge, called "Motolink", which detects these neural patterns and triggers a "spinal" stimulator for hindlimb movement. This hardware can be head-mounted or carried in a backpack. Neural data were processed in real-time and transmitted to a computer for analysis by an embedded processor. Off-line neural spike analysis was conducted to calculate and preset the spike threshold for "Motolink" hardware. We identified correlated activities of primary motor cortex neurons during treadmill walking of guinea pigs with spinal cord transection. These neural activities were used to predict the kinematic states of the animals. The appropriate selection of spike threshold value enabled the "Motolink" system to detect the neural "intent" of walking, which triggered electrical stimulation of the spinal cord and induced stepping-like hindlimb movements. We present a direct cortical "intent"-driven electronic spinal bridge to restore hindlimb locomotion after complete spinal cord injury.

Serotonergic Innervation of the Caudal Spinal Stump in Rats After Complete Spinal Transection: Effect of Olfactory Ensheathing Glia

PubMed Central

Takeoka, Aya; Kubasak, Marc D.; Zhong, Hui; Roy, Roland R.; Phelps, Patricia E.

2010-01-01

Spinal cord injury studies use the presence of serotonin (5-HT)-immunoreactive axons caudal to the injury site as evidence of axonal regeneration. As olfactory ensheathing glia (OEG) transplantation improves hindlimb locomotion in adult rats with complete spinal cord transection, we hypothesized that more 5-HT-positive axons would be found in the caudal stump of OEG- than media-injected rats. Previously we found 5-HT-immunolabeled axons that spanned the transection site only in OEG-injected rats but detected labeled axons just caudal to the lesion in both media- and OEG-injected rats. Now we report that many 5-HT-labeled axons are present throughout the caudal stump of both media- and OEG-injected rats. We found occasional 5-HT-positive interneurons that are one likely source of 5-HT-labeled axons. These results imply that the presence of 5-HT-labeled fibers in the caudal stump is not a reliable indicator of regeneration. We then asked if 5-HT-positive axons appose cholinergic neurons associated with motor functions: central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more 5-HT-positive varicosities in lamina X adjacent to central canal cluster cells in lumbar and sacral segments of OEG- than media-injected rats. SMNs and partition cells are less frequently apposed. As nonsynaptic release of 5-HT is common in the spinal cord, an increase in 5-HT-positive varicosities along motor-associated cholinergic neurons may contribute to the locomotor improvement observed in OEG-injected spinal rats. Furthermore, serotonin located within the caudal stump may activate lumbosacral locomotor networks. J. Comp. Neurol. 515: 664–676, 2009. PMID:19496067

Serotonergic innervation of the caudal spinal stump in rats after complete spinal transection: effect of olfactory ensheathing glia.

PubMed

Takeoka, Aya; Kubasak, Marc D; Zhong, Hui; Roy, Roland R; Phelps, Patricia E

2009-08-20

Spinal cord injury studies use the presence of serotonin (5-HT)-immunoreactive axons caudal to the injury site as evidence of axonal regeneration. As olfactory ensheathing glia (OEG) transplantation improves hindlimb locomotion in adult rats with complete spinal cord transection, we hypothesized that more 5-HT-positive axons would be found in the caudal stump of OEG- than media-injected rats. Previously we found 5-HT-immunolabeled axons that spanned the transection site only in OEG-injected rats but detected labeled axons just caudal to the lesion in both media- and OEG-injected rats. Now we report that many 5-HT-labeled axons are present throughout the caudal stump of both media- and OEG-injected rats. We found occasional 5-HT-positive interneurons that are one likely source of 5-HT-labeled axons. These results imply that the presence of 5-HT-labeled fibers in the caudal stump is not a reliable indicator of regeneration. We then asked if 5-HT-positive axons appose cholinergic neurons associated with motor functions: central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more 5-HT-positive varicosities in lamina X adjacent to central canal cluster cells in lumbar and sacral segments of OEG- than media-injected rats. SMNs and partition cells are less frequently apposed. As nonsynaptic release of 5-HT is common in the spinal cord, an increase in 5-HT-positive varicosities along motor-associated cholinergic neurons may contribute to the locomotor improvement observed in OEG-injected spinal rats. Furthermore, serotonin located within the caudal stump may activate lumbosacral locomotor networks. (c) 2009 Wiley-Liss, Inc.

Evaluation of purinergic mechanism for the treatment of voiding dysfunction: a study in conscious spinal cord-injured rats.

PubMed

Lu, Shing-Hwa; Groat, William C de; Lin, Alex T L; Chen, Kuang-Kuo; Chang, Luke S

2007-10-01

To investigate the effect of a selective P2X(3-)P2X(2/3) purinergic receptor antagonist (a-317491) on detrusor hyperreflexia in conscious chronic spinal cord-injured female rats. Six chronic spinal cord-transected female Sprague-Dawley rats (290-336 g) were used in this study. Spinal transection at the T8-T9 segmental level was performed using aseptic techniques under halothane anesthesia. Fourteen to 16 weeks after spinal transection, A-317491, a selective P2X(3-)P2X(2/3) purinergic receptor antagonist, was administered intravenously in cystometry studies at increasing doses of 0.03, 0.1, 0.3, 1, 3, 10 and 30 micromol/kg at 40-50 minute intervals. Cystometrograms (CMGs) were performed before and after the administration of each dose of the drug. The continuous filling of CMGs revealed a large number of small-amplitude (> 8 cmH(2)O), non-voiding contractions (NVCs) (average, 9.7 per voiding cycle) preceding voiding contractions (mean amplitude, 31 cmH(2)O; duration, 2.5 minutes), which occurred at an interval of 539 seconds and at a pressure threshold of 5.7 cmH(2)O. When tested in a range of doses (0.03-30 micromol/kg, intravenous), A-317491 in doses between 1 and 30 micromol/kg significantly (p < 0.05) increased the interval between voids by 25%, reduced the number of NVCs by 42-62%, and increased the pressure threshold for voiding by 53-73%, but did not change the amplitude of the duration of the voiding contractions. The effects of the drug were apparent within 10 minutes following administration. These results indicate that purinergic mechanisms, presumably involving P2X(3) or P2X(2/3) receptors on bladder C-fiber afferent nerves, play an important role in the detrusor hyperreflexia that occurs after spinal cord injury in rats.

Combination of edaravone and neural stem cell transplantation repairs injured spinal cord in rats.

PubMed

Song, Y Y; Peng, C G; Ye, X B

2015-12-29

This study sought to observe the effect of the combination of edaravone and neural stem cell (NSC) transplantation on the repair of complete spinal cord transection in rats. Eighty adult female Sprague-Dawley (SD) rats were used to establish the injury model of complete spinal cord transection at T9. Animals were divided randomly into four groups (N = 20 each): control, edaravone, transplantation, and edaravone + transplantation. The recovery of spinal function was evaluated with the Basso, Beattie, Bresnahan (BBB) rating scale on days 1, 3, and 7 each week after the surgery. After 8 weeks, the BBB scores of the control, edaravone, transplantation, and combination groups were 4.21 ± 0.11, 8.46 ± 0.1, 8.54 ± 0.13, and 11.21 ± 0.14, respectively. At 8 weeks after surgery, the spinal cord was collected; the survival and transportation of transplanted cells were observed with PKH-26 labeling, and the regeneration and distribution of spinal nerve fibers with fluorescent-gold (FG) retrograde tracing. Five rats died due to the injury. PKH-26-labeled NSCs had migrated into the spinal cord. A few intact nerve fibers and pyramidal neurons passed the injured area in the transplantation and combination groups. The numbers of PKH-26-labeled cells and FG-labeled nerve fibers were in the order: combination group > edaravone group and transplantation group > control group (P < 0.05 for each). Thus, edaravone can enhance the survival and differentiation of NSCs in injured areas; edaravone with NSC transplantation can improve the effectiveness of spinal cord injury repair in rats.

An animal model for the neuromodulation of neurogenic bladder dysfunction.

PubMed

Zvara, P; Sahi, S; Hassouna, M M

1998-08-01

To develop an animal model to examine the pathophysiology by which S3 sacral root electrostimulation alters the micturition reflex in patients with bladder hyper-reflexia. Chronic sacral nerve root electrostimulation was applied to spinally transected rats; 21 animals were divided into four groups. The spinal cord was completely transected at the T10-11 level and stainless-steel electrodes implanted into the sacral foramen in 17 animals; these animals were subsequently divided into two groups (1 and 2). Six rats in group 1 underwent sacral root elctrostimulation for 2 h/day and five in group 2 for 6 h/day, for 21 days. The sham group (group 3, six rats) received no stimulation and four rats were used as healthy controls (group 4). Voiding frequency was recorded and each animal was evaluated cystometrically at the end of the stimulation period. The results were compared with the sham and control groups. Spinal cord transection resulted in bladder areflexia and complete urinary retention; 7-9 days after the injury, the bladder recovered its activity. Twenty-one days after transection all animals had evidence of uninhibited bladder contractions. The mean (SD) hourly frequency of urination was 0.66 (0.18) in healthy controls, 0.83 (0.21) in group 1, 0.87 (0.34) in group 2 and 1.1 (0.31) in group 3. There was a significant decrease in eh cystometric signs of bladder hyper-reflexia in groups 1 and 2 when compared with group 3. This work reports and initial study showing that chronic electrostimulation of sacral nerve roots can reduce the signs of bladder hyper-reflexia in the spinally injured rat. To our knowledge, this is the first report describing the rat as an animal model to determine the effects of chronic electrostimulation on the micturition reflex.

Spinal cord injury below-level neuropathic pain relief with dorsal root entry zone microcoagulation performed caudal to level of complete spinal cord transection.

PubMed

Falci, Scott; Indeck, Charlotte; Barnkow, Dave

2018-06-01

OBJECTIVE Surgically created lesions of the spinal cord dorsal root entry zone (DREZ) to relieve central pain after spinal cord injury (SCI) have historically been performed at and cephalad to, but not below, the level of SCI. This study was initiated to investigate the validity of 3 proposed concepts regarding the DREZ in SCI central pain: 1) The spinal cord DREZ caudal to the level of SCI can be a primary generator of SCI below-level central pain. 2) Neuronal transmission from a DREZ that generates SCI below-level central pain to brain pain centers can be primarily through sympathetic nervous system (SNS) pathways. 3) Perceived SCI below-level central pain follows a unique somatotopic map of DREZ pain-generators. METHODS Three unique patients with both intractable SCI below-level central pain and complete spinal cord transection at the level of SCI were identified. All 3 patients had previously undergone surgical intervention to their spinal cords-only cephalad to the level of spinal cord transection-with either DREZ microcoagulation or cyst shunting, in failed attempts to relieve their SCI below-level central pain. Subsequent to these surgeries, DREZ lesioning of the spinal cord solely caudal to the level of complete spinal cord transection was performed using electrical intramedullary guidance. The follow-up period ranged from 1 1/2 to 11 years. RESULTS All 3 patients in this study had complete or near-complete relief of all below-level neuropathic pain. The analyzed electrical data confirmed and enhanced a previously proposed somatotopic map of SCI below-level DREZ pain generators. CONCLUSIONS The results of this study support the following hypotheses. 1) The spinal cord DREZ caudal to the level of SCI can be a primary generator of SCI below-level central pain. 2) Neuronal transmission from a DREZ that generates SCI below-level central pain to brain pain centers can be primarily through SNS pathways. 3) Perceived SCI below-level central pain follows a unique somatotopic map of DREZ pain generators.

VGLUT1 and VGLUT2 innervation in autonomic regions of intact and transected rat spinal cord.

PubMed

Llewellyn-Smith, Ida J; Martin, Carolyn L; Fenwick, Natalie M; Dicarlo, Stephen E; Lujan, Heidi L; Schreihofer, Ann M

2007-08-20

Fast excitatory neurotransmission to sympathetic and parasympathetic preganglionic neurons (SPN and PPN) is glutamatergic. To characterize this innervation in spinal autonomic regions, we localized immunoreactivity for vesicular glutamate transporters (VGLUTs) 1 and 2 in intact cords and after upper thoracic complete transections. Preganglionic neurons were retrogradely labeled by intraperitoneal Fluoro-Gold or with cholera toxin B (CTB) from superior cervical, celiac, or major pelvic ganglia or adrenal medulla. Glutamatergic somata were localized with in situ hybridization for VGLUT mRNA. In intact cords, all autonomic areas contained abundant VGLUT2-immunoreactive axons and synapses. CTB-immunoreactive SPN and PPN received many close appositions from VGLUT2-immunoreactive axons. VGLUT2-immunoreactive synapses occurred on Fluoro-Gold-labeled SPN. Somata with VGLUT2 mRNA occurred throughout the spinal gray matter. VGLUT2 immunoreactivity was not noticeably affected caudal to a transection. In contrast, in intact cords, VGLUT1-immunoreactive axons were sparse in the intermediolateral cell column (IML) and lumbosacral parasympathetic nucleus but moderately dense above the central canal. VGLUT1-immunoreactive close appositions were rare on SPN in the IML and the central autonomic area and on PPN. Transection reduced the density of VGLUT1-immunoreactive axons in sympathetic subnuclei but increased their density in the parasympathetic nucleus. Neuronal cell bodies with VGLUT1 mRNA occurred only in Clarke's column. These data indicate that SPN and PPN are densely innervated by VGLUT2-immunoreactive axons, some of which arise from spinal neurons. In contrast, the VGLUT1-immunoreactive innervation of spinal preganglionic neurons is sparse, and some may arise from supraspinal sources. Increased VGLUT1 immunoreactivity after transection may correlate with increased glutamatergic transmission to PPN. (c) 2007 Wiley-Liss, Inc.

[Review of the regeneration mechanism of complete spinal cord injury].

PubMed

Li, Jiayin; Li, Xing; Xiao, Zhifeng; Dai, Jianwu

2018-06-01

Spinal cord injury (SCI), especially the complete SCI, usually results in complete paralysis below the level of the injury and seriously affects the patient's quality of life. SCI repair is still a worldwide medical problem. In the last twenty years, Professor DAI Jianwu and his team pioneered complete SCI model by removing spinal tissue with varied lengths in rodents, canine, and non-human primates to verify therapeutic effect of different repair strategies. Moreover, they also started the first clinical study of functional collagen scaffold on patients with acute complete SCI on January 16th, 2015. This review mainly focusses on the possible mechanisms responsible for complete SCI. In common, recovery of some sensory and motor functions post complete SCI include the following three contributing reasons. ① Regeneration of long ascending and descending axons throughout the lesion site to re-connect the original targets; ② New neural circuits formed in the lesion site by newly generated neurons post injury, which effectively re-connect the transected stumps; ③ The combined effect of ① and ②. The numerous studies have confirmed that neural circuits rebuilt across the injury site by newborn neurons might be the main mechanisms for functional recovery of animals from rodents to dogs. In many SCI model, especially the complete spinal cord transection model, many studies have convincingly demonstrated that the quantity and length of regenerated long descending axons, particularly like CST fibers, are too few to across the lesion site that is millimeters in length to realize motor functional recovery. Hence, it is more feasible in guiding neuronal relays formation by bio-scaffolds implantation than directing long motor axons regeneration in improving motor function of animals with complete spinal cord transection. However, some other issues such as promoting more neuronal relays formation, debugging wrong connections, and maintaining adequate neural circuits for functional recovery are urgent problems to be addressed.

Olfactory Ensheathing Cell Transplantation after a Complete Spinal Cord Transection Mediates Neuroprotective and Immunomodulatory Mechanisms to Facilitate Regeneration

PubMed Central

Khankan, Rana R.; Griffis, Khris G.; Haggerty-Skeans, James R.; Zhong, Hui; Roy, Roland R.; Edgerton, V. Reggie

2016-01-01

Multiple neural and peripheral cell types rapidly respond to tissue damage after spinal cord injury to form a structurally and chemically inhibitory scar that limits axon regeneration. Astrocytes form an astroglial scar and produce chondroitin sulfate proteoglycans (CSPGs), activate microglia, and recruit blood-derived immune cells to the lesion for debris removal. One beneficial therapy, olfactory ensheathing cell (OEC) transplantation, results in functional improvements and promotes axon regeneration after spinal cord injury. The lack of an OEC-specific marker, however, has limited the investigation of mechanisms underlying their proregenerative effects. We compared the effects of enhanced green fluorescent protein-labeled fibroblast (FB) and OEC transplants acutely after a complete low-thoracic spinal cord transection in adult rats. We assessed the preservation of neurons and serotonergic axons, the levels of inhibitory CSPGs and myelin debris, and the extent of immune cell activation between 1 and 8 weeks postinjury. Our findings indicate that OECs survive longer than FBs post-transplantation, preserve axons and neurons, and reduce inhibitory molecules in the lesion core. Additionally, we show that OECs limit immune-cell activation and infiltration, whereas FBs alter astroglial scar formation and increase immune-cell infiltration and concomitant secondary tissue damage. Administration of cyclosporine-A to enhance graft survival demonstrated that immune suppression can augment OEC contact-mediated protection of axons and neurons during the first 2 weeks postinjury. Collectively, these data suggest that OECs have neuroprotective and immunomodulatory mechanisms that create a supportive environment for neuronal survival and axon regeneration after spinal cord injury. SIGNIFICANCE STATEMENT Spinal cord injury creates physical and chemical barriers to axon regeneration. We used a complete spinal cord transection model and olfactory ensheathing cell (OEC) or fibroblast (FB; control) transplantation as a repair strategy. OECs, but not FBs, intermingled with astrocytes, facilitated astroglial scar border formation and sequestered invading peripheral cells. OECs attenuated immune cell infiltration, reduced secondary tissue damage, protected neurons and axons in the lesion core, and helped clear myelin debris. Immunosuppression enhanced survival of OECs and FBs, but only OEC transplantation promoted scaffold formation in the lesion site that facilitated axon regeneration and neuron preservation. PMID:27277804

Significance of fixation of the vertebral column for spinal cord injury experiments.

PubMed

Liu, Fei; Luo, Zhuo-Jin; You, Si-Wei; Jiao, Xi-Ying; Meng, Xiao-Mei; Shi, Ming; Wang, Chun-Ting; Ju, Gong

2003-08-01

Thoracic spinal cord transections were performed in adult rats. The animals were divided into two groups, with or without internal fixation of the involved vertebral column. Histologic and immunohistochemical studies were performed to compare the effect of internal fixation of the vertebral column. To find out the aspects and extent of beneficial effects of vertebral column fixation for spinal cord repair. Vertebral column fixation is a routine procedure in clinical spinal cord surgery. Paradoxically, most, if not all, animal spinal cord experiments seem to have ignored the importance of vertebral column fixation. During trunk movements, the vertebral column flexes to different directions, accompanied by bending of the spinal cord. Following spinal cord lesions, with frequent bending of the cord there will be repeated bleeding, inflammation, and other pathologic processes at the lesion site. Thus, the healing process will be hampered. The severity of the damages that will be brought about by bending of the cord is, to a certain degree, unpredictable. There will be rather big individual variations in injury and repair among the same type of experiments, rendering quantification and conclusion difficult. Adult Sprague-Dawley rats were used. The thoracic spinal cord was transected. Strong stainless steel wires were used for internal fixation of the vertebral column. The histology of the horizontal sections of the spinal cord segment, which included the lesion site, was examined at the 14th postoperative day. The volumes of the secondary degeneration and meningeal scar, the gap between the borders of the proximal and distal stumps of the transected spinal cord, the thickness of the meningeal scar, the astrocytic reaction, and the abundance of regenerating nerve fibers at the lesion site were compared between the vertebral column fixed and nonfixed groups. Whenever possible, the results were evaluated quantitatively. In all these aspects, the internally fixed group was consistently far better than the unfixed group. The quantitative analyses were as follows (fixed/unfixed): 1)volume of secondary degeneration: 1.07 +/- 0.20/1.81 +/- 0.43 mm3 (P < 0.01); 2) volume of meningeal scar: 2.38 +/- 0.55/4.34 +/- 1.40 mm3 (P < 0.05); 3) distance between cord stumps: 1.38 +/- 0.34/2.35 +/- 0.79 mm (P < 0.05); 4) the mean thinnest dimension of the meningeal scar: 0.90 +/- 0.43/1.98 +/- 0.85 mm (P < 0.05). Vertebral column fixation is a crucial procedure for spinal cord animal experiments.

Respiration in vitro: I. Spontaneous activity.

PubMed

Hamada, O; Garcia-Rill, E; Skinner, R D

1992-01-01

The present report describes respiratory-like activity recorded from intercostal muscles in the neonatal rat in vitro brain stem-spinal cord, rib-attached preparation. In this preparation from 1- to 4-day-old rats, spontaneous rhythmic and synchronized upward movements of the rib cage coincided with the recorded muscle activity. Spontaneous respiratory-like activity showed a frequency in the range of 0.05-0.2 Hz, with single-, double-, and mixed-burst patterns. Spontaneous activity declined over time, but increased in frequency as temperature increased. Multilevel recordings showed a cephalocaudal order of bursting of intercostal muscles. Brain stem transections at the prepontine level did not affect spontaneous frequency, whereas premedullary transections resulted in an increase in spontaneous respiratory frequency. High spinal transections eliminated spontaneous respiratory-like activity. These results suggest that there is a well-organized pontomedullary pattern generator for respiratory-like activity in this preparation, which can be modulated by temperature. The characteristics of these electromyographic (EMG) recordings allow comparison with previous in vitro studies of respiratory-like activity using nerve activity and in vivo studies using EMG activity. These results provide basic information on the spontaneous activity of this preparation as a prelude to the study of the effects of electrical stimulation of the spinal cord to induce respiratory-like activity, as described in the companion article.

Right-sided vagus nerve stimulation inhibits induced spinal cord seizures.

PubMed

Tubbs, R Shane; Salter, E George; Killingsworth, Cheryl; Rollins, Dennis L; Smith, William M; Ideker, Raymond E; Wellons, John C; Blount, Jeffrey P; Oakes, W Jerry

2007-01-01

We have previously shown that left-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. To test our hypothesis that right-sided vagus nerve stimulation will also abort seizure activity, we have initiated seizures in the spinal cord and then performed right-sided vagus nerve stimulation in an animal model. Four pigs were anesthetized and placed in the lateral position and a small laminectomy performed in the lumbar region. Topical penicillin, a known epileptogenic drug to the cerebral cortex and spinal cord, was next applied to the dorsal surface of the exposed cord. With the exception of the control animal, once seizure activity was discernible via motor convulsion or increased electrical activity, the right vagus nerve previously isolated in the neck was stimulated. Following multiple stimulations of the vagus nerve and with seizure activity confirmed, the cord was transected in the midthoracic region and vagus nerve stimulation performed. Right-sided vagus nerve stimulation resulted in cessation of spinal cord seizure activity in all animals. Transection of the spinal cord superior to the site of seizure induction resulted in the ineffectiveness of vagus nerve stimulation in causing cessation of seizure activity in all study animals. As with left-sided vagus nerve stimulation, right-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. Additionally, the effects of right-sided vagus nerve stimulation on induced spinal cord seizures involve descending spinal pathways. These data may aid in the development of alternative mechanisms for electrical stimulation for patients with medically intractable seizures and add to our knowledge regarding the mechanism for seizure cessation following peripheral nerve stimulation.

Potential of human dental stem cells in repairing the complete transection of rat spinal cord

NASA Astrophysics Data System (ADS)

Yang, Chao; Li, Xinghan; Sun, Liang; Guo, Weihua; Tian, Weidong

2017-04-01

Objective. The adult spinal cord of mammals contains a certain amount of neural precursor cells, but these endogenous cells have a limited capacity for replacement of lost cells after spinal cord injury. The exogenous stem cells transplantation has become a therapeutic strategy for spinal cord repairing because of their immunomodulatory and differentiation capacity. In addition, dental stem cells originating from the cranial neural crest might be candidate cell sources for neural engineering. Approach. Human dental follicle stem cells (DFSCs), stem cells from apical papilla (SCAPs) and dental pulp stem cells (DPSCs) were isolated and identified in vitro, then green GFP-labeled stem cells with pellets were transplanted into completely transected spinal cord. The functional recovery of rats and multiple neuro-regenerative mechanisms were explored. Main results. The dental stem cells, especially DFSCs, demonstrated the potential in repairing the completely transected spinal cord and promote functional recovery after injury. The major involved mechanisms were speculated below: First, dental stem cells inhibited the expression of interleukin-1β to reduce the inflammatory response; second, they inhibited the expression of ras homolog gene family member A (RhoA) to promote neurite regeneration; third, they inhibited the sulfonylurea receptor1 (SUR-1) expression to reduce progressive hemorrhagic necrosis; lastly, parts of the transplanted cells survived and differentiated into mature neurons and oligodendrocytes but not astrocyte, which is beneficial for promoting axons growth. Significance. Dental stem cells presented remarkable tissue regenerative capability after spinal cord injury through immunomodulatory, differentiation and protection capacity.

The Effects of Intraspinal Microstimulation on Spinal Cord Tissue in the Rat

PubMed Central

Bamford, Jeremy A.; Todd, Kathryn G.; Mushahwar, Vivian K.

2010-01-01

Intraspinal microstimulation (ISMS) involves the implantation of microwires into the spinal cord below the level of an injury to excite neural networks involved in the control of locomotion in the lower limbs. The goal of this study was to examine the potential spinal cord damage that might occur with chronic ISMS. We employed functional measures of force recruitment and immunohistochemical processing of serial spinal cord sections to evaluate any damage induced by spinal transection, implantation of ISMS arrays, and electrical stimulation of 4 hours/day for 30 days. Functional measurements showed no change in force recruitment following transection and chronic ISMS, indicating no changes to underlying neural networks. The implantation of sham intraspinal microwires produced a spatially-limited increase in the density of microglia/macrophages and GFAP+ astrocytes adjacent to the microwire tracks, indicating a persistent immune response. Most importantly, these results were not different from those around microwires that were chronically pulsed with charge levels up to 48 nC/phase. Likewise, measurements of neuronal density indicated no decrease in neuronal cell bodies in the ventral grey matter surrounding ISMS microwires (243.6/mm2 ± 35.3/mm2) compared to tissue surrounding sham microwires (207.8/mm2 ± 38.8/mm2). We conclude that the implantation of intraspinal microwires and chronic application of ISMS are well tolerated by spinal cord tissue. PMID:20430436

A valuable animal model of spinal cord injury to study motor dysfunctions, comorbid conditions, and aging associated diseases.

PubMed

Rouleau, Pascal; Guertin, Pierre A

2013-01-01

Most animal models of contused, compressed or transected spinal cord injury (SCI) require a laminectomy to be performed. However, despite advantages and disadvantages associated with each of these models, the laminectomy itself is generally associated with significant problems including longer surgery and anaesthesia (related post-operative complications), neuropathic pain, spinal instabilities, deformities, lordosis, and biomechanical problems, etc. This review provides an overview of findings obtained mainly from our laboratory that are associated with the development and characterization of a novel murine model of spinal cord transection that does not require a laminectomy. A number of studies successfully conducted with this model provided strong evidence that it constitutes a simple, reliable and reproducible transection model of complete paraplegia which is particularly useful for studies on large cohorts of wild-type or mutant animals - e.g., drug screening studies in vivo or studies aimed at characterizing neuronal and non-neuronal adaptive changes post-trauma. It is highly suitable also for studies aimed at identifying and developing new pharmacological treatments against aging associated comorbid problems and specific SCI-related dysfunctions (e.g., stereotyped motor behaviours such as locomotion, sexual response, defecation and micturition) largely related with 'command centers' located in lumbosacral areas of the spinal cord.

Neuroprotective effects of (-)-epigallocatechin-3-gallate (EGCG) against peripheral nerve transection-induced apoptosis.

PubMed

Kian, Kosar; Khalatbary, Ali Reza; Ahmadvand, Hassan; Karimpour Malekshah, Abbasali; Shams, Zahra

2018-01-02

Recent studies revealed the neuroprotective effects of epigallocatechin-3-gallate (EGCG) on a variety of neural injury models. The purpose of this study was to determine the neuroprotective effects of EGCG following sciatic nerve transection (SNT). Rats were randomly divided into four groups each as follows: Sham-operated group, SNT group, and Pre-EGCG (50-mg/kg, i.p., 30 minutes before nerve transection and followed for 3 days) and Post-EGCG (50-mg/kg, i.p., 1 hour after nerve transection and followed for 3 days) groups. Spinal cord segments of the sciatic nerve and related dorsal root ganglions were removed four weeks after nerve transection for the assessment of malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities, immunohistochemistry of caspase-3, cyclooxygenase-2 (COX-2), S100beta (S100B), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). MDA levels were significantly decreased, and SOD and CAT activities were significantly increased in EGCG-treated rats after nerve transection. Attenuated caspase-3 and COX-2 expression, and TUNEL reaction could be significantly detected in the EGCG-treated rats after nerve transection. Also, EGCG significantly increased S100B expression. We propose that EGCG may be effective in the protection of neuronal cells against retrograde apoptosis and may enhance neuronal survival time following nerve transection.

Weight-Bearing Locomotion in the Developing Opossum, Monodelphis domestica following Spinal Transection: Remodeling of Neuronal Circuits Caudal to Lesion

PubMed Central

Wheaton, Benjamin J.; Noor, Natassya M.; Whish, Sophie C.; Truettner, Jessie S.; Dietrich, W. Dalton; Zhang, Moses; Crack, Peter J.; Dziegielewska, Katarzyna M.; Saunders, Norman R.

2013-01-01

Complete spinal transection in the mature nervous system is typically followed by minimal axonal repair, extensive motor paralysis and loss of sensory functions caudal to the injury. In contrast, the immature nervous system has greater capacity for repair, a phenomenon sometimes called the infant lesion effect. This study investigates spinal injuries early in development using the marsupial opossum Monodelphis domestica whose young are born very immature, allowing access to developmental stages only accessible in utero in eutherian mammals. Spinal cords of Monodelphis pups were completely transected in the lower thoracic region, T10, on postnatal-day (P)7 or P28 and the animals grew to adulthood. In P7-injured animals regrown supraspinal and propriospinal axons through the injury site were demonstrated using retrograde axonal labelling. These animals recovered near-normal coordinated overground locomotion, but with altered gait characteristics including foot placement phase lags. In P28-injured animals no axonal regrowth through the injury site could be demonstrated yet they were able to perform weight-supporting hindlimb stepping overground and on the treadmill. When placed in an environment of reduced sensory feedback (swimming) P7-injured animals swam using their hindlimbs, suggesting that the axons that grew across the lesion made functional connections; P28-injured animals swam using their forelimbs only, suggesting that their overground hindlimb movements were reflex-dependent and thus likely to be generated locally in the lumbar spinal cord. Modifications to propriospinal circuitry in P7- and P28-injured opossums were demonstrated by changes in the number of fluorescently labelled neurons detected in the lumbar cord following tracer studies and changes in the balance of excitatory, inhibitory and neuromodulatory neurotransmitter receptors’ gene expression shown by qRT-PCR. These results are discussed in the context of studies indicating that although following injury the isolated segment of the spinal cord retains some capability of rhythmic movement the mechanisms involved in weight-bearing locomotion are distinct. PMID:23951105

Weight-bearing locomotion in the developing opossum, Monodelphis domestica following spinal transection: remodeling of neuronal circuits caudal to lesion.

PubMed

Wheaton, Benjamin J; Noor, Natassya M; Whish, Sophie C; Truettner, Jessie S; Dietrich, W Dalton; Zhang, Moses; Crack, Peter J; Dziegielewska, Katarzyna M; Saunders, Norman R

2013-01-01

Complete spinal transection in the mature nervous system is typically followed by minimal axonal repair, extensive motor paralysis and loss of sensory functions caudal to the injury. In contrast, the immature nervous system has greater capacity for repair, a phenomenon sometimes called the infant lesion effect. This study investigates spinal injuries early in development using the marsupial opossum Monodelphis domestica whose young are born very immature, allowing access to developmental stages only accessible in utero in eutherian mammals. Spinal cords of Monodelphis pups were completely transected in the lower thoracic region, T10, on postnatal-day (P)7 or P28 and the animals grew to adulthood. In P7-injured animals regrown supraspinal and propriospinal axons through the injury site were demonstrated using retrograde axonal labelling. These animals recovered near-normal coordinated overground locomotion, but with altered gait characteristics including foot placement phase lags. In P28-injured animals no axonal regrowth through the injury site could be demonstrated yet they were able to perform weight-supporting hindlimb stepping overground and on the treadmill. When placed in an environment of reduced sensory feedback (swimming) P7-injured animals swam using their hindlimbs, suggesting that the axons that grew across the lesion made functional connections; P28-injured animals swam using their forelimbs only, suggesting that their overground hindlimb movements were reflex-dependent and thus likely to be generated locally in the lumbar spinal cord. Modifications to propriospinal circuitry in P7- and P28-injured opossums were demonstrated by changes in the number of fluorescently labelled neurons detected in the lumbar cord following tracer studies and changes in the balance of excitatory, inhibitory and neuromodulatory neurotransmitter receptors' gene expression shown by qRT-PCR. These results are discussed in the context of studies indicating that although following injury the isolated segment of the spinal cord retains some capability of rhythmic movement the mechanisms involved in weight-bearing locomotion are distinct.

Improved axonal regeneration of transected spinal cord mediated by multichannel collagen conduits functionalized with neurotrophin-3 gene.

PubMed

Yao, L; Daly, W; Newland, B; Yao, S; Wang, W; Chen, B K K; Madigan, N; Windebank, A; Pandit, A

2013-12-01

Functionalized biomaterial scaffolds targeted at improving axonal regeneration by enhancing guided axonal growth provide a promising approach for the repair of spinal cord injury. Collagen neural conduits provide structural guidance for neural tissue regeneration, and in this study it is shown that these conduits can also act as a reservoir for sustained gene delivery. Either a G-luciferase marker gene or a neurotrophin-3-encoding gene, complexed to a non-viral, cyclized, PEGylated transfection vector, was loaded within a multichannel collagen conduit. The complexed genes were then released in a controlled fashion using a dual release system both in vitro and in vivo. For evaluation of their biological performance, the loaded conduits were implanted into the completely transected rat thoracic spinal cord (T8-T10). Aligned axon regeneration through the channels of conduits was observed one month post-surgery. The conduits delivering neurotrophin-3 polyplexes resulted in significantly increased neurotrophin-3 levels in the surrounding tissue and a statistically higher number of regenerated axons versus the control conduits (P<0.05). This study suggests that collagen neural conduits delivering a highly effective non-viral therapeutic gene may hold promise for repair of the injured spinal cord.

Either brain-derived neurotrophic factor or neurotrophin-3 only neurotrophin-producing grafts promote locomotor recovery in untrained spinalized cats.

PubMed

Ollivier-Lanvin, Karen; Fischer, Itzhak; Tom, Veronica; Houlé, John D; Lemay, Michel A

2015-01-01

Background. Transplants of cellular grafts expressing a combination of 2 neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) have been shown to promote and enhance locomotor recovery in untrained spinalized cats. Based on the time course of recovery and the absence of axonal growth through the transplants, we hypothesized that recovery was due to neurotrophin-mediated plasticity within the existing locomotor circuitry of the lumbar cord. Since BDNF and NT-3 have different effects on axonal sprouting and synaptic connectivity/strengthening, it becomes important to ascertain the contribution of each individual neurotrophins to recovery. Objective. We studied whether BDNF or NT-3 only producing cellular grafts would be equally effective at restoring locomotion in untrained spinal cats. Methods. Rat fibroblasts secreting one of the 2 neurotrophins were grafted into the T12 spinal transection site of adult cats. Four cats in each group (BDNF alone or NT-3 alone) were evaluated. Locomotor recovery was tested on a treadmill at 3 and 5 weeks post-transection/grafting. Results. Animals in both groups were capable of plantar weight-bearing stepping at speed up to 0.8 m/s as early as 3 weeks and locomotor capabilities were similar at 3 and 5 weeks for both types of graft. Conclusions. Even without locomotor training, either BDNF or NT-3 only producing grafts promote locomotor recovery in complete spinal animals. More clinically applicable delivery methods need to be developed. © The Author(s) 2014.

Quantitative anatomical and behavioral analyses of regeneration and collateral sprouting following spinal cord transection in the nurse shark (ginglymostoma cirratum).

PubMed

Gelderd, J B

1979-01-01

The spinal cord was transected at the mid-thoracic level in 32 nurse sharks. Four animals per group were sacrificed at intervals of 10, 20, 30, 40, 60 and 90 days postoperative. Two groups of fish underwent a subsequent spinla1 cord retransection at the same site at 90 days and were sacrificed 10 and 20 days later. Three sections of spinal cord were removed from each shark for histological analysis. Behaviorally, timed trials for swimming speed and a strength test for axial musculature contraction caudal to the lesion site were performed at 5 day postoperative intervals. Histological analysis showed little regeneration (9-13 percent) of two descending tracts 90 days following the lesion and no return of rostrally controlled movements caudal to the lesion. However, synaptic readjustment did occur caudal to the lesion. This phenomenon was attributed to local segmental sprouting of adjacent, intact nerve fibers. A close correlation was shown between this synaptic readjustment and the strength of uncontrollable undulatory movements seen caudal to the lesion site following spinal cord transection. The relationship of regeneration and collateral sprouting to quantitative behavioral changes is discussed.

Integration of donor mesenchymal stem cell-derived neuron-like cells into host neural network after rat spinal cord transection.

PubMed

Zeng, Xiang; Qiu, Xue-Cheng; Ma, Yuan-Huan; Duan, Jing-Jing; Chen, Yuan-Feng; Gu, Huai-Yu; Wang, Jun-Mei; Ling, Eng-Ang; Wu, Jin-Lang; Wu, Wutian; Zeng, Yuan-Shan

2015-06-01

Functional deficits following spinal cord injury (SCI) primarily attribute to loss of neural connectivity. We therefore tested if novel tissue engineering approaches could enable neural network repair that facilitates functional recovery after spinal cord transection (SCT). Rat bone marrow-derived mesenchymal stem cells (MSCs), genetically engineered to overexpress TrkC, receptor of neurotrophin-3 (NT-3), were pre-differentiated into cells carrying neuronal features via co-culture with NT-3 overproducing Schwann cells in 3-dimensional gelatin sponge (GS) scaffold for 14 days in vitro. Intra-GS formation of MSC assemblies emulating neural network (MSC-GS) were verified morphologically via electron microscopy (EM) and functionally by whole-cell patch clamp recording of spontaneous post-synaptic currents. The differentiated MSCs still partially maintained prototypic property with the expression of some mesodermal cytokines. MSC-GS or GS was then grafted acutely into a 2 mm-wide transection gap in the T9-T10 spinal cord segments of adult rats. Eight weeks later, hindlimb function of the MSC-GS-treated SCT rats was significantly improved relative to controls receiving the GS or lesion only as indicated by BBB score. The MSC-GS transplantation also significantly recovered cortical motor evoked potential (CMEP). Histologically, MSC-derived neuron-like cells maintained their synapse-like structures in vivo; they additionally formed similar connections with host neurites (i.e., mostly serotonergic fibers plus a few corticospinal axons; validated by double-labeled immuno-EM). Moreover, motor cortex electrical stimulation triggered c-fos expression in the grafted and lumbar spinal cord cells of the treated rats only. Our data suggest that MSC-derived neuron-like cells resulting from NT-3-TrkC-induced differentiation can partially integrate into transected spinal cord and this strategy should be further investigated for reconstructing disrupted neural circuits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transplantation of Embryonic Spinal Cord Derived Cells Helps to Prevent Muscle Atrophy after Peripheral Nerve Injury

PubMed Central

Ruven, Carolin; Li, Wen; Li, Heng; Wong, Wai-Man; Wu, Wutian

2017-01-01

Injuries to peripheral nerves are frequent in serious traumas and spinal cord injuries. In addition to surgical approaches, other interventions, such as cell transplantation, should be considered to keep the muscles in good condition until the axons regenerate. In this study, E14.5 rat embryonic spinal cord fetal cells and cultured neural progenitor cells from different spinal cord segments were injected into transected musculocutaneous nerve of 200–300 g female Sprague Dawley (SD) rats, and atrophy in biceps brachii was assessed. Both kinds of cells were able to survive, extend their axons towards the muscle and form neuromuscular junctions that were functional in electromyographic studies. As a result, muscle endplates were preserved and atrophy was reduced. Furthermore, we observed that the fetal cells had a better effect in reducing the muscle atrophy compared to the pure neural progenitor cells, whereas lumbar cells were more beneficial compared to thoracic and cervical cells. In addition, fetal lumbar cells were used to supplement six weeks delayed surgical repair after the nerve transection. Cell transplantation helped to preserve the muscle endplates, which in turn lead to earlier functional recovery seen in behavioral test and electromyography. In conclusion, we were able to show that embryonic spinal cord derived cells, especially the lumbar fetal cells, are beneficial in the treatment of peripheral nerve injuries due to their ability to prevent the muscle atrophy. PMID:28264437

Mechanism of the cardiovascular activity of dibenzoxazepine in cats.

PubMed

Lundy, P M

1978-04-01

Small i.v. doses of dibenzoxazepine (DBO) (50--400 microgram/kg) given to anesthetized cats resulted in dose related increases in heart rate (up to 70 beats/min) and blood pressure (up to 80 mm Hg). The pressor response was blocked by pretreatment of the animals with phentolamine; pretreatment for 3 days with 6-hydroxdopamine; with mecamylamine and spinal transection between C1 and C2 but not by propranolol or adrenalectomy. The increase in heart rate was blocked by pretreatment with propranolol, 6-hydroxydopamine, mecamylamine and spinal transection whereas adrenalectomy only affected the response slightly. DBO produced only negative effects on the isolated rabbit heart. Bioassay of arterial blood showed an increased level of circulating catecholamines corresponding to the cardiovascular stimulation. DBO had no tyramine-like activity on the isolated rabbit aortic strip but slightly potentiated the contraction induced by noradrenaline. These findings strongly suggest that the cardiovascular effects resulted from central stimulation of the sympathetic nervous system. A minor part of the observed sympathomimetic effects may also be the result of the ability of DBO to potentiate the effects of noradrenaline perhaps by blocking catecholamine uptake.

Therapy induces widespread reorganization of motor cortex after complete spinal transection that supports motor recovery.

PubMed

Ganzer, Patrick D; Manohar, Anitha; Shumsky, Jed S; Moxon, Karen A

2016-05-01

Reorganization of the somatosensory system and its relationship to functional recovery after spinal cord injury (SCI) has been well studied. However, little is known about the impact of SCI on organization of the motor system. Recent studies suggest that step-training paradigms in combination with spinal stimulation, either electrically or through pharmacology, are more effective than step training alone at inducing recovery and that reorganization of descending corticospinal circuits is necessary. However, simpler, passive exercise combined with pharmacotherapy has also shown functional improvement after SCI and reorganization of, at least, the sensory cortex. In this study we assessed the effect of passive exercise and serotonergic (5-HT) pharmacological therapies on behavioral recovery and organization of the motor cortex. We compared the effects of passive hindlimb bike exercise to bike exercise combined with daily injections of 5-HT agonists in a rat model of complete mid-thoracic transection. 5-HT pharmacotherapy combined with bike exercise allowed the animals to achieve unassisted weight support in the open field. This combination of therapies also produced extensive expansion of the axial trunk motor cortex into the deafferented hindlimb motor cortex and, surprisingly, reorganization within the caudal and even the rostral forelimb motor cortex areas. The extent of the axial trunk expansion was correlated to improvement in behavioral recovery of hindlimbs during open field locomotion, including weight support. From a translational perspective, these data suggest a rationale for developing and optimizing cost-effective, non-invasive, pharmacological and passive exercise regimes to promote plasticity that supports restoration of movement after spinal cord injury. Copyright © 2016. Published by Elsevier Inc.

Why New Spinal Cord Plasticity Does Not Disrupt Old Motor Behaviors.

PubMed

Chen, Yi; Chen, Lu; Wang, Yu; Chen, Xiang Yang; Wolpaw, Jonathan R

2017-08-23

When new motor learning changes the spinal cord, old behaviors are not impaired; their key features are preserved by additional compensatory plasticity. To explore the mechanisms responsible for this compensatory plasticity, we transected the spinal dorsal ascending tract before or after female rats acquired a new behavior-operantly conditioned increase or decrease in the right soleus H-reflex-and examined an old behavior-locomotion. Neither spinal dorsal ascending tract transection nor H-reflex conditioning alone impaired locomotion. Nevertheless, when spinal dorsal ascending tract transection and H-reflex conditioning were combined, the rats developed a limp and a tilted posture that correlated in direction and magnitude with the H-reflex change. When the right H-reflex was increased by conditioning, the right step lasted longer than the left and the right hip was higher than the left; when the right H-reflex was decreased by conditioning, the opposite occurred. These results indicate that ascending sensory input guides the compensatory plasticity that normally prevents the plasticity underlying H-reflex change from impairing locomotion. They support the concept of the state of the spinal cord as a negotiated equilibrium that reflects the concurrent influences of all the behaviors in an individual's repertoire; and they support the new therapeutic strategies this concept introduces. SIGNIFICANCE STATEMENT The spinal cord provides a reliable final common pathway for motor behaviors throughout life. Until recently, its reliability was explained by the assumption that it is hardwired; but it is now clear that the spinal cord changes continually as new behaviors are acquired. Nevertheless, old behaviors are preserved. This study shows that their preservation depends on sensory feedback from the spinal cord to the brain: if feedback is removed, the acquisition of a new behavior may disrupt an old behavior. In sum, when a new behavior changes the spinal cord, sensory feedback to the brain guides further change that preserves old behaviors. This finding contributes to a new understanding of spinal cord function and to development of new rehabilitation therapies. Copyright © 2017 the authors 0270-6474/17/378198-09$15.00/0.

A spinal thecal sac constriction model supports the theory that induced pressure gradients in the cord cause edema and cyst formation.

PubMed

Josephson, A; Greitz, D; Klason, T; Olson, L; Spenger, C

2001-03-01

Spinal cord cysts are a devastating condition that occur secondary to obstructions of the spinal canal, which may be caused by congenital malformations, trauma, spinal canal stenosis, tumors, meningitis, or arachnoiditis. A hypothesis that could explain how spinal cord cysts form in these situations has been presented recently. Therefore, a novel spinal thecal sac constriction model was implemented to test various aspects of this hypothesis. Thecal sac constriction was achieved by subjecting rats to an extradural silk ligature at the T8 spinal cord level. Rats with complete spinal cord transection served as a second model for comparison. The animals underwent high-resolution magnetic resonance imaging and histological analysis. Thecal sac constriction caused edema cranial and caudal to the ligation within 3 weeks, and cysts developed after 8 to 13 weeks. In contrast, cysts in rats with spinal cord transection were located predominantly in the cranial spinal cord. Histological sections of spinal cords confirmed the magnetic resonance imaging results. Magnetic resonance imaging provided the specific advantage of enabling characterization of events as they occurred repeatedly over time in the spinal cords of individual living animals. The spinal thecal sac constriction model proved useful for investigation of features of the cerebrospinal fluid pulse pressure theory. Edema and cyst distributions were in accordance with this theory. We conclude that induced intramedullary pressure gradients originating from the cerebrospinal fluid pulse pressure may underlie cyst formation in the vicinity of spinal canal obstructions and that cysts are preceded by edema.

Transformation of synaptic vesicle phenotype in the intramedullary axonal arbors of cat spinal motoneurons following peripheral nerve injury.

PubMed

Havton, L A; Kellerth, J O

2001-08-01

Permanent transection of a peripheral motor nerve induces a gradual elimination of whole axon collateral systems in the axotomized spinal motoneurons. There is also an initial concurrent decrease in the amount of recurrent inhibition exerted by these arbors in the spinal cord for up to 6 weeks after the injury, whereas the same reflex action returns to normal by the 12-week postoperative state. The aim of the present investigation was to study the fine structure of the intramedullary axonal arbors of axotomized alpha-motoneurons in the adult cat spinal cord following a permanent peripheral motor nerve lesion. For this purpose, single axotomized alpha-motoneurons were labeled intracellularly with horseradish peroxidase at 12 weeks after permanent transection of their peripheral motor nerve. The intramedullary portions of their motor axon and axon collateral arbors were first reconstructed at the light microscopic level and subsequently studied ultrastructurally. This study shows that the synaptic contacts made by the intramedullary axon collateral arbors of axotomized motoneurons have undergone a change in synaptic vesicle ultrastructure from spherical and clear vesicles to spherical and dense-cored vesicles at 12 weeks after the transection of their peripheral axons. We suggest that the present transformation in synaptic vesicle fine structure may also correspond to a change in the contents of these boutons. This may, in turn, be responsible for the strengthening and recovery of the recurrent inhibitory reflex action exerted by the axotomized spinal motoneurons following a prolonged permanent motor nerve injury.

Fractionated radiation facilitates repair and functional motor recovery after spinal cord transection in rat.

PubMed

Kalderon, N; Xu, S; Koutcher, J A; Fuks, Z

2001-06-22

Previous studies suggest that motor recovery does not occur after spinal cord injury because reactive glia abort the natural repair processes. A permanent wound gap is left in the cord and the brain-cord circuitry consequently remains broken. Single-dose x-irradiation destroys reactive glia at the damage site in transected adult rat spinal cord. The wound then heals naturally, and a partially functional brain-cord circuitry is reconstructed. Timing is crucial; cell ablation is beneficial only within the third week after injury. Data presented here point to the possibility of translating these observations into a clinical therapy for preventing the paralysis following spinal cord injury in the human. The lesion site (at low thoracic level) in severed adult rat spinal cord was treated daily, over the third week postinjury, with protocols of fractionated radiation similar to those for treating human spinal cord tumors. This resulted, as with the single-dose protocol, in wound healing and restoration of some hindquarter motor function; in addition, the beneficial outcome was augmented. Of the restored hindlimb motor functions, weight-support and posture in stance was the only obvious one. Recovery of this motor function was partial to substantial and its incidence was 100% instead of about 50% obtained with the single-dose treatment. None of the hindlimbs, however, regained frequent stepping or any weight-bearing locomotion. These data indicate that the therapeutic outcome may be further augmented by tuning the radiation parameters within the critical time-window after injury. These data also indicate that dose-fractionation is an effective strategy and better than the single-dose treatment for targeting of reactive cells that abort the natural repair, suggesting that radiation therapy could be developed into a therapeutic procedure for repairing injured spinal cord.

Epidural meperidine for control of autonomic hyperreflexia in a quadriplegic undergoing cystoscopy.

PubMed

Baraka, A; Noueihid, R; Sibai, A N; Baroody, M; Louis, F; Hemady, K

1989-06-01

Epidural meperidine was used to control autonomic hyperreflexia (AH) during cystoscopy and transuretheral sphincterotomy, in a quadriplegic patient who had chronic spinal cord transection at C6 level. Meperidine 100 mg diluted in 10 ml saline was injected in the epidural space at L3-L4 level. Within 10 minutes and throughout the surgical procedure, the blood pressure stabilized at 125/70-140/80 mmHg. Epidural meperidine produces selective blockade of the spinal opiate receptors and hence may block the nociceptive reflexes below the level of cord transection and prevent AH.

Activation of Central Pattern Generator for Respiration Following Complete High Cervical Spinal Cord Interruption

DTIC Science & Technology

2016-09-01

suppression of the respiratory CPG in both intact and post-injury (high cervical transection) conditions. Adhering to the experiments outlined in our SOW...spinal respiratory neurons (cervical C3-C5 and C1-C2 levels) were characterized by their location, pattern (via extra- and intracellular recordings...Marchenko, 2016). These ‘spinal bursts’ were not phase-locked to the supraspinal (ponto-medullary) respiratory rhythm. We recorded spinal interneurons

Cardiovascular and temperature changes in spinal cord injured rats at rest and during autonomic dysreflexia

PubMed Central

Laird, A S; Carrive, P; Waite, P M E

2006-01-01

In patients with high spinal cord injuries autonomic dysfunction can be dangerous, leading to medical complications such as postural hypotension, autonomic dysreflexia and temperature disturbance. While animal models have been developed to study autonomic dysreflexia, associated temperature changes have not been documented. Our aim here was to use radiotelemetry and infrared thermography in rodents to record the development of cardiovascular and skin temperature changes following complete T4 transection. In adult male Wistar rats (n = 5), responses were assessed prior to spinal cord injury (intact) and for 6 weeks following injury. Statistical analysis by a repeated-measure ANOVA revealed that following spinal cord injury (SCI), rats exhibited decreased mean arterial pressure (MAP, average decrease of 26 mmHg; P < 0.035) and elevated heart rate (HR, average increase of 65 bpm, P < 0.035) at rest. The basal core body temperature following SCI was also significantly lower than intact levels (−0.9°C; P < 0.0035). Associated with this decreased basal core temperature following SCI was an increased skin temperature of the mid-tail and hindpaw (+5.6 and +4.0°C, respectively; P < 0.0003) consistent with decreased cutaneous vasoconstrictor tone. Autonomic dysreflexia, in response to a 1 min colorectal distension (25 mmHg), was fully developed by 4 weeks after spinal cord transection, producing increases in MAP greater than 25 mmHg (P < 0.0003). In contrast to the tachycardia seen in intact animals in response to colorectal distension, SCI animals exhibited bradycardia (P < 0.0023). During episodes of autonomic dysreflexia mid-tail surface temperature decreased (approx. −1.7°C, P < 0.012), consistent with cutaneous vasoconstriction. This is the first study to compare cardiovascular dysfunction with temperature changes following spinal cord transection in rats. PMID:16973703

Effects of antidromic stimulation of the ventral root on glucose utilization in the ventral horn of the spinal cord in the rat.

PubMed Central

Kadekaro, M; Vance, W H; Terrell, M L; Gary, H; Eisenberg, H M; Sokoloff, L

1987-01-01

Electrical stimulation of the proximal stump of the transected sciatic nerve increased glucose utilization in the ventral horn of the spinal cord, with the greater increase in Rexed's lamina IX. Antidromic stimulation of the ventral root, however, did not change glucose utilization in the ventral horn. These results suggest that the axon terminals and not the cell bodies are the sites of enhanced metabolic activity during increased electrical activity in these elements. Images PMID:3474665

Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats.

PubMed

Gad, Parag; Choe, Jaehoon; Nandra, Mandheerej Singh; Zhong, Hui; Roy, Roland R; Tai, Yu-Chong; Edgerton, V Reggie

2013-01-21

Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array. We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1-100 Hz and 1-10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats. In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia. Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles.

Adenovirus vector-mediated ex vivo gene transfer of brain-derived neurotrophic factor to bone marrow stromal cells promotes axonal regeneration after transplantation in completely transected adult rat spinal cord

PubMed Central

Kamada, Takahito; Hashimoto, Masayuki; Murakami, Masazumi; Shirasawa, Hiroshi; Sakao, Seiichiro; Ino, Hidetoshi; Yoshinaga, Katsunori; Koshizuka, Shuhei; Moriya, Hideshige; Yamazaki, Masashi

2007-01-01

The aim of this study was to evaluate the efficacy in adult rat completely transected spinal cord of adenovirus vector-mediated brain-derived neurotrophic factor (BDNF) ex vivo gene transfer to bone marrow stromal cells (BMSC). BMSC were infected with adenovirus vectors carrying β-galactosidase (AxCALacZ) or BDNF (AxCABDNF) genes. The T8 segment of spinal cord was removed and replaced by graft containing Matrigel alone (MG group) or Matrigel and BMSC infected by AxCALacZ (BMSC-LacZ group) or AxCABDNF (BMSC-BDNF group). Axons in the graft were evaluated by immunohistochemistry and functional recovery was assessed with BBB locomotor scale. In the BMSC-BDNF group, the number of fibers positive for growth associated protein-43, tyrosine hydroxylase, and calcitonin gene-related peptide was significantly larger than numbers found for the MG and BMSC-LacZ groups. Rats from BMSC-BDNF and BMSC-LacZ groups showed significant recovery of hind limb function compared with MG rats; however, there was no significant difference between groups in degree of functional recovery. These findings demonstrate that adenovirus vector-mediated ex vivo gene transfer of BDNF enhances the capacity of BMSC to promote axonal regeneration in this completely transected spinal cord model; however, BDNF failed to enhance hind limb functional recovery. Further investigation is needed to establish an optimal combination of cell therapy and neurotrophin gene transfer for cases of spinal cord injury. PMID:17885772

Upper motor neurone modulation of the structure of the terminal cisternae in rat skeletal muscle fibres.

PubMed

Dulhunty, A F; Gage, P W; Valois, A A

1981-12-23

There are fewer indentations on the flat surfaces of terminal cisternae in soleus (slow-twitch) than in extensor digitorum longus (EDL, fast-twitch) muscle fibres of rats. Following mid-thoracic spinal cord transection, there is an increase in the number of indentations in soleus fibres but no change in EDL fibres. The increase in the numbers of indentations after spinal cord transections is correlated with changes in the contractile and charge movement properties of the soleus fibres so that they resemble normal EDL fibres. The indentations appear to have an important role in excitation-contraction coupling.

Large and persistent electrical currents enter the transected lamprey spinal cord.

PubMed Central

Borgens, R B; Jaffe, L F; Cohen, M J

1980-01-01

The electrical currents at the surface of the proximal portion of an isolated and transected lamprey spinal cord were measured with an extracellular vibrating probe. Soon after transection, currents of about 0.5 mA/cm2 enter the cut surface of the spinal cord. These currents fall to about a quarter of their initial value within an hour; within the next 2 days they gradually decline from about 100 microA/cm2 to about 4 microA/cm2; they then remain constant up to 6 days posttransection, when the measurements were ended. The pattern of current entry included substantial peaks opposite (and presumably into) the cut ends of giant axons. Response to changes in the ionic composition of the medium indicates that about half of the injury current consists of Na+, and that much of the rest may consist of Ca2+. The measured influx of ions, which adds up to several coulombs per cm2 in a few days, should radically alter the ionic composition of the terminal few millimeters of neural tissue. Thus it may be important in the degenerative and regenerative responses of neurons to axotomy. Images PMID:6928670

Two chronic motor training paradigms differentially influe nce acute instrume ntal learning in spinally transected rats

PubMed Central

Bigbee, Allison J.; Crown, Eric D.; Ferguson, Adam R.; Roy, Roland R.; Tillakaratne, Niranjala J.K.; Grau, James W.; Edgerton, V. Reggie

2008-01-01

The effect of two chronic motor training paradigms on the ability of the lumbar spinal cord to perform an acute instrumental learning task was examined in neonatally (postnatal day 5; P5) spinal cord transected (i.e., spinal) rats. At ∼P30, rats began either unipedal hindlimb stand training (Stand-Tr; 20-25 min/day, 5 days/wk), or bipedal hindlimb step training (Step-Tr; 20 min/day; 5 days/wk) for 7 wks. Non-trained spinal rats (Non-Tr) served as controls. After 7 wks all groups were tested on the flexor-biased instrumental learning paradigm. We hypothesized that 1) Step-Tr rats would exhibit an increased capacity to learn the flexor-biased task relative to Non-Tr subjects, as locomotion involves repetitive training of the tibialis anterior (TA), the ankle flexor whose activation is important for successful instrumental learning, and 2) Stand-Tr rats would exhibit a deficit in acute motor learning, as unipedal training activates the ipsilateral ankle extensors, but not flexors. Results showed no differences in acute learning potential between Non-Tr and Step-Tr rats, while the Stand-Tr group showed a reduced capacity to learn the acute task. Further investigation of the Stand-Tr group showed that, while both the ipsilateral and contralateral hindlimbs were significantly impaired in their acute learning potential, the contralateral, untrained hindlimbs exhibited significantly greater learning deficits. These results suggest that different types of chronic peripheral input may have a significant impact on the ability to learn a novel motor task, and demonstrate the potential for experience-dependent plasticity in the spinal cord in the absence of supraspinal connectivity. PMID:17434606

Surgical treatment for old subaxial cervical dislocation with bilateral locked facets in a 3-year-old girl: A case report.

PubMed

Li, Cheng; Li, Lei; Duan, Jingzhu; Zhang, Lijun; Liu, Zhenjiang

2018-05-01

This study aimed to describe the case of a 3-year-old girl with old bilateral facet dislocation on cervical vertebrae 6 and 7, who had spinal cord transection, received surgical treatment, and achieved a relative satisfactory therapeutic effect. A 3-year-old girl was urgently transferred to the hospital after a car accident. DIAGNOSES:: she was diagnosed with splenic rupture, intracranial hemorrhage, cervical dislocation, spinal transection, and Monteggia fracture of the left upper limb. The girl underwent emergency splenectomy and was transferred to the intensive care unit of the hospital 15 days later. One-stage anterior-posterior approach surgery (anterior discectomy, posterior laminectomy, and pedicle screw fixation) was performed when the patient stabilized after 45-day symptomatic treatment. The operation was uneventful. The reduction of lower cervical dislocation was satisfactory, with sufficient spinal cord decompression. The internal fixation position was good, and the spinal sequence was well restored. The girl was discharged 2 weeks later after the operation and followed up for 2 years. The major nerve function of both upper limbs was recovered, with no obvious retardation of the growth of immature spine. A satisfactory therapeutic effect was achieved for a pediatric old subaxial cervical dislocation with bilateral locked facets using anterior discectomy, posterior laminectomy, and pedicle screw fixation. The posterior pedicle screw fixation provided a good three-dimensional stability of the spine, with reduced risk and complications caused by anterior internal fixation. The growth of immature spine was not obviously affected during the 2-year follow-up.

Automated quantitative gait analysis during overground locomotion in the rat: its application to spinal cord contusion and transection injuries.

PubMed

Hamers, F P; Lankhorst, A J; van Laar, T J; Veldhuis, W B; Gispen, W H

2001-02-01

Analysis of locomotion is an important tool in the study of peripheral and central nervous system damage. Most locomotor scoring systems in rodents are based either upon open field locomotion assessment, for example, the BBB score or upon foot print analysis. The former yields a semiquantitative description of locomotion as a whole, whereas the latter generates quantitative data on several selected gait parameters. In this paper, we describe the use of a newly developed gait analysis method that allows easy quantitation of a large number of locomotion parameters during walkway crossing. We were able to extract data on interlimb coordination, swing duration, paw print areas (total over stance, and at 20-msec time resolution), stride length, and base of support: Similar data can not be gathered by any single previously described method. We compare changes in gait parameters induced by two different models of spinal cord injury in rats, transection of the dorsal half of the spinal cord and spinal cord contusion injury induced by the NYU or MASCIS device. Although we applied this method to rats with spinal cord injury, the usefulness of this method is not limited to rats or to the investigation of spinal cord injuries alone.

Acute spinal cord injury (SCI) transforms how GABA affects nociceptive sensitization.

PubMed

Huang, Yung-Jen; Lee, Kuan H; Murphy, Lauren; Garraway, Sandra M; Grau, James W

2016-11-01

Noxious input can sensitize pain (nociceptive) circuits within the spinal cord, inducing a lasting increase in spinal cord neural excitability (central sensitization) that is thought to contribute to chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. The current study provides evidence that spinal cord injury (SCI) transforms how GABA affects nociceptive transmission within the spinal cord, recapitulating an earlier developmental state wherein GABA has an excitatory effect. In spinally transected rats, noxious electrical stimulation and inflammation induce enhanced mechanical reactivity (EMR), a behavioral index of nociceptive sensitization. Pretreatment with the GABA A receptor antagonist bicuculline blocked these effects. Peripheral application of an irritant (capsaicin) also induced EMR. Both the induction and maintenance of this effect were blocked by bicuculline. Cellular indices of central sensitization [c-fos expression and ERK phosphorylation (pERK)] were also attenuated. In intact (sham operated) rats, bicuculline had the opposite effect. Pretreatment with a GABA agonist (muscimol) attenuated nociceptive sensitization in intact, but not spinally injured, rats. The effect of SCI on GABA function was linked to a reduction in the Cl - transporter, KCC2, leading to a reduction in intracellular Cl - that would attenuate GABA-mediated inhibition. Pharmacologically blocking the KCC2 channel (with i.t. DIOA) in intact rats mimicked the effect of SCI. Conversely, a pharmacological treatment (bumetanide) that should increase intracellular Cl - levels blocked the effect of SCI. The results suggest that GABAergic neurons drive, rather than inhibit, the development of nociceptive sensitization after spinal injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.

PubMed

Sabino, Luzzi; Maria, Crovace Alberto; Luca, Lacitignola; Valerio, Valentini; Edda, Francioso; Giacomo, Rossi; Gloria, Invernici; Juan, Galzio Renato; Antonio, Crovace

2018-01-01

Proof of the efficacy and safety of a xenogeneic mesenchymal stem cell (MSCs) transplant for spinal cord injury (SCI) may theoretically widen the spectrum of possible grafts for neuroregeneration. Twenty rats were submitted to complete spinal cord transection. Ovine bone marrow MSCs, retrovirally transfected with red fluorescent protein and not previously induced for neuroglial differentiation, were applied in 10 study rats (MSCG). Fibrin glue was injected in 10 control rats (FGG). All rats were evaluated on a weekly basis and scored using the Basso-Beattie-Bresnahan (BBB) locomotor scale for 10 weeks, when the collected data were statistically analyzed. The spinal cords were then harvested and analyzed with light microscopy, immunohistochemistry, and immunofluorescence. Ovine MSCs culture showed positivity for Nestin. MSCG had a significant and durable recovery of motor functions ( P <.001). Red fluorescence was found at the injury sites in MSCG. Positivity for Nestin, tubulin βIII, NG2 glia, neuron-specific enolase, vimentin, and 200 kD neurofilament were also found at the same sites. Xenogeneic ovine bone marrow MSCs proved capable of engrafting into the injured rat spinal cord. Transdifferentiation into a neuroglial phenotype was able to support partial functional recovery.

Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats

PubMed Central

Sabino, Luzzi; Maria, Crovace Alberto; Luca, Lacitignola; Valerio, Valentini; Edda, Francioso; Giacomo, Rossi; Gloria, Invernici; Juan, Galzio Renato; Antonio, Crovace

2018-01-01

Background: Proof of the efficacy and safety of a xenogeneic mesenchymal stem cell (MSCs) transplant for spinal cord injury (SCI) may theoretically widen the spectrum of possible grafts for neuroregeneration. Methods: Twenty rats were submitted to complete spinal cord transection. Ovine bone marrow MSCs, retrovirally transfected with red fluorescent protein and not previously induced for neuroglial differentiation, were applied in 10 study rats (MSCG). Fibrin glue was injected in 10 control rats (FGG). All rats were evaluated on a weekly basis and scored using the Basso–Beattie–Bresnahan (BBB) locomotor scale for 10 weeks, when the collected data were statistically analyzed. The spinal cords were then harvested and analyzed with light microscopy, immunohistochemistry, and immunofluorescence. Results: Ovine MSCs culture showed positivity for Nestin. MSCG had a significant and durable recovery of motor functions (P <.001). Red fluorescence was found at the injury sites in MSCG. Positivity for Nestin, tubulin βIII, NG2 glia, neuron-specific enolase, vimentin, and 200 kD neurofilament were also found at the same sites. Conclusions: Xenogeneic ovine bone marrow MSCs proved capable of engrafting into the injured rat spinal cord. Transdifferentiation into a neuroglial phenotype was able to support partial functional recovery. PMID:29497572

Olfactory ensheathing cells but not fibroblasts reduce the duration of autonomic dysreflexia in spinal cord injured rats.

PubMed

Cloutier, Frank; Kalincik, Tomas; Lauschke, Jenny; Tuxworth, Gervase; Cavanagh, Brenton; Meedeniya, Adrian; Mackay-Sim, Alan; Carrive, Pascal; Waite, Phil

2016-12-01

Autonomic dysreflexia is a common complication after high level spinal cord injury and can be life-threatening. We have previously shown that the acute transplantation of olfactory ensheathing cells into the lesion site of rats transected at the fourth thoracic spinal cord level reduced autonomic dysreflexia up to 8weeks after spinal cord injury. This beneficial effect was correlated with changes in the morphology of sympathetic preganglionic neurons despite the olfactory cells surviving no longer than 3weeks. Thus the transitory presence of olfactory ensheathing cells at the injury site initiated long-term functional as well as morphological changes in the sympathetic preganglionic neurons. The primary aim of the present study was to evaluate whether olfactory ensheathing cells survive after transplantation within the parenchyma close to sympathetic preganglionic neurons and whether, in this position, they still reduce the duration of autonomic dysreflexia and modulate sympathetic preganglionic neuron morphology. The second aim was to quantify the density of synapses on the somata of sympathetic preganglionic neurons with the hypothesis that the reduction of autonomic dysreflexia requires synaptic changes. As a third aim, we evaluated the cell type-specificity of olfactory ensheathing cells by comparing their effects with a control group transplanted with fibroblasts. Animals transplanted with OECs had a faster recovery from hypertension induced by colorectal distension at 6 and 7weeks but not at 8weeks after T4 spinal cord transection. Olfactory ensheathing cells survived for at least 8weeks and were observed adjacent to sympathetic preganglionic neurons whose overall number of primary dendrites was reduced and the synaptic density on the somata increased, both caudal to the lesion site. Our results showed a long term cell type-specific effects of olfactory ensheathing cells on sympathetic preganglionic neurons morphology and on the synaptic density on their somata, and a transient cell type-specific reduction of autonomic dysreflexia. Copyright © 2016 Elsevier B.V. All rights reserved.

Aetioepidemiological profile of spinal injury patients in Eastern Nepal.

PubMed

Lakhey, S; Jha, N; Shrestha, B P; Niraula, S

2005-10-01

This is a retrospective case series of 233 spinal injury patients admitted to the orthopaedic ward of BPKIHS from May 1997 to April 2001. The inpatient records were analysed. In all, 40.3% of spinal injuries resulted from falls from trees while cutting leaves for fodder, and 27.9% resulted from falls from first/second floors. More than 75% of total spinal injuries are largely preventable. Overall, 46.8% of our spinal injury patients had complete cord transection at the level of injury. All adolescents and adults, irrespective of age or sex, should be the target groups for community education and intervention programmes for prevention of spinal injury.

Learning from the spinal cord: How the study of spinal cord plasticity informs our view of learning

PubMed Central

Grau, James W.

2013-01-01

The paper reviews research examining whether and how training can induce a lasting change in spinal cord function. A framework for the study of learning, and some essential issues in experimental design, are discussed. A core element involves delayed assessment under common conditions. Research has shown that brain systems can induce a lasting (memory-like) alteration in spinal function. Neurons within the lower (lumbosacral) spinal cord can also adapt when isolated from the brain by means of a thoracic transection. Using traditional learning paradigms, evidence suggests that spinal neurons support habituation and sensitization as well as Pavlovian and instrumental conditioning. At a neurobiological level, spinal systems support phenomena (e.g., long-term potentiation), and involve mechanisms (e.g., NMDA mediated plasticity, protein synthesis) implicated in brain-dependent learning and memory. Spinal learning also induces modulatory effects that alter the capacity for learning. Uncontrollable/unpredictable stimulation disables the capacity for instrumental learning and this effect has been linked to the cytokine tumor necrosis factor (TNF). Predictable/controllable stimulation enables learning and counters the adverse effects of uncontrollable simulation through a process that depends upon brain-derived neurotrophic factor (BDNF). Finally, uncontrollable, but not controllable, nociceptive stimulation impairs recovery after a contusion injury. A process-oriented approach (neurofunctionalism) is outlined that encourages a broader view of learning phenomena. PMID:23973905

Modules in the brain stem and spinal cord underlying motor behaviors

PubMed Central

Cheung, Vincent C. K.; Bizzi, Emilio

2011-01-01

Previous studies using intact and spinalized animals have suggested that coordinated movements can be generated by appropriate combinations of muscle synergies controlled by the central nervous system (CNS). However, which CNS regions are responsible for expressing muscle synergies remains an open question. We address whether the brain stem and spinal cord are involved in expressing muscle synergies used for executing a range of natural movements. We analyzed the electromyographic (EMG) data recorded from frog leg muscles before and after transection at different levels of the neuraxis—rostral midbrain (brain stem preparations), rostral medulla (medullary preparations), and the spinal-medullary junction (spinal preparations). Brain stem frogs could jump, swim, kick, and step, while medullary frogs could perform only a partial repertoire of movements. In spinal frogs, cutaneous reflexes could be elicited. Systematic EMG analysis found two different synergy types: 1) synergies shared between pre- and posttransection states and 2) synergies specific to individual states. Almost all synergies found in natural movements persisted after transection at rostral midbrain or medulla but not at the spinal-medullary junction for swim and step. Some pretransection- and posttransection-specific synergies for a certain behavior appeared as shared synergies for other motor behaviors of the same animal. These results suggest that the medulla and spinal cord are sufficient for the expression of most muscle synergies in frog behaviors. Overall, this study provides further evidence supporting the idea that motor behaviors may be constructed by muscle synergies organized within the brain stem and spinal cord and activated by descending commands from supraspinal areas. PMID:21653716

Peripheral Inflammation Undermines the Plasticity of the Isolated Spinal Cord

PubMed Central

Huie, John R.; Grau, James W.

2009-01-01

Peripheral capsaicin treatment induces molecular changes that sensitize the responses of nociceptive neurons in the spinal dorsal horn. The current studies demonstrate that capsaicin also undermines the adaptive plasticity of the spinal cord, rendering the system incapable of learning a simple instrumental task. In these studies, male rats are transected at the second thoracic vertebra and are tested 24 to 48 hours later. During testing, subjects receive shock to one hindleg when it is extended (controllable stimulation). Rats quickly learn to maintain the leg in a flexed position. Rats that have been injected with capsaicin (1% or 3%) in the hindpaw fail to learn, even when tested on the leg contralateral to the injection. This learning deficit lasts at least 24 hours. Interestingly, training with controllable electrical stimulation prior to capsaicin administration protects the spinal cord against the maladaptive effects. Rats pretrained with controllable stimulation do not display a learning deficit or tactile allodynia. Moreover, controllable stimulation, combined with naltrexone, reverses the capsaicin-induced deficit. These data suggest that peripheral inflammation, accompanying spinal cord injuries, might have an adverse effect on recovery. PMID:18298266

Mechanisms of inhibitory action of TRK-130 (Naltalimide), a μ-opioid receptor partial agonist, on the micturition reflex.

PubMed

Fujimura, Morihiro; Izumimoto, Naoki; Kanie, Sayoko; Kobayashi, Ryosuke; Yoshikawa, Satoru; Momen, Shinobu; Hirakata, Mikito; Komagata, Toshikazu; Okanishi, Satoshi; Iwata, Masashi; Hashimoto, Tadatoshi; Doi, Takayuki; Yoshimura, Naoki; Kawai, Koji

2017-04-01

To clarify the mechanism of inhibitory action of TRK-130 (Naltalimide), a unique µ-opioid receptor partial agonist, on the micturition reflex. The effect of TRK-130 on isovolumetric rhythmic bladder contractions (RBCs) was examined in guinea pigs, the effect of which was clarified by co-treatment with naloxone or in spinal cord transection. The effect of TRK-130 on urodynamic parameters was also observed in guinea pigs. In addition, the effect of TRK-130 on bladder contraction induced by peripheral stimulation of the pelvic nerve was investigated in rats. TRK-130 (0.001-0.01 mg/kg, iv) dose-dependently inhibited RBCs, which was dose-dependently antagonized by naloxone; however, the antagonism susceptibility was different from morphine (1 mg/kg, iv). The minimum effective dose (0.003 mg/kg) of TRK-130 remained similar in spinal cord-transected animals. TRK-130 (0.0025 mg/kg, iv) increased bladder capacity without changing the voiding efficiency, maximum flow rate, and intravesical pressure at the maximum flow rate, whereas oxybutynin (1 mg/kg, iv) increased the bladder capacity but affected the other parameters. TRK-130 (0.005 mg/kg, iv) did not produce significant changes on the bladder contractions induced by peripheral stimulation of the pelvic nerve, while oxybutynin (1 mg/kg, iv) significantly suppressed the bladder contractions. These results suggest that TRK-130 enhances the bladder storage function by modulating the afferent limb of the micturition reflex through µ-opioid receptors in the spinal cord. TRK-130 could be a more effective and safer therapeutic agent with a different fashion from antimuscarinics and conventional opioids for overactive bladder.

Episodic swimming in the larval zebrafish is generated by a spatially distributed spinal network with modular functional organization

PubMed Central

Wiggin, Timothy D.; Anderson, Tatiana M.; Eian, John; Peck, Jack H.

2012-01-01

Despite the diverse methods vertebrates use for locomotion, there is evidence that components of the locomotor central pattern generator (CPG) are conserved across species. When zebrafish begin swimming early in development, they perform short episodes of activity separated by periods of inactivity. Within these episodes, the trunk flexes with side-to-side alternation and the traveling body wave progresses rostrocaudally. To characterize the distribution of the swimming CPG along the rostrocaudal axis, we performed transections of the larval zebrafish spinal cord and induced fictive swimming using N-methyl-d-aspartate (NMDA). In both intact and spinalized larvae, bursting is found throughout the rostrocaudal extent of the spinal cord, and the properties of fictive swimming observed were dependent on the concentration of NMDA. We isolated series of contiguous spinal segments by performing multiple spinal transections on the same larvae. Although series from all regions of the spinal cord have the capacity to produce bursts, the capacity to produce organized episodes of fictive swimming has a rostral bias: in the rostral spinal cord, only 12 contiguous body segments are necessary, whereas 23 contiguous body segments are necessary in the caudal spinal cord. Shorter series of segments were often active but produced either continuous rhythmic bursting or sporadic, nonrhythmic bursting. Both episodic and continuous bursting alternated between the left and right sides of the body and showed rostrocaudal progression, demonstrating the functional dissociation of the circuits responsible for episodic structure and fine burst timing. These findings parallel results in mammalian locomotion, and we propose a hierarchical model of the larval zebrafish swimming CPG. PMID:22572943

Differential Adaptations of the Musculoskeletal System after Spinal Cord Contusion and Transection in Rats.

PubMed

Lin, Ching-Yi; Androjna, Charlie; Rozic, Richard; Nguyen, Bichtram; Parsons, Brett; Midura, Ronald J; Lee, Yu-Shang

2018-04-05

Spinal cord injury (SCI) causes impaired neuronal function with associated deficits in the musculoskeletal system, which can lead to permanent disability. Here, the impact of SCI on in vivo musculoskeletal adaptation was determined by studying deficits in locomotor function and analyzing changes that occur in the muscle and bone compartments within the rat hindlimb after contusion or transection SCI. Analyses of locomotor patterns, as assessed via the Basso, Beattie, and Bresnahan (BBB) rating scale, revealed that transection animals showed significant deficits, while the contusion group had moderate deficits, compared with naïve groups. Muscle myofiber cross-sectional areas (CSA) of both the soleus and tibialis anterior muscles were significantly decreased three months after contusion SCI. Such decreases in CSA were even more dramatic in the transection SCI group, suggesting a dependence on muscle activity, which is further validated by the correlation analyses between BBB score and myofiber CSA. Bone compartment analyses, however, revealed that transection animals showed the most significant deficits, while contusion animals showed no significant differences in the trabecular bone content within the proximal tibia compartment. In general, values of bone volume per total bone volume (BV/TV) were similar across the SCI groups. Significant decreases were observed, however, in the transection animals for bone mineral content, bone mineral density, and three-dimensional trabecular structure parameters (trabecular number, thickness, and spacing) compared with the naïve and contusion groups. Together, these findings suggest an altered musculoskeletal system can be correlated directly to motor dysfunctions seen after SCI.

Trunk Robot Rehabilitation Training with Active Stepping Reorganizes and Enriches Trunk Motor Cortex Representations in Spinal Transected Rats

PubMed Central

Oza, Chintan S.

2015-01-01

Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we examine effects of robot rehabilitation that promotes recovery of hindlimb weight support functions on trunk motor cortex representations. Adult rats spinal transected as neonates (NTX rats) at the T9/10 level significantly improve function with our robot rehabilitation paradigm, whereas treadmill-only trained do not. We used intracortical microstimulation to map motor cortex in two NTX groups: (1) treadmill trained (control group); and (2) robot-assisted treadmill trained (improved function group). We found significant robot rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk cortex motor representations, as examined by cumulative entropy and mutual information for different trunk representations, increased; (4) trunk motor representations in the cortex moved toward more normal topography; and (5) trunk and forelimb motor representations that SCI-driven plasticity and compensations had caused to overlap were segregated. We conclude that effective robot rehabilitation training induces significant reorganization of trunk motor cortex and partially reverses some plastic changes that may be adaptive in non-stepping paraplegia after SCI. PMID:25948267

Timing in the Absence of Supraspinal Input I: Variable, but not Fixed, Spaced Stimulation of the Sciatic Nerve Undermines Spinally-Mediated Instrumental Learning

PubMed Central

Baumbauer, Kyle M.; Hoy, Kevin C.; Huie, John R.; Hughes, Abbey J.; Woller, Sarah A.; Puga, Denise A.; Setlow, Barry; Grau, James W.

2008-01-01

Rats with complete spinal transections are capable of acquiring a simple instrumentally trained response. If rats receive shock to one hindlimb when the limb is extended (controllable shock), the spinal cord will learn to hold the leg in a flexed position that minimizes shock exposure. If shock is delivered irrespective of leg position, subjects do not exhibit an increase in flexion duration and subsequently fail to learn when tested with controllable shock (learning deficit). Just 6 min of variable intermittent shock produces a learning deficit that lasts 24 hrs. Evidence suggests that the neural mechanisms underlying the learning deficit may be related to those involved in other instances of spinal plasticity (e.g., wind-up, long-term potentiation). The present paper begins to explore these relations by demonstrating that direct stimulation of the sciatic nerve also impairs instrumental learning. Six minutes of electrical stimulation (mono- or biphasic direct current [DC]) of the sciatic nerve in spinally transected rats produced a voltage-dependent learning deficit that persisted for 24 hr (Experiments 1–2) and was dependent on C-fiber activation (Experiment 7). Exposure to continuous stimulation did not produce a deficit, but intermittent burst or single pulse (as short as 0.1 ms) stimulation (delivered at a frequency of 0.5 Hz) did, irrespective of the pattern (fixed or variable) of stimulus delivery (Experiments 3–6, 8). When the duration of stimulation was extended from 6 to 30 min, a surprising result emerged; shocks applied in a random (variable) fashion impaired subsequent learning whereas shocks given in a regular pattern (fixed spacing) did not (Experiments 9–10). The results imply that spinal neurons are sensitive to temporal relations and that stimulation at regular intervals can have a restorative effect. PMID:18674601

Neurotrophic factors and receptors in the immature and adult spinal cord after mechanical injury or kainic acid.

PubMed

Widenfalk, J; Lundströmer, K; Jubran, M; Brene, S; Olson, L

2001-05-15

Delivery of neurotrophic factors to the injured spinal cord has been shown to stimulate neuronal survival and regeneration. This indicates that a lack of sufficient trophic support is one factor contributing to the absence of spontaneous regeneration in the mammalian spinal cord. Regulation of the expression of neurotrophic factors and receptors after spinal cord injury has not been studied in detail. We investigated levels of mRNA-encoding neurotrophins, glial cell line-derived neurotrophic factor (GDNF) family members and related receptors, ciliary neurotrophic factor (CNTF), and c-fos in normal and injured spinal cord. Injuries in adult rats included weight-drop, transection, and excitotoxic kainic acid delivery; in newborn rats, partial transection was performed. The regulation of expression patterns in the adult spinal cord was compared with that in the PNS and the neonate spinal cord. After mechanical injury of the adult rat spinal cord, upregulations of NGF and GDNF mRNA occurred in meningeal cells adjacent to the lesion. BDNF and p75 mRNA increased in neurons, GDNF mRNA increased in astrocytes close to the lesion, and GFRalpha-1 and truncated TrkB mRNA increased in astrocytes of degenerating white matter. The relatively limited upregulation of neurotrophic factors in the spinal cord contrasted with the response of affected nerve roots, in which marked increases of NGF and GDNF mRNA levels were observed in Schwann cells. The difference between the ability of the PNS and CNS to provide trophic support correlates with their different abilities to regenerate. Kainic acid delivery led to only weak upregulations of BDNF and CNTF mRNA. Compared with several brain regions, the overall response of the spinal cord tissue to kainic acid was weak. The relative sparseness of upregulations of endogenous neurotrophic factors after injury strengthens the hypothesis that lack of regeneration in the spinal cord is attributable at least partly to lack of trophic support.

An animal model of functional electrical stimulation: evidence that the central nervous system modulates the consequences of training

PubMed Central

Hook, MA; Grau, JW

2011-01-01

Study Design Review of how spinal neurons can modulate the consequences of functional electrical stimulation (FES) in an animal model. Methods Spinal effects of FES are examined in male Sprague–Dawley rats transected at the second thoracic vertebra. The rats are exposed to FES training 24–48 h after surgery. Experimental manipulations of stimulation parameters, combined with physiological and pharmacological procedures, are used to examine the potential role of spinal neurons. Results The isolated spinal cord is inherently capable of learning the response–outcome relations imposed in FES training contingencies. Adaptive behavioral modifications are observed when an outcome (electrical stimulation) is contingent on a behavioral response. In contrast, a lack of correlation between the response and outcome in training produces a learning deficit in the spinal cord, rendering it incapable of adaptive learning for up to 48 h. The N-methyl-D-aspartic acid receptor appears to mediate both the adaptive plasticity and loss of plasticity, seen in this spinal model. Conclusion The behavioral effects observed with FES therapies are not simply due to the direct (motor) consequences of stimulation elicited by the activation of efferent motor neurons and/or selected muscles. FES training has the capacity to shape inherent spinal circuits and to produce a long-lasting behavioral modification. Further understanding of the spinal mechanisms underlying adaptive behavioral modification will be integral for establishing functional neural connections in a regenerating spinal system. PMID:17700514

Initiating or blocking locomotion in spinal cats by applying noradrenergic drugs to restricted lumbar spinal segments.

PubMed

Marcoux, J; Rossignol, S

2000-11-15

After an acute low thoracic spinal transection (T13), cats can be made to walk with the hindlimbs on a treadmill with clonidine, an alpha2-noradrenergic agonist. Because previous studies of neonatal rat spinal cord in vitro suggest that the most important lumbar segments for rhythmogenesis are L1-L2, we investigated the role of various lumbar segments in the initiation of walking movements on a treadmill of adult cats spinalized (T13), 5-6 d earlier. The locomotor activities were evaluated from electromyographic and video recordings. The results show that: (1) localized topical application of clonidine in restricted baths over either the L3-L4 or the L5-L7 segments was sufficient to induce walking movements. Yohimbine, an alpha2-noradrenergic antagonist, could block this locomotion when applied over L3-L4 or L5-L7; (2) microinjections of clonidine in one or two lumbar segments from L3 to L5 could also induce locomotion; (3) after an intravenous injection of clonidine, locomotion was blocked by microinjections of yohimbine in segments L3, L4, or L5 but not if the injection was in L6; (4) locomotion was also blocked in all cases by additional spinal transections at L3 or L4. These results show that it is possible to initiate walking in the adult spinal cat with a pharmacological stimulation of a restricted number of lumbar segments and also that the integrity of the L3-L4 segments is necessary to sustain the locomotor activity.

Functional Multichannel Poly(Propylene Fumarate)-Collagen Scaffold with Collagen-Binding Neurotrophic Factor 3 Promotes Neural Regeneration After Transected Spinal Cord Injury.

PubMed

Chen, Xi; Zhao, Yannan; Li, Xing; Xiao, Zhifeng; Yao, Yuanjiang; Chu, Yun; Farkas, Balázs; Romano, Ilaria; Brandi, Fernando; Dai, Jianwu

2018-06-19

Many factors contribute to the poor axonal regrowth and ineffective functional recovery after spinal cord injury (SCI). Biomaterials have been used for SCI repair by promoting bridge formation and reconnecting the neural tissue at the lesion site. The mechanical properties of biomaterials are critical for successful design to ensure the stable support as soon as possible when compressed by the surrounding spine and musculature. Poly(propylene fumarate) (PPF) scaffolds with high mechanical strength have been shown to provide firm spatial maintenance and to promote repair of tissue defects. A multichannel PPF scaffold is combined with collagen biomaterial to build a novel biocompatible delivery system coated with neurotrophin-3 containing an engineered collagen-binding domain (CBD-NT3). The parallel-aligned multichannel structure of PPF scaffolds guide the direction of neural tissue regeneration across the lesion site and promote reestablishment of bridge connectivity. The combinatorial treatment consisting of PPF and collagen loaded with CBD-NT3 improves the inhibitory microenvironment, facilitates axonal and neuronal regeneration, survival of various types of functional neurons and remyelination and synapse formation of regenerated axons following SCI. This novel treatment strategy for SCI repair effectively promotes neural tissue regeneration after transected spinal injury by providing a regrowth-supportive microenvironment and eventually induces functional improvement. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Production of high quality brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) RNA from isolated populations of rat spinal cord motor neurons obtained by Laser Capture Microdissection (LCM).

PubMed

Mehta, Prachi; Premkumar, Brian; Morris, Renée

2016-08-03

The mammalian central nervous system (CNS) is composed of multiple cellular elements, making it challenging to segregate one particular cell type to study their gene expression profile. For instance, as motor neurons represent only 5-10% of the total cell population of the spinal cord, meaningful transcriptional analysis on these neurons is almost impossible to achieve from homogenized spinal cord tissue. A major challenge faced by scientists is to obtain good quality RNA from small amounts of starting material. In this paper, we used Laser Capture Microdissection (LCM) techniques to identify and isolate spinal cord motor neurons. The present analysis revealed that perfusion with paraformaldehyde (PFA) does not alter RNA quality. RNA integrity numbers (RINs) of tissue samples from rubrospinal tract (RST)-transected, intact spinal cord or from whole spinal cord homogenate were all above 8, which indicates intact, high-quality RNA. Levels of mRNA for brain-derived neurotrophic factor (BDNF) or for its tropomyosin receptor kinase B (TrkB) were not affected by rubrospinal tract (RST) transection, a surgical procedure that deprive motor neurons from one of their main supraspinal input. The isolation of pure populations of neurons with LCM techniques allows for robust transcriptional characterization that cannot be achieved with spinal cord homogenates. Such preparations of pure population of motor neurons will provide valuable tools to advance our understanding of the molecular mechanisms underlying spinal cord injury and neuromuscular diseases. In the near future, LCM techniques might be instrumental to the success of gene therapy for these debilitating conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The beneficial effects of treadmill step training on activity-dependent synaptic and cellular plasticity markers after complete spinal cord injury.

PubMed

Ilha, Jocemar; Centenaro, Lígia A; Broetto Cunha, Núbia; de Souza, Daniela F; Jaeger, Mariane; do Nascimento, Patrícia S; Kolling, Janaína; Ben, Juliana; Marcuzzo, Simone; Wyse, Angela T S; Gottfried, Carmem; Achaval, Matilde

2011-06-01

Several studies have shown that treadmill training improves neurological outcomes and promotes plasticity in lumbar spinal cord of spinal animals. The morphological and biochemical mechanisms underlying these phenomena remain unclear. The purpose of this study was to provide evidence of activity-dependent plasticity in spinal cord segment (L5) below a complete spinal cord transection (SCT) at T8-9 in rats in which the lower spinal cord segments have been fully separated from supraspinal control and that subsequently underwent treadmill step training. Five days after SCT, spinal animals started a step-training program on a treadmill with partial body weight support and manual step help. Hindlimb movements were evaluated over time and scored on the basis of the open-field BBB scale and were significantly improved at post-injury weeks 8 and 10 in trained spinal animals. Treadmill training also showed normalization of withdrawal reflex in trained spinal animals, which was significantly different from the untrained animals at post-injury weeks 8 and 10. Additionally, compared to controls, spinal rats had alpha motoneuronal soma size atrophy and reduced synaptophysin protein expression and Na(+), K(+)-ATPase activity in lumbar spinal cord. Step-trained rats had motoneuronal soma size, synaptophysin expression and Na(+), K(+)-ATPase activity similar to control animals. These findings suggest that treadmill step training can promote activity-dependent neural plasticity in lumbar spinal cord, which may lead to neurological improvements without supraspinal descending control after complete spinal cord injury.

[Serotoninergic system morphofunctional aspects in control of postural and locomotion function].

PubMed

Gerasimenko, Iu P; Moshonkina, T R; Pavlova, N V; Tomilovskaia, E S; Kozlovskaia, I B

2012-12-01

Different mediator systems including serotoninergic one can influence animal's locomotor behavior. It has been shown that the spinal cord in the absence of supraspinal control is able to induce the locomotor activity in hindlimbs and afferent system can activate this mechanism. In behavioral studies on the rats with complete transection of the spinal cord it has been demonstrated that the pharmacological blocking of serotoninergic system results in depression of motor activity mediated by activation of support reactions. Histological studies did not reveal any effects of activation of support reactions on the safety of neurons as well as on the distribution of synaptic contacts within L2-L4 spinal segments. At the same time it has been shown that blockade of the serotoninergic system results in alterations of cells located in 1-3 laminae of dorsal horns, and in 7 Rexed's lamina as well as in redistribution of synaptic contacts in 1-4 Rexed laminae of the spinal cord dorsal horns.

Time-dependent, bidirectional, anti- and pro-spinal hyper-reflexia and muscle spasticity effect after chronic spinal glycine transporter 2 (GlyT2) oligonucleotide-induced downregulation.

PubMed

Kamizato, Kota; Marsala, Silvia; Navarro, Michael; Kakinohana, Manabu; Platoshyn, Oleksandr; Yoshizumi, Tetsuya; Lukacova, Nadezda; Wancewicz, Ed; Powers, Berit; Mazur, Curt; Marsala, Martin

2018-07-01

The loss of local spinal glycine-ergic tone has been postulated as one of the mechanisms contributing to the development of spinal injury-induced spasticity. In our present study using a model of spinal transection-induced muscle spasticity, we characterize the effect of spinally-targeted GlyT2 downregulation once initiated at chronic stages after induction of spasticity in rats. In animals with identified hyper-reflexia, the anti-spasticity effect was studied after intrathecal treatment with: i) glycine, ii) GlyT2 inhibitor (ALX 1393), and iii) GlyT2 antisense oligonucleotide (GlyT2-ASO). Administration of glycine and GlyT2 inhibitor led to significant suppression of spasticity lasting for a minimum of 45-60 min. Treatment with GlyT2-ASO led to progressive suppression of muscle spasticity seen at 2-3 weeks after treatment. Over the subsequent 4-12 weeks, however, the gradual appearance of profound spinal hyper-reflexia was seen. This was presented as spontaneous or slight-tactile stimulus-evoked muscle oscillations in the hind limbs (but not in upper limbs) with individual hyper-reflexive episodes lasting between 3 and 5 min. Chronic hyper-reflexia induced by GlyT2-ASO treatment was effectively blocked by intrathecal glycine. Immunofluorescence staining and Q-PCR analysis of the lumbar spinal cord region showed a significant (>90%) decrease in GlyT2 mRNA and GlyT2 protein. These data demonstrate that spinal GlyT2 downregulation provides only a time-limited therapeutic benefit and that subsequent loss of glycine vesicular synthesis resulting from chronic GlyT2 downregulation near completely eliminates the tonic glycine-ergic activity and is functionally expressed as profound spinal hyper-reflexia. These characteristics also suggest that chronic spinal GlyT2 silencing may be associated with pro-nociceptive activity. Copyright © 2018 Elsevier Inc. All rights reserved.

Trunk robot rehabilitation training with active stepping reorganizes and enriches trunk motor cortex representations in spinal transected rats.

PubMed

Oza, Chintan S; Giszter, Simon F

2015-05-06

Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we examine effects of robot rehabilitation that promotes recovery of hindlimb weight support functions on trunk motor cortex representations. Adult rats spinal transected as neonates (NTX rats) at the T9/10 level significantly improve function with our robot rehabilitation paradigm, whereas treadmill-only trained do not. We used intracortical microstimulation to map motor cortex in two NTX groups: (1) treadmill trained (control group); and (2) robot-assisted treadmill trained (improved function group). We found significant robot rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk cortex motor representations, as examined by cumulative entropy and mutual information for different trunk representations, increased; (4) trunk motor representations in the cortex moved toward more normal topography; and (5) trunk and forelimb motor representations that SCI-driven plasticity and compensations had caused to overlap were segregated. We conclude that effective robot rehabilitation training induces significant reorganization of trunk motor cortex and partially reverses some plastic changes that may be adaptive in non-stepping paraplegia after SCI. Copyright © 2015 the authors 0270-6474/15/357174-16$15.00/0.

Slow- and fast-twitch rat hind limb skeletal muscle phenotypes 8 months after spinal cord transection and olfactory ensheathing glia transplantation

PubMed Central

Negredo, Pilar; Rivero, José-Luis L; González, Beatriz; Ramón-Cueto, Almudena; Manso, Rafael

2008-01-01

Paralysed skeletal muscle of rats with spinal cord injury (SCI) undergoes atrophy and a switch in gene expression pattern which leads to faster, more fatigable phenotypes. Olfactory ensheathing glia (OEG) transplants have been reported to promote axonal regeneration and to restore sensory-motor function in animals with SCI. We hypothesized that OEG transplants could attenuate skeletal muscle phenotypic deterioration and that this effect could underlie the functional recovery observed in behavioural tests. A variety of morphological, metabolic and molecular markers were assessed in soleus (SOL) and extensor digitorum longus (EDL) muscles of spinal cord transected (SCT), OEG-transplanted rats 8 months after the intervention and compared with non-transplanted SCT rats and sham-operated (without SCT) controls (C). A multivariate analysis encompassing all the parameters indicated that OEG-transplanted rats displayed skeletal muscle phenotypes intermediate between non-transplanted and sham-operated controls, but different from both. A high correlation was observed between behaviourally tested sensory-motor functional capacity and expression level of slow- and fast-twitch hind limb skeletal muscle phenotypic markers, particularly the histochemical glycerol-3-phosphate dehydrogenase activity (−0.843, P < 0.0001) and the fraction of variant 2s of the slow regulatory myosin light chain isoform (0.848, P < 0.0001) in SOL. Despite the mean overall effect of OEG transplants in patterning skeletal muscle protein expression towards normal, in 6 out of 9 animals they appeared insufficient to overcome fibre type switching and to support a consistent and generalized long-term maintenance of normal skeletal muscle characteristics. The interplay of OEG and exercise-mediated neurotrophic actions is a plausible mechanism underlying OEG transplantation effects on paralysed skeletal muscle. PMID:18372308

Alleviating Autonomic Dysreflexia after Spinal Cord Injury

DTIC Science & Technology

2015-10-01

nerve into a T3 transection site diminishes autonomic dysreflexia were continued. We began implantation of radiotelelmeters into the descending aorta via the femoral artery. We are also currently analyzing the data.

[Impacts on urodynamic parameters and the protein expressions of M2 and M3 receptors of detrusor in the rats of detrusor hyperreflexia treated with ginger-salt-isolated moxibustion at "Shenque" (CV 8)].

PubMed

Liu, Yi; Wang, Xuerui; Li, Tianran; Lin, Liting; Shi, Guangxia; Fu, Yuanbo; Liu, Cunzhi

2017-04-12

To discuss the effects on detrusor hyperreflexia treated with ginger-salt-isolated moxibustion at "Shenque" (CV 8) and its mechanism. Thirty female adult SD rats were selected. The model of detrusor hyperreflexia was prepared with complete spinal transection at T 9 , of which, 20 rats were randomized into a model group (10 rats) and a moxibustion group (10 rats). A sham-operation group (10 rats) was set up for sham-spinal transection. In the moxibustion group, when urine incontinence occurred (about in 2 weeks of modeling), the ginger-salt-isolated moxibustion at "Shenque" (CV 8) was given, 3 moxa cones each time, once a day, continuously for 7 days. After treatment, in each group, the urodynamic parameters were determined, after which, the bladder detrusor was collected. Western blot was used to determine the protein expressions of M2 and M3 receptors. Compared with the sham-operation group, the micturition interval was shortened apparently ( P <0.01); the maximal bladder pressure was increased apparently ( P <0.01); the protein expression of M2 receptor in the detrusor was increased significantly ( P <0.05) and that of M3 receptor had no apparent change ( P >0.05) in the rats of the model group. Compared with the model group, the micturition interval was longer apparently ( P <0.01), the maximal bladder pressure was reduced apparently ( P <0.01), the protein expression of M2 receptor in the detrusor was reduced significantly ( P <0.05) and that of M3 receptor had no apparent change ( P >0.05) in the rats of the moxibustion group.Compared with the sham-operation group, the results of the above indicators were not different significantly in the moxibustion group (all P >0.05). The ginger-salt-isolated moxibustion at "Shenque" (CV 8) suppresses the overactive bladder in the rat with spinal transection and its effect mechanism is possibly relevant with reducing the protein expression of detrusor M2 and inhibiting the excessive contraction of the detrusor.

The role of spinal cord transmission in the ventilatory response to electrically induced exercise in the anaesthetized dog

PubMed Central

Cross, Brenda A.; Davey, A.; Guz, A.; Katona, P. G.; Maclean, M.; Murphy, K.; Semple, S. J. G.; Stidwill, R.

1982-01-01

1. The ventilatory response to electrically induced `exercise' was studied in six chloralose-anaesthetized dogs. The on-transient and steady-state responses to `exercise' were compared in the same dogs before and after spinal cord transection at T8/9 (dermatome level T6/7) on fifteen occasions. 2. Phasic hind limb `exercise' was induced for periods of 4 min by passing current (2 Hz modulated 50 Hz sine wave) between two needles inserted through the hamstring muscles. The maximum current used was 30 mA. This was below the level previously found to produce an artifactual stimulation of breathing with the cord intact. 3. Cord transection produced no significant change in either the resting values of ventilation (˙VI) and CO2 production (˙VCO2) or the ventilatory equivalent for CO2 during `exercise' (△ ˙VI/ △ ˙VCO2). 4. During the steady state of exercise Pa, CO2 was on average significantly lower than at rest with the cord intact (mean △Pa, CO2, - 2·1 mmHg; range - 5·7 to + 1), and higher, though not significantly, with the cord cut (mean Pa, CO2, + 1·2 mmHg; range - 1·5 to + 4·3). However, even in the absence of spinal cord transmission, the ventilatory response to exercise could not be accounted for on the basis of CO2 sensitivity; the △ ˙VI/ △Pa,CO2 obtained with exercise (apparent sensitivity) was significantly greater than that obtained with CO2 inhalation (true sensitivity) both before and after cord section. 5. ˙VI and ˙VCO2 increased more slowly with the cord cut than with the cord intact. This was thought to be due to a slower increase in venous return in the absence of sympathetic innervation of the lower half of the body following cord transection. 6. Similar experiments were performed during muscle paralysis (following gallamine triethiodide). Ventilation was maintained with a respirator controlled by phrenic nerve activity. These experiments showed an increase in ventilation, independent of muscle contraction, which was only present when the cord was intact and which was confined to the on-transient. Only in the absence of spinal cord transmission could there be certainty that the dynamics of the ventilatory response to electrically induced `exercise' was free of artifact. 7. It was concluded that spinal cord transmission is not necessary for the steady-state ventilatory response to electrically induced exercise of the hind limbs. 8. The dog with spinal cord transection provides a suitable model for the study of the chemical control of breathing during electrically induced exercise. PMID:6292406

Effect of noxious electrical stimulation of the peroneal nerve on stretch reflex activity of the hamstring muscle in rats: possible implications of neuronal mechanisms in the development of tight hamstrings in lumbar disc herniation.

PubMed

Hirayama, Jiro; Yamagata, Masatsune; Takahashi, Kazuhisa; Moriya, Hideshige

2005-05-01

The effect of noxious electrical stimulation of the peroneal nerve on the stretch reflex electromyogram activity of the hamstring muscle (semitendinous) was studied. To verify the following hypothetical mechanisms underlying tight hamstrings in lumbar disc herniation: stretch reflex muscle activity of hamstrings is increased by painful inputs from an injured spinal nerve root and the increased stretch reflex muscle activity is maintained by central sensitization. It is reported that stretch reflex activity of the trunk muscles is induced by noxious stimulation of the sciatic nerve and maintained by central sensitization. In spinalized rats (transected spinal cord), the peroneal nerve was stimulated electrically as a conditioning stimulus. Stretch reflex electromyogram activity of the semitendinous muscle was recorded before and after the conditioning stimulus. Even after electrical stimulation was terminated, an increased stretch reflex activity of the hamstring muscle was observed. It is likely that a central sensitization mechanism at the spinal cord level was involved in the increased reflex activity. Central sensitization may play a part in the neuronal mechanisms of tight hamstrings in lumbar disc herniation.

Expression and Cellular Distribution of Ubiquitin in Response to Injury in the Developing Spinal Cord of Monodelphis domestica

PubMed Central

Noor, Natassya M.; Møllgård, Kjeld; Wheaton, Benjamin J.; Steer, David L.; Truettner, Jessie S.; Dziegielewska, Katarzyna M.; Dietrich, W. Dalton; Smith, A. Ian; Saunders, Norman R.

2013-01-01

Ubiquitin, an 8.5 kDa protein associated with the proteasome degradation pathway has been recently identified as differentially expressed in segment of cord caudal to site of injury in developing spinal cord. Here we describe ubiquitin expression and cellular distribution in spinal cord up to postnatal day P35 in control opossums (Monodelphis domestica) and in response to complete spinal transection (T10) at P7, when axonal growth through site of injury occurs, and P28 when this is no longer possible. Cords were collected 1 or 7 days after injury, with age-matched controls and segments rostral to lesion were studied. Following spinal injury ubiquitin levels (western blotting) appeared reduced compared to controls especially one day after injury at P28. In contrast, after injury mRNA expression (qRT-PCR) was slightly increased at P7 but decreased at P28. Changes in isoelectric point of separated ubiquitin indicated possible post-translational modifications. Cellular distribution demonstrated a developmental shift between earliest (P8) and latest (P35) ages examined, from a predominantly cytoplasmic immunoreactivity to a nuclear expression; staining level and shift to nuclear staining was more pronounced following injury, except 7 days after transection at P28. After injury at P7 immunostaining increased in neurons and additionally in oligodendrocytes at P28. Mass spectrometry showed two ubiquitin bands; the heavier was identified as a fusion product, likely to be an ubiquitin precursor. Apparent changes in ubiquitin expression and cellular distribution in development and response to spinal injury suggest an intricate regulatory system that modulates these responses which, when better understood, may lead to potential therapeutic targets. PMID:23626776

Transection of Preganglionic Axons Leads to CNS Neuronal Plasticity Followed by Survival and Target Reinnervation

PubMed Central

Coulibaly, Aminata P.; Gannon, Sean M.; Hawk, Kiel; Walsh, Brian F.; Isaacson, Lori G.

2013-01-01

The goals of the present study were to investigate the changes in sympathetic preganglionic neurons following transection of distal axons in the cervical sympathetic trunk (CST) that innervate the superior cervical ganglion (SCG) and to assess changes in the protein expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB in the thoracic spinal cord. . At 1 week, a significant decrease in soma volume and reduced soma expression of choline acetyltransferase (ChAT) in the intermediolateral cell column (IML) of T1 spinal cord were observed, with both ChAT-ir and non-immunoreactive neurons expressing the injury marker activating transcription factor 3. . These changes were transient, and at later time points, ChAT expression and soma volume returned to control values and the number of ATF3 neurons declined. No evidence for cell loss or neuronal apoptosis was detected at any time point. Protein levels of BDNF and/or full length TrkB in the spinal cord were increased throughout the survival period. In the SCG, both ChAT-ir axons and ChAT protein remained decreased at 16 weeks, but were increased compared to the 10 week time point. These results suggest that though IML neurons show reduced ChAT expression and cell volume at 1 week following CST transection, at later time points, the neurons recovered and exhibited no significant signs of neurodegeneration. The alterations in BDNF and/or TrkB may have contributed to the survival of the IML neurons and the recovery of ChAT expression, as well as to the reinnervation of the SCG. PMID:23891533

The up-regulation of IL-6 in DRG and spinal dorsal horn contributes to neuropathic pain following L5 ventral root transection.

PubMed

Wei, Xu-Hong; Na, Xiao-Dong; Liao, Guang-Jie; Chen, Qiu-Ying; Cui, Yu; Chen, Feng-Ying; Li, Yong-Yong; Zang, Ying; Liu, Xian-Guo

2013-03-01

Our previous works have shown that pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) plays an important role in neuropathic pain produced by lumber 5 ventral root transection (L5-VRT). In the present work we evaluate the role of interleukin-6 (IL-6), another key inflammatory cytokine, in the L5-VRT model. We found that IL-6 was up-regulated in the ipsilateral L4 and L5 dorsal root ganglian (DRG) neurons and in bilateral lumbar spinal cord following L5-VRT. Double immunofluorescence stainings revealed that in DRGs the increased immunoreactivity (IR) of IL-6 was almost restricted in neuronal cells, while in the spinal dorsal horn IL-6-IR up-regulated in both glial cells (astrocyte and microglia) and neurons. Intrathecal administration of IL-6 neutralizing antibody significantly delayed the induction of mechanical allodynia in bilateral hindpaws after L5-VRT. Furthermore, inhibition of TNF-α synthesis by intraperitoneal thalidomide prevented both mechanical allodynia and the up-regulation of IL-6 in DRGs following L5-VRT. These data suggested that the increased IL-6 in afferent neurons and spinal cord contribute to the development of neuropathic pain following motor fiber injury, and that TNF-α is responsible for the up-regulation of IL-6. Copyright © 2012 Elsevier Inc. All rights reserved.

Activated cranial cervical cord neurons affect left ventricular infarct size and the potential for sudden cardiac death

PubMed Central

Southerland, E. Marie; Gibbons, David D.; Smith, S. Brooks; Sipe, Adam; Williams, Carole Ann; Beaumont, Eric; Armour, J. Andrew; Foreman, Robert D.; Ardell, Jeffrey L.

2012-01-01

To evaluate whether cervical spinal neurons can influence cardiac indices and myocyte viability in the acutely ischemic heart, the hearts of anesthetized rabbits subjected to 30 min of LAD coronary arterial occlusion (CAO) were studied 3 hours after reperfusion. Control animals were compared to those exposed to pre-emptive high cervical cord stimulation (SCS; the dorsal aspect of the C1-C2 spinal cord was stimulated electrically at 50 Hz; 0.2 ms; 90% of motor threshold, starting 15 min prior to and continuing throughout CAO). Four groups of animals were so tested: 1) neuroaxis intact; 2) prior cervical vagotomy; 3) prior transection of the dorsal spinal columns at C6; and 4) following pharmacological treatment [muscarinic (atropine) or adrenergic (atenolol, prazosin or yohimbine) receptor blockade]. Infarct size (IS) was measured by tetrazolium, expressed as percentage of risk zone. C1-C2 SCS reduced acute ischemia induced IS by 43%, without changing the incidence of sudden cardiac death (SCD). While SCS-induced reduction in IS was unaffected by vagotomy, it was no longer evident following transection of C6 dorsal columns or atropinization. Beta-adrenoceptor blockade eliminated ischemia induced SCD, while alpha-receptor blockade doubled its incidence. During SCS, myocardial ischemia induced SCD was eliminated following vagotomy while remaining unaffected by atropinization. These data indicate that, in contrast to thoracic spinal neurons, i) cranial cervical spinal neurons affect both adrenergic and cholinergic motor outflows to the heart such that ii) their activation modifies ventricular infarct size and lethal arrhythmogenesis. PMID:22502863

Mondia whitei (Periplocaceae) prevents and Guibourtia tessmannii (Caesalpiniaceae) facilitates fictive ejaculation in spinal male rats

PubMed Central

2013-01-01

Background Mondia whitei and Guibourtia tessmannii are used in Cameroon traditional medicine as aphrodisiacs. The present study was undertaken to evaluate the pro-ejaculatory effects of the aqueous and organic solvent extracts of these plants in spinal male rats. Methods In spinal cord transected and urethane-anesthetized rats, two electrodes where inserted into the bulbospongiosus muscles and the ejaculatory motor pattern was recorded on a polygraph after urethral and penile stimulations, intravenous injection of saline (0.1 ml/100 g), dopamine (0.1 μM/kg), aqueous and organic solvent plant extracts (20 mg/kg). Results In all spinal rats, urethral and penile stimulations always induced the ejaculatory motor pattern. Aqueous or hexane extract of Mondia whitei (20 mg/kg) prevented the expression of the ejaculatory motor pattern. The pro-ejaculatory effects of dopamine (0.1 μM/kg) were not abolished in spinal rats pre-treated with Mondia whitei extracts. Aqueous and methanolic stem bark extracts of Guibourtia tessmannii (20 mg/kg) induced fictive ejaculation characterized by rhythmic contractions of the bulbospongiosus muscles followed sometimes with expulsion of seminal plugs. In rats pre-treated with haloperidol (0.26 μM/kg), no ejaculatory motor pattern was recorded after intravenous injection of Guibourtia tessmannii extracts (20 mg/kg). Conclusion These results show that Mondia whitei possesses preventive effects on the expression of fictive ejaculation in spinal male rats, which is not mediated through dopaminergic pathway; on the contrary, the pro-ejaculatory activities of Guibourtia tessmannii require the integrity of dopaminergic system to exert its effects. The present findings further justify the ethno-medicinal claims of Mondia whitei and Guibourtia tessmannii. PMID:23295154

Olfactory neural cells: an untapped diagnostic and therapeutic resource. The 2000 Ogura Lecture.

PubMed

Perry, Christopher; Mackay-Sim, Alan; Feron, Francois; McGrath, John

2002-04-01

This is an overview of the cellular biology of upper nasal mucosal cells that have special characteristics that enable them to be used to diagnose and study congenital neurological diseases and to aid neural repair. After mapping the distribution of neural cells in the upper nose, the authors' investigations moved to the use of olfactory neurones to diagnose neurological diseases of development, especially schizophrenia. Olfactory-ensheathing glial cells (OEGs) from the cranial cavity promote axonal penetration of the central nervous system and aid spinal cord repair in rodents. The authors sought to isolate these cells from the more accessible upper nasal cavity in rats and in humans and prove they could likewise promote neural regeneration, making these cells suitable for human spinal repair investigations. The schizophrenia-diagnosis aspect of the study entailed the biopsy of the olfactory areas of 10 schizophrenic patients and 10 control subjects. The tissue samples were sliced and grown in culture medium. The ease of cell attachment to fibronectin (artificial epithelial basement membrane), as well as the mitotic and apoptotic indices, was studied in the presence and absence of dopamine in those cell cultures. The neural repair part of the study entailed a harvesting and insertion of first rat olfactory lamina propria rich in OEGs between cut ends of the spinal cords and then later the microinjection of an OEG-rich suspension into rat spinal cords previously transected by open laminectomy. Further studies were done in which OEG insertion was performed up to 1 month after rat cord transection and also in monkeys. Schizophrenic patients' olfactory tissues do not easily attach to basement membrane compared with control subjects, adding evidence to the theory that cell wall anomalies are part of the schizophrenic "lesion" of neurones. Schizophrenic patient cell cultures had higher mitotic and apoptotic indices compared with control subjects. The addition of dopamine altered these indices enough to allow accurate differentiation of schizophrenics from control patients, leading to, possibly for the first time, an early objective diagnosis of schizophrenia and possible assessment of preventive strategies. OEGs from the nose were shown to be as effective as those from the olfactory bulb in promoting axonal growth across transected spinal cords even when added 1 month after injury in the rat. These otherwise paraplegic rats grew motor and proprioceptive and fine touch fibers with corresponding behavioral improvement. The tissues of the olfactory mucosa are readily available to the otolaryngologist. Being surface cells, they must regenerate (called "neurogenesis"). Biopsy of this area and amplification of cells in culture gives the scientist a "window to the developing brain," including early diagnosis of schizophrenia. The "Holy Grail" of neurological disease is the cure of traumatic paraplegia and OEGs from the nose promote that repair. The otolaryngologist may become the necessary partner of the neurophysiologist and spinal surgeon to take the laboratory potential of paraplegic cure into the day-to-day realm of clinical reality.

Swimming Training Reduces Neuroma Pain by Regulating Neurotrophins

PubMed Central

TIAN, JINGE; YU, TINGTING; XU, YONGMING; PU, SHAOFENG; LV, YINGYING; ZHANG, XIN; DU, DONGPING

2018-01-01

ABSTRACT Introduction Neuroma formation after peripheral nerve transection leads to severe neuropathic pain in amputees. Previous studies suggested that physical exercise could bring beneficial effect on alleviating neuropathic pain. However, the effect of exercise on neuroma pain still remained unclear. In addition, long-term exercise can affect the expression of neurotrophins (NT), such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which play key roles in nociceptor sensitization and nerve sprouting after nerve injury. Here, we investigated whether long-term swimming exercise could relieve neuroma pain by modulating NT expression. Methods We used a tibial neuroma transposition (TNT) rat model to mimic neuroma pain. After TNT surgery, rats performed swimming exercise for 5 wk. Neuroma pain and tactile sensitivities were detected using von Frey filaments. Immunofluorescence was applied to analyze neuroma formation. NGF and BDNF expressions in peripheral neuroma, dorsal root ganglion, and the spinal cord were measured using enzyme-linked immunosorbent assay and Western blotting. Results TNT led to neuroma formation, induced neuroma pain, and mechanical allodynia in hind paw. Five-week swimming exercise inhibited neuroma formation and relieved mechanical allodynia in the hind paw and neuroma pain in the lateral ankle. The analgesic effect lasted for at least 1 wk, even when the exercise ceased. TNT elevated the expressions of BDNF and NGF in peripheral neuroma, dorsal root ganglion, and the spinal cord to different extents. Swimming also decreased the elevation of NT expression. Conclusions Swimming exercise not only inhibits neuroma formation induced by nerve transection but also relieves pain behavior. These effects might be associated with the modulation of NT. PMID:28846565

Swimming Training Reduces Neuroma Pain by Regulating Neurotrophins.

PubMed

Tian, Jinge; Yu, Tingting; Xu, Yongming; Pu, Shaofeng; Lv, Yingying; Zhang, Xin; DU, Dongping

2018-01-01

Neuroma formation after peripheral nerve transection leads to severe neuropathic pain in amputees. Previous studies suggested that physical exercise could bring beneficial effect on alleviating neuropathic pain. However, the effect of exercise on neuroma pain still remained unclear. In addition, long-term exercise can affect the expression of neurotrophins (NT), such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which play key roles in nociceptor sensitization and nerve sprouting after nerve injury. Here, we investigated whether long-term swimming exercise could relieve neuroma pain by modulating NT expression. We used a tibial neuroma transposition (TNT) rat model to mimic neuroma pain. After TNT surgery, rats performed swimming exercise for 5 wk. Neuroma pain and tactile sensitivities were detected using von Frey filaments. Immunofluorescence was applied to analyze neuroma formation. NGF and BDNF expressions in peripheral neuroma, dorsal root ganglion, and the spinal cord were measured using enzyme-linked immunosorbent assay and Western blotting. TNT led to neuroma formation, induced neuroma pain, and mechanical allodynia in hind paw. Five-week swimming exercise inhibited neuroma formation and relieved mechanical allodynia in the hind paw and neuroma pain in the lateral ankle. The analgesic effect lasted for at least 1 wk, even when the exercise ceased. TNT elevated the expressions of BDNF and NGF in peripheral neuroma, dorsal root ganglion, and the spinal cord to different extents. Swimming also decreased the elevation of NT expression. Swimming exercise not only inhibits neuroma formation induced by nerve transection but also relieves pain behavior. These effects might be associated with the modulation of NT.

Effect of electrical stimulation on neural regeneration via the p38-RhoA and ERK1/2-Bcl-2 pathways in spinal cord-injured rats

PubMed Central

Joo, Min Cheol; Jang, Chul Hwan; Park, Jong Tae; Choi, Seung Won; Ro, Seungil; Kim, Min Seob; Lee, Moon Young

2018-01-01

Although electrical stimulation is therapeutically applied for neural regeneration in patients, it remains unclear how electrical stimulation exerts its effects at the molecular level on spinal cord injury (SCI). To identify the signaling pathway involved in electrical stimulation improving the function of injured spinal cord, 21 female Sprague-Dawley rats were randomly assigned to three groups: control (no surgical intervention, n = 6), SCI (SCI only, n = 5), and electrical simulation (ES; SCI induction followed by ES treatment, n = 10). A complete spinal cord transection was performed at the 10th thoracic level. Electrical stimulation of the injured spinal cord region was applied for 4 hours per day for 7 days. On days 2 and 7 post SCI, the Touch-Test Sensory Evaluators and the Basso-Beattie-Bresnahan locomotor scale were used to evaluate rat sensory and motor function. Somatosensory-evoked potentials of the tibial nerve of a hind paw of the rat were measured to evaluate the electrophysiological function of injured spinal cord. Western blot analysis was performed to measure p38-RhoA and ERK1/2-Bcl-2 pathways related protein levels in the injured spinal cord. Rat sensory and motor functions were similar between SCI and ES groups. Compared with the SCI group, in the ES group, the latencies of the somatosensory-evoked potential of the tibial nerve of rats were significantly shortened, the amplitudes were significantly increased, RhoA protein level was significantly decreased, protein gene product 9.5 expression, ERK1/2, p38, and Bcl-2 protein levels in the spinal cord were significantly increased. These data suggest that ES can promote the recovery of electrophysiological function of the injured spinal cord through regulating p38-RhoA and ERK1/2-Bcl-2 pathway-related protein levels in the injured spinal cord. PMID:29557386

End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration.

PubMed

Yu, Qing; Zhang, She-Hong; Wang, Tao; Peng, Feng; Han, Dong; Gu, Yu-Dong

2017-10-01

End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.

End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration

PubMed Central

Yu, Qing; Zhang, She-hong; Wang, Tao; Peng, Feng; Han, Dong; Gu, Yu-dong

2017-01-01

End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy. PMID:29171436

Pharmacologically inhibiting kinesin-5 activity with monastrol promotes axonal regeneration following spinal cord injury

PubMed Central

Xu, Chen; Klaw, Michelle C.; Lemay, Michel A.; Baas, Peter W.; Tom, Veronica J.

2014-01-01

While it is well established that the axons of adult neurons have a lower capacity for regrowth, some regeneration of certain CNS populations after spinal cord injury (SCI) is possible if their axons are provided with a permissive substrate, such as an injured peripheral nerve. While some axons readily regenerate into a peripheral nerve graft (PNG), these axons almost always stall at the distal interface and fail to re-innervate spinal cord tissue. Treatment of the glial scar at the distal graft interface with chondroitinase ABC (ChABC) can improve regeneration, but most regenerated axons need further stimulation to extend beyond the interface. Previous studies demonstrate that pharmacologically inhibiting kinesin-5, a motor protein best known for its essential role in mitosis but also expressed in neurons, with the pharmacological agent monastrol increases axon growth on inhibitory substrates in vitro. We sought to determine if monastrol treatment after a SCI improves functional axon regeneration. Animals received complete thoracic level 7 (T7) transections and PNGs and were treated intrathecally with ChABC and either monastrol or DMSO vehicle. We found that combining ChABC with monastrol significantly enhanced axon regeneration. However, there were no further improvements in function or enhanced c-Fos induction upon stimulation of spinal cord rostral to the transection. This indicates that monastrol improves ChABC-mediated axon regeneration but that further treatments are needed to enhance the integration of these regrown axons. PMID:25447935

Intramuscular Neurotrophin-3 normalizes low threshold spinal reflexes, reduces spasms and improves mobility after bilateral corticospinal tract injury in rats.

PubMed

Kathe, Claudia; Hutson, Thomas Haynes; McMahon, Stephen Brendan; Moon, Lawrence David Falcon

2016-10-19

Brain and spinal injury reduce mobility and often impair sensorimotor processing in the spinal cord leading to spasticity. Here, we establish that complete transection of corticospinal pathways in the pyramids impairs locomotion and leads to increased spasms and excessive mono- and polysynaptic low threshold spinal reflexes in rats. Treatment of affected forelimb muscles with an adeno-associated viral vector (AAV) encoding human Neurotrophin-3 at a clinically-feasible time-point after injury reduced spasticity. Neurotrophin-3 normalized the short latency Hoffmann reflex to a treated hand muscle as well as low threshold polysynaptic spinal reflexes involving afferents from other treated muscles. Neurotrophin-3 also enhanced locomotor recovery. Furthermore, the balance of inhibitory and excitatory boutons in the spinal cord and the level of an ion co-transporter in motor neuron membranes required for normal reflexes were normalized. Our findings pave the way for Neurotrophin-3 as a therapy that treats the underlying causes of spasticity and not only its symptoms.

[Constitutional narrowing of the cervical spinal canal. Radiological and clinical findings].

PubMed

Ritter, G; Rittmeyer, K; Hopf, H C

1975-02-21

A constitutional narrowing of the cervical spinal canal was seen in 31 patients with neurological disorders. The ratio of the inner diameter of the spinal canal to the diameter of the vertebral body was smaller than 1 (normal greater than 1). Clinical signs were observed from 45 years upwards where reactivedegenerative changes cause additional narrowing. The majority of patients were male, predominantly heavy manual labourers. There is often a trauma preceding. On myelography multilocular deformations of the spinal subarachnoid space and nerve roots are seen. On the mechanical narrowing of the spinal canal a vascular factor supervenes, caused by exostoses, intervertebral disc protrusions, and fibrosing processes. Clinically a chronic progressive spinal transection syndrome (cervical myelopathy) dominates besides a multilocular root involvement. Posterior column sensibility is predominantly lost. Pain in the extemities and the cervical column is an early symptom. Non-specific CSF changes occur frequently. In case of root involvement the electromyogram is pathological. The prognosis is bad. Operation can only remove reactive processes but not the constitutional anomaly.

Complete spinal cord injury (SCI) transforms how brain derived neurotrophic factor (BDNF) affects nociceptive sensitization.

PubMed

Huang, Yung-Jen; Lee, Kuan H; Grau, James W

2017-02-01

Noxious stimulation can induce a lasting increase in neural excitability within the spinal cord (central sensitization) that can promote pain and disrupt adaptive function (maladaptive plasticity). Brain-derived neurotrophic factor (BDNF) is known to regulate the development of plasticity and has been shown to impact the development of spinally-mediated central sensitization. The latter effect has been linked to an alteration in GABA-dependent inhibition. Prior studies have shown that, in spinally transected rats, exposure to regular (fixed spaced) stimulation can counter the development of maladaptive plasticity and have linked this effect to an up-regulation of BDNF. Here it is shown that application of the irritant capsaicin to one hind paw induces enhanced mechanical reactivity (EMR) after spinal cord injury (SCI) and that the induction of this effect is blocked by pretreatment with fixed spaced shock. This protective effect was eliminated if rats were pretreated with the BDNF sequestering antibody TrkB-IgG. Intrathecal (i.t.) application of BDNF prevented, but did not reverse, capsaicin-induced EMR. BDNF also attenuated cellular indices (ERK and pERK expression) of central sensitization after SCI. In uninjured rats, i.t. BDNF enhanced, rather than attenuated, capsaicin-induced EMR and ERK/pERK expression. These opposing effects were related to a transformation in GABA function. In uninjured rats, BDNF reduced membrane-bound KCC2 and the inhibitory effect of the GABA A agonist muscimol. After SCI, BDNF increased KCC2 expression, which would help restore GABAergic inhibition. The results suggest that SCI transforms how BDNF affects GABA function and imply that the clinical usefulness of BDNF will depend upon the extent of fiber sparing. Copyright © 2016 Elsevier Inc. All rights reserved.

Axotomy increases NADPH-diaphorase activity in the dorsal root ganglia and lumbar spinal cord of the turtle Trachemys dorbigni.

PubMed

Partata, W A; Krepsky, A M; Marques, M; Achaval, M

1999-04-01

Seven days after transection of the sciatic nerve NADPH-diaphorase activity increased in the small and medium neurons of the dorsal root ganglia of the turtle. However, this increase was observed only in medium neurons for up to 90 days. At this time a bilateral increase of NADPH-diaphorase staining was observed in all areas and neuronal types of the dorsal horn, and in positive motoneurons in the lumbar spinal cord, ipsilateral to the lesion. A similar increase was also demonstrable in spinal glial and endothelial cells. These findings are discussed in relation to the role of nitric oxide in hyperalgesia and neuronal regeneration or degeneration.

Pharmacodynamic evaluation of Lys5, MeLeu9, Nle10-NKA(4–10) prokinetic effects on bladder and colon activity in acute spinal cord transected and spinally intact rats

PubMed Central

Kullmann, F. Aura; Katofiasc, M.; Thor, K.B.; Marson, L.

2017-01-01

Purpose To determine feasibility of a novel therapeutic approach to drug-induced voiding after spinal cord injury (SCI) using a well-characterized, peptide, neurokinin 2 receptor (NK2 receptor) agonist, Lys5, MeLeu9, Nle10-NKA(4–10) (LMN-NKA). Methods Cystometry and colorectal pressure measurements were performed in urethane anesthetized, intact and acutely spinalized, female rats. Bladder pressure and voiding were monitored in response to intravenous LMN-NKA given with the bladder filled to 70% capacity. Results LMN-NKA (0.1–300 µg/kg) produced dose dependent, rapid (< 60 s), short duration (< 15 min) increases in bladder pressure. In intact rats, doses above 0.3–1 µg/kg induced urine release (voiding efficiency of ~ 70% at ≥ 1 µg/kg). In spinalized rats, urine release required higher doses (≥ 10 µg/kg) and was less efficient (30–50%). LMN-NKA (0.1–100 µg/kg) also produced dose dependent increases in colorectal pressure. No tachyphylaxis was observed, and the responses were blocked by an NK2 receptor antagonist (GR159897, 1 mg/kg i.v.). No obvious cardiorespiratory effects were noted. Conclusions These results suggest that rapid-onset, short duration, drug-induced voiding is possible in acute spinal and intact rats with intravenous administration of an NK2 receptor agonist. Future challenges remain in regards to finding alternative routes of administration that produce clinically significant voiding, multiple times per day, in animal models of chronic SCI. PMID:27889808

In Vivo Rodent Models of Skeletal Muscle Adaptation to Decreased Use.

PubMed

Cho, Su Han; Kim, Jang Hoe; Song, Wook

2016-03-01

Skeletal muscle possesses plasticity and adaptability to external and internal physiological changes. Due to these characteristics, skeletal muscle shows dramatic changes depending on its response to stimuli such as physical activity, nutritional changes, disease status, and environmental changes. Modulation of the rate of protein synthesis/degradation plays an important role in atrophic responses. The purpose of this review is to describe different features of skeletal muscle adaptation with various models of deceased use. In this review, four models were addressed: immobilization, spinal cord transection, hindlimb unloading, and aging. Immobilization is a form of decreased use in which skeletal muscle shows electrical activity, tension development, and motion. These results differ by muscle group. Spinal cord transection was selected to simulate spinal cord injury. Similar to the immobilization model, dramatic atrophy occurs in addition to fiber type conversion in this model. Despite the fact that electromyography shows unremarkable changes in muscle after hindlimb unloading, decreased muscle mass and contractile force are observed. Lastly, aging significantly decreases the numbers of muscle fibers and motor units. Skeletal muscle responses to decreased use include decreased strength, decreased fiber numbers, and fiber type transformation. These four models demonstrated different changes in the skeletal muscle. This review elucidates the different skeletal muscle adaptations in these four decreased use animal models and encourages further studies.

Intraspinal AAV Injections Immediately Rostral to a Thoracic Spinal Cord Injury Site Efficiently Transduces Neurons in Spinal Cord and Brain

PubMed Central

Klaw, Michelle C; Xu, Chen; Tom, Veronica J

2013-01-01

In the vast majority of studies utilizing adeno-associated virus (AAV) in central nervous system applications, including those published with spinal cord injury (SCI) models, AAV has been administered at the level of the cell body of neurons targeted for genetic modification, resulting in transduction of neurons in the vicinity of the injection site. However, as SCI interrupts many axon tracts, it may be more beneficial to transduce a diverse pool of supraspinal neurons. We determined if descending axons severed by SCI are capable of retrogradely transporting AAV to remotely transduce a variety of brain regions. Different AAV serotypes encoding the reporter green fluorescent protein (GFP) were injected into gray and white matter immediately rostral to a spinal transection site. This resulted in the transduction of thousands of neurons within the spinal cord and in multiple regions within the brainstem that project to spinal cord. In addition, we established that different serotypes had disparate regional specificity and that AAV5 transduced the most brain and spinal cord neurons. This is the first demonstration that retrograde transport of AAV by axons severed by SCI is an effective means to transduce a collection of supraspinal neurons. Thus, we identify a novel, minimally invasive means to transduce a variety of neuronal populations within both the spinal cord and the brain following SCI. This paradigm to broadly distribute viral vectors has the potential to be an important component of a combinatorial strategy to promote functional axonal regeneration. PMID:23881451

Dual spinal lesion paradigm in the cat: evolution of the kinematic locomotor pattern.

PubMed

Barrière, Grégory; Frigon, Alain; Leblond, Hugues; Provencher, Janyne; Rossignol, Serge

2010-08-01

The recovery of voluntary quadrupedal locomotion after an incomplete spinal cord injury can involve different levels of the CNS, including the spinal locomotor circuitry. The latter conclusion was reached using a dual spinal lesion paradigm in which a low thoracic partial spinal lesion is followed, several weeks later, by a complete spinal transection (i.e., spinalization). In this dual spinal lesion paradigm, cats can express hindlimb walking 1 day after spinalization, a process that normally takes several weeks, suggesting that the locomotor circuitry within the lumbosacral spinal cord had been modified after the partial lesion. Here we detail the evolution of the kinematic locomotor pattern throughout the dual spinal lesion paradigm in five cats to gain further insight into putative neurophysiological mechanisms involved in locomotor recovery after a partial spinal lesion. All cats recovered voluntary quadrupedal locomotion with treadmill training (3-5 days/wk) over several weeks. After the partial lesion, the locomotor pattern was characterized by several left/right asymmetries in various kinematic parameters, such as homolateral and homologous interlimb coupling, cycle duration, and swing/stance durations. When no further locomotor improvement was observed, cats were spinalized. After spinalization, the hindlimb locomotor pattern rapidly reappeared, but left/right asymmetries in swing/stance durations observed after the partial lesion could disappear or reverse. It is concluded that, after a partial spinal lesion, the hindlimb locomotor pattern was actively maintained by new dynamic interactions between spinal and supraspinal levels but also by intrinsic changes within the spinal cord.

Mechanical hypersensitivity, sympathetic sprouting, and glial activation are attenuated by local injection of corticosteroid near the lumbar ganglion in a rat model of neuropathic pain.

PubMed

Li, Jing-Yi; Xie, Wenrui; Strong, Judith A; Guo, Qu-Lian; Zhang, Jun-Ming

2011-01-01

Inflammatory responses in the lumbar dorsal root ganglion (DRG) play a key role in pathologic pain states. Systemic administration of a common anti-inflammatory corticosteroid, triamcinolone acetonide (TA), reduces sympathetic sprouting, mechanical pain behavior, spontaneous bursting activity, and cytokine and nerve growth factor production in the DRG. We hypothesized that systemic TA effects are primarily due to local effects on the DRG. Male Sprague-Dawley rats were divided into 4 groups: SNL (tight ligation and transection of spinal nerves) and normal with and without a single dose of TA injectable suspension slowly injected onto the surface of DRG and surrounding region at the time of SNL or sham surgery. Mechanical threshold was tested on postoperative days 1, 3, 5, and 7. Immunohistochemical staining examined tyrosine hydroxylase and glial fibrillary acidic protein in DRG and CD11B antibody (OX-42) in spinal cord. Local TA treatment attenuated mechanical sensitivity, reduced sympathetic sprouting in the DRG, and decreased satellite glia activation in the DRG and microglia activation in the spinal cord after SNL. A single injection of corticosteroid in the vicinity of the axotomized DRG can mimic many effects of systemic TA, mitigating behavioral and cellular abnormalities induced by spinal nerve ligation. This provides a further rationale for the use of localized steroid injections clinically and provides further support for the idea that localized inflammation at the level of the DRG is an important component of the spinal nerve ligation model, commonly classified as neuropathic pain model.

Complete segmental resection of the spine, including the spinal cord, for telangiectatic osteosarcoma: a report of 2 cases.

PubMed

Murakami, Hideki; Tomita, Katsuro; Kawahara, Norio; Oda, Makoto; Yahata, Tetsutaro; Yamaguchi, Takehiko

2006-02-15

Two case reports of telangiectatic osteosarcoma treated with complete segmental resection of the spine, including the spinal cord. To report the en bloc tumor excision, including the spinal cord, for telangiectatic osteosarcoma, and discuss the indication of cord transection and influence after cutting the spinal cord. To our knowledge, there are no previous reports describing telangiectatic osteosarcoma of the spine and the subsequent en bloc excision of the spine, including the spinal cord. The clinical and radiographic presentations of 2 cases with telangiectatic osteosarcoma are presented. Because these 2 cases already had complete paralysis for at least 1 month, it was suspected that there was no possibility of recovering spinal cord function. Complete segmental spinal resection (total en bloc spondylectomy) was performed. At that level, the spinal cord was also cut and resected. En bloc excision of the tumor with a wide margin was achieved in both cases. In the resected specimen, the nerve cells in the spinal cord had lapsed into degenerative necrosis. The pathologic findings showed that there was no hope for recovery of spinal cord function. En bloc spinal resection, including the spinal cord, is an operation allowed when there is no hope for recovery of spinal cord function. This surgery should be accepted as an option in spine tumor surgeries.

IN VIVO MEASUREMENT OF PHENYLGLUCUCURONIDE IN RAINBOW TROUT BY ON-LINE INJECTION MICRODIALYSIS

EPA Science Inventory

Phenylglucuronide (PG) was measured in vivo in arterial blood of rainbow trout using on-line injection microdialysis. A microdialysis probe was surgically implanted in the dorsal aorta of spinally-transected trout. The trout were dosed continuously with PG for 24 h using a ventra...

Recovery of locomotion in the cat following spinal cord lesions.

PubMed

Rossignol, S; Bouyer, L; Barthélemy, D; Langlet, C; Leblond, H

2002-10-01

In most species, locomotor function beneath the level of a spinal cord lesion can be restored even if the cord is completely transected. This suggests that there is, within the spinal cord, an autonomous network of neurons capable of generating a locomotor pattern independently of supraspinal inputs. Recent studies suggest that several physiological and neurochemical changes have to occur in the neuronal networks located caudally to the lesion to allow the expression of spinal locomotion. Some evidence of this plasticity will be addressed in this review. In addition, original data on the functional organisation of the lumbar spinal cord will also be presented. Recent works in our lab show that segmental responsiveness of the spinal cord of the cat to locally micro-injected drugs in different lumbar segments, in combination with complete lesions at various level of the spinal cord, suggest a rostro-caudal organisation of spinal locomotor control. Moreover, the integrity of midlumbar segments seems to be crucial for the expression of spinal locomotion. These data suggest that the regions of critical importance for locomotion can be confined to a restricted portion of the spinal cord. Later, these midlumbar segments could be targeted by electrical stimulation or grafts to improve recovery of function. Understanding the changes in spinal cord neurophysiology and neurochemistry after a lesion is of critical importance to the improvement of treatments for locomotor rehabilitation in spinal-cord-injured patients.

Receptor activated bladder and spinal ATP release in neurally intact and chronic spinal cord injured rats

PubMed Central

Salas, Nilson A.; Somogyi, George T.; Gangitano, David A.; Boone, Timothy B.; Smith, Christopher P.

2009-01-01

Neurally intact (NI) rats and chronic spinal cord injured (SCI) rats were studied to determine how activation of mechanosensory or cholinergic receptors in the bladder urothelium evokes ATP release from afferent terminals in the bladder as well as in the spinal cord. Spinal cord transection was performed at the T9-T10 level 2–3 weeks prior to the experiment and a microdialysis fiber was inserted in the L6-S1 lumbosacral spinal cord. Mechanically evoked (i.e. 10cm/w bladder pressure) ATP release into the bladder lumen was approximately 6.5 fold higher in SCI compared to NI rats (p<0.05). Intravesical carbachol (CCh) induced a significantly greater release of ATP in the bladder from SCI as compared to NI rats (3424.32 ± 1255.57 vs. 613.74 ± 470.44 pmol/ml, respectively, p<0.05). However, ATP release in NI or SCI rats to intravesical CCh was not affected by the muscarinic antagonist atropine (Atr). Spinal release of ATP to bladder stimulation with 10cm/w pressure was 5-fold higher in SCI compared to NI rats (p<0.05). CCh also induced a significantly greater release of spinal ATP in SCI rats compared to controls (4.3 ± 0.9 vs. 0.90 ± 0.15 pmol, p < 0.05). Surprisingly, the percent inhibitory effect of Atr on CCh-induced ATP release was significantly less in SCI as compared to NI rats (49% vs. 89%, respectively). SCI induces a dramatic increase in intravesical pressure and cholinergic receptor evoked bladder and spinal ATP release. Muscarinic receptors do not mediate intravesical CCh induced ATP release into the bladder lumen in NI or SCI rats. In NI rats sensory muscarinic receptors are the predominant mechanism by which CCh induces ATP release from primary afferents within the lumbosacral spinal cord. Following SCI, however, nicotinic or purinergic receptor mechanisms become active, as evidenced by the fact that Atr was only partially effective in inhibiting CCh-induced spinal ATP release. PMID:17067723

Contribution of capsaicin-sensitive primary afferents to mechanical hyperalgesia induced by ventral root transection in rats: the possible role of BDNF.

PubMed

Li, Wei; Wang, Jian-Xiu; Zhou, Zhong-He; Lu, Yao; Li, Xiao-Qiu; Liu, Bao-Jun; Chen, Hui-Sheng

2016-01-01

A recent study showed that brain-derived neurotrophic factor (BDNF) may play a role in the development of the neuropathic pain resulting from injury to motor efferent fibres, such as that in the ventral root transection (VRT) model. Capsaicin stimulation of afferent fibres was also shown to result in the release of BDNF into the spinal cord. Here, the effects of ablation of capsaicin-sensitive primary afferents (CSPAs) by local application of capsaicin on the sciatic nerve on VRT-induced mechanical hyperalgesia were observed. The paw withdrawal mechanical threshold (PWMT) was measured before and then 1 and 3 days and 1, 2, 3, 4 and 6 weeks after VRT. The results showed that local application of capsaicin significantly inhibited the decrease in the PWMT induced by VRT, suggesting the inhibitory effect of locally delivered capsaicin. Furthermore, intrathecal administration of exogenous BDNF not only produced mechanical hyperalgesia but also significantly blocked the inhibitory effect of capsaicin. Taken together, the results of this study suggest that CSPA fibres may contribute to mechanical hyperalgesia in the VRT model.

Intramuscular Neurotrophin-3 normalizes low threshold spinal reflexes, reduces spasms and improves mobility after bilateral corticospinal tract injury in rats

PubMed Central

Kathe, Claudia; Hutson, Thomas Haynes; McMahon, Stephen Brendan; Moon, Lawrence David Falcon

2016-01-01

Brain and spinal injury reduce mobility and often impair sensorimotor processing in the spinal cord leading to spasticity. Here, we establish that complete transection of corticospinal pathways in the pyramids impairs locomotion and leads to increased spasms and excessive mono- and polysynaptic low threshold spinal reflexes in rats. Treatment of affected forelimb muscles with an adeno-associated viral vector (AAV) encoding human Neurotrophin-3 at a clinically-feasible time-point after injury reduced spasticity. Neurotrophin-3 normalized the short latency Hoffmann reflex to a treated hand muscle as well as low threshold polysynaptic spinal reflexes involving afferents from other treated muscles. Neurotrophin-3 also enhanced locomotor recovery. Furthermore, the balance of inhibitory and excitatory boutons in the spinal cord and the level of an ion co-transporter in motor neuron membranes required for normal reflexes were normalized. Our findings pave the way for Neurotrophin-3 as a therapy that treats the underlying causes of spasticity and not only its symptoms. DOI: http://dx.doi.org/10.7554/eLife.18146.001 PMID:27759565

Spinal cord stimulation modulates intraspinal colorectal visceroreceptive transmission in rats

PubMed Central

Qin, C.; Lehew, R.T.; Khan, K.A.; Wienecke, G.M.; Foreman, R.D.

2007-01-01

Previous studies have shown that spinal cord stimulation (SCS) of upper lumbar segments decreases visceromotor responses to mechanical stimuli in a sensitized rat colon and reduces symptoms of irritable bowel syndrome in patients. SCS applied to the upper cervical spinal dorsal column reduces pain of chronic refractory angina. Further, chemical stimulation of C1-C2 propriospinal neurons in rats modulates the responses of lumbosacral spinal neurons to colorectal distension. The present study was designed to compare the effects of upper cervical and lumbar SCS on activity of lumbosacral neurons receiving noxious colorectal input. Extracellular potentials of L6-S2 spinal neurons were recorded in pentobarbital anesthetized, paralyzed and ventilated male rats. SCS (50 Hz, 0.2 ms) at low intensity (90% of motor threshold) was applied to the dorsal column of upper cervical (C1-C2) or upper lumbar (L2-L3) ipsilateral spinal segments. Colorectal distension (CRD, 20, 40, 60 mmHg, 20 s) was produced by air inflation of a latex balloon. Results showed that SCS applied to L2-L3 and C1-C2 segments significantly reduced the excitatory responses to noxious CRD from 417.6±68.0 imp to 296.3±53.6 imp (P<0.05, n=24) and from 336.2±64.5 imp to 225.0±73.3 imp (P<0.05, n= 18), respectively. Effects of L2-L3 and C1-C2 SCS lasted 10.2±1.9 min and 8.0±0.9 min after offset of CRD. Effects of SCS were observed on spinal neurons with either high or low threshold excitatory responses to CRD. However, L2-L3 or C1-C2 SCS did not significantly affect inhibitory neuronal responses to CRD. C1-C2 SCS-induced effects were abolished by cutting the C7-C8 dorsal column but not by spinal transection at cervicomedullary junction. These data demonstrated that upper cervical or lumbar SCS modulated responses of lumbosacral spinal neurons to noxious mechanical stimulation of the colon, thereby, proved two loci for a potential therapeutic effect of SCS in patients with irritable bowel syndrome and other colonic disorders. PMID:17324482

Spastic long-lasting reflexes in the awake rat after sacral spinal cord injury.

PubMed

Bennett, D J; Sanelli, L; Cooke, C L; Harvey, P J; Gorassini, M A

2004-05-01

Following chronic sacral spinal cord transection in rats the affected tail muscles exhibit marked spasticity, with characteristic long-lasting tail spasms evoked by mild stimulation. The purpose of the present paper was to characterize the long-lasting reflex seen in tail muscles in response to electrical stimulation of the tail nerves in the awake spastic rat, including its development with time and relation to spasticity. Before and after sacral spinal transection, surface electrodes were placed on the tail for electrical stimulation of the caudal nerve trunk (mixed nerve) and for recording EMG from segmental tail muscles. In normal and acute spinal rats caudal nerve trunk stimulation evoked little or no EMG reflex. By 2 wk after injury, the same stimulation evoked long-lasting reflexes that were 1) very low threshold, 2) evoked from rest without prior EMG activity, 3) of polysynaptic latency with >6 ms central delay, 4) about 2 s long, and 5) enhanced by repeated stimulation (windup). These reflexes produced powerful whole tail contractions (spasms) and developed gradually over the weeks after the injury (< or =52 wk tested), in close parallel to the development of spasticity. Pure low-threshold cutaneous stimulation, from electrical stimulation of the tip of the tail, also evoked long-lasting spastic reflexes, not seen in acute spinal or normal rats. In acute spinal rats a strong C-fiber stimulation of the tip of the tail (20 x T) could evoke a weak EMG response lasting about 1 s. Interestingly, when this C-fiber stimulation was used as a conditioning stimulation to depolarize the motoneuron pool in acute spinal rats, a subsequent low-threshold stimulation of the caudal nerve trunk evoked a 300-500 ms long reflex, similar to the onset of the long-lasting reflex in chronic spinal rats. A similar conditioned reflex was not seen in normal rats. Thus there is an unusually long low-threshold polysynaptic input to the motoneurons (pEPSP) that is normally inhibited by descending control. This pEPSP is released from inhibition immediately after injury but does not produce a long-lasting reflex because of a lack of motoneuron excitability. With chronic injury the motoneuron excitability is increased markedly, and the pEPSP then triggers sustained motoneuron discharges associated with long-lasting reflexes and muscle spasms.

Beneficial effects of early hemostasis on spinal cord injury in the rat

PubMed Central

Fan, H; Chen, K; Duan, L; Wang, Y-Z; Ju, G

2016-01-01

Study design: Experimental study. Objectives: To investigate the effect of early hemostasis on spinal cord injury (SCI). Setting: Fourth Military Medical University, Xi'an, China. Methods: Sprague Dawley rats were used. Hematoxylin and eosin (HE) staining was performed to observe hemorrhage at different time points (2, 6, 12, 24 and 48 h) after SCI to determine the time window of hemostatic drug administration (n=3 per time point). Three different concentrations of Etamsylate (0.025, 0.05 and 0.1 g kg−1) were administered immediately and 5 and 10 h after SCI to evaluate the effective dosage (n=6 per group). Another 82 rats were then randomly divided into two groups, Etamsylate group (0.1 g kg−1, n=41) and glucose control group (n=41). Nissl staining was performed to observe neurons at 10 days post injury. Immunohistochemistry, western blot and quantitative real-time PCR were performed to detect tissue necrosis at 7 d.p.i., the activation of astrocytes and microglia/macrophages and lesion cavity at 10 d.p.i. Basso–Beattie–Bresnahan scoring and rump height index assay were used to examine locomotion recovery. Results: Early hemostasis reduced the lesion area and tissue necrosis, enhanced neuronal survival, alleviated the activation of microglia/macrophages and astrocytes and facilitated functional recovery after spinal cord contusion in rats. Early hemostasis decreased hemorrhage area and lesion area after spinal cord transection in rats. Conclusion: The present study demonstrated that early hemostasis has beneficial effects on SCI in the rat. It has the potential to be translated into clinical practice. PMID:27137123

Time Course of Substance P Expression in Dorsal Root Ganglia Following Complete Spinal Nerve Transection

PubMed Central

Weissner, Wendy; Winterson, Barbara J.; Stuart-Tilley, Alan; Devor, Marshall; Bove, Geoffrey M.

2008-01-01

Recent evidence suggests that substance P (SP) is upregulated in primary sensory neurons following axotomy, and that this change occurs in larger neurons that do not usually produce SP. If so, this upregulation may allow normally neighboring, uninjured, and non-nociceptive dorsal root ganglion (DRG) neurons to become effective in activating pain pathways. Using immunohistochemistry, we performed a unilateral L5 spinal nerve transection upon male Wistar rats, and measured SP expression in ipsilateral L4 and L5 DRGs and contralateral L5 DRGs, at 1 to 14 days postoperatively (dpo), and in control and sham operated rats. In normal and sham operated DRGs, SP was detectable almost exclusively in small neurons (≤ 800 μm2). Following surgery, the mean size of SP-positive neurons from the axotomized L5 ganglia was greater at 2, 4, 7 and 14 dpo. Among large neurons (> 800 μm2) from the axotomized L5, the percentage of SP-positive neurons increased at 2, 4, 7, and 14 dpo. Among small neurons from the axotomized L5, the percentage of SP-positive neurons was increased at 1 and 3 dpo, but was decreased at 7 and 14 dpo. Thus, SP expression is affected by axonal damage, and the time course of the expression is different between large and small DRG neurons. These data support a role of SP-producing, large DRG neurons in persistent sensory changes due to nerve injury. PMID:16680762

IN VIVO KINETICS OF PHENYLGLUCURONIDE, A PHASE II CONJUGATE OF PHENOLE, IN BLOOD AND URINE OF RAINBOW TROUT

EPA Science Inventory

The kinetics of phenylglucuronide (PG) in blood and urine of spinally-transected rainbow trout were investigated using microdialysis sampling techniques. Trout weighing 0.9 to 1.3 kg were dosed continuously with PG for an additional 48 h. PG could not be detected in expired branc...

Impact of Behavioral Control on the Processing of Nociceptive Stimulation

PubMed Central

Grau, James W.; Huie, J. Russell; Garraway, Sandra M.; Hook, Michelle A.; Crown, Eric D.; Baumbauer, Kyle M.; Lee, Kuan H.; Hoy, Kevin C.; Ferguson, Adam R.

2012-01-01

How nociceptive signals are processed within the spinal cord, and whether these signals lead to behavioral signs of neuropathic pain, depends upon their relation to other events and behavior. Our work shows that these relations can have a lasting effect on spinal plasticity, inducing a form of learning that alters the effect of subsequent nociceptive stimuli. The capacity of lower spinal systems to adapt, in the absence of brain input, is examined in spinally transected rats that receive a nociceptive shock to the tibialis anterior muscle of one hind leg. If shock is delivered whenever the leg is extended (controllable stimulation), it induces an increase in flexion duration that minimizes net shock exposure. This learning is not observed in subjects that receive the same amount of shock independent of leg position (uncontrollable stimulation). These two forms of stimulation have a lasting, and divergent, effect on subsequent learning: controllable stimulation enables learning whereas uncontrollable stimulation disables it (learning deficit). Uncontrollable stimulation also enhances mechanical reactivity. We review evidence that training with controllable stimulation engages a brain-derived neurotrophic factor (BDNF)-dependent process that can both prevent and reverse the consequences of uncontrollable shock. We relate these effects to changes in BDNF protein and TrkB signaling. Controllable stimulation is also shown to counter the effects of peripheral inflammation (from intradermal capsaicin). A model is proposed that assumes nociceptive input is gated at an early sensory stage. This gate is sensitive to current environmental relations (between proprioceptive and nociceptive input), allowing stimulation to be classified as controllable or uncontrollable. We further propose that the status of this gate is affected by past experience and that a history of uncontrollable stimulation will promote the development of neuropathic pain. PMID:22934018

Spontaneous motor rhythms of the back and legs in a patient with a complete spinal cord transection.

PubMed

Nadeau, Sylvie; Jacquemin, Géraldine; Fournier, Christine; Lamarre, Yves; Rossignol, Serge

2010-05-01

Spontaneous activity originating from the spinal cord has been sporadically reported in humans. Investigation of such rhythmic activity of the trunk and legs in a 49-year-old male patient who had a complete severance of the spinal cord at the fifth thoracic vertebra. A multichannel electromyography (EMG) study was performed together with kinematics measurements obtained from an Optotrak system. Episodes of rhythmic trunk and lower limb movements started 6 to 7 years after the spinal lesion, recurred at 2 to 3 month intervals, and continued uninterrupted for 2 to 3 days despite continuous delivery of intrathecal baclofen. Several muscles discharged more or less synchronously on both sides but others clearly alternated, for instance, between hip flexors and knee or ankle extensors. Sensory stimuli (hip repositioning or skin pinch) altered significantly the baseline rhythm of about 1 Hz. The patient had both hips injected with corticosteroids and was free of these episodic rhythmic crises for more than 6 months. The rhythmic activity observed in the patient appeared related to the activation of a spinal pattern generator akin to what has been described in most animal species after complete spinal lesions.

Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic Rehabilitation: Elements of Success, Failure, and Dependence

PubMed Central

Udoekwere, Ubong I.; Oza, Chintan S.

2016-01-01

Robot therapy promotes functional recovery after spinal cord injury (SCI) in animal and clinical studies. Trunk actions are important in adult rats spinalized as neonates (NTX rats) that walk autonomously. Quadrupedal robot rehabilitation was tested using an implanted orthosis at the pelvis. Trunk cortical reorganization follows such rehabilitation. Here, we test the functional outcomes of such training. Robot impedance control at the pelvis allowed hindlimb, trunk, and forelimb mechanical interactions. Rats gradually increased weight support. Rats showed significant improvement in hindlimb stepping ability, quadrupedal weight support, and all measures examined. Function in NTX rats both before and after training showed bimodal distributions, with “poor” and “high weight support” groupings. A total of 35% of rats initially classified as “poor” were able to increase their weight-supported step measures to a level considered “high weight support” after robot training, thus moving between weight support groups. Recovered function in these rats persisted on treadmill with the robot both actuated and nonactuated, but returned to pretraining levels if they were completely disconnected from the robot. Locomotor recovery in robot rehabilitation of NTX rats thus likely included context dependence and/or incorporation of models of robot mechanics that became essential parts of their learned strategy. Such learned dependence is likely a hurdle to autonomy to be overcome for many robot locomotor therapies. Notwithstanding these limitations, trunk-based quadrupedal robot rehabilitation helped the rats to visit mechanical states they would never have achieved alone, to learn novel coordinations, and to achieve major improvements in locomotor function. SIGNIFICANCE STATEMENT Neonatal spinal transected rats without any weight support can be taught weight support as adults by using robot rehabilitation at trunk. No adult control rats with neonatal spinal transections spontaneously achieve similar changes. The robot rehabilitation system can be inactivated and the skills that were learned persist. Responding rats cannot be detached from the robot altogether, a dependence develops in the skill learned. From data and analysis here, the likelihood of such rats to respond to the robot therapy can also now be predicted. These results are all novel. Understanding trunk roles in voluntary and spinal reflex integration after spinal cord injury and in recovery of function are broadly significant for basic and clinical understanding of motor function. PMID:27511008

Gene therapy approaches for spinal cord injury

NASA Astrophysics Data System (ADS)

Bright, Corinne

As the biomedical engineering field expands, combination technologies are demonstrating enormous potential for treating human disease. In particular, intersections between the rapidly developing fields of gene therapy and tissue engineering hold promise to achieve tissue regeneration. Nonviral gene therapy uses plasmid DNA to deliver therapeutic proteins in vivo for extended periods of time. Tissue engineering employs biomedical materials, such as polymers, to support the regrowth of injured tissue. In this thesis, a combination strategy to deliver genes and drugs in a polymeric scaffold was applied to a spinal cord injury model. In order to develop a platform technology to treat spinal cord injury, several nonviral gene delivery systems and polymeric scaffolds were evaluated in vitro and in vivo. Nonviral vector trafficking was evaluated in primary neuronal culture to develop an understanding of the barriers to gene transfer in neurons and their supporting glia. Although the most efficient gene carrier in vitro differed from the optimal gene carrier in vivo, confocal and electron microscopy of these nonviral vectors provided insights into the interaction of these vectors with the nucleus. A novel pathway for delivering nanoparticles into the nuclei of neurons and Schwann cells via vesicle trafficking was observed in this study. Reporter gene expression levels were evaluated after direct and remote delivery to the spinal cord, and the optimal nonviral vector, dose, and delivery strategy were applied to deliver the gene encoding the basic fibroblast growth factor (bFGF) to the spinal cord. An injectable and biocompatible gel, composed of the amphiphillic polymer poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) was evaluated as a drug and gene delivery system in vitro, and combined with the optimized nonviral gene delivery system to treat spinal cord injury. Plasmid DNA encoding the bFGF gene and the therapeutic NEP1--40 peptide were incorporated in the PEG-PCL-PEG gel and injected into a lesion transecting the main dorsomedial and minor ventral medial corticospinal tract (CST). The degree of collateralization of the transected CST was quantified as an indicator of the regenerative potential of these treatments. At one month post-injury, we observed the robust rostral collateralization of the CST tract in response to the bFGF plasmid-loaded gel. In conclusion, we hope that this platform technology can be applied to the sustained local delivery of other proteins for the treatment of spinal cord injury.

Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic Rehabilitation: Elements of Success, Failure, and Dependence.

PubMed

Udoekwere, Ubong I; Oza, Chintan S; Giszter, Simon F

2016-08-10

Robot therapy promotes functional recovery after spinal cord injury (SCI) in animal and clinical studies. Trunk actions are important in adult rats spinalized as neonates (NTX rats) that walk autonomously. Quadrupedal robot rehabilitation was tested using an implanted orthosis at the pelvis. Trunk cortical reorganization follows such rehabilitation. Here, we test the functional outcomes of such training. Robot impedance control at the pelvis allowed hindlimb, trunk, and forelimb mechanical interactions. Rats gradually increased weight support. Rats showed significant improvement in hindlimb stepping ability, quadrupedal weight support, and all measures examined. Function in NTX rats both before and after training showed bimodal distributions, with "poor" and "high weight support" groupings. A total of 35% of rats initially classified as "poor" were able to increase their weight-supported step measures to a level considered "high weight support" after robot training, thus moving between weight support groups. Recovered function in these rats persisted on treadmill with the robot both actuated and nonactuated, but returned to pretraining levels if they were completely disconnected from the robot. Locomotor recovery in robot rehabilitation of NTX rats thus likely included context dependence and/or incorporation of models of robot mechanics that became essential parts of their learned strategy. Such learned dependence is likely a hurdle to autonomy to be overcome for many robot locomotor therapies. Notwithstanding these limitations, trunk-based quadrupedal robot rehabilitation helped the rats to visit mechanical states they would never have achieved alone, to learn novel coordinations, and to achieve major improvements in locomotor function. Neonatal spinal transected rats without any weight support can be taught weight support as adults by using robot rehabilitation at trunk. No adult control rats with neonatal spinal transections spontaneously achieve similar changes. The robot rehabilitation system can be inactivated and the skills that were learned persist. Responding rats cannot be detached from the robot altogether, a dependence develops in the skill learned. From data and analysis here, the likelihood of such rats to respond to the robot therapy can also now be predicted. These results are all novel. Understanding trunk roles in voluntary and spinal reflex integration after spinal cord injury and in recovery of function are broadly significant for basic and clinical understanding of motor function. Copyright © 2016 the authors 0270-6474/16/368341-15$15.00/0.

NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury

PubMed Central

Yang, Zhaoyang; Zhang, Aifeng; Duan, Hongmei; Zhang, Sa; Hao, Peng; Ye, Keqiang; Sun, Yi E.; Li, Xiaoguang

2015-01-01

Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial, when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury. PMID:26460015

A re-assessment of the effects of intracortical delivery of inosine on transmidline growth of corticospinal tract axons after unilateral lesions of the medullary pyramid

PubMed Central

Steward, Oswald; Sharp, Kelli; Yee, Kelly Matsudaira

2011-01-01

This study was undertaken as part of the NIH “Facilities of Research Excellence-Spinal Cord Injury”, which supports independent replication of published studies. Here, we repeat an experiment reporting that intracortical delivery of inosine promoted trans-midline growth of corticospinal tract (CST) axons in the spinal cord after unilateral injury to the medullary pyramid. Rats received unilateral transections of the medullary pyramid and 1 day later, a cannula assembly was implanted into the sensorimotor cortex contralateral to the pyramidotomy to deliver either inosine or vehicle. The cannula assembly was attached to an osmotic minipump that was implanted sub-cutaneously. Seventeen or 18 days post-injury, the CST was traced by making multiple injections of miniruby-BDA into the sensorimotor cortex. Rats were killed for tract tracing 14 days after the BDA injections. Sections through the cervical spinal cord were stained for BDA and immunostained for GAP43 and GFAP. Our results revealed no evidence for enhanced growth of CST axons across the midline of the dorsal column in rats that received intracortical infusion of inosine. Possible reasons for the failure to replicate are discussed. PMID:21946267

Plasticity and alterations of trunk motor cortex following spinal cord injury and non-stepping robot and treadmill training.

PubMed

Oza, Chintan S; Giszter, Simon F

2014-06-01

Spinal cord injury (SCI) induces significant reorganization in the sensorimotor cortex. Trunk motor control is crucial for postural stability and propulsion after low thoracic SCI and several rehabilitative strategies are aimed at trunk stability and control. However little is known about the effect of SCI and rehabilitation training on trunk motor representations and their plasticity in the cortex. Here, we used intracortical microstimulation to examine the motor cortex representations of the trunk in relation to other representations in three groups of chronic adult complete low thoracic SCI rats: chronic untrained, treadmill trained (but 'non-stepping') and robot assisted treadmill trained (but 'non-stepping') and compared with a group of normal rats. Our results demonstrate extensive and significant reorganization of the trunk motor cortex after chronic adult SCI which includes (1) expansion and rostral displacement of trunk motor representations in the cortex, with the greatest significant increase observed for rostral (to injury) trunk, and slight but significant increase of motor representation for caudal (to injury) trunk at low thoracic levels in all spinalized rats; (2) significant changes in coactivation and the synergy representation (or map overlap) between different trunk muscles and between trunk and forelimb. No significant differences were observed between the groups of transected rats for the majority of the comparisons. However, (3) the treadmill and robot-treadmill trained groups of rats showed a further small but significant rostral migration of the trunk representations, beyond the shift caused by transection alone. We conclude that SCI induces a significant reorganization of the trunk motor cortex, which is not qualitatively altered by non-stepping treadmill training or non-stepping robot assisted treadmill training, but is shifted further from normal topography by the training. This shift may potentially make subsequent rehabilitation with stepping longer or less successful. Copyright © 2014 Elsevier Inc. All rights reserved.

Neuroprotection and reduction of glial reaction by cannabidiol treatment after sciatic nerve transection in neonatal rats.

PubMed

Perez, Matheus; Benitez, Suzana U; Cartarozzi, Luciana P; Del Bel, Elaine; Guimarães, Francisco S; Oliveira, Alexandre L R

2013-11-01

In neonatal rats, the transection of a peripheral nerve leads to an intense retrograde degeneration of both motor and sensory neurons. Most of the axotomy-induced neuronal loss is a result of apoptotic processes. The clinical use of neurotrophic factors is difficult due to side effects and elevated costs, but other molecules might be effective and more easily obtained. Among them, some are derived from Cannabis sativa. Cannabidiol (CBD) is the major non-psychotropic component found on the surface of such plant leaves. The present study aimed to investigate the neuroprotective potential of CBD. Thus, 2-day-old Wistar rats were divided into the following experimental groups: sciatic nerve axotomy + CBD treatment (CBD group), axotomy + vehicle treatment (phosphate buffer group) and a control group (no-treatment group). The results were analysed by Nissl staining, immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling at 5 days post-lesion. Neuronal counting revealed both motor and sensory neuron rescue following treatment with CBD (15 and 30 mg/kg). Immunohistochemical analysis (obtained by synaptophysin staining) revealed 30% greater synaptic preservation within the spinal cord in the CBD-treated group. CBD administration decreased the astroglial and microglial reaction by 30 and 27%, respectively, as seen by glial fibrillary acidic protein and ionised calcium binding adaptor molecule 1 immunolabeling quantification. In line with such results, the terminal deoxynucleotidyl transferase dUTP nick end labeling reaction revealed a reduction of apoptotic cells, mostly located in the spinal cord intermediate zone, where interneurons promote sensory-motor integration. The present results show that CBD possesses neuroprotective characteristics that may, in turn, be promising for future clinical use. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Effects of co-administration of clenbuterol and testosterone propionate on skeletal muscle in paraplegic mice.

PubMed

Ung, Roth-Visal; Rouleau, Pascal; Guertin, Pierre A

2010-06-01

Spinal cord injury (SCI) is generally associated with a rapid and significant decrease in muscle mass and corresponding changes in skeletal muscle properties. Although beta(2)-adrenergic and androgen receptor agonists are anabolic substances clearly shown to prevent or reverse muscle wasting in some pathological conditions, their effects in SCI patients remain largely unknown. Here we studied the effects of clenbuterol and testosterone propionate administered separately or in combination on skeletal muscle properties and adipose tissue in adult CD1 mice spinal-cord-transected (Tx) at the low-thoracic level (i.e., induced complete paraplegia). Administered shortly post-Tx, these substances were found to differentially reduce loss in body weight, muscle mass, and muscle fiber cross-sectional area (CSA) values. Although all three treatments induced significant effects, testosterone-treated animals were generally less protected against Tx-related changes. However, none of the treatments prevented fat tissue loss or muscle fiber type conversion and functional loss generally found in Tx animals. These results provide evidence suggesting that clenbuterol alone or combined with testosterone may constitute better clinically-relevant treatments than testosterone alone to decrease muscle atrophy (mass and fiber CSA) in SCI subjects.

Exercise modulates chloride homeostasis after spinal cord injury.

PubMed

Côté, Marie-Pascale; Gandhi, Sapan; Zambrotta, Marina; Houlé, John D

2014-07-02

Activity-based therapies are routinely integrated in spinal cord injury (SCI) rehabilitation programs because they result in a reduction of hyperreflexia and spasticity. However, the mechanisms by which exercise regulates activity in spinal pathways to reduce spasticity and improve functional recovery are poorly understood. Persisting alterations in the action of GABA on postsynaptic targets is a signature of CNS injuries, including SCI. The action of GABA depends on the intracellular chloride concentration, which is determined largely by the expression of two cation-chloride cotransporters (CCCs), KCC2 and NKCC1, which serve as chloride exporters and importers, respectively. We hypothesized that the reduction in hyperreflexia with exercise after SCI relies on a return to chloride homeostasis. Sprague Dawley rats received a spinal cord transection at T12 and were assigned to SCI-7d, SCI-14d, SCI-14d+exercise, SCI-28d, SCI-28d+exercise, or SCI-56d groups. During a terminal experiment, H-reflexes were recorded from interosseus muscles after stimulation of the tibial nerve and the low-frequency-dependent depression (FDD) was assessed. We provide evidence that exercise returns spinal excitability and levels of KCC2 and NKCC1 toward normal levels in the lumbar spinal cord. Acutely altering chloride extrusion using the KCC2 blocker DIOA masked the effect of exercise on FDD, whereas blocking NKCC1 with bumetanide returned FDD toward intact levels after SCI. Our results indicate that exercise contributes to reflex recovery and restoration of endogenous inhibition through a return to chloride homeostasis after SCI. This lends support for CCCs as part of a pathway that could be manipulated to improve functional recovery when combined with rehabilitation programs. Copyright © 2014 the authors 0270-6474/14/348976-12$15.00/0.

Selectivity in the Reinnervation of the Lateral Gastrocnemius Muscle after Nerve Repair with Ethyl Cyanoacrylate in the Rat

PubMed Central

Landegren, Thomas; Risling, Mårten; Hammarberg, Henrik; Persson, Jonas K. E.

2011-01-01

There is a need for complementary surgical techniques that enable rapid and reliable primary repair of transected nerves. Previous studies after peripheral nerve transection and repair with synthetic adhesives have demonstrated regeneration to an extent comparable to that of conventional techniques. The aim of this study was to compare two different repair techniques on the selectivity of muscle reinnervation after repair and completed regeneration. We used the cholera toxin B technique of retrograde axonal tracing to evaluate the morphology, the number, and the three-dimensional location of α-motoneurons innervating the lateral gastrocnemius muscle and compared the results after repair with either ethyl cyanoacrylate (ECA) or epineural sutures of the transected parent sciatic nerve. In addition, we recorded the wet weight of the muscle. Six months after transection and repair of the sciatic nerve, the redistribution of the motoneuron pool was markedly disorganized, the motoneurons had apparently increased in number, and they were scattered throughout a larger volume of the spinal cord gray matter with a decrease in the synaptic coverage compared to controls. A reduction in muscle weight was observed as well. No difference in morphometric variables or muscle weight between the two repair methods could be detected. We conclude that the selectivity of motor reinnervation following sciatic nerve transection and subsequent repair with ECA is comparable to that following conventional micro suturing. PMID:21577248

Complement Protein C1q Modulates Neurite Outgrowth In Vitro and Spinal Cord Axon Regeneration In Vivo

PubMed Central

Peterson, Sheri L.; Nguyen, Hal X.; Mendez, Oscar A.

2015-01-01

Traumatic injury to CNS fiber tracts is accompanied by failure of severed axons to regenerate and results in lifelong functional deficits. The inflammatory response to CNS trauma is mediated by a diverse set of cells and proteins with varied, overlapping, and opposing effects on histological and behavioral recovery. Importantly, the contribution of individual inflammatory complement proteins to spinal cord injury (SCI) pathology is not well understood. Although the presence of complement components increases after SCI in association with axons and myelin, it is unknown whether complement proteins affect axon growth or regeneration. We report a novel role for complement C1q in neurite outgrowth in vitro and axon regrowth after SCI. In culture, C1q increased neurite length on myelin. Protein and molecular assays revealed that C1q interacts directly with myelin associated glycoprotein (MAG) in myelin, resulting in reduced activation of growth inhibitory signaling in neurons. In agreement with a C1q-outgrowth-enhancing mechanism in which C1q binding to MAG reduces MAG signaling to neurons, complement C1q blocked both the growth inhibitory and repulsive turning effects of MAG in vitro. Furthermore, C1q KO mice demonstrated increased sensory axon turning within the spinal cord lesion after SCI with peripheral conditioning injury, consistent with C1q-mediated neutralization of MAG. Finally, we present data that extend the role for C1q in axon growth and guidance to include the sprouting patterns of descending corticospinal tract axons into spinal gray matter after dorsal column transection SCI. PMID:25762679

In vitro and in vivo analysis and characterization of engineered spinal neural implants (Conference Presentation)

NASA Astrophysics Data System (ADS)

Shor, Erez; Shoham, Shy; Levenberg, Shulamit

2016-03-01

Spinal cord injury is a devastating medical condition. Recent developments in pre-clinical and clinical research have started to yield neural implants inducing functional recovery after spinal cord transection injury. However, the functional performance of the transplants was assessed using histology and behavioral experiments which are unable to study cell dynamics and the therapeutic response. Here, we use neurophotonic tools and optogenetic probes to investigate cellular level morphology and activity characteristics of neural implants over time at the cellular level. These methods were used in-vitro and in-vivo, in a mouse spinal cord injury implant model. Following previous attempts to induce recovery after spinal cord injury, we engineered a pre-vascularized implant to obtain better functional performance. To image network activity of a construct implanted in a mouse spinal cord, we transfected the implant to express GCaMP6 calcium activity indicators and implanted these constructs under a spinal cord chamber enabling 2-photon chronic in vivo neural activity imaging. Activity and morphology analysis image processing software was developed to automatically quantify the behavior of the neural and vascular networks. Our experimental results and analyses demonstrate that vascularized and non-vascularized constructs exhibit very different morphologic and activity patterns at the cellular level. This work enables further optimization of neural implants and also provides valuable tools for continuous cellular level monitoring and evaluation of transplants designed for various neurodegenerative disease models.

Multilevel Analysis of Locomotion in Immature Preparations Suggests Innovative Strategies to Reactivate Stepping after Spinal Cord Injury.

PubMed

Brumley, Michele R; Guertin, Pierre A; Taccola, Giuliano

2017-01-01

Locomotion is one of the most complex motor behaviors. Locomotor patterns change during early life, reflecting development of numerous peripheral and hierarchically organized central structures. Among them, the spinal cord is of particular interest since it houses the central pattern generator (CPG) for locomotion. This main command center is capable of eliciting and coordinating complex series of rhythmic neural signals sent to motoneurons and to corresponding target-muscles for basic locomotor activity. For a long-time, the CPG has been considered a black box. In recent years, complementary insights from in vitro and in vivo animal models have contributed significantly to a better understanding of its constituents, properties and ways to recover locomotion after a spinal cord injury (SCI). This review discusses key findings made by comparing the results of in vitro isolated spinal cord preparations and spinal-transected in vivo models from neonatal animals. Pharmacological, electrical, and sensory stimulation approaches largely used to further understand CPG function may also soon become therapeutic tools for potent CPG reactivation and locomotor movement induction in persons with SCI or developmental neuromuscular disorder. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evidence that central pathways that mediate defecation utilize ghrelin receptors but do not require endogenous ghrelin.

PubMed

Pustovit, Ruslan V; Callaghan, Brid; Ringuet, Mitchell T; Kerr, Nicole F; Hunne, Billie; Smyth, Ian M; Pietra, Claudio; Furness, John B

2017-08-01

In laboratory animals and in human, centrally penetrant ghrelin receptor agonists, given systemically or orally, cause defecation. Animal studies show that the effect is due to activation of ghrelin receptors in the spinal lumbosacral defecation centers. However, it is not known whether there is a physiological role of ghrelin or the ghrelin receptor in the control of defecation. Using immunohistochemistry and immunoassay, we detected and measured ghrelin in the stomach, but were unable to detect ghrelin by either method in the lumbosacral spinal cord, or other regions of the CNS In rats in which the thoracic spinal cord was transected 5 weeks before, the effects of a ghrelin agonist on colorectal propulsion were significantly enhanced, but defecation caused by water avoidance stress (WAS) was reduced. In knockout rats that expressed no ghrelin and in wild-type rats, WAS-induced defecation was reduced by a ghrelin receptor antagonist, to similar extents. We conclude that the ghrelin receptors of the lumbosacral defecation centers have a physiological role in the control of defecation, but that their role is not dependent on ghrelin. This implies that a transmitter other than ghrelin engages the ghrelin receptor or a ghrelin receptor complex. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Metaplasticity within the spinal cord: Evidence brain-derived neurotrophic factor (BDNF), tumor necrosis factor (TNF), and alterations in GABA function (ionic plasticity) modulate pain and the capacity to learn.

PubMed

Grau, James W; Huang, Yung-Jen

2018-04-07

Evidence is reviewed that behavioral training and neural injury can engage metaplastic processes that regulate adaptive potential. This issue is explored within a model system that examines how training affects the capacity to learn within the lower (lumbosacral) spinal cord. Response-contingent (controllable) stimulation applied caudal to a spinal transection induces a behavioral modification indicative of learning. This behavioral change is not observed in animals that receive stimulation in an uncontrollable manner. Exposure to uncontrollable stimulation also engages a process that disables spinal learning for 24-48 h. Controllable stimulation has the opposite effect; it engages a process that enables learning and prevents/reverses the learning deficit induced by uncontrollable stimulation. These observations suggest that a learning episode can impact the capacity to learn in future situations, providing an example of behavioral metaplasticity. The protective/restorative effect of controllable stimulation has been linked to an up-regulation of brain-derived neurotrophic factor (BDNF). The disruption of learning has been linked to the sensitization of pain (nociceptive) circuits, which is enabled by a reduction in GABA-dependent inhibition. After spinal cord injury (SCI), the co-transporter (KCC2) that regulates the outward flow of Cl - is down-regulated. This causes the intracellular concentration of Cl - to increase, reducing (and potentially reversing) the inward flow of Cl - through the GABA-A receptor. The shift in GABA function (ionic plasticity) increases neural excitability caudal to injury and sets the stage for nociceptive sensitization. The injury-induced shift in KCC2 is related to the loss of descending serotonergic (5HT) fibers that regulate plasticity within the spinal cord dorsal horn through the 5HT-1A receptor. Evidence is presented that these alterations in spinal plasticity impact pain in a brain-dependent task (place conditioning). The findings suggest that ionic plasticity can affect learning potential, shifting a neural circuit from dampened/hard-wired to excitable/plastic. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparative cardiovascular effects of four fishery anesthetics in spinally transected rainbow trout, oncorhynchus mykiss

USGS Publications Warehouse

Fredricks, K.T.; Gingerich, W.H.; Fater, D.C.

1993-01-01

1. We compared the effects of four anesthetics on heart rate, dorsal and ventral aortic blood pressure, and electrocardiograms of rainbow trout (Oncorhynchus mykiss).2. Exposure to the local anesthetics tricaine methanesulfonate (MS-222) and benzocaine hydrochloride (BZH) produced minimal cardiovascular alterations. Mean dorsal aortic pressure (DAP) decreased during exposure to MS-222, and mean DAP and mean ventral aortic pressure (VAP) increased 15% during recovery from BZH.3. Exposure to the general anesthetic 2-phenoxyethanol (2-PE) or the hypnotic agent etomidate (ET) dramatically decreased heart rate and blood pressures and altered EKG patterns.4. During recovery, VAP and DAP increased above baseline for an extended period. Heart rate and EKG patterns rapidly returned to normal.

Peripheral denervation participates in heterotopic ossification in a spinal cord injury model

PubMed Central

Salga, Marjorie; Begot, Laurent; Holy, Xavier; Chedik, Malha; de l’Escalopier, Nicolas; Torossian, Fréderic; Levesque, Jean-Pierre; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline; Genêt, François

2017-01-01

We previously reported the development of a new acquired neurogenic HO (NHO) mouse model, combining spinal cord transection (SCI) and chemical muscle injury. Pathological mechanisms responsible for ectopic osteogenesis after central neurological damage are still to be elucidated. In this study, we first hypothesized that peripheral nervous system (PNS) might convey pathological signals from injured spinal cord to muscles in NHO mouse model. Secondly, we sought to determine whether SCI could lead to intramuscular modifications of BMP2 signaling pathways. Twenty one C57Bl6 mice were included in this protocol. Bilateral cardiotoxin (CTX) injection in hamstring muscles was associated with a two-stage surgical procedure, combining thoracic SCI with unilateral peripheral denervation. Volumes of HO (Bone Volume, BV) were measured 28 days after surgery using micro-computed tomography imaging techniques and histological analyses were made to confirm intramuscular osteogenesis. Volume comparisons were conducted between right and left hind limb of each animal, using a Wilcoxon signed rank test. Quantitative polymerase chain reaction (qPCR) was performed to explore intra muscular expression of BMP2, Alk3 and Id1. Nineteen mice survive the complete SCI and peripheral denervation procedure. When CTX injections were done right after surgery (n = 7), bilateral HO were detected in all animals after 28 days. Micro-CT measurements showed significantly increased BV in denervated paws (1.47 mm3 +/- 0.5) compared to contralateral sides (0.56 mm3 +/-0.4), p = 0.03. When peripheral denervation and CTX injections were performed after sham SCI surgery (n = 6), bilateral HO were present in three mice at day 28. Quantitative PCR analyses showed no changes in intra muscular BMP2 expression after SCI as compared to control mice (shamSCI). Peripheral denervation can be reliably added to spinal cord transection in NHO mouse model. This new experimental design confirms that neuro inflammatory mechanisms induced by central or peripheral nervous system injury plays a key role in triggering ectopic osteogenesis. PMID:28854256

Potential of adult mammalian lumbosacral spinal cord to execute and acquire improved locomotion in the absence of supraspinal input

NASA Technical Reports Server (NTRS)

Edgerton, V. R.; Roy, R. R.; Hodgson, J. A.; Prober, R. J.; de Guzman, C. P.; de Leon, R.

1992-01-01

The neural circuitry of the lumbar spinal cord can generate alternating extension and flexion of the hindlimbs. The hindlimbs of adult cats with complete transection of the spinal cord at a low thoracic level (T12-T13) can perform full weight-supporting locomotion on a treadmill belt moving at a range of speeds. Some limitations in the locomotor capacity can be associated with a deficit in the recruitment level of the fast extensors during the stance phase and the flexors during the swing phase of a step cycle. The level of locomotor performance, however, can be enhanced by daily training on a treadmill while emphasizing full weight-support stepping and by providing appropriately timed sensory stimulation, loading, and/or pharmacologic stimulation of the hindlimb neuromuscular apparatus. Furthermore, there appears to be an interactive effect of these interventions. For example, the maximum treadmill speed that a spinal adult cat can attain and maintain is significantly improved with daily full weight-supporting treadmill training, but progressive recruitment of fast extensors becomes apparent only when the hindlimbs are loaded by gently pulling down on the tail during the stepping. Stimulation of the sural nerve at the initiation of the flexion phase of the step cycle can likewise markedly improve the locomotor capability. Administration of clonidine, in particular in combination with an elevated load, resulted in the most distinct and consistent alternating bursts of electromyographic activity during spinal stepping. These data indicate that the spinal cord has the ability to execute alternating activation of the extensor and flexor musculature of the hindlimbs (stepping) and that this ability can be improved by several interventions such as training, sensory stimulation, and use of some pharmacologic agents. Thus, it appears that the spinal cord, without supraspinal input, is highly plastic and has the potential to "learn," that is, to acquire and improve its ability to execute full weight-supporting locomotion on a treadmill belt.

Endoplasmic Reticulum Stress as a Mediator of Neurotoxin-Induced Dopamine Neuron Death

DTIC Science & Technology

2006-07-01

reversible reduction in choline acetyl- transferase concentration in rat hypoglossal nucleus after hypoglossal nerve transection. Nature 275, 324–325...cally, analogs were evaluated for their ability to enhance choline acetyltransferase (ChAT) activity in embryonic rat spinal cord and basal forebrain...of ibotenate, CEP1347 protected basal forebrain cholinergic neurons.102 In a model of apoptosis induced in auditory hair cells by noise trauma, CEP1347

WITHDRAWN: H-reflex up-conditioning after sciatic nerve transection and regeneration may increase VGLUT-1 terminals and GluR2/3 immunoreactivity in spinal motoneurons.

PubMed

Sun, Chenyou; Wang, Yu; Chen, Xiang Yang

2011-12-17

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. Copyright © 2011. Published by Elsevier Ireland Ltd.. All rights reserved.

The control of male sexual responses.

PubMed

Courtois, Frédérique; Carrier, Serge; Charvier, Kathleen; Guertin, Pierre A; Journel, Nicolas Morel

2013-01-01

Male sexual responses are reflexes mediated by the spinal cord and modulated by neural circuitries involving both the peripheral and central nervous system. While the brain interact with the reflexes to allow perception of sexual sensations and to exert excitatory or inhibitory influences, penile reflexes can occur despite complete transections of the spinal cord, as demonstrated by the reviewed animal studies on spinalization and human studies on spinal cord injury. Neurophysiological and neuropharmacological substrates of the male sexual responses will be discussed in this review, starting with the spinal mediation of erection and its underlying mechanism with nitric oxide (NO), followed by the description of the ejaculation process, its neural mediation and its coordination by the spinal generator of ejaculation (SGE), followed by the occurrence of climax as a multisegmental sympathetic reflex discharge. Brain modulation of these reflexes will be discussed through neurophysiological evidence involving structures such as the medial preoptic area of hypothalamus (MPOA), the paraventricular nucleus (PVN), the periaqueductal gray (PAG), and the nucleus para-gigantocellularis (nPGI), and through neuropharmacological evidence involving neurotransmitters such as serotonin (5-HT), dopamine and oxytocin. The pharmacological developments based on these mechanisms to treat male sexual dysfunctions will complete this review, including phosphodiesterase (PDE-5) inhibitors and intracavernous injections (ICI) for the treatment of erectile dysfunctions (ED), selective serotonin reuptake inhibitor (SSRI) for the treatment of premature ejaculation, and cholinesterase inhibitors as well as alpha adrenergic drugs for the treatment of anejaculation and retrograde ejaculation. Evidence from spinal cord injured studies will be highlighted upon each step.

NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain

PubMed Central

Kim, Donghoon; You, Byunghyun; Jo, Eun-Kyeong; Han, Sang-Kyou; Simon, Melvin I.; Lee, Sung Joong

2010-01-01

Increasing evidence supports the notion that spinal cord microglia activation plays a causal role in the development of neuropathic pain after peripheral nerve injury; yet the mechanisms for microglia activation remain elusive. Here, we provide evidence that NADPH oxidase 2 (Nox2)-derived ROS production plays a critical role in nerve injury-induced spinal cord microglia activation and subsequent pain hypersensitivity. Nox2 expression was induced in dorsal horn microglia immediately after L5 spinal nerve transection (SNT). Studies using Nox2-deficient mice show that Nox2 is required for SNT-induced ROS generation, microglia activation, and proinflammatory cytokine expression in the spinal cord. SNT-induced mechanical allodynia and thermal hyperalgesia were similarly attenuated in Nox2-deficient mice. In addition, reducing microglial ROS level via intrathecal sulforaphane administration attenuated mechanical allodynia and thermal hyperalgesia in SNT-injured mice. Sulforaphane also inhibited SNT-induced proinflammatory gene expression in microglia, and studies using primary microglia indicate that ROS generation is required for proinflammatory gene expression in microglia. These studies delineate a pathway involving nerve damage leading to microglial Nox2-generated ROS, resulting in the expression of proinflammatory cytokines that are involved in the initiation of neuropathic pain. PMID:20679217

Neuronal BDNF Signaling Is Necessary for the Effects of Treadmill Exercise on Synaptic Stripping of Axotomized Motoneurons

PubMed Central

Krakowiak, Joey; Liu, Caiyue; Papudesu, Chandana; Ward, P. Jillian; Wilhelm, Jennifer C.; English, Arthur W.

2015-01-01

The withdrawal of synaptic inputs from the somata and proximal dendrites of spinal motoneurons following peripheral nerve injury could contribute to poor functional recovery. Decreased availability of neurotrophins to afferent terminals on axotomized motoneurons has been implicated as one cause of the withdrawal. No reduction in contacts made by synaptic inputs immunoreactive to the vesicular glutamate transporter 1 and glutamic acid decarboxylase 67 is noted on axotomized motoneurons if modest treadmill exercise, which stimulates the production of neurotrophins by spinal motoneurons, is applied after nerve injury. In conditional, neuron-specific brain-derived neurotrophic factor (BDNF) knockout mice, a reduction in synaptic contacts onto motoneurons was noted in intact animals which was similar in magnitude to that observed after nerve transection in wild-type controls. No further reduction in coverage was found if nerves were cut in knockout mice. Two weeks of moderate daily treadmill exercise following nerve injury in these BDNF knockout mice did not affect synaptic inputs onto motoneurons. Treadmill exercise has a profound effect on synaptic inputs to motoneurons after peripheral nerve injury which requires BDNF production by those postsynaptic cells. PMID:25918648

The respective contribution of lumbar segments to the generation of locomotion in the isolated spinal cord of newborn rat.

PubMed

Bertrand, S; Cazalets, Jean-René

2002-11-01

Various studies on isolated neonatal rat spinal cord have pointed to the predominant role played by the rostral lumbar area in the generation of locomotor activity. In the present study, the role of the various regions of the lumbar spinal cord in locomotor genesis was further examined using compartmentalization and transections of the cord. We report that the synaptic drive received by caudal motoneurons following N-methyl-d-l-aspartate (NMA)/5-HT superfusion on the entire lumbar cord is different from that triggered by the same compounds specifically applied on the rostral segments. These differences appear to be due to the direct action of NMA/5-HT on motoneuron membrane potential, rather than on premotoneuronal input activation. In order to assess the possible participation of the caudal lumbar segments in locomotor rhythm generation, the segments were over-stimulated with high concentrations of NMA or K+. We find that significant variations in motor cycle period occurred during the over-activation of the rostral segments. Over-activation of caudal segments only si+gnificantly increased the caudal ventral roots burst amplitude. We find that low 5-HT concentrations were unable to induce fictive locomotion under our experimental conditions. When a hemi-transection of the cord was performed between the L2-L3 segments, rhythmic bursting in the ipsilateral L5 disappeared while rhythmicity persisted on the contralateral side. Sectioning of the remaining L2-L3 side totally suppressed rhythmic activity in both L5 ventral roots. These results show that the thoracolumbar part of the cord constitutes the key area for locomotor pattern generation.

Segmental neuropathic pain does not develop in male rats with complete spinal transections.

PubMed

Hubscher, Charles H; Kaddumi, Ezidin G; Johnson, Richard D

2008-10-01

In a previous study using male rats, a correlation was found between the development of "at-level" allodynia in T6-7 dermatomes following severe T8 spinal contusion injury and the sparing of some myelinated axons within the core of the lesion epicenter. To further test our hypothesis that this sparing is important for the expression of allodynia and the supraspinal plasticity that ensues, an injury that severs all axons (i.e., a complete spinal cord transection) was made in 15 male rats. Behavioral assessments were done at level throughout the 30-day recovery period followed by terminal electrophysiological recordings (urethane anesthesia) from single medullary reticular formation (MRF) neurons receiving convergent nociceptive inputs from receptive fields above, at, and below the lesion level. None of the rats developed signs of at-level allodynia (versus 18 of 26 male rats following severe contusion). However, the terminal recording (206 MRF neurons) data resembled those obtained previously post-contusion. That is, there was evidence of neuronal hyper-excitability (relative to previous data from intact controls) to high- and low-threshold mechanical stimulation for "at-level" (dorsal trunk) and "above-level" (eyelids and face) cutaneous territories. These results, when combined with prior data on intact controls and severe/moderate contusions, indicate that (1) an anatomically incomplete injury (some lesion epicenter axonal sparing) following severe contusion is likely important for the development of allodynia and (2) the neuronal hyper-excitability at the level of the medulla is likely involved in nociceptive processes that are not directly related to the conscious expression of pain-like avoidance behaviors that are being used as evidence of allodynia.

Anabolic steroids reduce spinal cord injury-related bone loss in rats associated with increased Wnt signaling

PubMed Central

Sun, Li; Pan, Jiangping; Peng, Yuanzhen; Wu, Yong; Li, Jianghua; Liu, Xuan; Qin, Yiwen; Bauman, William A.; Cardozo, Christopher; Zaidi, Mone; Qin, Weiping

2013-01-01

Background Spinal cord injury (SCI) causes severe bone loss. At present, there is no practical treatment to delay or prevent bone loss in individuals with motor-complete SCI. Hypogonadism is common in men after SCI and may exacerbate bone loss. The anabolic steroid nandrolone reduces bone loss due to microgravity or nerve transection. Objective To determine whether nandrolone reduced bone loss after SCI and, if so, to explore the mechanisms of nandrolone action. Methods Male rats with complete transection of the spinal cord were administered nandrolone combined with a physiological replacement dose of testosterone, or vehicle, beginning on day 29 after SCI and continued for 28 days. Results SCI reduced distal femoral and proximal tibial bone mineral density (BMD) by 25 and 16%, respectively, at 56 days. This bone loss was attenuated by nandrolone. In ex vivo osteoclasts cultures, SCI increased mRNA levels for tartrate-resistant acid phosphatase (TRAP) and calcitonin receptor; nandrolone-normalized expression levels of these transcripts. In ex vivo osteoblast cultures, SCI increased receptor activator of NF-kB ligand (RANKL) mRNA levels but did not alter osteoprotegerin (OPG) mRNA expression; nandrolone-increased expression of OPG and OPG/RANKL ratio. SCI reduced mRNA levels of Wnt signaling-related genes Wnt3a, low-density lipoprotein receptor-related protein 5 (LRP5), Fzd5, Tcf7, and ectodermal-neural cortex 1 (ENC1) in osteoblasts, whereas nandrolone increased expression of each of these genes. Conclusions The results demonstrate that nandrolone reduces bone loss after SCI. A potential mechanism is suggested by our findings wherein nandrolone modulates genes for differentiation and activity of osteoclasts and osteoblasts, at least in part, through the activation of Wnt signaling. PMID:24090150

Antisense Morpholino Oligonucleotides Reduce Neurofilament Synthesis and Inhibit Axon Regeneration in Lamprey Reticulospinal Neurons.

PubMed

Zhang, Guixin; Jin, Li-qing; Hu, Jianli; Rodemer, William; Selzer, Michael E

2015-01-01

The sea lamprey has been used as a model for the study of axonal regeneration after spinal cord injury. Previous studies have suggested that, unlike developing axons in mammal, the tips of regenerating axons in lamprey spinal cord are simple in shape, packed with neurofilaments (NFs), and contain very little F-actin. Thus it has been proposed that regeneration of axons in the central nervous system of mature vertebrates is not based on the canonical actin-dependent pulling mechanism of growth cones, but involves an internal protrusive force, perhaps generated by the transport or assembly of NFs in the distal axon. In order to assess this hypothesis, expression of NFs was manipulated by antisense morpholino oligonucleotides (MO). A standard, company-supplied MO was used as control. Axon retraction and regeneration were assessed at 2, 4 and 9 weeks after MOs were applied to a spinal cord transection (TX) site. Antisense MO inhibited NF180 expression compared to control MO. The effect of inhibiting NF expression on axon retraction and regeneration was studied by measuring the distance of axon tips from the TX site at 2 and 4 weeks post-TX, and counting the number of reticulospinal neurons (RNs) retrogradely labeled by fluorescently-tagged dextran injected caudal to the injury at 9 weeks post-TX. There was no statistically significant effect of MO on axon retraction at 2 weeks post-TX. However, at both 4 and 9 weeks post-TX, inhibition of NF expression inhibited axon regeneration.

Electrical treatment of spinal cord injuries in the 18th and 19th centuries.

PubMed

Silver, John R; Weiner, M-F

2013-05-01

Two centuries ago, electricity was being used for the treatment of paraplegia and trials were taking place in France. This study aims to identify cases of traumatic paraplegia treated with electricity in the 19th century in order to assess the therapeutic benefit. Only four such cases were identified, none with a complete transection of the spinal cord since these patients would have died from pressure sores and urinary tract infections. The personalities involved, William Gull, William Erb, Guillaume Duchenne and Cyril Henry Golding Bird are portrayed and contemporaneous views on electrotherapy analysed. While the four patients apparently benefited from the treatment, the lack of follow-up and the incomplete data prevented a definitive conclusion on the therapeutic value of electrical treatment in traumatic paraplegia.

Optimization of low-level light therapy's illumination parameters for spinal cord injury in a rat model

NASA Astrophysics Data System (ADS)

Shuaib, Ali; Bourisly, Ali

2018-02-01

Spinal cord injury (SCI) can result in complete or partial loss of sensation and motor function due to interruption along the severed axonal tract(s). SCI can result in tetraplegia or paraplegia, which can have prohibitive lifetime medical costs and result in shorter life expectancy. A promising therapeutic technique that is currently in experimental phase and that has the potential to be used to treat SCI is Low-level light therapy (LLLT). Preclinical studies have shown that LLLT has reparative and regenerative capabilities on transected spinal cords, and that LLLT can enhance axonal sprouting in animal models. However, despite the promising effects of LLLT as a therapy for SCI, it remains difficult to compare published results due to the use of a wide range of illumination parameters (i.e. different wavelengths, fluences, beam types, and beam diameter), and due to the lack of a standardized experimental protocol(s). Before any clinical applications of LLLT for SCI treatment, it is crucial to standardize illumination parameters and efficacy of light delivery. Therefore, in this study we aim to evaluate the light fluence distribution on a 3D voxelated SCI rat model with different illumination parameters (wavelengths: 660, 810, and 980 nm; beam types: Gaussian and Flat; and beam diameters: 0.1, 0.2, and 0.3 cm) for LLLT using Monte Carlo simulation. This study provides an efficient approach to guide researchers in optimizing the illumination parameters for LLLT spinal cord injury in an experimental model and will aid in quantitative and qualitative standardization of LLLT-SCI treatment.

Agar-based bridges as biocompatible candidates to provide guide cues in spinal cord injury repair.

PubMed

Martín-López, Eduardo; Darder, Margarita; Ruiz-Hitzky, Eduardo; Nieto Sampedro, Manuel

2013-01-01

Spinal bridge implants are strategic to provide growth surfaces for axonal regeneration after spinal cord injuries. The design of an appropriate substrate, one that is suitable for implantation, must involve careful testing of the biomaterial properties both in vitro and in vivo. The goal of this work was to test the structure, stability and biological response after spinal bridges implantation of several biopolymers, composed of mixtures of agar (AG), as structural matrix scaffold, with κ-carrageenan (Kc), gelatin (G), xanthan gum (Xn) and polysulfone (PS). Biopolymer structures were studied by environmental scanning electron microscopy, whereas the stability of gels was analyzed by in vitro degradation and swelling tests. The biocompatibility of these materials and their ability to promote cell growth and axonal regeneration were studied by implantation of spinal bridges containing empty linear channels in an acute rat spinal cord transection model at thoracic level (T8). All gel mixtures gave rise to porous structures and they were stables to degradation, excepting the AG+G mixture. Spinal bridges constructed from all mixtures were implanted during a month in adult rats. After this time a low host reaction occurred to all bridge materials as well as neurite and cell ingrowths through the empty channels. Neurites within the bridges were mostly peripheral sensory fibers such as those positive for CGRP, whereas there was a lack of regeneration of central axons crossing from the spinal tissue to bridges. Many of these neurites established closed contacts with non-myelin Schwann cells. The histological analysis revealed a high accumulation of collagen fibers within the channels. Unexpected was the apparent loss of channels linearity which affected the growth of neurites and cells, indicating the need for additional regeneration strategies and vertebrae bridge fixing.

Characterization of spinal injuries sustained by American service members killed in Iraq and Afghanistan: a study of 2,089 instances of spine trauma.

PubMed

Schoenfeld, Andrew J; Newcomb, Ronald L; Pallis, Mark P; Cleveland, Andrew W; Serrano, Jose A; Bader, Julia O; Waterman, Brian R; Belmont, Philip J

2013-04-01

This study sought to characterize spine injuries among soldiers killed in Iraq or Afghanistan whose autopsy results were stored by the Armed Forces Medical Examiner System. The Armed Forces Medical Examiner System data set was queried to identify American military personnel who sustained a spine injury in conjunction with wounds that resulted in death during deployment in Iraq or Afghanistan from 2003 to 2011. Demographic and injury-specific characteristics were abstracted for each individual identified. The raw incidence of spinal injuries was calculated and correlations were drawn between the presence of spinal trauma and military specialty, mechanism and manner of injury, and wounds in other body regions. Significant associations were also sought for specific injury patterns, including spinal cord injury, atlantooccipital injury, low lumbar vertebral fractures, and lumbosacral dissociation. Statistical calculations were performed using χ statistic, z test, t test with Satterthwaite correction, and multivariate logistic regression. Among 5,424 deceased service members, 2,089 (38.5%) were found to have sustained at least one spinal injury. Sixty-seven percent of all fatalities with spinal injury were caused by explosion, while 15% occurred by gunshot. Spinal fracture was the most common type of injury (n = 2,328), while spinal dislocations occurred in 378, and vertebral column transection occurred in 223. Fifty-two percent sustained at least one cervical spine injury, and spinal cord injury occurred in 40%. Spinal cord injuries were more likely to occur as a result of gunshot (p < 0.001), while atlantooccipital injuries (p < 0.001) and low lumbar fractures (p = 0.01) were significantly higher among combat specialty soldiers. No significant association was identified between spinal injury risk and the periods 2003 to 2007 and 2008 to 2011, although atlantooccipital injuries and spinal cord injury were significantly reduced beginning in 2008 (p < 0.001). The results of this study indicate that the incidence of spinal trauma in modern warfare seems to be higher than previously reported. Epidemiologic study, level III.

Spontaneous cord transection due to invasive aspergillus spondylitis in an immunocompetent child.

PubMed

Karthik, K; Shetty, Ajoy Prasad; Rajasekaran, S

2011-07-01

Invasive spinal aspergillosis in an immunocompetent child is rare and often there is a considerable delay in diagnosis. A 13-year-old male child treated medically as tuberculosis of spine elsewhere for 1 year, came with complete paraplegia, dorsolumbar kyphosis and intermittently discharging sinus in the back. The child was taken up for surgical decompression and stabilization. Intraoperatively black granulomatous material was noted inside the canal extending anteriorly towards the vertebral body. There was complete cord transection with severe vertebral destruction and osteoporosis. The pathology and microbiology confirmed aspergillosis and the child was started on antifungal treatment. At further follow up, the infection was found to spread to the lung and caused further vertebral destruction. A change in the antifungal medication controlled further spread but failed to eradicate the infection at 2-year follow-up. In this patient, the delay led to extensive vertebral destruction with spine deformity and spontaneous cord transection. Retrospective review of the clinical and radiological findings suggests that this complication could have been prevented if these findings were carefully interpreted. In this era of transplantation and increase in use of immunosuppressive drugs the authors suggests having fungal infection as a differential diagnosis for infections of the spine.

Preclinical evidence supporting the clinical development of central pattern generator-modulating therapies for chronic spinal cord-injured patients

PubMed Central

2014-01-01

Ambulation or walking is one of the main gaits of locomotion. In terrestrial animals, it may be defined as a series of rhythmic and bilaterally coordinated movement of the limbs which creates a forward movement of the body. This applies regardless of the number of limbs—from arthropods with six or more limbs to bipedal primates. These fundamental similarities among species may explain why comparable neural systems and cellular properties have been found, thus far, to control in similar ways locomotor rhythm generation in most animal models. The aim of this article is to provide a comprehensive review of the known structural and functional features associated with central nervous system (CNS) networks that are involved in the control of ambulation and other stereotyped motor patterns—specifically Central Pattern Generators (CPGs) that produce basic rhythmic patterned outputs for locomotion, micturition, ejaculation, and defecation. Although there is compelling evidence of their existence in humans, CPGs have been most studied in reduced models including in vitro isolated preparations, genetically-engineered mice and spinal cord-transected animals. Compared with other structures of the CNS, the spinal cord is generally considered as being well-preserved phylogenetically. As such, most animal models of spinal cord-injured (SCI) should be considered as valuable tools for the development of novel pharmacological strategies aimed at modulating spinal activity and restoring corresponding functions in chronic SCI patients. PMID:24910602

Nandrolone slows hindlimb bone loss in a rat model of bone loss due to denervation.

PubMed

Cardozo, Christopher P; Qin, Weiping; Peng, Yuanzhen; Liu, Xuan; Wu, Yong; Pan, Jiangping; Bauman, William A; Zaidi, Mone; Sun, Li

2010-03-01

Nandrolone is an anabolic steroid that has been demonstrated to reduce the loss of bone and muscle from hindlimb unweighting and to slow muscle atrophy after nerve transection. To determine whether nandrolone has the ability to protect bone against loss due to disuse after denervation, male rats underwent sciatic nerve transaction, followed 28 days later by treatment with nandrolone or vehicle for 28 days. Bone mineral density (BMD) was determined 28 days later or 56 days after nerve transection. Denervation led to reductions in BMD of 7% and 12% for femur and tibia, respectively. Nandrolone preserved 80% and 60% of BMD in femur and tibia, respectively, demonstrating that nandrolone administration significantly reduced loss of BMD from denervation. This study offers a potential novel pharmacological strategy for use of nandrolone to reduce bone loss in severe disuse- and denervation-related bone loss, such as that which occurs after spinal cord injury.

Retrograde influences of SCG axotomy on uninjured preganglionic neurons.

PubMed

Gannon, Sean M; Hawk, Kiel; Walsh, Brian F; Coulibaly, Aminata; Isaacson, Lori G

2018-07-15

There is evidence that neuronal injury can affect uninjured neurons in the same neural circuit. The overall goal of this study was to understand the effects of peripheral nerve injury on uninjured neurons located in the central nervous system (CNS). As a model, we examined whether axotomy (transection of postganglionic axons) of the superior cervical ganglion (SCG) affected the uninjured, preganglionic neurons that innervate the SCG. At 7 days post-injury a reduction in choline acetyltransferase (ChAT) and synaptophysin immunoreactivity in the SCG, both markers for preganglionic axons, was observed, and this reduction persisted at 8 and 12 weeks post-injury. No changes were observed in the number or size of the parent cell bodies in the intermediolateral cell column (IML) of the spinal cord, yet synaptic input to the IML neurons was decreased at both 8 and 12 weeks post-injury. In order to understand the mechanisms underlying these changes, protein levels of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) were examined and reductions were observed at 7 days post-injury in both the SCG and spinal cord. Taken together these results suggest that axotomy of the SCG led to reduced BDNF in the SCG and spinal cord, which in turn influenced ChAT and synaptophysin expression in the SCG and also contributed to the altered synaptic input to the IML neurons. More generally these findings provide evidence that the effects of peripheral injury can cascade into the CNS and affect uninjured neurons. Copyright © 2018 Elsevier B.V. All rights reserved.

Testing the hypothesis of neurodegeneracy in respiratory network function with a priori transected arterially perfused brain stem preparation of rat

PubMed Central

Jones, Sarah E.

2016-01-01

Degeneracy of respiratory network function would imply that anatomically discrete aspects of the brain stem are capable of producing respiratory rhythm. To test this theory we a priori transected brain stem preparations before reperfusion and reoxygenation at 4 rostrocaudal levels: 1.5 mm caudal to obex (n = 5), at obex (n = 5), and 1.5 (n = 7) and 3 mm (n = 6) rostral to obex. The respiratory activity of these preparations was assessed via recordings of phrenic and vagal nerves and lumbar spinal expiratory motor output. Preparations with a priori transection at level of the caudal brain stem did not produce stable rhythmic respiratory bursting, even when the arterial chemoreceptors were stimulated with sodium cyanide (NaCN). Reperfusion of brain stems that preserved the pre-Bötzinger complex (pre-BötC) showed spontaneous and sustained rhythmic respiratory bursting at low phrenic nerve activity (PNA) amplitude that occurred simultaneously in all respiratory motor outputs. We refer to this rhythm as the pre-BötC burstlet-type rhythm. Conserving circuitry up to the pontomedullary junction consistently produced robust high-amplitude PNA at lower burst rates, whereas sequential motor patterning across the respiratory motor outputs remained absent. Some of the rostrally transected preparations expressed both burstlet-type and regular PNA amplitude rhythms. Further analysis showed that the burstlet-type rhythm and high-amplitude PNA had 1:2 quantal relation, with burstlets appearing to trigger high-amplitude bursts. We conclude that no degenerate rhythmogenic circuits are located in the caudal medulla oblongata and confirm the pre-BötC as the primary rhythmogenic kernel. The absence of sequential motor patterning in a priori transected preparations suggests that pontine circuits govern respiratory pattern formation. PMID:26888109

Testing the hypothesis of neurodegeneracy in respiratory network function with a priori transected arterially perfused brain stem preparation of rat.

PubMed

Jones, Sarah E; Dutschmann, Mathias

2016-05-01

Degeneracy of respiratory network function would imply that anatomically discrete aspects of the brain stem are capable of producing respiratory rhythm. To test this theory we a priori transected brain stem preparations before reperfusion and reoxygenation at 4 rostrocaudal levels: 1.5 mm caudal to obex (n = 5), at obex (n = 5), and 1.5 (n = 7) and 3 mm (n = 6) rostral to obex. The respiratory activity of these preparations was assessed via recordings of phrenic and vagal nerves and lumbar spinal expiratory motor output. Preparations with a priori transection at level of the caudal brain stem did not produce stable rhythmic respiratory bursting, even when the arterial chemoreceptors were stimulated with sodium cyanide (NaCN). Reperfusion of brain stems that preserved the pre-Bötzinger complex (pre-BötC) showed spontaneous and sustained rhythmic respiratory bursting at low phrenic nerve activity (PNA) amplitude that occurred simultaneously in all respiratory motor outputs. We refer to this rhythm as the pre-BötC burstlet-type rhythm. Conserving circuitry up to the pontomedullary junction consistently produced robust high-amplitude PNA at lower burst rates, whereas sequential motor patterning across the respiratory motor outputs remained absent. Some of the rostrally transected preparations expressed both burstlet-type and regular PNA amplitude rhythms. Further analysis showed that the burstlet-type rhythm and high-amplitude PNA had 1:2 quantal relation, with burstlets appearing to trigger high-amplitude bursts. We conclude that no degenerate rhythmogenic circuits are located in the caudal medulla oblongata and confirm the pre-BötC as the primary rhythmogenic kernel. The absence of sequential motor patterning in a priori transected preparations suggests that pontine circuits govern respiratory pattern formation. Copyright © 2016 the American Physiological Society.

[Influence of acupunction on NT-4 expression in spared root ganglion and spinal cord].

PubMed

Long, Shuang-Lian; Liu, Fen; Wang, Ting-Hua; Wang, Te-Wei; Ke, Qing; Yuan, Yuan

2005-09-01

To explore the changes of the expression of NT-4 in spared dorsal root ganglia (DRG,L6) on both the operation/Acup side and the nonoperation/non-Acup side as well as in the spinal lamina II (L3, L5, L6) and Clarke' nucleus (L3) of the normal adult cats, partial dorsal rhizotomy cats, and Acup spared DRG cats so as to disclose the relation between NT-4 and the plasticity of spinal cord as well as the Acup promoting spinal cord plasticity. Twenty-five adult cats were divided into 5 groups; normal control group; unilateral partial root rhizotomy 7 d and 14 d groups (unilateral L1-L5, L7-S2 DRG were transected, but L6 DRG was spared); Acup spared DRG 7 d and 14 d groups (electro-needle stimulation was performed following unilateral partial root rhizotomy). The cats survived for 7 or 14 days after operation respectively. Bilateral L6 dorsal root ganglia and L3, L5, L6 spinal cord of every group were made into 20 microm frozen sections. Then, sections were stained under the same condition using specific NT-4 (1 : 200) antibody by the immunohistochemistry ABC method. The distribution and the number of NT-4 immunoreactive neurons in bilateral spared DRG (L6) on the operation/Acup side and the nonoperation/Acup side as well as in the, spinal lamina II (L3, L5, L6) and Clarke' nucleus (L3) of each cat were oberserved and counted. All data were analyzed by one-way ANOVA, SNK-q test and paired-t test. Partial dorsal root rhizotomy led to continuous declination of total NT-4 immunoreactive neurons in spared ganglia, till the 14 d, while Acup reversed this tendency and made NT-4 immunoreactive neurons decrease firstly and then approach to normal level till the 14 d after Acup. In addition, Acup increased NT-4 expression in L5, L6 spinal lamina II. The above finding indicate that NT-4 plays an important role in the mechanism by which Acup promotes spinal cord plasticity. Partial dorsal root rhizotomy and Acup spared DRG may exert effects on the expression of NT-4 in the/non-operrtion non-Acup side of DRG.

Grafting of fetal brainstem 5-HT neurons into the sublesional spinal cord of paraplegic rats restores coordinated hindlimb locomotion.

PubMed

Sławińska, Urszula; Miazga, Krzysztof; Cabaj, Anna M; Leszczyńska, Anna N; Majczyński, Henryk; Nagy, James I; Jordan, Larry M

2013-09-01

In rodent models of spinal cord injury, there is increasing evidence that activation of the locomotor central pattern generator (CPG) below the site of injury with 5-hydroxytryptamine (5-HT) agonists improves locomotor recovery and restores coordination. A promising means of replacing 5-HT control of locomotion is to graft brainstem 5-HT neurons into the spinal cord below the level of the spinal cord injury. However, it is not known whether this approach improves limb coordination because recovery of coordinated stepping has not been documented in detail in previous studies employing this transplantation strategy. Here, adult rats with complete spinal cord transections at the T9/10 level were grafted with E14 fetal neurons from the medulla at the T10/11 vertebra level one month after injury. The B1, B2 and B3 fetal anlagen of brainstem 5-HT neurons, a grouping that included the presumed precursors of recently described 5-HT locomotor command neurons, were used in these grafts. EMG and video recordings of treadmill locomotion evoked by tail stimulation showed full recovery of inter- and intralimb coordination in the grafted rats. We showed, using systemically applied antagonists, that 5-HT₂ and 5-HT₇ receptors mediate the improved locomotion after grafting, but through actions on different populations of spinal locomotor neurons. Specifically, 5-HT₂ receptors control CPG activation as well as motoneuron output, while 5-HT₇ receptors contribute primarily to activity of the locomotor CPG. These results are consistent with the roles for these receptors during locomotion in intact rodents and in rodent brainstem-spinal cord in vitro preparations. Copyright © 2013 Elsevier Inc. All rights reserved.

Regeneration of Xenopus laevis spinal cord requires Sox2/3 expressing cells

PubMed Central

Muñoz, Rosana; Edwards-Faret, Gabriela; Moreno, Mauricio; Zuñiga, Nikole; Cline, Hollis; Larraín, Juan

2016-01-01

Spinal cord regeneration is very inefficient in humans, causing paraplegia and quadriplegia. Studying model organisms that can regenerate the spinal cord in response to injury could be useful for understanding the cellular and molecular mechanisms that explain why this process fails in humans. Here, we use Xenopus laevis as a model organism to study spinal cord repair. Histological and functional analyses showed that larvae at pre-metamorphic stages restore anatomical continuity of the spinal cord and recover swimming after complete spinal cord transection. These regenerative capabilities decrease with onset of metamorphosis. The ability to study regenerative and non-regenerative stages in Xenopus laevis makes it a unique model system to study regeneration. We studied the response of Sox2/3 expressing cells to spinal cord injury and their function in the regenerative process. We found that cells expressing Sox2 and/or Sox3 are present in the ventricular zone of regenerative animals and decrease in non-regenerative froglets. Bromodeoxyuridine (BrdU) experiments and in vivo time-lapse imaging studies using green fluorescent protein (GFP) expression driven by the Sox3 promoter showed a rapid, transient and massive proliferation of Sox2/3+ cells in response to injury in the regenerative stages. The in vivo imaging also demonstrated that Sox2/3+ neural progenitor cells generate neurons in response to injury. In contrast, these cells showed a delayed and very limited response in non-regenerative froglets. Sox2 knockdown and overexpression of a dominant negative form of Sox2 disrupts locomotor and anatomical-histological recovery. We also found that neurogenesis markers increase in response to injury in regenerative but not in non-regenerative animals. We conclude that Sox2 is necessary for spinal cord regeneration and suggest a model whereby spinal cord injury activates proliferation of Sox2/3 expressing cells and their differentiation into neurons, a mechanism that is lost in non-regenerative froglets. PMID:25797152

Functional and physiological effects of treadmill training induced by buspirone, carbidopa, and L-DOPA in clenbuterol-treated paraplegic mice.

PubMed

Ung, Roth-Visal; Rouleau, Pascal; Guertin, Pierre A

2012-05-01

Chronic spinal cord injury may be complicated by weight loss, muscle atrophy, and bone loss. The authors identified a combination pharmacotherapy using buspirone, carbidopa, and L-DOPA (BCD) that elicits bouts of locomotor-like movements in spinal cord-transected (Tx) mice. They then evaluated the effects of 8 weeks of treadmill training in Tx mice that received BCD or BCD + clenbuterol, a monoaminergic agent with anabolic properties, on locomotor function, muscle atrophy, adipose tissue loss, and bone density measures. Induced locomotor movement, adipose tissue, skeletal muscle, and femoral bone properties were compared in unoperated control mice, operated controls (untreated, untrained Tx mice), and 2 groups of treated, trained Tx mice (Tx + BCD, Tx + BCD + clenbuterol) that also received training. BCD- and BCD + clenbuterol-treated mice showed comparable levels of locomotor movements that significantly improved over time. Soleus muscle mass and soleus and extensor digitorum longus cross-sectional area significantly increased in both groups of BCD-treated mice, with greater effects in BCD + clenbuterol-treated animals. Fiber type conversion, adipose tissues, bone mineral density, and content were reduced in all Tx groups compared with unoperated control mice. These findings suggest that locomotor movement and muscle properties can be restored to near-normal levels after several weeks of BCD treatment, regular training, and clenbuterol in completely paraplegic animals.

Elimination of Left-Right Reciprocal Coupling in the Adult Lamprey Spinal Cord Abolishes the Generation of Locomotor Activity

PubMed Central

Messina, J. A.; St. Paul, Alison; Hargis, Sarah; Thompson, Wengora E.; McClellan, Andrew D.

2017-01-01

The contribution of left-right reciprocal coupling between spinal locomotor networks to the generation of locomotor activity was tested in adult lampreys. Muscle recordings were made from normal animals as well as from experimental animals with rostral midline (ML) spinal lesions (~13%→35% body length, BL), before and after spinal transections (T) at 35% BL. Importantly, in the present study actual locomotor movements and muscle burst activity, as well as other motor activity, were initiated in whole animals by descending brain-spinal pathways in response to sensory stimulation of the anterior head. For experimental animals with ML spinal lesions, sensory stimulation could elicit well-coordinated locomotor muscle burst activity, but with some significant differences in the parameters of locomotor activity compared to those for normal animals. Computer models representing normal animals or experimental animals with ML spinal lesions could mimic many of the differences in locomotor activity. For experimental animals with ML and T spinal lesions, right and left rostral hemi-spinal cords, disconnected from intact caudal cord, usually produced tonic or unpatterned muscle activity. Hemi-spinal cords sometimes generated spontaneous or sensory-evoked relatively high frequency “burstlet” activity that probably is analogous to the previously described in vitro “fast rhythm”, which is thought to represent lamprey locomotor activity. However, “burstlet” activity in the present study had parameters and features that were very different than those for lamprey locomotor activity: average frequencies were ~25 Hz, but individual frequencies could be >50 Hz; burst proportions (BPs) often varied with cycled time; “burstlet” activity usually was not accompanied by a rostrocaudal phase lag; and following ML spinal lesions alone, “burstlet” activity could occur in the presence or absence of swimming burst activity, suggesting the two were generated by different mechanisms. In summary, for adult lampreys, left and right hemi-spinal cords did not generate rhythmic locomotor activity in response to descending inputs from the brain, suggesting that left-right reciprocal coupling of spinal locomotor networks contributes to both phase control and rhythmogenesis. In addition, the present study indicates that extreme caution should be exercised when testing the operation of spinal locomotor networks using artificial activation of isolated or reduced nervous system preparations. PMID:29225569

Cutaneous texture discrimination following transection of the dorsal spinal column in monkeys.

PubMed

Vierck, C J; Cooper, B Y

1998-01-01

Transection of the dorsal spinal column in monkeys has been shown to impair discrimination of the frequency or duration of repetitive tactile stimulation, without recovery over extended periods of postoperative testing. These deficits would be likely to prevent discrimination between textures presented passively and in sequence, if repetitive temporal sequences were distinguishing features of the textures. However, previous investigations of texture discrimination after dorsal column section did not obtain a deficit on tests involving active palpation of sandpaper surfaces. In the present study, rows of raised dots were stroked across the glabrous skin of one foot so that temporal entrainment of neural activity would constitute a prominent cue. The rows were oriented mediolaterally, and the textures moved proximodistally across the skin surface (varying the spacing between the rows). Four monkeys were trained to release a lever when the rougher of two textures was in contact with the skin, and the rough texture was preceded by one to three passes of a smooth texture. Stable levels of preoperative performance ranged from 78.6 to 85.7% correct responses. After interruption of the ipsilateral dorsal column, each monkey was impaired over at least 2 months of testing. One animal did not show evidence of recovery; two recovered partially from the initial deficit; and one returned to preoperative levels of performance after extensive retraining. These results are interpreted in terms of aberrant inhibitory influences which result from repetitive stimulation after a dorsal column lesion.

Descending pathways controlling visually guided updating of reaching in cats.

PubMed

Pettersson, L-G; Perfiliev, S

2002-10-01

This study uses a previously described paradigm (Pettersson et al., 1997) to investigate the ability of cats to change the direction of ongoing reaching when the target is shifted sideways; the effect on the switching latency of spinal cord lesions was investigated. Large ventral lesions transecting the ventral funicle and the ventral half of the lateral funicle gave a 20-30 ms latency prolongation of switching in the medial (right) direction, but less prolongation of switching directed laterally (left), and in one cat the latencies of switching directed laterally were unchanged. It may be inferred that the command for switching in the lateral direction can be mediated by the dorsally located cortico- and rubrospinal tracts whereas the command for short-latency switching in the medial direction is mediated by ventral pathways. A restricted ventral lesion transecting the tectospinal pathway did not change the switching latency. Comparison of different ventral lesions revealed prolongation of the latency if the lesion included a region extending dorsally along the ventral horn and from there ventrally as a vertical strip, so it may be postulated that the command for fast switching, directed medially, is mediated by a reticulospinal pathway within this location. A hypothesis is forwarded suggesting that the visual control is exerted via ponto-cerebellar pathways.

Role of afferent input and mechanical load for size regulation of rat soleus muscle

NASA Astrophysics Data System (ADS)

Kawano, Fuminori; Matsuka, Yoshikazu; Oke, Yoshihiko; Higo, Yoko; Terada, Masahiro; Umemoto, Shiori; Kawabe, Naoko; Wang, Xiao Dong; Shinoda, Yo; Lan, Yong Bo; Fukuda, Hiroyuki; Ohmi, Shinobu; Ohira, Yoshinobu

2005-08-01

Effects of deafferentation on the phosphorylation of ribosomal protein S6 (S6), 27 kDa heat shock protein (HSP27) and extracellular signal-regulated kinase (ERK) 1/2 were studied in rat soleus muscle. Adult male Wistar rats were randomly separated into the pre- and post- experimental control, functionally overloaded (FO), sham-operated, deafferentated (DA), FO+DA, and hindlimb-unloaded (U) groups. The distal tendons of left plantaris and gastrocnemius muscles were transected in the FO rats. The left dorsal roots of the spinal cord at the L4-5 segmental levels were transected in the DA rats. The rats in U were tail-suspended. The sampling of the soleus muscle was performed 2 weeks after the treatments shown above. The cytoplasmic fraction of the soleus muscle homogenate was used for the quantitative analyses of the phosphorylation levels of S6, HSP27, and ERK 1/2. The phosphorylation levels of these proteins were up-regulated by FO. On the contrary, the phosphorylation of all of these proteins was down-regulated by U and DA. Further, the FO-related increase of the protein phosphorylation was inhibited by additional treatment with DA. These results indicated that the afferent feedback plays crucial roles in the intramuscular regulation of the soleus muscle mass.

Intracellular calcium release through IP3R or RyR contributes to secondary axonal degeneration.

PubMed

Orem, Ben C; Pelisch, Nicolas; Williams, Joshua; Nally, Jacqueline M; Stirling, David P

2017-10-01

Severed CNS axons often retract or dieback away from the injury site and fail to regenerate. The precise mechanisms underlying acute axonal dieback and secondary axonal degeneration remain poorly understood. Here we investigate the role of Ca 2+ store mediated intra-axonal Ca 2+ release in acute axonal dieback and secondary axonal degeneration. To differentiate between primary (directly transected) and "bystander" axonal injury (axons spared by the initial injury but then succumb to secondary degeneration) in real-time we use our previously published highly focal laser-induced spinal cord injury (LiSCI) ex vivo model. Ascending spinal cord dorsal column axons that express YFP were severed using an 800 nm laser pulse while being imaged continuously using two-photon excitation microscopy. We inhibited two major intra-axonal Ca 2+ store channels, ryanodine receptors (RyR) and IP 3 R, with ryanodine or 2-APB, respectively, to individually determine their role in axonal dieback and secondary axonal degeneration. Each antagonist was dissolved in artificial CSF and applied 1h post-injury alone or in combination, and continuously perfused for the remainder of the imaging session. Initially following LiSCI, transected axons retracted equal distances both distal and proximal to the lesion. However, by 4h after injury, the distal axonal segments that are destined for Wallerian degeneration had significantly retracted further than their proximal counterparts. We also found that targeting either RyR or IP 3 R using pharmacological and genetic approaches significantly reduced proximal axonal dieback and "bystander" secondary degeneration of axons compared to vehicle controls at 6h post-injury. Combined treatment effects on secondary axonal degeneration were similar to either drug in isolation. Together, these results suggest that intra-axonal Ca 2+ store mediated Ca 2+ release through RyR or IP 3 R contributes to secondary axonal degeneration following SCI. Copyright © 2017 Elsevier Inc. All rights reserved.

Aphrodisiac Activity of the Aqueous Crude Extract of Purple Corn ( Zea mays) in Male Rats.

PubMed

Carro-Juárez, Miguel; Rodríguez-Santiago, Magdalena G; Franco, Miguel Angel; Hueletl-Soto, María Eugenia

2017-10-01

In the present study, the aphrodisiac properties of the purple corn ( Zea mays) in male rats were analyzed. The aqueous crude extract of purple corn (at 25, 50, and 75 mg/kg) was administered to ( a) copulating male rats and ( b) anesthetized and spinal cord transected male rats. Behavioral parameters of copulatory behavior and parameters of the genital motor pattern of ejaculation previous to its inhibition, under the influence of the purple corn extract, are described. Administration of the aqueous crude extract of purple corn significantly facilitates the arousal and execution of male rat sexual behavior without significant influences on the ambulatory behavior. In addition, purple corn extract elicit a significant increase in the number of discharges of the ejaculatory motor patterns and in the total number of genital motor patterns evoked in spinal rats. The present findings show that the aqueous crude extract of purple corn possesses aphrodisiac activity.

Aphrodisiac Activity of the Aqueous Crude Extract of Purple Corn (Zea mays) in Male Rats

PubMed Central

Carro-Juárez, Miguel; Rodríguez-Santiago, Magdalena G.; Franco, Miguel Angel; Hueletl-Soto, María Eugenia

2017-01-01

In the present study, the aphrodisiac properties of the purple corn (Zea mays) in male rats were analyzed. The aqueous crude extract of purple corn (at 25, 50, and 75 mg/kg) was administered to (a) copulating male rats and (b) anesthetized and spinal cord transected male rats. Behavioral parameters of copulatory behavior and parameters of the genital motor pattern of ejaculation previous to its inhibition, under the influence of the purple corn extract, are described. Administration of the aqueous crude extract of purple corn significantly facilitates the arousal and execution of male rat sexual behavior without significant influences on the ambulatory behavior. In addition, purple corn extract elicit a significant increase in the number of discharges of the ejaculatory motor patterns and in the total number of genital motor patterns evoked in spinal rats. The present findings show that the aqueous crude extract of purple corn possesses aphrodisiac activity. PMID:28508664

An ex vivo laser-induced spinal cord injury model to assess mechanisms of axonal degeneration in real-time.

PubMed

Okada, Starlyn L M; Stivers, Nicole S; Stys, Peter K; Stirling, David P

2014-11-25

Injured CNS axons fail to regenerate and often retract away from the injury site. Axons spared from the initial injury may later undergo secondary axonal degeneration. Lack of growth cone formation, regeneration, and loss of additional myelinated axonal projections within the spinal cord greatly limits neurological recovery following injury. To assess how central myelinated axons of the spinal cord respond to injury, we developed an ex vivo living spinal cord model utilizing transgenic mice that express yellow fluorescent protein in axons and a focal and highly reproducible laser-induced spinal cord injury to document the fate of axons and myelin (lipophilic fluorescent dye Nile Red) over time using two-photon excitation time-lapse microscopy. Dynamic processes such as acute axonal injury, axonal retraction, and myelin degeneration are best studied in real-time. However, the non-focal nature of contusion-based injuries and movement artifacts encountered during in vivo spinal cord imaging make differentiating primary and secondary axonal injury responses using high resolution microscopy challenging. The ex vivo spinal cord model described here mimics several aspects of clinically relevant contusion/compression-induced axonal pathologies including axonal swelling, spheroid formation, axonal transection, and peri-axonal swelling providing a useful model to study these dynamic processes in real-time. Major advantages of this model are excellent spatiotemporal resolution that allows differentiation between the primary insult that directly injures axons and secondary injury mechanisms; controlled infusion of reagents directly to the perfusate bathing the cord; precise alterations of the environmental milieu (e.g., calcium, sodium ions, known contributors to axonal injury, but near impossible to manipulate in vivo); and murine models also offer an advantage as they provide an opportunity to visualize and manipulate genetically identified cell populations and subcellular structures. Here, we describe how to isolate and image the living spinal cord from mice to capture dynamics of acute axonal injury.

Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury

PubMed Central

Benthall, Katelyn N.; Hough, Ryan A.

2016-01-01

Following spinal cord injury (SCI) in the lamprey, there is virtually complete recovery of locomotion within a few weeks, but interestingly, axonal regeneration of reticulospinal (RS) neurons is mostly limited to short distances caudal to the injury site. To explain this situation, we hypothesize that descending propriospinal (PS) neurons relay descending drive from RS neurons to indirectly activate spinal central pattern generators (CPGs). In the present study, the contributions of PS neurons to locomotor recovery were tested in the lamprey following SCI. First, long RS neuron projections were interrupted by staggered spinal hemitransections on the right side at 10% body length (BL; normalized from the tip of the oral hood) and on the left side at 30% BL. For acute recovery conditions (≤1 wk) and before axonal regeneration, swimming muscle burst activity was relatively normal, but with some deficits in coordination. Second, lampreys received two spaced complete spinal transections, one at 10% BL and one at 30% BL, to interrupt long-axon RS neuron projections. At short recovery times (3–5 wk), RS and PS neurons will have regenerated their axons for short distances and potentially established a polysynaptic descending command pathway. At these short recovery times, swimming muscle burst activity had only minor coordination deficits. A computer model that incorporated either of the two spinal lesions could mimic many aspects of the experimental data. In conclusion, descending PS neurons are a viable mechanism for indirect activation of spinal locomotor CPGs, although there can be coordination deficits of locomotor activity. NEW & NOTEWORTHY In the lamprey following spinal lesion-mediated interruption of long axonal projections of reticulospinal (RS) neurons, sensory stimulation still elicited relatively normal locomotor muscle burst activity, but with some coordination deficits. Computer models incorporating the spinal lesions could mimic many aspects of the experimental results. Thus, after disruption of long-axon projections from RS neurons in the lamprey, descending propriospinal (PS) neurons appear to be a viable compensatory mechanism for indirect activation of spinal locomotor networks. PMID:27760818

Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury.

PubMed

Benthall, Katelyn N; Hough, Ryan A; McClellan, Andrew D

2017-01-01

Following spinal cord injury (SCI) in the lamprey, there is virtually complete recovery of locomotion within a few weeks, but interestingly, axonal regeneration of reticulospinal (RS) neurons is mostly limited to short distances caudal to the injury site. To explain this situation, we hypothesize that descending propriospinal (PS) neurons relay descending drive from RS neurons to indirectly activate spinal central pattern generators (CPGs). In the present study, the contributions of PS neurons to locomotor recovery were tested in the lamprey following SCI. First, long RS neuron projections were interrupted by staggered spinal hemitransections on the right side at 10% body length (BL; normalized from the tip of the oral hood) and on the left side at 30% BL. For acute recovery conditions (≤1 wk) and before axonal regeneration, swimming muscle burst activity was relatively normal, but with some deficits in coordination. Second, lampreys received two spaced complete spinal transections, one at 10% BL and one at 30% BL, to interrupt long-axon RS neuron projections. At short recovery times (3-5 wk), RS and PS neurons will have regenerated their axons for short distances and potentially established a polysynaptic descending command pathway. At these short recovery times, swimming muscle burst activity had only minor coordination deficits. A computer model that incorporated either of the two spinal lesions could mimic many aspects of the experimental data. In conclusion, descending PS neurons are a viable mechanism for indirect activation of spinal locomotor CPGs, although there can be coordination deficits of locomotor activity. In the lamprey following spinal lesion-mediated interruption of long axonal projections of reticulospinal (RS) neurons, sensory stimulation still elicited relatively normal locomotor muscle burst activity, but with some coordination deficits. Computer models incorporating the spinal lesions could mimic many aspects of the experimental results. Thus, after disruption of long-axon projections from RS neurons in the lamprey, descending propriospinal (PS) neurons appear to be a viable compensatory mechanism for indirect activation of spinal locomotor networks. Copyright © 2017 the American Physiological Society.

Directing Induced Pluripotent Stem Cell Derived Neural Stem Cell Fate with a Three-Dimensional Biomimetic Hydrogel for Spinal Cord Injury Repair.

PubMed

Fan, Lei; Liu, Can; Chen, Xiuxing; Zou, Yan; Zhou, Zhengnan; Lin, Chenkai; Tan, Guoxin; Zhou, Lei; Ning, Chenyun; Wang, Qiyou

2018-05-30

Current treatment approaches for spinal cord injuries (SCIs) are mainly based on cellular transplantation. Induced pluripotent stem cells (iPSCs) without supply constraints and ethical concerns have emerged as a viable treatment option for repairing neurological disorders. However, the primarily limitations in the neuroregeneration field are uncontrolled cell differentiation, and low cell viability caused by the ischemic environment. The mechanical property of three-dimensional (3D) hydrogel can be easily controlled and shared similar characteristics with nerve tissue, thus promoting cell survival and controlled cell differentiation. We propose the combination of a 3D gelatin methacrylate (GelMA) hydrogel with iPSC-derived NSCs (iNSCs) to promote regeneration after SCI. In vitro, the iNSCs photoencapsulated in the 3D GelMA hydrogel survived and differentiated well, especially in lower-moduli hydrogels. More robust neurite outgrowth and more neuronal differentiation were detected in the soft hydrogel group. To further evaluate the in vivo neuronal regeneration effect of the GelMA hydrogels, a mouse spinal cord transection model was generated. We found that GelMA/iNSC implants significantly promoted functional recovery. Further histological analysis showed that the cavity areas were significantly reduced, and less collagen was deposited in the GelMA/iNSC group. Furthermore, the GelMA and iNSC combined transplantation decreased inflammation by reducing activated macrophages/microglia (CD68-positive cells). Additionally, GelMA/iNSC implantation showed striking therapeutic effects of inhibiting GFAP-positive cells and glial scar formation while simultaneously promoting axonal regeneration. Undoubtedly, use of this 3D hydrogel stem cell-loaded system is a promising therapeutic strategy for SCI repair.

N-Acetylcysteine Prevents Retrograde Motor Neuron Death after Neonatal Peripheral Nerve Injury.

PubMed

Catapano, Joseph; Zhang, Jennifer; Scholl, David; Chiang, Cameron; Gordon, Tessa; Borschel, Gregory H

2017-05-01

Neuronal death may be an overlooked and unaddressed component of disability following neonatal nerve injuries, such as obstetric brachial plexus injury. N-acetylcysteine and acetyl-L-carnitine improve survival of neurons after adult nerve injury, but it is unknown whether they improve survival after neonatal injury, when neurons are most susceptible to retrograde neuronal death. The authors' objective was to examine whether N-acetylcysteine or acetyl-L-carnitine treatment improves survival of neonatal motor or sensory neurons in a rat model of neonatal nerve injury. Rat pups received either a sciatic nerve crush or transection injury at postnatal day 3 and were then randomized to receive either intraperitoneal vehicle (5% dextrose), N-acetylcysteine (750 mg/kg), or acetyl-L-carnitine (300 mg/kg) once or twice daily. Four weeks after injury, surviving neurons were retrograde-labeled with 4% Fluoro-Gold. The lumbar spinal cord and L4/L5 dorsal root ganglia were then harvested and sectioned to count surviving motor and sensory neurons. Transection and crush injuries resulted in significant motor and sensory neuron loss, with transection injury resulting in significantly less neuron survival. High-dose N-acetylcysteine (750 mg/kg twice daily) significantly increased motor neuron survival after neonatal sciatic nerve crush and transection injury. Neither N-acetylcysteine nor acetyl-L-carnitine treatment improved sensory neuron survival. Proximal neonatal nerve injuries, such as obstetric brachial plexus injury, produce significant retrograde neuronal death after injury. High-dose N-acetylcysteine significantly increases motor neuron survival, which may improve functional outcomes after obstetrical brachial plexus injury.

The spinal control of locomotion and step-to-step variability in left-right symmetry from slow to moderate speeds

PubMed Central

Dambreville, Charline; Labarre, Audrey; Thibaudier, Yann; Hurteau, Marie-France

2015-01-01

When speed changes during locomotion, both temporal and spatial parameters of the pattern must adjust. Moreover, at slow speeds the step-to-step pattern becomes increasingly variable. The objectives of the present study were to assess if the spinal locomotor network adjusts both temporal and spatial parameters from slow to moderate stepping speeds and to determine if it contributes to step-to-step variability in left-right symmetry observed at slow speeds. To determine the role of the spinal locomotor network, the spinal cord of 6 adult cats was transected (spinalized) at low thoracic levels and the cats were trained to recover hindlimb locomotion. Cats were implanted with electrodes to chronically record electromyography (EMG) in several hindlimb muscles. Experiments began once a stable hindlimb locomotor pattern emerged. During experiments, EMG and bilateral video recordings were made during treadmill locomotion from 0.1 to 0.4 m/s in 0.05 m/s increments. Cycle and stance durations significantly decreased with increasing speed, whereas swing duration remained unaffected. Extensor burst duration significantly decreased with increasing speed, whereas sartorius burst duration remained unchanged. Stride length, step length, and the relative distance of the paw at stance offset significantly increased with increasing speed, whereas the relative distance at stance onset and both the temporal and spatial phasing between hindlimbs were unaffected. Both temporal and spatial step-to-step left-right asymmetry decreased with increasing speed. Therefore, the spinal cord is capable of adjusting both temporal and spatial parameters during treadmill locomotion, and it is responsible, at least in part, for the step-to-step variability in left-right symmetry observed at slow speeds. PMID:26084910

Connexin36 identified at morphologically mixed chemical/electrical synapses on trigeminal motoneurons and at primary afferent terminals on spinal cord neurons in adult mouse and rat

PubMed Central

Bautista, W.; McCrea, D. A.; Nagy, J. I.

2014-01-01

Morphologically mixed chemical/electrical synapses at axon terminals, with the electrical component formed by gap junctions, is common in the CNS of lower vertebrates. In mammalian CNS, evidence for morphologically mixed synapses has been obtained in only a few locations. Here, we used immunofluorescence approaches to examine the localization of the neuronally expressed gap junction forming protein connexin36 (Cx36) in relation to the axon terminal marker vesicular glutamate transporter1 (vglut1) in spinal cord and trigeminal motor nucleus (Mo5) of rat and mouse. In adult rodents, immunolabelling for Cx36 appeared exclusively as Cx36-puncta, and was widely distributed at all rostro-caudal levels in most spinal cord laminae and in the Mo5. A high proportion of Cx36-puncta was co-localized with vglut1, forming morphologically mixed synapses on motoneurons, in intermediate spinal cord lamina, and in regions of medial lamina VII, where vglut1-containing terminals associated with Cx36 converged on neurons adjacent to the central canal. Unilateral transection of lumbar dorsal roots reduced immunolabelling of both vglut1 and Cx36 in intermediate laminae and lamina IX. Further, vglut1-terminals displaying Cx36-puncta were contacted by terminals labelled for glutamic acid decarboxylase65, which is known to be contained in presynaptic terminals on large diameter primary afferents. Developmentally, mixed synapses begin to emerge in the spinal cord only after the second to third postnatal week and thereafter increase to adult levels. Our findings demonstrate that axon terminals of primary afferent origin form morphologically mixed synapses containing Cx36 in broadly distributed areas of adult rodent spinal cord and Mo5. PMID:24406437

Neuropathy-induced spinal GAP-43 expression is not a main player in the onset of mechanical pain hypersensitivity.

PubMed

Jaken, Robby J; van Gorp, Sebastiaan; Joosten, Elbert A; Losen, Mario; Martínez-Martínez, Pilar; De Baets, Marc; Marcus, Marco A; Deumens, Ronald

2011-12-01

Structural plasticity within the spinal nociceptive network may be fundamental to the chronic nature of neuropathic pain. In the present study, the spatiotemporal expression of growth-associated protein-43 (GAP-43), a protein which has been traditionally implicated in nerve fiber growth and sprouting, was investigated in relation to mechanical pain hypersensitivity. An L5 spinal nerve transection model was validated by the presence of mechanical pain hypersensitivity and an increase in the early neuronal activation marker cFos within the superficial spinal dorsal horn upon innocuous hindpaw stimulation. Spinal GAP-43 was found to be upregulated in the superficial L5 dorsal horn from 5 up to 10 days after injury. GAP-43 was co-localized with calcitonin-gene related peptide (CGRP), but not vesicular glutamate transporter-1 (VGLUT-1), IB4, or protein kinase-γ (PKC-γ), suggesting the regulation of GAP-43 in peptidergic nociceptive afferents. These GAP-43/CGRP fibers may be indicative of sprouting peptidergic fibers. Fiber sprouting largely depends on growth factors, which are typically associated with neuro-inflammatory processes. The putative role of neuropathy-induced GAP-43 expression in the development of mechanical pain hypersensitivity was investigated using the immune modulator propentofylline. Propentofylline treatment strongly attenuated the development of mechanical pain hypersensitivity and glial responses to nerve injury as measured by microglial and astroglial markers, but did not affect neuropathy-induced levels of spinal GAP-43 or GAP-43 regulation in CGRP fibers. We conclude that nerve injury induces structural plasticity in fibers expressing CGRP, which is regarded as a main player in central sensitization. Our data do not, however, support a major role of these structural changes in the onset of mechanical pain hypersensitivity.

Dissociating movement from movement timing in the rat primary motor cortex.

PubMed

Knudsen, Eric B; Powers, Marissa E; Moxon, Karen A

2014-11-19

Neural encoding of the passage of time to produce temporally precise movements remains an open question. Neurons in several brain regions across different experimental contexts encode estimates of temporal intervals by scaling their activity in proportion to the interval duration. In motor cortex the degree to which this scaled activity relies upon afferent feedback and is guided by motor output remains unclear. Using a neural reward paradigm to dissociate neural activity from motor output before and after complete spinal transection, we show that temporally scaled activity occurs in the rat hindlimb motor cortex in the absence of motor output and after transection. Context-dependent changes in the encoding are plastic, reversible, and re-established following injury. Therefore, in the absence of motor output and despite a loss of afferent feedback, thought necessary for timed movements, the rat motor cortex displays scaled activity during a broad range of temporally demanding tasks similar to that identified in other brain regions. Copyright © 2014 the authors 0270-6474/14/3415576-11$15.00/0.

Select spinal lesions reveal multiple ascending pathways in the rat conveying input from the male genitalia

PubMed Central

Hubscher, C H; Reed, W R; Kaddumi, E G; Armstrong, J E; Johnson, R D

2010-01-01

The specific white matter location of all the spinal pathways conveying penile input to the rostral medulla is not known. Our previous studies using rats demonstrated the loss of low but not high threshold penile inputs to medullary reticular formation (MRF) neurons after acute and chronic dorsal column (DC) lesions of the T8 spinal cord and loss of all penile inputs after lesioning the dorsal three-fifths of the cord. In the present study, select T8 lesions were made and terminal electrophysiological recordings were performed 45–60 days later in a limited portion of the nucleus reticularis gigantocellularis (Gi) and Gi pars alpha. Lesions included subtotal dorsal hemisections that spared only the lateral half of the dorsal portion of the lateral funiculus on one side, dorsal and over-dorsal hemisections, and subtotal transections that spared predominantly just the ventromedial white matter. Electrophysiological data for 448 single unit recordings obtained from 32 urethane-anaesthetized rats, when analysed in groups based upon histological lesion reconstructions, revealed (1) ascending bilateral projections in the dorsal, dorsolateral and ventrolateral white matter of the spinal cord conveying information from the male external genitalia to MRF, and (2) ascending bilateral projections in the ventrolateral white matter conveying information from the pelvic visceral organs (bladder, descending colon, urethra) to MRF. Multiple spinal pathways from the penis to the MRF may correspond to different functions, including those processing affective/pleasure/motivational, nociception, and mating-specific (such as for erection and ejaculation) inputs. PMID:20142271

STUDIES IN RESUSCITATION: IV. THE RETURN OF FUNCTION IN THE CENTRAL NERVOUS SYSTEM AFTER TEMPORARY CEREBRAL ANÆMIA

PubMed Central

Pike, F. H.; Guthrie, C. C.; Stewart, G. N.

1908-01-01

The experiments on cerebral anæmia have enabled us to duplicate, by an entirely different method, many of the results obtained by anatomical division or removal of parts of the central nervous system. In some respects the method of anæmia permits of greater precision than the method of division or excision, and avoids, in great measure, the disturbances due to the wound and to the hemorrhage caused by the latter method. The method of general anæmia, as Couty pointed out long ago, leaves something to be desired in the matter of exact localization, but this objection may be met, in some degree at least, by appropriate methods of investigation. It is desirable that the results obtained by the method of section should be duplicated by some other method in order to eliminate as much as possible the effects due to the irritation produced by the anatomical lesion. Our results show, as we believe, that, of the bulbar mechanisms studied, the respiratory is the most automatic, the vasomotor in part automatic, and the cardiac like the swallowing mechanism, almost wholly dependent upon afferent impulses for the arousal and discharge of its normal activity. The eye reflexes return during the resuscitation period in the animals in which the cerebral anæmia has not been too prolonged. The motor cortex loses its excitability during anæmia, but may regain it after the reëstablishment of the circulation. The pilomotor mechanism is disturbed during the spasms which occur at a certain stage in the resuscitation. The temperature falls during the occlusion period, but rises again, often to far above normal, in the days following the anæmia. So many disturbing factors, such as the violent muscular contractions during spasms, enter into the problem that it is impossible to say that there is an actual disturbance of the temperature regulating mechanism although we are inclined to believe that this is the case. All the senses return, following cerebral anæmia, but sight and hearing may afterwards fail without causing the death of the animal. The mental processes may return without any apparent deficiency, if the period of anæmia has been short. After longer occlusion, apparent insanity has been seen, and in one case, apparent total loss of mental processes occurred. The reflex excitability of the cord returns rather early in the resuscitation period. Reflexes from the anterior part of the cord first involve muscles on the same side as the stimulus, and later cross to involve muscles of the opposite side. The spinal cord sometimes falls into much the same condition as that following spinal transection, and the scratch reflex appears. Spinal transection, when these reflexes have appeared, does not produce shock. Practically all phenomena of spinal shock may be reproduced without section of the cord. We conclude, therefore, that spinal shock is due more to the cutting off of the reflex pathways through the higher centers of the nervous system than to the stimulation of inhibitory fibers by the anæmia. PMID:19867144

Rewiring of regenerated axons by combining treadmill training with semaphorin3A inhibition

PubMed Central

2014-01-01

Background Rats exhibit extremely limited motor function recovery after total transection of the spinal cord (SCT). We previously reported that SM-216289, a semaphorin3A inhibitor, enhanced axon regeneration and motor function recovery in SCT adult rats. However, these effects were limited because most regenerated axons likely do not connect to the right targets. Thus, rebuilding the appropriate connections for regenerated axons may enhance recovery. In this study, we combined semaphorin3A inhibitor treatment with extensive treadmill training to determine whether combined treatment would further enhance the “rewiring” of regenerated axons. In this study, which aimed for clinical applicability, we administered a newly developed, potent semaphorin3A inhibitor, SM-345431 (Vinaxanthone), using a novel drug delivery system that enables continuous drug delivery over the period of the experiment. Results Treatment with SM-345431 using this delivery system enhanced axon regeneration and produced significant, but limited, hindlimb motor function recovery. Although extensive treadmill training combined with SM-345431 administration did not further improve axon regeneration, hindlimb motor performance was restored, as evidenced by the significant improvement in the execution of plantar steps on a treadmill. In contrast, control SCT rats could not execute plantar steps at any point during the experimental period. Further analyses suggested that this strategy reinforced the wiring of central pattern generators in lumbar spinal circuits, which, in turn, led to enhanced motor function recovery (especially in extensor muscles). Conclusions This study highlights the importance of combining treatments that promote axon regeneration with specific and appropriate rehabilitations that promote rewiring for the treatment of spinal cord injury. PMID:24618249

Involvement of μ-opioid receptors in antinociceptive action of botulinum toxin type A.

PubMed

Drinovac, V; Bach-Rojecky, L; Matak, I; Lacković, Z

2013-07-01

Botulinum toxin A (BTX-A) is approved for treatment of chronic migraine and has been investigated in various other painful conditions. Recent evidence demonstrated retrograde axonal transport and suggested the involvement of CNS in antinociceptive effect of BTX-A. However, the mechanism of BTX-A central antinociceptive action is unknown. In this study we investigated the potential role of opioid receptors in BTX-A's antinociceptive activity. In formalin-induced inflammatory pain we assessed the effect of opioid antagonists on antinociceptive activity of BTX-A. Naltrexone was injected subcutaneously (0.02-2 mg/kg) or intrathecally (0.07 μg/10 μl-350 μg/10 μl), while selective μ-antagonist naloxonazine was administered intraperitoneally (5 mg/kg) prior to nociceptive testing. The influence of naltrexone (2 mg/kg s.c.) on BTX-A antinociceptive activity was examined additionally in an experimental neuropathy induced by partial sciatic nerve transection. To investigate the effects of naltrexone and BTX-A on neuronal activation in spinal cord, c-Fos expression was immunohistochemically examined in a model of formalin-induced pain. Antinociceptive effects of BTX-A in formalin and sciatic nerve transection-induced pain were prevented by non-selective opioid antagonist naltrexone. Similarly, BTX-A-induced pain reduction was abolished by low dose of intrathecal naltrexone and by selective μ-antagonist naloxonazine. BTX-A-induced decrease in dorsal horn c-Fos expression was prevented by naltrexone. Prevention of BTX-A effects on pain and c-Fos expression by opioid antagonists suggest that the central antinociceptive action of BTX-A might be associated with the activity of endogenous opioid system (involving μ-opioid receptor). These results provide first insights into the mechanism of BTX-A's central antinociceptive activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Switching control of sympathetic activity from forebrain to hindbrain in chronic dehydration

PubMed Central

Colombari, Débora S A; Colombari, Eduardo; Freiria-Oliveira, Andre H; Antunes, Vagner R; Yao, Song T; Hindmarch, Charles; Ferguson, Alastair V; Fry, Mark; Murphy, David; Paton, Julian F R

2011-01-01

Abstract We investigated the mechanisms responsible for increased blood pressure and sympathetic nerve activity (SNA) caused by 2–3 days dehydration (DH) both in vivo and in situ preparations. In euhydrated (EH) rats, systemic application of the AT1 receptor antagonist Losartan and subsequent pre-collicular transection (to remove the hypothalamus) significantly reduced thoracic (t)SNA. In contrast, in DH rats, Losartan, followed by pre-collicular and pontine transections, failed to reduce tSNA, whereas transection at the medulla–spinal cord junction massively reduced tSNA. In DH but not EH rats, selective inhibition of the commissural nucleus tractus solitarii (cNTS) significantly reduced tSNA. Comparable data were obtained in both in situ and in vivo (anaesthetized/conscious) rats and suggest that following chronic dehydration, the control of tSNA transfers from supra-brainstem structures (e.g. hypothalamus) to the medulla oblongata, particularly the cNTS. As microarray analysis revealed up-regulation of AP1 transcription factor JunD in the dehydrated cNTS, we tested the hypothesis that AP1 transcription factor activity is responsible for dehydration-induced functional plasticity. When AP1 activity was blocked in the cNTS using a viral vector expressing a dominant negative FosB, cNTS inactivation was ineffective. However, tSNA was decreased after pre-collicular transection, a response similar to that seen in EH rats. Thus, the dehydration-induced switch in control of tSNA from hypothalamus to cNTS seems to be mediated via activation of AP1 transcription factors in the cNTS. If AP1 activity is blocked in the cNTS during dehydration, sympathetic activity control reverts back to forebrain regions. This unique reciprocating neural structure-switching plasticity between brain centres emphasizes the multiple mechanisms available for the adaptive response to dehydration. PMID:21708906

Pneumocephalus Following Thoracic Surgery with Posterior Chest Wall Resection.

PubMed

Müller, Ina; Tönnies, Mario; Pfannschmidt, Joachim; Kaiser, Dirk

2015-12-01

Pneumocephalus can be seen after head injury with fracture of the skull-base or in cerebral neoplasm, infection, or after intracranial or spinal surgery. We report on a 69-year-old male patient with pneumocephalus after right-sided lobectomy and en bloc resection of the chest wall for non-small-cell lung cancer. Postoperatively, the patient showed a reduced vigilance level with no response to pain stimuli and anisocoria. The CCT scan revealed an extensive pneumocephalus; following which, the patient underwent neurosurgery with laminectomy and ligature of the transected nerve roots. After operation the patient returned to his baseline mental status.

Early CALP2 expression and microglial activation are potential inducers of spinal IL-6 up-regulation and bilateral pain following motor nerve injury.

PubMed

Chen, Shao-Xia; Wang, Shao-Kun; Yao, Pei-Wen; Liao, Guang-Jie; Na, Xiao-Dong; Li, Yong-Yong; Zeng, Wei-An; Liu, Xian-Guo; Zang, Ying

2018-04-01

Previous work from our laboratory showed that motor nerve injury by lumbar 5 ventral root transection (L5-VRT) led to interleukin-6 (IL-6) over-expression in bilateral spinal cord, and that intrathecal administration of IL-6 neutralizing antibody delayed the induction of mechanical allodynia in bilateral hind paws. However, early events and upstream mechanisms underlying spinal IL-6 expression following L5-VRT require elucidation. The model of L5-VRT was used to induce neuropathic pain, which was assessed with von Frey hairs and the plantar tester in adult male Sprague-Dawley rats. Calpain-2 (CALP2, a calcium-dependent protease) knockdown or over-expression and microglia depletion were conducted intrathecally. Western blots and immunohistochemistry were performed to explore the possible mechanisms. Here, we provide the first evidence that both IL-6 and CALP2 levels are increased in lumbar spinal cord within 30 min following L5-VRT. IL-6 and CALP2 co-localized in both spinal dorsal horn (SDH) and spinal ventral horn. Post-operative (PO) increase in CALP2 in ipsilateral SDH was evident at 10 min PO, preceding increased IL-6 at 20 min PO. Knockdown of spinal CALP2 by intrathecal CALP2-shRNA administration prevented VRT-induced IL-6 overproduction in ipsilateral spinal cord and alleviated bilateral mechanical allodynia. Spinal microglia activation also played a role in early IL-6 up-regulation. Macrophage/microglia markers ED1/Iba1 were increased at 30 min PO, while glial fibrillary acidic protein (astrocyte) and CNPase (oligodendrocyte) markers were not. Increased Iba1 was detected as early as 20 min PO and peaked at 3 days. Morphology changed from a small soma with fine processes in resting cells to an activated ameboid shape. Depletion of microglia using Mac-1-saporin partially prevented IL-6 up-regulation and attenuated VRT-induced bilateral mechanical allodynia. Taken together, our findings provide evidence that increased spinal cord CALP2 and microglia cell activation may have early causative roles in IL-6 over-expression following motor nerve injury. Agents that inhibit CALP2 and/or microglia activation may therefore prove valuable for treating neuropathic pain. © 2018 International Society for Neurochemistry.

Assessment of hindlimb locomotor strength in spinal cord transected rats through animal-robot contact force.

PubMed

Nessler, Jeff A; Moustafa-Bayoumi, Moustafa; Soto, Dalziel; Duhon, Jessica; Schmitt, Ryan

2011-12-01

Robotic locomotor training devices have gained popularity in recent years, yet little has been reported regarding contact forces experienced by the subject performing automated locomotor training, particularly in animal models of neurological injury. The purpose of this study was to develop a means for acquiring contact forces between a robotic device and a rodent model of spinal cord injury through instrumentation of a robotic gait training device (the rat stepper) with miniature force/torque sensors. Sensors were placed at each interface between the robot arm and animal's hindlimb and underneath the stepping surface of both hindpaws (four sensors total). Twenty four female, Sprague-Dawley rats received mid-thoracic spinal cord transections as neonates and were included in the study. Of these 24 animals, training began for 18 animals at 21 days of age and continued for four weeks at five min/day, five days/week. The remaining six animals were untrained. Animal-robot contact forces were acquired for trained animals weekly and untrained animals every two weeks while stepping in the robotic device with both 60 and 90% of their body weight supported (BWS). Animals that received training significantly increased the number of weight supported steps over the four week training period. Analysis of raw contact forces revealed significant increases in forward swing and ground reaction forces during this time, and multiple aspects of animal-robot contact forces were significantly correlated with weight bearing stepping. However, when contact forces were normalized to animal body weight, these increasing trends were no longer present. Comparison of trained and untrained animals revealed significant differences in normalized ground reaction forces (both horizontal and vertical) and normalized forward swing force. Finally, both forward swing and ground reaction forces were significantly reduced at 90% BWS when compared to the 60% condition. These results suggest that measurement of animal-robot contact forces using the instrumented rat stepper can provide a sensitive and reliable measure of hindlimb locomotor strength and control of flexor and extensor muscle activity in neurologically impaired animals. Additionally, these measures may be useful as a means to quantify training intensity or dose-related functional outcomes of automated training.

TENS attenuates response to colon distension in paraplegic and quadriplegic rats.

PubMed

Collins, Heidi L; DiCarlo, Stephen E

2002-10-01

Individuals with spinal cord injuries above thoracic level 6 experience episodic bouts of life-threatening hypertension as part of a condition termed autonomic dysreflexia (AD). The hypertension can be caused by stimulation of the skin, distension of the urinary bladder or colon, and/or muscle spasms. Transcutaneous electrical nerve stimulation (TENS) may reduce the severity of AD because TENS has been used to inhibit second-order neurons in the dorsal horn. Therefore, we tested the hypothesis that TENS attenuates the hemodynamic responses to colon distension. Eleven Wistar rats underwent spinal cord transection between thoracic vertebrae 4 and 5 (paraplegic, n = 6) or between cervical vertebra 7 and thoracic vertebra 1 (quadriplegic, n = 5). After recovery, all rats were instrumented with a radiotelemetry device for recording arterial pressure. Subsequently, the hemodynamic responses to graded colon distension were determined before and during TENS. During TENS the hemodynamic responses to colon distension were significantly attenuated. Thus TENS may be a preventive approach to reduce the severity of AD in paraplegic and quadriplegic individuals.

The "pseudo-CT myelogram sign": an aid to the diagnosis of underlying brain stem and spinal cord trauma in the presence of major craniocervical region injury on post-mortem CT.

PubMed

Bolster, F; Ali, Z; Daly, B

2017-12-01

To document the detection of underlying low-attenuation spinal cord or brain stem injuries in the presence of the "pseudo-CT myelogram sign" (PCMS) on post-mortem computed tomography (PMCT). The PCMS was identified on PMCT in 20 decedents (11 male, nine female; age 3-83 years, mean age 35.3 years) following fatal blunt trauma at a single forensic centre. Osseous and ligamentous craniocervical region injuries and brain stem or spinal cord trauma detectable on PMCT were recorded. PMCT findings were compared to conventional autopsy in all cases. PMCT-detected transection of the brain stem or high cervical cord in nine of 10 cases compared to autopsy (90% sensitivity). PMCT was 92.86% sensitive in detection of atlanto-occipital joint injuries (n=14), and 100% sensitive for atlanto-axial joint (n=8) injuries. PMCT detected more cervical spine and skull base fractures (n=22, and n=10, respectively) compared to autopsy (n=13, and n=5, respectively). The PCMS is a novel description of a diagnostic finding, which if present in fatal craniocervical region trauma, is very sensitive for underlying spinal cord and brain stem injuries not ordinarily visible on PMCT. Its presence may also predict major osseous and/or ligamentous injuries in this region when anatomical displacement is not evident on PMCT. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

A novel device for studying weight supported, quadrupedal overground locomotion in spinal cord injured rats.

PubMed

Hamlin, Marvin; Traughber, Terence; Reinkensmeyer, David J; de Leon, Ray D

2015-05-15

Providing weight support facilitates locomotion in spinal cord injured animals. To control weight support, robotic systems have been developed for treadmill stepping and more recently for overground walking. We developed a novel device, the body weight supported ambulatory rodent trainer (i.e. BART). It has a small pneumatic cylinder that moves along a linear track above the rat. When air is supplied to the cylinder, the rats are lifted as they perform overground walking. We tested the BART device in rats that received a moderate spinal cord contusion injury and in normal rats. Locomotor training with the BART device was not performed. All of the rats learned to walk in the BART device. In the contused rats, significantly greater paw dragging and dorsal stepping occurred in the hindlimbs compared to normal. Providing weight support significantly raised hip position and significantly reduced locomotor deficits. Hindlimb stepping was tightly coupled to forelimb stepping but only when the contused rats stepped without weight support. Three weeks after the contused rats received a complete spinal cord transection, significantly fewer hindlimb steps were performed. Relative to rodent robotic systems, the BART device is a simpler system for studying overground locomotion. The BART device lacks sophisticated control and sensing capability, but it can be assembled relatively easily and cheaply. These findings suggest that the BART device is a useful tool for assessing quadrupedal, overground locomotion which is a more natural form of locomotion relative to treadmill locomotion. Published by Elsevier B.V.

Modeling the functional repair of nervous tissue in spinal cord injury

NASA Astrophysics Data System (ADS)

Mantila, Sara M.; Camp, Jon J.; Krych, Aaron J.; Robb, Richard A.

2004-05-01

Functional repair of traumatic spinal cord injury (SCI) is one of the most challenging goals in modern medicine. The annual incidence of SCI in the United States is approximately 11,000 new cases. The prevalence of people in the U.S. currently living with SCI is approximately 200,000. Exploring and understanding nerve regeneration in the central nervous system (CNS) is a critical first step in attempting to reverse the devastating consequences of SCI. At Mayo Clinic, a preliminary study of implants in the transected rat spinal cord model demonstrates potential for promoting axon regeneration. In collaborative research between neuroscientists and bioengineers, this procedure holds promise for solving two critical aspects of axon repair-providing a resorbable structural scaffold to direct focused axon repair, and delivery of relevant signaling molecules necessary to facilitate regeneration. In our preliminary study, regeneration in the rat's spinal cord was modeled in three dimensions utilizing an image processing software system developed in the Biomedical Imaging Resource at Mayo Clinic. Advanced methods for image registration, segmentation, and rendering were used. The raw images were collected at three different magnifications. After image processing the individual channels in the scaffold, axon bundles, and macrophages could be identified. Several axon bundles could be visualized and traced through the entire volume, suggesting axonal growth throughout the length of the scaffold. Such information could potentially allow researchers and physicians to better understand and improve the nerve regeneration process for individuals with SCI.

Effect and reporting bias of RhoA/ROCK-blockade intervention on locomotor recovery after spinal cord injury: a systematic review and meta-analysis.

PubMed

Watzlawick, Ralf; Sena, Emily S; Dirnagl, Ulrich; Brommer, Benedikt; Kopp, Marcel A; Macleod, Malcolm R; Howells, David W; Schwab, Jan M

2014-01-01

Blockade of small GTPase-RhoA signaling pathway is considered a candidate translational strategy to improve functional outcome after spinal cord injury (SCI) in humans. Pooling preclinical evidence by orthodox meta-analysis is confounded by missing data (publication bias). To conduct a systematic review and meta-analysis of RhoA/Rho-associated coiled-coil containing protein kinase (ROCK) blocking approaches to (1) analyze the impact of bias that may lead to inflated effect sizes and (2) determine the normalized effect size of functional locomotor recovery after experimental thoracic SCI. We conducted a systematic search of PubMed, EMBASE, and Web of Science and hand searched related references. Studies were selected if they reported the effect of RhoA/ROCK inhibitors (C3-exoenzmye, fasudil, Y-27632, ibuprofen, siRhoA, and p21) in experimental spinal cord hemisection, contusion, or transection on locomotor recovery measured by the Basso, Beattie, and Bresnahan score or the Basso Mouse Scale for Locomotion. Two investigators independently assessed the identified studies. Details of individual study characteristics from each publication were extracted and effect sizes pooled using a random effects model. We assessed risk for bias using a 9-point-item quality checklist and calculated publication bias with Egger regression and the trim and fill method. A stratified meta-analysis was used to assess the impact of study characteristics on locomotor recovery. Thirty studies (725 animals) were identified. RhoA/ROCK inhibition was found to improve locomotor outcome by 21% (95% CI, 16.0-26.6). Assessment of publication bias by the trim and fill method suggested that 30% of experiments remain unpublished. Inclusion of these theoretical missing studies suggested a 27% overestimation of efficacy, reducing the overall efficacy to a 15% improvement in locomotor recovery. Low study quality was associated with larger estimates of neurobehavioral outcome. Taking into account publication bias, RhoA/ROCK inhibition improves functional outcome in experimental SCI by 15%. This is a plausible strategy for the pharmacological augmentation of neurorehabilitation after human SCI. These findings support the necessity of a systematic analysis to identify preclinical bias before embarking on a clinical trial.

Fyn kinase-mediated phosphorylation of NMDA receptor NR2B subunit at Tyr1472 is essential for maintenance of neuropathic pain.

PubMed

Abe, Tetsuya; Matsumura, Shinji; Katano, Tayo; Mabuchi, Tamaki; Takagi, Kunio; Xu, Li; Yamamoto, Akitsugu; Hattori, Kotaro; Yagi, Takeshi; Watanabe, Masahiko; Nakazawa, Takanobu; Yamamoto, Tadashi; Mishina, Masayoshi; Nakai, Yoshihide; Ito, Seiji

2005-09-01

Despite abundant evidence implicating the importance of N-methyl-D-aspartate (NMDA) receptors in the spinal cord for pain transmission, the signal transduction coupled to NMDA receptor activation is largely unknown for the neuropathic pain state that lasts over periods of weeks. To address this, we prepared mice with neuropathic pain by transection of spinal nerve L5. Wild-type, NR2A-deficient, and NR2D-deficient mice developed neuropathic pain; in addition, phosphorylation of NR2B subunits of NMDA receptors at Tyr1472 was observed in the superficial dorsal horn of the spinal cord 1 week after nerve injury. Neuropathic pain and NR2B phosphorylation at Tyr1472 were attenuated by the NR2B-selective antagonist CP-101,606 and disappeared in mice lacking Fyn kinase, a Src-family tyrosine kinase. Concomitant with the NR2B phosphorylation, an increase in neuronal nitric oxide synthase activity was visualized in the superficial dorsal horn of neuropathic pain mice by NADPH diaphorase histochemistry. Electron microscopy showed that the phosphorylated NR2B was localized at the postsynaptic density in the spinal cord of mice with neuropathic pain. Indomethacin, an inhibitor of prostaglandin (PG) synthesis, and PGE receptor subtype EP1-selective antagonist reduced the NR2B phosphorylation in these mice. Conversely, EP1-selective agonist stimulated Fyn kinase-dependent nitric oxide formation in the spinal cord. The present study demonstrates that Tyr1472 phosphorylation of NR2B subunits by Fyn kinase may have dual roles in the retention of NMDA receptors in the postsynaptic density and in activation of nitric oxide synthase, and suggests that PGE2 is involved in the maintenance of neuropathic pain via the EP1 subtype.

Long-term effect of sphincteric fatigue during bladder neurostimulation.

PubMed

Li, J S; Hassouna, M; Sawan, M; Duval, F; Elhilali, M M

1995-01-01

Commercially available stimulators lack several features, including multiple channel capability and flexible stimulation parameters. These factors limit clinical application. A new computerized electrical stimulator system was developed by our team and evaluated for its efficacy in bladder evacuation in an animal model after spinal cord transection. The system can generate a wide range of stimulation characteristics and has the feature of being a programmable multichannel pacemaker. It has enabled us to induce a reversible fatigue to the external sphincter that results in proper bladder emptying on stimulation. Using this new bladder pacemaker, 8 dogs were studied. We applied the concept of fatiguing of the external sphincter via the pudendal nerve to avoid rhizotomy. We determined the optimal stimulation parameters that can reliably empty the dog's bladder for the duration of the experiment, which lasted for 8 months. The new computerized electrical stimulation system achieved the objective of reducing bladder outlet resistance without the need for sacral rhizotomy.

Role of calpains in the injury-induced dysfunction and degeneration of the mammalian axon.

PubMed

Ma, Marek

2013-12-01

Axonal injury and degeneration, whether primary or secondary, contribute to the morbidity and mortality seen in many acquired and inherited central nervous system (CNS) and peripheral nervous system (PNS) disorders, such as traumatic brain injury, spinal cord injury, cerebral ischemia, neurodegenerative diseases, and peripheral neuropathies. The calpain family of proteases has been mechanistically linked to the dysfunction and degeneration of axons. While the direct mechanisms by which transection, mechanical strain, ischemia, or complement activation trigger intra-axonal calpain activity are likely different, the downstream effects of unregulated calpain activity may be similar in seemingly disparate diseases. In this review, a brief examination of axonal structure is followed by a focused overview of the calpain family. Finally, the mechanisms by which calpains may disrupt the axonal cytoskeleton, transport, and specialized domains (axon initial segment, nodes, and terminals) are discussed. © 2013.

[Effects of grazing on zoobenthos community in beach].

PubMed

Zhao, Yun-long; An, Chuan-guang; Lin, Ling; Duan, Xiao-wei; Zeng, Cuo; Cui, Li-li

2007-05-01

In May (spring) and October (autumn) 2005, the effects of grazing on the zoobenthos community in Chongming Dongtan wetland of Shanghai were investigated. A total of 3 transects including 90 sampling plots were set up. Transects I and II were in feeding area, and transect III was in non-pasture area. All of these three transects were set in mid-tidal zone. 13 zoobenthos species were observed, with 7 species of arthropod, 4 species of mollusk, and 2 species of annelid. In spring, there were 6, 8 and 10 species in transects I , II and III while in autumn, the species number was 6, 8 and 12, respectively. The mean abundance of zoobenthos community in all transects was higher in autumn than in spring, and transect III had the highest mean abundance and biomass both in autumn and spring. Transect III also had the highest evenness, richness and diversity, indicating that grazing could change the species distribution of zoobenthos, and affect their abundance and biomass to different degree. Grazing had made certain negative effects on the biodiversity of zoobenthos community in Chongming Dongtan wetland.

What Did We Learn from the Animal Studies of Body Weight–Supported Treadmill Training and Where Do We Go from Here?

PubMed Central

Dy, Christine J.

2017-01-01

Abstract Body weight–supported treadmill training (BWSTT) developed from animal studies of spinal cord injury (SCI). Evidence that spinal cats (i.e., cats that have a complete surgical transection of the cord) could regain the ability to step on a moving treadmill indicated a vast potential for spinal circuits to generate walking without the brain. BWSTT represented a means to unlock that potential. As the technique was adapted as a rehabilitation intervention for humans with SCI, shortcomings in the translation to walking in the real world were exposed. Evidence that BWSTT has not been as successful for humans with SCI leads us to revisit key animal studies. In this short review, we describe the task-specific nature of BWSTT and discuss how this specificity may pose limits on the recovery of overground walking. Also discussed are more recent studies that have introduced new strategies and tools that adapt BWSTT ideas to more functionally-relevant tasks. We introduce a new device for weight-supported overground walking in rats called Circular BART (Body weight supported Ambulatory Rat Trainer) and demonstrate that it is relatively easy and inexpensive to produce. Future animal studies will benefit from the development of simple tools that facilitate training and testing of overground walking. PMID:27863455

What Did We Learn from the Animal Studies of Body Weight-Supported Treadmill Training and Where Do We Go from Here?

PubMed

de Leon, Ray D; Dy, Christine J

2017-05-01

Body weight-supported treadmill training (BWSTT) developed from animal studies of spinal cord injury (SCI). Evidence that spinal cats (i.e., cats that have a complete surgical transection of the cord) could regain the ability to step on a moving treadmill indicated a vast potential for spinal circuits to generate walking without the brain. BWSTT represented a means to unlock that potential. As the technique was adapted as a rehabilitation intervention for humans with SCI, shortcomings in the translation to walking in the real world were exposed. Evidence that BWSTT has not been as successful for humans with SCI leads us to revisit key animal studies. In this short review, we describe the task-specific nature of BWSTT and discuss how this specificity may pose limits on the recovery of overground walking. Also discussed are more recent studies that have introduced new strategies and tools that adapt BWSTT ideas to more functionally-relevant tasks. We introduce a new device for weight-supported overground walking in rats called Circular BART (Body weight supported Ambulatory Rat Trainer) and demonstrate that it is relatively easy and inexpensive to produce. Future animal studies will benefit from the development of simple tools that facilitate training and testing of overground walking.

Bladder volume-dependent excitatory and inhibitory influence of lumbosacral dorsal and ventral roots on bladder activity in rats

PubMed Central

Sugaya, Kimio; de Groat, William C.

2011-01-01

This study was undertaken to examine the role of the afferent and efferent pathways of the lumbosacral spinal nerve roots in the tonic control of bladder activity. Changes of isovolumetric bladder activity were recorded in 21 sympathectomized female rats under urethane anesthesia following transection of the dorsal (DRT) and ventral (VRT) lumbosacral spinal roots, and after intraperitoneal administration of hexamethonium. DRT altered the baseline intravesical pressure in a bladder volume-dependent manner in each animal. The percent change of baseline pressure after VRT following DRT was also dependent upon bladder volume. The percent change of baseline pressure after VRT alone was similarly dependent on bladder volume, but not after VRT followed by DRT. The percent change of baseline intravesical pressure (y)(−9 to +8 cm H2O, −56 to +46%) after DRT and VRT depended upon bladder volume (x)(y = 44.7 x −40.4) in all rats. Hexamethonium increased the amplitude of small myogenic bladder contractions after DRT and VRT. In conclusion, the bladder is tonically excited or inhibited by a local reflex pathway and by a parasympathetic reflex pathway that depends on connections with the lumbosacral spinal cord and the pelvic nerves. Both reflex mechanisms are influenced by bladder volume. PMID:17878597

[Expression and significance of p75NTR in dorsal root ganglia in different injury models].

PubMed

Li, Fang; Cai, Yan; Zhang, Jian-Yi

2008-12-01

To determine the expression and significance of p75NTR in the neuron and glia of dorsal root ganglia (DRG) in different injury models. The models of sciatic nerve injury, spinal cord injury, and combined injury (sciatic nerve injury one week prior to spinal cord injury) were established. The rats were randomly divided into a normal group,a sciatic nerve injury group,a spinal cord injury group, and a combined injury group. The sensory neurons in the DRG were labeled by fast blue (FB) injected in the dorsal column of spinal cord 0.5mm rostral to the transection site. The expression of p75NTR in the neurons and glia of the DRG was examined with immunofluorescence histochemistry after different kinds of injury and its expression in the FB positive neurons was further observed with immunofluorescence histochemistry combined with FB retrograde labeling. The expression of p75NTR was increased in the glia, but was downregulated in sensory neurons in the sciatic nerve injury group compared with the normal group. p75NTR immunoreactive products were downregulated in the glia in the spinal cord injury group compared with the sciatic nerve injury group or the combined injury group. In the combined lesion animals, the expression of p75NTR was similar to that of the sciatic nerve injury group. Its expression in the sensory neurons of DRG was downregulated,but was upregulated in the glia. The majority of sensory neurons labeled by FB in the combined injury group were p75NTR-negative, but surrounded by p75NTR-positive glia. p75NTR immunoreactive products in the glia and neurons of DRG have significant discrepancy after injury. The glial p75NTR in the DRG may play a role in the enhanced regeneration of acsending tract in the injured spinal cord after combined injury.

Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury.

PubMed

Ryge, Jesper; Winther, Ole; Wienecke, Jacob; Sandelin, Albin; Westerdahl, Ann-Charlotte; Hultborn, Hans; Kiehn, Ole

2010-06-09

Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be used to alter the transcriptional response to prevent the motor neurons from entering a state of hyper-excitability.

Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury

PubMed Central

2010-01-01

Background Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. Results Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. Conclusions This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be used to alter the transcriptional response to prevent the motor neurons from entering a state of hyper-excitability. PMID:20534130

Regulated viral BDNF delivery in combination with Schwann cells promotes axonal regeneration through capillary alginate hydrogels after spinal cord injury.

PubMed

Liu, Shengwen; Sandner, Beatrice; Schackel, Thomas; Nicholson, LaShae; Chtarto, Abdelwahed; Tenenbaum, Liliane; Puttagunta, Radhika; Müller, Rainer; Weidner, Norbert; Blesch, Armin

2017-09-15

Grafting of cell-seeded alginate capillary hydrogels into a spinal cord lesion site provides an axonal bridge while physically directing regenerating axonal growth in a linear pattern. However, without an additional growth stimulus, bridging axons fail to extend into the distal host spinal cord. Here we examined whether a combinatory strategy would support regeneration of descending axons across a cervical (C5) lateral hemisection lesion in the rat spinal cord. Following spinal cord transections, Schwann cell (SC)-seeded alginate hydrogels were grafted to the lesion site and AAV5 expressing brain-derived neurotrophic factor (BDNF) under control of a tetracycline-regulated promoter was injected caudally. In addition, we examined whether SC injection into the caudal spinal parenchyma would further enhance regeneration of descending axons to re-enter the host spinal cord. Our data show that both serotonergic and descending axons traced by biotinylated dextran amine (BDA) extend throughout the scaffolds. The number of regenerating axons is significantly increased when caudal BDNF expression is activated and transient BDNF delivery is able to sustain axons after gene expression is switched off. Descending axons are confined to the caudal graft/host interface even with continuous BDNF expression for 8weeks. Only with a caudal injection of SCs, a pathway facilitating axonal regeneration through the host/graft interface is generated allowing axons to successfully re-enter the caudal spinal cord. Recovery from spinal cord injury is poor due to the limited regeneration observed in the adult mammalian central nervous system. Biomaterials, cell transplantation and growth factors that can guide axons across a lesion site, provide a cellular substrate, stimulate axon growth and have shown some promise in increasing the growth distance of regenerating axons. In the present study, we combined an alginate biomaterial with linear channels with transplantation of Schwann cells within and beyond the lesion site and injection of a regulatable vector for the transient expression of brain-derived neurotrophic factor (BDNF). Our data show that only with the full combination axons extend across the lesion site and that expression of BDNF beyond 4weeks does not further increase the number of regenerating axons. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Rehabilitation Strategies after Spinal Cord Injury: Inquiry into the Mechanisms of Success and Failure

PubMed Central

Murray, Marion; Lemay, Michel A.

2017-01-01

Abstract Body-weight supported locomotor training (BWST) promotes recovery of load-bearing stepping in lower mammals, but its efficacy in individuals with a spinal cord injury (SCI) is limited and highly dependent on injury severity. While animal models with complete spinal transections recover stepping with step-training, motor complete SCI individuals do not, despite similarly intensive training. In this review, we examine the significant differences between humans and animal models that may explain this discrepancy in the results obtained with BWST. We also summarize the known effects of SCI and locomotor training on the muscular, motoneuronal, interneuronal, and supraspinal systems in human and non-human models of SCI and address the potential causes for failure to translate to the clinic. The evidence points to a deficiency in neuronal activation as the mechanism of failure, rather than muscular insufficiency. While motoneuronal and interneuronal systems cannot be directly probed in humans, the changes brought upon by step-training in SCI animal models suggest a beneficial re-organization of the systems’ responsiveness to descending and afferent feedback that support locomotor recovery. The literature on partial lesions in humans and animal models clearly demonstrate a greater dependency on supraspinal input to the lumbar cord in humans than in non-human mammals for locomotion. Recent results with epidural stimulation that activates the lumbar interneuronal networks and/or increases the overall excitability of the locomotor centers suggest that these centers are much more dependent on the supraspinal tonic drive in humans. Sensory feedback shapes the locomotor output in animal models but does not appear to be sufficient to drive it in humans. PMID:27762657

Interactions between superficial and deep dorsal horn spinal cord neurons in the processing of nociceptive information.

PubMed

Petitjean, Hugues; Rodeau, Jean-Luc; Schlichter, Rémy

2012-12-01

In acute rat spinal cord slices, the application of capsaicin (5 μm, 90 s), an agonist of transient receptor potential vanilloid 1 receptors expressed by a subset of nociceptors that project to laminae I-II of the spinal cord dorsal horn, induced an increase in the frequency of spontaneous excitatory and spontaneous inhibitory postsynaptic currents in about half of the neurons in laminae II, III-IV and V. In the presence of tetrodotoxin, which blocks action potential generation and polysynaptic transmission, capsaicin increased the frequency of miniature excitatory postsynaptic currents in only 30% of lamina II neurons and had no effect on the frequency of miniature excitatory postsynaptic currents in laminae III-V or on the frequency of miniature inhibitory postsynaptic currents in laminae II-V. When the communication between lamina V and more superficial laminae was interrupted by performing a mechanical section between laminae IV and V, capsaicin induced an increase in spontaneous excitatory postsynaptic current frequency in laminae II-IV and an increase in spontaneous inhibitory postsynaptic current frequency in lamina II that were similar to those observed in intact slices. However, in laminae III-IV of transected slices, the increase in spontaneous inhibitory postsynaptic current frequency was virtually abolished. Our results indicate that nociceptive information conveyed by transient receptor potential vanilloid 1-expressing nociceptors is transmitted from lamina II to deeper laminae essentially by an excitatory pathway and that deep laminae exert a 'feedback' control over neurons in laminae III-IV by increasing inhibitory synaptic transmission in these laminae. Moreover, we provide evidence that laminae III-IV might play an important role in the processing of nociceptive information in the dorsal horn. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Nandrolone Normalizes Determinants of Muscle Mass and Fiber Type after Spinal Cord Injury

PubMed Central

Wu, Yong; Zhao, Jingbo; Zhao, Weidong; Pan, Jiangping; Bauman, William A.

2012-01-01

Abstract Spinal cord injury (SCI) results in atrophy of skeletal muscle and changes from slow oxidative to fast glycolytic fibers, which may reflect reduced levels of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), increased myostatin signaling, or both. In animals, testosterone reduces loss of muscle fiber cross-sectional area and activity of enzymes of energy metabolism. To identify the molecular mechanisms behind the benefits of androgens on paralyzed muscle, male rats were spinal cord transected and treated for 8 weeks with vehicle, testosterone at a physiological replacement dose, or testosterone plus nandrolone, an anabolic steroid. Treatments were initiated immediately after SCI and continued until the day animals were euthanized. In the SCI animals, gastrocnemius muscle mass was significantly increased by testosterone plus nandrolone, but not by testosterone alone. Both treatments significantly reduced nuclear content of Smad2/3 and mRNA levels of activin receptor IIB and follistatin-like 3. Testosterone alone or with nandrolone reversed SCI-induced declines in cellular and nuclear levels of PGC-1α protein and PGC-1α mRNA levels. For PGC-1α target genes, testosterone plus nandrolone partially reversed SCI-induced decreases in levels of proteins without corresponding increases in their mRNA levels. Thus, the findings demonstrate that following SCI, signaling through activin receptors and Smad2/3 is increased, and that androgens suppress activation of this signaling pathway. The findings also indicate that androgens upregulate PGC-1α in paralyzed muscle and promote its nuclear localization, but that these effects are insufficient to fully activate transcription of PGC-1α target genes. Furthermore, the transcription of these genes is not tightly coupled with their translation. PMID:22208735

Nandrolone normalizes determinants of muscle mass and fiber type after spinal cord injury.

PubMed

Wu, Yong; Zhao, Jingbo; Zhao, Weidong; Pan, Jiangping; Bauman, William A; Cardozo, Christopher P

2012-05-20

Spinal cord injury (SCI) results in atrophy of skeletal muscle and changes from slow oxidative to fast glycolytic fibers, which may reflect reduced levels of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), increased myostatin signaling, or both. In animals, testosterone reduces loss of muscle fiber cross-sectional area and activity of enzymes of energy metabolism. To identify the molecular mechanisms behind the benefits of androgens on paralyzed muscle, male rats were spinal cord transected and treated for 8 weeks with vehicle, testosterone at a physiological replacement dose, or testosterone plus nandrolone, an anabolic steroid. Treatments were initiated immediately after SCI and continued until the day animals were euthanized. In the SCI animals, gastrocnemius muscle mass was significantly increased by testosterone plus nandrolone, but not by testosterone alone. Both treatments significantly reduced nuclear content of Smad2/3 and mRNA levels of activin receptor IIB and follistatin-like 3. Testosterone alone or with nandrolone reversed SCI-induced declines in cellular and nuclear levels of PGC-1α protein and PGC-1α mRNA levels. For PGC-1α target genes, testosterone plus nandrolone partially reversed SCI-induced decreases in levels of proteins without corresponding increases in their mRNA levels. Thus, the findings demonstrate that following SCI, signaling through activin receptors and Smad2/3 is increased, and that androgens suppress activation of this signaling pathway. The findings also indicate that androgens upregulate PGC-1α in paralyzed muscle and promote its nuclear localization, but that these effects are insufficient to fully activate transcription of PGC-1α target genes. Furthermore, the transcription of these genes is not tightly coupled with their translation.

Barrier effects of remote high mountain on atmospheric metal transport in the eastern Tibetan Plateau.

PubMed

Bing, Haijian; Zhou, Jun; Wu, Yanhong; Luo, Xiaosan; Xiang, Zhongxiang; Sun, Hongyang; Wang, Jipeng; Zhu, He

2018-07-01

Anthropogenic metals adsorbed on suspended fine particles can be deposited on remote and inaccessible high mountains by long-range atmospheric transport. In this study, we investigated the cadmium (Cd) and lead (Pb) in the soils, mosses and rainfall of three transects on the Gongga Mountain, eastern Tibetan Plateau, to understand the mountain interception effects on their atmospheric transport. The concentrations of Cd and Pb in the soils and mosses displayed a pattern of eastern transect>northern transect>western transect. The distribution of Cd and Pb on the eastern transect increased from 2000 to 2900m a.s.l. (above sea level), decreased toward the timberline, and increased again with altitude; on the northern transect, it generally decreased with altitude whereas a distribution trend was not clearly observed on the western transect. The Cd and Pb concentrations in the rainfall of the eastern transect generally decreased with altitude, and they were higher inside forests than outside forests and temporally higher in the winter than the summer. The Pb isotopic ratios coupled with moss bio-monitoring distinguished anthropogenic sources of Cd and Pb on the eastern and northern transects, whereas bedrock weathering was the main source of Cd and Pb on the western transect. We proposed a conceptual model to delineate the effects of terrain, local climate and vegetation on the transport of atmospheric metals. Our results highlighted the high mountains in the eastern Tibetan Plateau as an effective natural barrier limiting atmospheric metal transport. Copyright © 2018 Elsevier B.V. All rights reserved.

THE CRITICAL ROLE OF VOLTAGE-DEPENDENT CALCIUM CHANNEL IN AXONAL REPAIR FOLLOWING MECHANICAL TRAUMA

PubMed Central

Nehrt, Ashley; Rodgers, Richard; Shapiro, Scott; Borgens, Richard; Shi, Riyi

2009-01-01

Membrane disruption following mechanical injury likely plays a critical role in the pathology of spinal cord trauma. It is known that intracellular calcium is a key factor that is essential to membrane resealing. However, the differential role of calcium influx through the injury site and through voltage dependent calcium channels (VDCC) has not been examined in detail. Using a well established ex vivo guinea pig spinal cord white matter preparation, we have found that axonal membrane resealing was significantly inhibited following transection or compression in the presence of cadmiun, a non-specific calcium channel blocker, or nimodipine, a specific L-type calcium channel blocker. Membrane resealing was assessed by the changes of membrane potential and compound action potential (CAP), and exclusion of horseradish peroxidase 60 minutes following trauma. Furthermore, 1 μM BayK 8644, a VDCC agonist, significantly enhanced membrane resealing. Interestingly, this effect was completely abolished when the concentration of BayK 8644 was increased to 30 μM. These data suggest that VDCC play a critical role in membrane resealing. Further, there is likely an appropriate range of calcium influx through VDCC which ensures effective axonal membrane resealing. Since elevated intracellular calcium has also been linked to axonal deterioration, blockage of VDCC is proposed to be a clinical treatment for various injuries. The knowledge gained in this study will likely help us better understand the role of calcium in various CNS trauma, which is critical for designing new approaches or perhaps optimizing the effectiveness of existing methods in the treatment of CNS trauma. PMID:17448606

Differential Effects of 670 and 830 nm Red near Infrared Irradiation Therapy: A Comparative Study of Optic Nerve Injury, Retinal Degeneration, Traumatic Brain and Spinal Cord Injury

PubMed Central

Giacci, Marcus K.; Wheeler, Lachlan; Lovett, Sarah; Dishington, Emma; Majda, Bernadette; Bartlett, Carole A.; Thornton, Emma; Harford-Wright, Elizabeth; Leonard, Anna; Vink, Robert; Harvey, Alan R.; Provis, Jan; Dunlop, Sarah A.; Fitzgerald, Melinda

2014-01-01

Red/near-infrared irradiation therapy (R/NIR-IT) delivered by laser or light-emitting diode (LED) has improved functional outcomes in a range of CNS injuries. However, translation of R/NIR-IT to the clinic for treatment of neurotrauma has been hampered by lack of comparative information regarding the degree of penetration of the delivered irradiation to the injury site and the optimal treatment parameters for different CNS injuries. We compared the treatment efficacy of R/NIR-IT at 670 nm and 830 nm, provided by narrow-band LED arrays adjusted to produce equal irradiance, in four in vivo rat models of CNS injury: partial optic nerve transection, light-induced retinal degeneration, traumatic brain injury (TBI) and spinal cord injury (SCI). The number of photons of 670 nm or 830 nm light reaching the SCI injury site was 6.6% and 11.3% of emitted light respectively. Treatment of rats with 670 nm R/NIR-IT following partial optic nerve transection significantly increased the number of visual responses at 7 days after injury (P≤0.05); 830 nm R/NIR-IT was partially effective. 670 nm R/NIR-IT also significantly reduced reactive species and both 670 nm and 830 nm R/NIR-IT reduced hydroxynonenal immunoreactivity (P≤0.05) in this model. Pre-treatment of light-induced retinal degeneration with 670 nm R/NIR-IT significantly reduced the number of Tunel+ cells and 8-hydroxyguanosine immunoreactivity (P≤0.05); outcomes in 830 nm R/NIR-IT treated animals were not significantly different to controls. Treatment of fluid-percussion TBI with 670 nm or 830 nm R/NIR-IT did not result in improvements in motor or sensory function or lesion size at 7 days (P>0.05). Similarly, treatment of contusive SCI with 670 nm or 830 nm R/NIR-IT did not result in significant improvements in functional recovery or reduced cyst size at 28 days (P>0.05). Outcomes from this comparative study indicate that it will be necessary to optimise delivery devices, wavelength, intensity and duration of R/NIR-IT individually for different CNS injury types. PMID:25105800

Compensatory plasticity restores locomotion after chronic removal of descending projections.

PubMed

Harley, Cynthia M; Reilly, Melissa G; Stewart, Christopher; Schlegel, Chantel; Morley, Emma; Puhl, Joshua G; Nagel, Christian; Crisp, Kevin M; Mesce, Karen A

2015-06-01

Homeostatic plasticity is an important attribute of neurons and their networks, enabling functional recovery after perturbation. Furthermore, the directed nature of this plasticity may hold a key to the restoration of locomotion after spinal cord injury. Here we studied the recovery of crawling in the leech Hirudo verbana after descending cephalic fibers were surgically separated from crawl central pattern generators shown previously to be regulated by dopamine. We observed that immediately after nerve cord transection leeches were unable to crawl, but remarkably, after a day to weeks, animals began to show elements of crawling and intersegmental coordination. Over a similar time course, excessive swimming due to the loss of descending inhibition returned to control levels. Additionally, removal of the brain did not prevent crawl recovery, indicating that connectivity of severed descending neurons was not essential. After crawl recovery, a subset of animals received a second transection immediately below the anterior-most ganglion remaining. Similar to their initial transection, a loss of crawling with subsequent recovery was observed. These data, in recovered individuals, support the idea that compensatory plasticity directly below the site of injury is essential for the initiation and coordination of crawling. We maintain that the leech provides a valuable model to understand the neural mechanisms underlying locomotor recovery after injury because of its experimental accessibility, segmental organization, and dependence on higher-order control involved in the initiation, modulation, and coordination of locomotor behavior. Copyright © 2015 the American Physiological Society.

The rostral medulla of bullfrog tadpoles contains critical lung rhythmogenic and chemosensitive regions across metamorphosis.

PubMed

Reed, Mitchell D; Iceman, Kimberly E; Harris, Michael B; Taylor, Barbara E

2018-06-08

The development of amphibian breathing provides insight into vertebrate respiratory control mechanisms. Neural oscillators in the rostral and caudal medulla drive ventilation in amphibians, and previous reports describe ventilatory oscillators and CO 2 sensitive regions arise during different stages of amphibian metamorphosis. However, inconsistent findings have been enigmatic, and make comparisons to potential mammalian counterparts challenging. In the current study we assessed amphibian central CO 2 responsiveness and respiratory rhythm generation during two different developmental stages. Whole-nerve recordings of respiratory burst activity in cranial and spinal nerves were made from intact or transected brainstems isolated from tadpoles during early or late stages of metamorphosis. Brainstems were transected at the level of the trigeminal nerve, removing rostral structures including the nucleus isthmi, midbrain, and locus coeruleus, or transected at the level of the glossopharyngeal nerve, removing the putative buccal oscillator and caudal medulla. Removal of caudal structures stimulated the frequency of lung ventilatory bursts and revealed a hypercapnic response in normally unresponsive preparations derived from early stage tadpoles. In preparations derived from late stage tadpoles, removal of rostral or caudal structures reduced lung burst frequency, while CO 2 responsiveness was retained. Our results illustrate that structures within the rostral medulla are capable of sensing CO 2 throughout metamorphic development. Similarly, the region controlling lung ventilation appears to be contained in the rostral medulla throughout metamorphosis. This work offers insight into the consistency of rhythmic respiratory and chemosensitive capacities during metamorphosis. Copyright © 2018. Published by Elsevier Inc.

A novel device for studying weight supported, quadrupedal overground locomotion in spinal cord injured rats

PubMed Central

Hamlin, Marvin; Traughber, Terrance; Reinkensmeyer, David J.; de Leon, Ray D.

2015-01-01

Background Providing weight support facilitates locomotion in spinal cord injured animals. To control weight support, robotic systems have been developed for treadmill stepping and more recently for overground walking. New Method We developed a novel device, the body weight supported ambulatory rodent trainer (i.e. BART). It has a small pneumatic cylinder that moves along a linear track above the rat. When air is supplied to the cylinder, the rats are lifted as they perform overground walking. We tested the BART device in rats that received a moderate spinal cord contusion injury and in normal rats. Locomotor training with the BART device was not performed. Results All of the rats learned to walk in the BART device. In the contused rats, significantly greater paw dragging and dorsal stepping occurred in the hindlimbs compared to normal. Providing weight support significantly raised hip position and significantly reduced locomotor deficits. Hindlimb stepping was tightly coupled to forelimb stepping but only when the contused rats stepped without weight support. Three weeks after the contused rats received a complete spinal cord transection, significantly fewer hindlimb steps were performed. Comparison with Existing Methods Relative to rodent robotic systems, the BART device is a simpler system for studying overground locomotion. The BART device lacks sophisticated control and sensing capability, but it can be assembled relatively easily and cheaply. Conclusions These findings suggest that the BART device is a useful tool for assessing quadrupedal, overground locomotion which is a more natural form of locomotion relative to treadmill locomotion. PMID:25794460

In silico modeling of axonal reconnection within a discrete fiber tract after spinal cord injury.

PubMed

Woolfe, Franco; Waxman, Stephen G; Hains, Bryan C

2007-02-01

Following spinal cord injury (SCI), descending axons that carry motor commands from the brain to the spinal cord are injured or transected, producing chronic motor dysfunction and paralysis. Reconnection of these axons is a major prerequisite for restoration of function after SCI. Thus far, only modest gains in motor function have been achieved experimentally or in the clinic after SCI, identifying the practical limitations of current treatment approaches. In this paper, we use an ordinary differential equation (ODE) to simulate the relative and synergistic contributions of several experimentally-established biological factors related to inhibition or promotion of axonal repair and restoration of function after SCI. The factors were mathematically modeled by the ODE. The results of our simulation show that in a model system, many factors influenced the achievability of axonal reconnection. Certain factors more strongly affected axonal reconnection in isolation, and some factors interacted in a synergistic fashion to produce further improvements in axonal reconnection. Our data suggest that mathematical modeling may be useful in evaluating the complex interactions of discrete therapeutic factors not possible in experimental preparations, and highlight the benefit of a combinatorial therapeutic approach focused on promoting axonal sprouting, attraction of cut ends, and removal of growth inhibition for achieving axonal reconnection. Predictions of this simulation may be of utility in guiding future experiments aimed at restoring function after SCI.

Development of an Algorithm to Perform a Comprehensive Study of Autonomic Dysreflexia in Animals with High Spinal Cord Injury Using a Telemetry Device.

PubMed

Popok, David; West, Christopher; Frias, Barbara; Krassioukov, Andrei V

2016-07-29

Spinal cord injury (SCI) is a debilitating neurological condition characterized by somatic and autonomic dysfunctions. In particular, SCI above the mid-thoracic level can lead to a potentially life-threatening hypertensive condition called autonomic dysreflexia (AD) that is often triggered by noxious or non-noxious somatic or visceral stimuli below the level of injury. One of the most common triggers of AD is the distension of pelvic viscera, such as during bladder and bowel distension or evacuation. This protocol presents a novel pattern recognition algorithm developed for a JAVA platform software to study the fluctuations of cardiovascular parameters as well as the number, severity and duration of spontaneously occurring AD events. The software is able to apply a pattern recognition algorithm on hemodynamic data such as systolic blood pressure (SBP) and heart rate (HR) extracted from telemetry recordings of conscious and unrestrained animals before and after thoracic (T3) complete transection. With this software, hemodynamic parameters and episodes of AD are able to be detected and analyzed with minimal experimenter bias.

Substance P immunoreactivity in the lumbar spinal cord of the turtle Trachemys dorbigni following peripheral nerve injury.

PubMed

Partata, W A; Krepsky, A M R; Xavier, L L; Marques, M; Achaval, M

2003-04-01

Immunoreactive substance P was investigated in turtle lumbar spinal cord after sciatic nerve transection. In control animals immunoreactive fibers were densest in synaptic field Ia, where the longest axons invaded synaptic field III. Positive neuronal bodies were identified in the lateral column of the dorsal horn and substance P immunoreactive varicosities were observed in the ventral horn, in close relationship with presumed motoneurons. Other varicosities appeared in the lateral and anterior funiculi. After axotomy, substance P immunoreactive fibers were reduced slightly on the side of the lesion, which was located in long fibers that invaded synaptic field III and in the varicosities of the lateral and anterior funiculus. The changes were observed at 7 days after axonal injury and persisted at 15, 30, 60 and 90 days after the lesion. These findings show that turtles should be considered as a model to study the role of substance P in peripheral axonal injury, since the distribution and temporal changes of substance P were similar to those found in mammals.

Development and regeneration of the electric organ.

PubMed

Zakon, H H; Unguez, G A

1999-05-01

The electric organ has evolved independently from muscle in at least six lineages of fish. How does a differentiated muscle cell change its fate to become an electrocyte? Is the process by which this occurs similar in different lineages? We have begun to answer these questions by studying the formation and maintenance of electrocytes in the genus Sternopygus, a weakly electric teleost. Electrocytes arise from the fusion of fully differentiated muscle fibers, mainly those expressing fast isoforms of myosin. Electrocytes briefly co-express sarcomeric proteins, such as myosin and tropomyosin, and keratin, a protein not found in mature muscle. The sarcomeric proteins are subsequently down-regulated, but keratin expression persists. We investigated whether the maintenance of the electrocyte phenotype depends on innervation. We found that, after spinal cord transection, which silences the electromotor neurons that innervate the electrocytes, or destruction of the spinal cord, which denervates the electrocytes, mature electrocytes re-express sarcomeric myosin and tropomyosin, although keratin expression persists. Ultrastructural examination of denervated electrocytes revealed nascent sarcomeres. Thus, the maintenance of the electrocyte phenotype depends on neural activity.

Amount of torque and duration of stretching affects correction of knee contracture in a rat model of spinal cord injury.

PubMed

Moriyama, Hideki; Tobimatsu, Yoshiko; Ozawa, Junya; Kito, Nobuhiro; Tanaka, Ryo

2013-11-01

Joint contractures are a common complication of many neurologic conditions, and stretching often is advocated to prevent and treat these contractures. However, the magnitude and duration of the stretching done in practice usually are guided by subjective clinical impressions. Using an established T8 spinal cord injury rat model of knee contracture, we sought to determine what combination of static or intermittent stretching, varied by magnitude (high or low) and duration (long or short), leads to the best (1) improvement in the limitation in ROM; (2) restoration of the muscular and articular factors leading to contractures; and (3) prevention and treatment of contracture-associated histologic alterations of joint capsule and articular cartilage. Using a rat animal model, the spinal cord was transected completely at the level of T8. The rats were randomly assigned to seven treatment groups (n = 4 per group), which were composed of static or intermittent stretching in combination with different amounts of applied torque magnitude and duration. We assessed the effect of stretching by measuring the ROM and evaluating the histologic alteration of the capsule and cartilage. Contractures improved in all treated groups except for the low-torque and short-duration static stretching conditions. High-torque stretching was effective against shortening of the synovial membrane and adhesions in the posterosuperior regions. Collagen Type II and VEGF in the cartilage were increased by stretching. High-torque and long-duration static stretching led to greater restoration of ROM than the other torque and duration treatment groups. Stretching was more effective in improving articular components of contractures compared with the muscular components. Stretching in this rat model prevented shortening and adhesion of the joint capsule, and affected biochemical composition, but did not change morphologic features of the cartilage. This animal study tends to support the ideas that static stretching can influence joint ROM and histologic qualities of joint tissues, and that the way stretching is performed influences its efficacy. However, further studies are warranted to determine if our findings are clinically applicable.

Orofacial neuropathic pain reduces spontaneous burrowing behavior in rats.

PubMed

Deseure, K; Hans, G

2018-07-01

It was recently reported that spontaneous burrowing behavior is decreased after tibial nerve transection, spinal nerve transection and partial sciatic nerve ligation. It was proposed that spontaneous burrowing could be used as a measure of the impact of neuropathic pain after peripheral nerve injury. It has remained unclear whether the reduction in burrowing behavior is caused directly by pain or hypersensitivity in the affected limbs, making it more difficult to perform burrowing, or by a pain induced decrease in the general wellbeing, thus reducing the motivation to burrow. We studied burrowing behavior after infraorbital nerve injury, a model of orofacial neuropathic pain that does not affect the limbs. Burrowing behavior was significantly reduced after infraorbital nerve injury. Isolated face grooming and responsiveness to mechanical von Frey stimulation of the infraorbital nerve territory were significantly increased after infraorbital nerve injury, indicative, respectively, of spontaneous pain and mechanical allodynia. It is concluded that spontaneous burrowing may provide a measure of the global impact of pain on the animal's wellbeing after peripheral nerve injury and incorporation of this behavioral assay in preclinical drug testing may improve the predictive validity of currently used pain models. Copyright © 2018 Elsevier Inc. All rights reserved.

Left–right coordination from simple to extreme conditions during split‐belt locomotion in the chronic spinal adult cat

PubMed Central

Desrochers, Étienne; Thibaudier, Yann; Hurteau, Marie‐France; Dambreville, Charline

2016-01-01

Key points Coordination between the left and right sides is essential for dynamic stability during locomotion.The immature or neonatal mammalian spinal cord can adjust to differences in speed between the left and right sides during split‐belt locomotion by taking more steps on the fast side.We show that the adult mammalian spinal cord can also adjust its output so that the fast side can take more steps.During split‐belt locomotion, only certain parts of the cycle are modified to adjust left–right coordination, primarily those associated with swing onset.When the fast limb takes more steps than the slow limb, strong left–right interactions persist.Therefore, the adult mammalian spinal cord has a remarkable adaptive capacity for left–right coordination, from simple to extreme conditions. Abstract Although left–right coordination is essential for locomotion, its control is poorly understood, particularly in adult mammals. To investigate the spinal control of left–right coordination, a spinal transection was performed in six adult cats that were then trained to recover hindlimb locomotion. Spinal cats performed tied‐belt locomotion from 0.1 to 1.0 m s−1 and split‐belt locomotion with low to high (1:1.25–10) slow/fast speed ratios. With the left hindlimb stepping at 0.1 m s−1 and the right hindlimb stepping from 0.2 to 1.0 m s−1, 1:1, 1:2, 1:3, 1:4 and 1:5 left–right step relationships could appear. The appearance of 1:2+ relationships was not linearly dependent on the difference in speed between the slow and fast belts. The last step taken by the fast hindlimb displayed longer cycle, stance and swing durations and increased extensor activity, as the slow limb transitioned to swing. During split‐belt locomotion with 1:1, 1:2 and 1:3 relationships, the timing of stance onset of the fast limb relative to the slow limb and placement of both limbs at contact were invariant with increasing slow/fast speed ratios. In contrast, the timing of stance onset of the slow limb relative to the fast limb and the placement of both limbs at swing onset were modulated with slow/fast speed ratios. Thus, left–right coordination is adjusted by modifying specific parts of the cycle. Results highlight the remarkable adaptive capacity of the adult mammalian spinal cord, providing insight into spinal mechanisms and sensory signals regulating left–right coordination. PMID:27426732

Cortical sensory map rearrangement after spinal cord injury: fMRI responses linked to Nogo signalling.

PubMed

Endo, Toshiki; Spenger, Christian; Tominaga, Teiji; Brené, Stefan; Olson, Lars

2007-11-01

Cortical sensory maps can reorganize in the adult brain in an experience-dependent manner. We monitored somatosensory cortical reorganization after sensory deafferentation using functional magnetic resonance imaging (fMRI) in rats subjected to complete transection of the mid-thoracic spinal cord. Cortical representation in response to spared forelimb stimulation was observed to enlarge and invade adjacent sensory-deprived hind limb territory in the primary somatosensory cortex as early as 3 days after injury. Functional MRI also demonstrated long-term cortical plasticity accompanied by increased thalamic activation. To support the notion that alterations of cortical neuronal circuitry after spinal cord injury may underlie the fMRI changes, we quantified transcriptional activities of several genes related to cortical plasticity including the Nogo receptor (NgR), its co-receptor LINGO-1 and brain derived neurotrophic factor (BDNF), using in situ hybridization. We demonstrate that NgR and LINGO-1 are down-regulated specifically in cortical areas deprived of sensory input and in adjacent cortex from 1 day after injury, while BDNF is up-regulated. Our results demonstrate that cortical neurons react to sensory deprivation by decreasing transcriptional activities of genes encoding the Nogo receptor components in the sensory deprived and the anatomically adjacent non-deprived area. Combined with the BDNF up-regulation, these changes presumably allow structural changes in the neuropil. Our observations therefore suggest an involvement of Nogo signalling in cortical activity-dependent plasticity in the somatosensory system. In spinal cord injury, cortical reorganization as shown here can become a disadvantage, much like the situation in amblyopia or phantom sensation. Successful strategies to repair sensory pathways at the spinal cord level may not lead to proper reestablishment of cortical connections, once deprived hind limb cortical areas have been reallocated to forelimb use. In such situations, methods to control cortical plasticity, possibly by targeting Nogo signalling, may become helpful.

Sediment loads and transport at constructed chutes along the Missouri River - Upper Hamburg Chute near Nebraska City, Nebraska, and Kansas Chute near Peru, Nebraska

USGS Publications Warehouse

Densmore, Brenda K.; Rus, David L.; Moser, Matthew T.; Hall, Brent M.; Andersen, Michael J.

2016-02-04

Comparisons of concentrations and loads from EWI samples collected from different transects within a study site resulted in few significant differences, but comparisons are limited by small sample sizes and large within-transect variability. When comparing the Missouri River upstream transect to the chute inlet transect, similar results were determined in 2012 as were determined in 2008—the chute inlet affected the amount of sediment entering the chute from the main channel. In addition, the Kansas chute is potentially affecting the sediment concentration within the Missouri River main channel, but small sample size and construction activities within the chute limit the ability to fully understand either the effect of the chute in 2012 or the effect of the chute on the main channel during a year without construction. Finally, some differences in SSC were detected between the Missouri River upstream transects and the chute downstream transects; however, the effect of the chutes on the Missouri River main-channel sediment transport was difficult to isolate because of construction activities and sampling variability.

New Method of Injured Nerve Repair.

PubMed

Korsak, Alina; Likhodiievskyi, Volodymyr; Sokurenko, Liudmyla; Chaikovsky, Yuri

2018-07-01

 Innovative surgical techniques form the basis of therapeutic approaches to address the negative consequences of nerve damage. This study evaluated the effectiveness of nerve trunk regeneration after the use of an electrosurgical instrument by looking at the patterns of morphological changes in the injured nerve and the structural elements of the segment motor center.  The study was performed on male Wistar rats divided into four groups: group 1, control; group 2, rats with simulated sciatic nerve injury with epineural sutures; 3, rats subjected to an experimental surgical procedure using high-frequency electric welding technology; and 4, rats with simulated sciatic nerve injury without posttransection repair. To study changes in the peripheral stump of the transected nerves and L5 segments of the spinal cord, we used histologic, immunohistochemical, and morphometric methods.  At week 12 after the surgery, there were more S-100+ Schwann cells, increased expression of neurofilaments (NFs), and glial fibrillary acidic protein in the peripheral stump in group 3 than in groups 2 and 4, which indicates enhanced neurotization and myelination. Group 3 animals demonstrated reduced expression of S-100 and NFs in the motor center of the spinal cord compared with group 2 that suggests less pronounced reactive changes caused by electric welding technology.  The study showed a novel surgical method using an electrosurgical instrument in a welding mode to stimulate regeneration of the injured nerve and to cause less prominent reactive changes in its segment motor center. Georg Thieme Verlag KG Stuttgart · New York.

Aurora kinase B regulates axonal outgrowth and regeneration in the spinal motor neurons of developing zebrafish.

PubMed

Gwee, Serene S L; Radford, Rowan A W; Chow, Sharron; Syal, Monisha D; Morsch, Marco; Formella, Isabel; Lee, Albert; Don, Emily K; Badrock, Andrew P; Cole, Nicholas J; West, Adrian K; Cheung, Steve N S; Chung, Roger S

2018-02-21

Aurora kinase B (AurkB) is a serine/threonine protein kinase with a well-characterised role in orchestrating cell division and cytokinesis, and is prominently expressed in healthy proliferating and cancerous cells. However, the role of AurkB in differentiated and non-dividing cells has not been extensively explored. Previously, we have described a significant upregulation of AurkB expression in cultured cortical neurons following an experimental axonal transection. This is somewhat surprising, as AurkB expression is generally associated only with dividing cells Frangini et al. (Mol Cell 51:647-661, 2013); Hegarat et al. (J Cell Biol 195:1103-1113, 2011); Lu et al. (J Biol Chem 283:31785-31790, 2008); Trakala et al. (Cell Cycle 12:1030-1041, 2014). Herein, we present the first description of a role for AurkB in terminally differentiated neurons. AurkB was prominently expressed within post-mitotic neurons of the zebrafish brain and spinal cord. The expression of AurkB varied during the development of the zebrafish spinal motor neurons. Utilising pharmacological and genetic manipulation to impair AurkB activity resulted in truncation and aberrant motor axon morphology, while overexpression of AurkB resulted in extended axonal outgrowth. Further pharmacological inhibition of AurkB activity in regenerating axons delayed their recovery following UV laser-mediated injury. Collectively, these results suggest a hitherto unreported role of AurkB in regulating neuronal development and axonal outgrowth.

Chronic neuromuscular electrical stimulation of paralyzed hindlimbs in a rodent model.

PubMed

Jung, Ranu; Ichihara, Kazuhiko; Venkatasubramanian, Ganapriya; Abbas, James J

2009-10-15

Neuromuscular electrical stimulation (NMES) can be used to activate paralyzed or paretic muscles to generate functional or therapeutic movements. The goal of this research was to develop a rodent model of NMES-assisted movement therapy after spinal cord injury (SCI) that will enable investigation of mechanisms of NMES-induced plasticity, from the molecular to systems level. Development of the model requires accurate mapping of electrode and muscle stimulation sites, the capability to selectively activate muscles to produce graded contractions of sufficient strength, stable anchoring of the implanted electrode within the muscles and stable performance with functional reliability over several weeks of the therapy window. Custom designed electrodes were implanted chronically in hindlimb muscles of spinal cord transected rats. Mechanical and electrical stability of electrodes and the ability to achieve appropriate muscle recruitment and joint angle excursion were assessed by characterizing the strength duration curves, isometric torque recruitment curves and kinematics of joint angle excursion over 6-8 weeks post implantation. Results indicate that the custom designed electrodes and implantation techniques provided sufficient anchoring and produced stable and reliable recruitment of muscles both in the absence of daily NMES (for 8 weeks) as well as with daily NMES that is initiated 3 weeks post implantation (for 6 weeks). The completed work establishes a rodent model that can be used to investigate mechanisms of neuroplasticity that underlie NMES-based movement therapy after spinal cord injury and to optimize the timing of its delivery.

Upregulation of eIF-5A1 in the paralyzed muscle after spinal cord transection associates with spontaneous hindlimb locomotor recovery in rats by upregulation of the ErbB, MAPK and neurotrophin signal pathways.

PubMed

Shang, Fei-Fei; Zhao, Wei; Zhao, Qi; Liu, Jia; Li, Da-Wei; Zhang, Hua; Zhou, Xin-Fu; Li, Cheng-Yun; Wang, Ting-Hua

2013-10-08

It is well known that trauma is frequently accompanied by spontaneous functional recovery after spinal cord injury (SCI), but the underlying mechanisms remain elusive. In this study, BBB scores showed a gradual return of locomotor functions after SCT. Proteomics analysis revealed 16 differential protein spots in the gastrocnemius muscle between SCT and normal rats. Of these differential proteins, eukaryotic translation initiation factor 5A1 (elf-5A1), a highly conserved molecule throughout eukaryotes, exhibited marked upregulation in the gastrocnemius muscle after SCT. To study the role of eIF-5A1 in the restoration of hindlimb locomotor functions following SCT, we used siRNA to downregulate the mRNA level of eIF-5A1. Compared with untreated SCT control rats, those subjected to eIF-5A1 knockdown exhibited impaired functional recovery. Moreover, gene expression microarrays and bioinformatic analysis showed high correlation between three main signal pathways (ErbB, MAPK and neurotrophin signal pathways) and eIF-5A1. These signal pathways regulate cell proliferation, differentiation and neurocyte growth. Consequently, eIF-5A1 played a pivotal role via these signal pathways in hindlimb locomotor functional recovery after SCT, which could pave the way for the development of a new strategy for the treatment of spinal cord injury in clinical trials. Copyright © 2012. Published by Elsevier B.V.

Blockade of anoctamin-1 in injured and uninjured nerves reduces neuropathic pain.

PubMed

García, Guadalupe; Martínez-Rojas, Vladimir A; Oviedo, Norma; Murbartián, Janet

2018-06-02

The aim of this study was to determine the participation of anoctamin-1 in 2 models of neuropathic pain in rats (L5/L6 spinal nerve ligation [SNL] and L5 spinal nerve transection [SNT]). SNL and SNT diminished withdrawal threshold in rats. Moreover, SNL up-regulated anoctamin-1 protein expression in injured L5 and uninjured L4 DRG whereas that it enhanced activating transcription factor 3 (ATF-3) and caspase-3 expression only in injured L5 DRG. In marked contrast, SNT enhanced ATF-3 and caspase-3, but not anoctamin-1, expression in injured L5 DRG but it did not modify anoctamin-1, ATF-3 nor caspase-3 expression in uninjured L4 DRG. Accordingly, repeated (3 times) intrathecal injection of the anoctamin-1 blocker T16A inh-A01 (0.1-1 µg) or MONNA (1-10 µg) partially reverted SNL-induced mechanical allodynia in a dose-dependent manner. In contrast, anoctamin-1 blockers only produced a modest effect in SNT-induced mechanical allodynia. Interestingly, intrathecal injection of T16A inh-A01 (1 µg) or MONNA (10 µg) prevented SNL-induced up-regulation of anoctamin-1, ATF-3 and caspase-3 in injured L5 DRG. Repeated intrathecal injection of T16A inh-A01 or MONNA also reduced SNT-induced up-regulation of ATF-3 in injured L5 DRG. In contrast, T16A inh-A01 and MONNA did not affect SNT-induced up-regulation of caspase-3 expression in L5 DRG. Likewise, gabapentin (100 µg) diminished SNL-induced up-regulation of anoctamin-1, ATF-3 and caspase-3 expression in injured L5 DRG. These data suggest that spinal anoctamin-1 in injured and uninjured DRG participates in the maintenance of neuropathic pain in rats. Our data also indicate that expression of anoctamin-1 in DRG is differentially regulated depending on the neuropathic pain model. Copyright © 2018. Published by Elsevier B.V.

Effect of luminal contents on postresectional longitudinal and mucosal growth in the ileum of suckling rats.

PubMed

Ford, W D; de Vries, J E; Ross, J S; Malt, R A

1985-11-01

Effects of luminal contents on adaptive growth of the ileum in the neonatal small bowel of rats were examined after resection of the proximal small bowel and after removal of the ileum from the enteric stream. Four weeks after resection of the proximal 60% of the small bowel in 10-day-old rats, the distal 40% of the small bowel elongated by 281%. This distal segment also elongated by 265% after intestinal transection (p greater than 0.05), but by only 191% when it was bypassed (bypass versus resection or transection, p less than 0.001). After resection the distal villi were 81% taller, but after transection they were only 19% taller (p less than 0.001 versus resection); after bypass they did not grow (p less than 0.001 versus resection or transection). The distal crypts were 404% deeper after resection, 331% deeper after transection (p less than 0.05), and 291% deeper after bypass (p less than 0.001 versus resection, p greater than 0.05 versus transection). The DNA content was 517% greater after resection, 364% greater after transection (p less than 0.001), and 73% greater after bypass (p less than 0.001 versus transection or resection). Maximal elongation of the small bowel occurs in the presence of luminal nutrition. Increasing luminal nutrition is associated with increasing mucosal hyperplasia.

Do cervical collars and cervicothoracic orthoses effectively stabilize the injured cervical spine? A biomechanical investigation.

PubMed

Ivancic, Paul C

2013-06-01

In vitro biomechanical study. Our objective was to determine the effectiveness of cervical collars and cervicothoracic orthoses for stabilizing clinically relevant, experimentally produced cervical spine injuries. Most previous in vitro studies of cervical orthoses used a simplified injury model with all ligaments transected at a single spinal level, which differs from real-life neck injuries. Human volunteer studies are limited to measuring only sagittal motions or 3-dimensional motions only of the head or 1 or 2 spinal levels. Three-plane flexibility tests were performed to evaluate 2 cervical collars (Vista Collar and Vista Multipost Collar) and 2 cervicothoracic orthoses (Vista TS and Vista TS4) using a skull-neck-thorax model with 8 injured cervical spine specimens (manufacturer of orthoses: Aspen Medical Products Inc, Irvine, CA). The injuries consisted of flexion-compression at the lower cervical spine and extension-compression at superior spinal levels. Pair-wise repeated measures analysis of variance (P < 0.05) and Bonferroni post hoc tests determined significant differences in average range of motions of the head relative to the base, C7 or T1, among experimental conditions. RESULTS.: All orthoses significantly reduced unrestricted head/base flexion and extension. The orthoses allowed between 8.4% and 25.8% of unrestricted head/base motion in flexion/extension, 57.8% to 75.5% in axial rotation, and 53.8% to 73.7% in lateral bending. The average percentages of unrestricted motion allowed by the Vista Collar, Vista Multipost Collar, Vista TS, and Vista TS4 were: 14.0, 9.7, 6.1, and 4.7, respectively, for middle cervical spine extension and 13.2, 11.8, 3.3, and 0.4, respectively, for lower cervical spine flexion. Successive increases in immobilization were observed from Vista Collar to Vista Multipost Collar, Vista TS, and Vista TS4 in extension at the injured middle cervical spine and in flexion at the injured lower cervical spine. Our results may assist clinicians in selecting the most appropriate orthosis based upon patient-specific cervical spine injuries.

Adaptability of the oxidative capacity of motoneurons

NASA Technical Reports Server (NTRS)

Chalmers, G. R.; Roy, R. R.; Edgerton, V. R.

1992-01-01

Previous studies have demonstrated that a chronic change in neuronal activation can produce a change in soma oxidative capacity, suggesting that: (i) these 2 variables are directly related in neurons and (ii) ion pumping is an important energy requiring activity of a neuron. Most of these studies, however, have focused on reduced activation levels of sensory systems. In the present study the effect of a chronic increase or decrease in motoneuronal activity on motoneuron oxidative capacity and soma size was studied. In addition, the effect of chronic axotomy was studied as an indicator of whether cytoplasmic volume may also be related to the oxidative capacity of motoneurons. A quantitative histochemical assay for succinate dehydrogenase activity was used as a measure of motoneuron oxidative capacity in experimental models in which chronic electromyography has been used to verify neuronal activity levels. Spinal transection reduced, and spinal isolation virtually eliminated lumbar motoneuron electrical activity. Functional overload of the plantaris by removal of its major synergists was used to chronically increase neural activity of the plantaris motor pool. No change in oxidative capacity or soma size resulted from either a chronic increase or decrease in neuronal activity level. These data indicate that the chronic modulation of ionic transport and neurotransmitter turnover associated with action potentials do not induce compensatory metabolic responses in the metabolic capacity of the soma of lumbar motoneurons. Soma oxidative capacity was reduced in the axotomized motoneurons, suggesting that a combination of axoplasmic transport, intracellular biosynthesis and perhaps neurotransmitter turnover represent the major energy demands on a motoneuron. While soma oxidative capacity may be closely related to neural activity in some neural systems, e.g. visual and auditory, lumbar motoneurons appear to be much less sensitive to modulations in chronic activity levels.

Effects of the dimeric PSD-95 inhibitor UCCB01-144 on functional recovery after fimbria-fornix transection in rats.

PubMed

Sommer, Jens Bak; Bach, Anders; Malá, Hana; Strømgaard, Kristian; Mogensen, Jesper; Pickering, Darryl S

2017-10-01

Pharmacological inhibition of PSD-95 is a promising therapeutic strategy in the treatment of stroke, and positive effects of monomeric and dimeric PSD-95 inhibitors have been reported in numerous studies. However, whether therapeutic effects will generalize to other types of acute brain injury such as traumatic brain injury (TBI), which has pathophysiological mechanisms in common with stroke, is currently uncertain. We have previously found a lack of neuroprotective effects of dimeric PSD-95 inhibitors in the controlled cortical impact model of TBI in rats. However, as no single animal model is currently able to mimic the complex and heterogeneous pathophysiology of TBI, it is necessary to assess treatment effects across a range of models. In this preliminary study we investigated the neuroprotective abilities of the dimeric PSD-95 inhibitor UCCB01-144 after fimbria-fornix (FF) transection in rats. UCCB01-144 or saline was injected into the lateral tail vein of rats immediately after sham surgery or FF-transection, and effects on spatial delayed alternation in a T-maze were assessed over a 28-day period. Task acquisition was significantly impaired in FF-transected animals, but there were no significant effects of UCCB01-144 on spatial delayed alternation after FF-transection or sham surgery, although decelerated learning curves were seen after treatment with UCCB01-144 in FF-transected animals. The results of the present study are consistent with previous research showing a lack of neuroprotective effects of PSD-95 inhibition in experimental models of TBI. Copyright © 2017 Elsevier Inc. All rights reserved.

Reinnervation of Urethral and Anal Sphincters With Femoral Motor Nerve to Pudendal Nerve Transfer

PubMed Central

Ruggieri, Michael R.; Braverman, Alan S.; Bernal, Raymond M.; Lamarre, Neil S.; Brown, Justin M.; Barbe, Mary F.

2012-01-01

Aims Lower motor neuron damage to sacral roots or nerves can result in incontinence and a flaccid urinary bladder. We showed bladder reinnervation after transfer of coccygeal to sacral ventral roots, and genitofemoral nerves (L1, 2 origin) to pelvic nerves. This study assesses the feasibility of urethral and anal sphincter reinnervation using transfer of motor branches of the femoral nerve (L2–4 origin) to pudendal nerves (S1, 2 origin) that innervate the urethral and anal sphincters in a canine model. Methods Sacral ventral roots were selected by their ability to stimulate bladder, urethral sphincter, and anal sphincter contraction and transected. Bilaterally, branches of the femoral nerve, specifically, nervus saphenous pars muscularis [Evans HE. Miller’s anatomy of the dog. Philadelphia: W.B. Saunders; 1993], were transferred and end-to-end anastomosed to transected pudendal nerve branches in the perineum, then enclosed in unipolar nerve cuff electrodes with leads to implanted RF micro-stimulators. Results Nerve stimulation induced increased anal and urethral sphincter pressures in five of six transferred nerves. Retrograde neurotracing from the bladder, urethral sphincter, and anal sphincter using fluorogold, fast blue, and fluororuby, demonstrated urethral and anal sphincter labeled neurons in L2–4 cord segments (but not S1–3) in nerve transfer canines, consistent with rein-nervation by the transferred femoral nerve motor branches. Controls had labeled neurons only in S1–3 segments. Postmortem DiI and DiO labeling confirmed axonal regrowth across the nerve repair site. Conclusions These results show spinal cord reinnervation of urethral and anal sphincter targets after sacral ventral root transection and femoral nerve transfer (NT) to the denervated pudendal nerve. These surgical procedures may allow patients to regain continence. PMID:21953679

Limits to the capacity of transplants of olfactory glia to promote axonal regrowth in the CNS.

PubMed

Gudiño-Cabrera, G; Pastor, A M; de la Cruz, R R; Delgado-García, J M; Nieto-Sampedro, M

2000-02-28

Olfactory bulb ensheathing cell (OBEC) transplants promoted axonal regeneration in the spinal cord dorsal root entry zone and in the corticospinal tract. However, OBECs failed to promote abducens internuclear neuron axon regeneration when transplanted at the site of nerve fibre transection. In experiments performed in both cats and rats, OBECs survived for up to 2 months, lining themselves up along the portion of the regrowing axons proximal to the interneuron cell body. However, OBECs migrated preferentially towards abducens somata, in the direction opposite to the oculomotor nucleus target. OBECs seem to promote nerve fibre regeneration only where preferred direction of glial migration coincides with the direction of axonal growth towards its target.

Olfactory ensheathing cell transplantation for spinal cord injury: An 18-year bibliometric analysis based on the Web of Science.

PubMed

Leng, Zikuan; He, Xijing; Li, Haopeng; Wang, Dong; Cao, Kai

2013-05-15

Olfactory ensheathing cell (OEC) transplantation is a promising new approach for the treatment of spinal cord injury (SCI), and an increasing number of scientific publications are devoted to this treatment strategy. This bibliometric analysis was conducted to assess global research trends in OEC transplantation for SCI. All of the data in this study originate from the Web of Science maintained by the Institute for Scientific Information, USA, and includes SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, CCR-EXPANDED and IC. The Institute for Scientific Information's Web of Science was searched using the keywords "olfactory ensheathing cells" or "OECs" or "olfactory ensheathing glia" or "OEG" or "olfactory ensheathing glial cells" or "OEGs" and "spinal cord injury" or "SCI" or "spinal injury" or "spinal transection" for literature published from January 1898 to May 2012. Original articles, reviews, proceedings papers and meeting abstracts, book chapters and editorial materials on OEC transplantation for SCI were included. Simultaneously, unpublished literature and literature for which manual information retrieval was required were excluded. ALL SELECTED LITERATURES ADDRESSING OEC TRANSPLANTATION FOR SCI WERE EVALUATED IN THE FOLLOWING ASPECTS: publication year, document type, language, author, institution, times cited, Web of Science category, core source title, countries/territories and funding agency. In the Web of Science published by the Institute for Scientific Information, the earliest literature record was in April, 1995. Four hundred and fourteen publications addressing OEC transplantation for SCI were added to the data library in the past 18 years, with an annually increasing trend. Of 415 records, 405 publications were in English. Two hundred and fifty-nine articles ranked first in the distribution of document type, followed by 141 reviews. Thirty articles and 20 reviews, cited more than 55 times by the date the publication data were downloaded by us, can be regarded as the most classical references. The journal Experimental Neurology published the most literature (32 records), followed by Glia. The United States had the most literature, followed by China. In addition, Yale University was the most productive institution in the world, while The Second Military Medical University contributed the most in China. The journal Experimental Neurology published the most OEC transplantation literature in the United States, while Neural Regeneration Research published the most in China. This analysis provides insight into the current state and trends in OEC transplantation for SCI research. Furthermore, we anticipate that this analysis will help encourage international cooperation and teamwork on OEC transplantation for SCI to facilitate the development of more effective treatments for SCI.

Mobile acoustic transects miss rare bat species: implications of survey method and spatio-temporal sampling for monitoring bats.

PubMed

Braun de Torrez, Elizabeth C; Wallrichs, Megan A; Ober, Holly K; McCleery, Robert A

2017-01-01

Due to increasing threats facing bats, long-term monitoring protocols are needed to inform conservation strategies. Effective monitoring should be easily repeatable while capturing spatio-temporal variation. Mobile acoustic driving transect surveys ('mobile transects') have been touted as a robust, cost-effective method to monitor bats; however, it is not clear how well mobile transects represent dynamic bat communities, especially when used as the sole survey approach. To assist biologists who must select a single survey method due to resource limitations, we assessed the effectiveness of three acoustic survey methods at detecting species richness in a vast protected area (Everglades National Park): (1) mobile transects, (2) stationary surveys that were strategically located by sources of open water and (3) stationary surveys that were replicated spatially across the landscape. We found that mobile transects underrepresented bat species richness compared to stationary surveys across all major vegetation communities and in two distinct seasons (dry/cool and wet/warm). Most critically, mobile transects failed to detect three rare bat species, one of which is federally endangered. Spatially replicated stationary surveys did not estimate higher species richness than strategically located stationary surveys, but increased the rate at which species were detected in one vegetation community. The survey strategy that detected maximum species richness and the highest mean nightly species richness with minimal effort was a strategically located stationary detector in each of two major vegetation communities during the wet/warm season.

Strip transect sampling and analysis for avian habitat studies

Treesearch

Richard N. Conner; James G. Dickson

1980-01-01

Censusing procedures that detect effects of habitat treatment on birds are outlined. We suggest that only relative values of bird species diversity, equitability, abundance, and species richness need be obtained. We also suggest that 4, 250-m strip transects per treatment and 8-10 trips over each transect are adequate. Aspects of sampling design that affect within-...

Dose-Dependent Differential Effect of Neurotrophic Factors on In Vitro and In Vivo Regeneration of Motor and Sensory Neurons

PubMed Central

Santos, Daniel; Gonzalez-Perez, Francisco; Navarro, Xavier

2016-01-01

Although peripheral axons can regenerate after nerve transection and repair, functional recovery is usually poor due to inaccurate reinnervation. Neurotrophic factors promote directional guidance to regenerating axons and their selective application may help to improve functional recovery. Hence, we have characterized in organotypic cultures of spinal cord and dorsal root ganglia the effect of GDNF, FGF-2, NGF, NT-3, and BDNF at different concentrations on motor and sensory neurite outgrowth. In vitro results show that GDNF and FGF-2 enhanced both motor and sensory neurite outgrowth, NGF and NT-3 were the most selective to enhance sensory neurite outgrowth, and high doses of BDNF selectively enhanced motor neurite outgrowth. Then, NGF, NT-3, and BDNF (as the most selective factors) were delivered in a collagen matrix within a silicone tube to repair the severed sciatic nerve of rats. Quantification of Fluorogold retrolabeled neurons showed that NGF and NT-3 did not show preferential effect on sensory regeneration whereas BDNF preferentially promoted motor axons regeneration. Therefore, the selective effects of NGF and NT-3 shown in vitro are lost when they are applied in vivo, but a high dose of BDNF is able to selectively enhance motor neuron regeneration both in vitro and in vivo. PMID:27867665

Effects of nicergoline on the cardiovascular system of dogs and rats.

PubMed

Huchet, A M; Mouillé, P; Chelly, J; Lucet, B; Doursout, M F; Lechat, P; Schmitt, H

1981-01-01

In pentobarbitalized closed-chest dogs, nicergoline (10--100 microgram/kg, i.v.) reduced blood pressure, heart rate, and splanchnic nerve activity. Intracisternal administration of nicergoline (3 microgram/kg) only reduced splanchnic nerve activity. In open-chest dogs, nicergoline reduced blood pressure, cardiac output, and total peripheral resistance but did not change heart rate. In pithed rats treated with a beta-adrenoceptor-blocking agent, nicergoline reduced the pressor responses to noradrenaline and adrenaline. Nicergoline slightly attenuated the pressor responses of dogs to noradrenaline and tyramine and, in addition, reversed the hypertension induced by adrenaline and dimethylphenylpiperazinium. Nicergoline (100 microgram/kg) increased the tachycardia induced in dogs by stimulation of the right cardiovascular nerve and prevented the inhibitory effect of clonidine on this response. However, nicergoline only partially antagonized the effect of clonidine once it was fully established. Nicergoline did not antagonize the hypotensive and bradycardic effects of clonidine when they were established. Nicergoline did not affect the vagally mediated bradycardia evoked by carotid nerve stimulation in beta-adrenoceptor-blocked dogs. The compound did not change blood pressure in Cl spinal cord transected dogs. In conclusion, nicergoline appears to decrease blood pressure by blocking alpha-adrenoceptors and, at least at some doses, by a central inhibition of the sympathetic tone. Nicergoline appears to be a preferential alpha 1-adrenoceptor-blocking agent.

Use of paper for treatment of a peripheral nerve trauma in the rat.

PubMed

Kauppila, T; Jyväsjärvi, E; Murtomäki, S; Mansikka, H; Pertovaara, A; Virtanen, I; Liesi, P

1997-09-29

Reinnervation of the muscles and skin in the rat hindpaw was studied after transection and attempted repair of the sciatic nerve. Reconnecting the transected nerve with lens cleaning paper was at least as effective in rejoining the transected nerves as traditional microsurgical neurorraphy. Paper induced a slightly bigger fibrous scar around the site of transection than neurorraphy, but this scar did not cause impairment of functional recovery or excessive signs of neuropathic pain. We conclude that a paper graft can be used in restorative surgery of severed peripheral nerves.

In vivo predegeneration of peripheral nerves: an effective technique to obtain activated Schwann cells for nerve conduits.

PubMed

Keilhoff, G; Fansa, H; Schneider, W; Wolf, G

1999-07-01

In vivo predegeneration of peripheral nerves is presented as a convenient and effective method to obtain activated Schwann cells and an enhanced cell yield following in vitro cultivation. The experiments conducted in rats were aimed at clinical use in gaining Schwann cell suspensions for filling artificial conduits in order to bridge peripheral nerve gaps. The rat sciatic nerve used as a model was transected distally to the spinal ganglia. Predegeneration in vivo was allowed to take place for 1, 2, 3 and 4 days and up to 1, 2 and 3 weeks. The nerve was then resected and prepared for cell cultivation. Schwann cells cultivated from the contralateral untreated nerve served as control. Immunostaining for S100, nerve growth factor receptor and the adhesion molecules N-cadherin and L1 was used to characterize the general state of the cultures. Viability was assessed by fluorescein fluorescence staining, and the proliferation index was determined by bromodeoxyuridine-DNA incorporation. The Schwann cells from predegenerated nerves revealed an increased proliferation rate compared to the control, whereas fibroblast contamination was decreased. Best results were obtained 1 week after predegeneration.

Effects of Adrenergic Blockade on Postpartum Adaptive Responses Induced by Labor Contractions

NASA Technical Reports Server (NTRS)

Ronca, April E.; Mills, N. A.; Lam, K. P.; Hayes, L. E.; Bowley, Susan M. (Technical Monitor)

2000-01-01

Prenatal exposure to labor contractions augments the expression of postnatal adaptive responses in newborn rats. Near-term rat fetuses exposed prenatally to simulated labor contractions and delivered by cesarean section breath and attach to nipples at greater frequencies than non-stimulated fetuses. Plasma NE (norepinephrine) and EPI (epinephrine) was significantly elevated in newborn rats exposed to vaginal birth or simulated labor contractions (compressions) with cesarean delivery as compared to non-compressed fetuses. In the present study, we investigated adrenergic mechanisms underlying labor-induced postnatal adaptive responses. Following spinal transection of late pregnant rat dams, fetuses were administered neurogenic or non-neurogenic adrenergic blockade: 1) bretylium (10 mg/kg sc) to prevent sympathetic neuronal release, 2) hexamethonium (30 mg/kg) to produce ganglionic blockade, 3) phenoxybenzanune (10mg/kg sc), an a- adrenergic receptor antagonist, 4) ICI-118551, 10 mg/kg sc), a b receptor antagonist, or 5) vehicle alone. Fetuses were either compressed (C) or non-compressed (NC) prior to cesarean delivery. a- and b- adrenergic antagonists reduced respiration and nipple attachment rates while sympathetic and vehicle alone did not. These results provide additional support for the hypothesis that adaptive neonatal effects of labor contractions are mediated by adrenal and extra-adrenal catecholamines.

Activation of somatosensory afferents elicit changes in vaginal blood flow and the urethrogenital reflex via autonomic efferents.

PubMed

Cai, R S; Alexander, M Sipski; Marson, L

2008-09-01

We examined the effects of pudendal sensory nerve stimulation and urethral distention on vaginal blood flow and the urethrogenital reflex, and the relationship between somatic and autonomic pathways regulating sexual responses. Distention of the urethra and stimulation of the pudendal sensory nerve were used to evoke changes in vaginal blood flow (laser Doppler perfusion monitoring) and pudendal motor nerve activity in anesthetized, spinally transected female rats. Bilateral cuts of either the pelvic or hypogastric nerve or both autonomic nerves were made, and blood flow and pudendal nerve responses were reexamined. Stimulation of the pudendal sensory nerve or urethral distention elicited consistent increases in vaginal blood flow and rhythmic firing of the pudendal motor nerve. Bilateral cuts of the pelvic plus hypogastric nerves significantly reduced vaginal blood flow responses without altering pudendal motor nerve responses. Pelvic nerve cuts also significantly reduced vaginal blood flow responses. In contrast, hypogastric nerve cuts did not significantly change vaginal blood flow. Bilateral cuts of the pudendal sensory nerve blocked pudendal motor nerve responses but stimulation of the central end evoked vaginal blood flow and pudendal motor nerve responses. Stimulation of the sensory branch of the pudendal nerve elicits vasodilatation of the vagina. The likely mechanism is via activation of spinal pathways that in turn activate pelvic nerve efferents to produced changes in vaginal blood flow. Climatic-like responses (firing of the pudendal motor nerve) occur in response to stimulation of the pudendal sensory nerve and do not require intact pelvic or hypogastric nerves.

Randomized clinical trial of stapler versus clamp-crushing transection in elective liver resection.

PubMed

Rahbari, N N; Elbers, H; Koch, M; Vogler, P; Striebel, F; Bruckner, T; Mehrabi, A; Schemmer, P; Büchler, M W; Weitz, J

2014-02-01

Various devices have been developed to facilitate liver transection and reduce blood loss in liver resections. None of these has proven superiority compared with the classical clamp-crushing technique. This randomized clinical trial compared the effectiveness and safety of stapler transection with that of clamp-crushing during open liver resection. Patients admitted for elective open liver resection between January 2010 and October 2011 were assigned randomly to stapler transection or the clamp-crushing technique. The primary endpoint was the total amount of intraoperative blood loss. Secondary endpoints included transection time, duration of operation, complication rates and resection margins. A total of 130 patients were enrolled, 65 to clamp-crushing and 65 to stapler transection. There was no difference between groups in total intraoperative blood loss: median (i.q.r.) 1050 (525-1650) versus 925 (450-1425) ml respectively (P = 0·279). The difference in total intraoperative blood loss normalized to the transection surface area was not statistically significant (P = 0·092). Blood loss during parenchymal transection was significantly lower in the stapler transection group (P = 0·002), as were the parenchymal transection time (mean(s.d.) 30(21) versus 9(7) min for clamp-crushing and stapler transection groups respectively; P < 0·001) and total duration of operation (mean(s.d.) 221(86) versus 190(85) min; P = 0·047). There were no significant differences in postoperative morbidity (P = 0·863) or mortality (P = 0·684) between groups. Stapler transection is a safe technique but does not reduce intraoperative blood loss in elective liver resection compared with the clamp-crushing technique. NCT01049607 (http://www.clinicaltrials.gov). © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

Targeted Delivery of TrkB Receptor to Phrenic Motoneurons Enhances Functional Recovery of Rhythmic Phrenic Activity after Cervical Spinal Hemisection

PubMed Central

Gransee, Heather M.; Zhan, Wen-Zhi; Sieck, Gary C.; Mantilla, Carlos B.

2013-01-01

Progressive recovery of rhythmic phrenic activity occurs over time after a spinal cord hemisection involving unilateral transection of anterolateral funiculi at C2 (SH). Brain-derived neurotrophic factor (BDNF) acting through its full-length tropomyosin related kinase receptor subtype B (TrkB.FL) contributes to neuroplasticity after spinal cord injury, but the specific cellular substrates remain unclear. We hypothesized that selectively targeting increased TrkB.FL expression to phrenic motoneurons would be sufficient to enhance recovery of rhythmic phrenic activity after SH. Several adeno-associated virus (AAV) serotypes expressing GFP were screened to determine specificity for phrenic motoneuron transduction via intrapleural injection in adult rats. GFP expression was present in the cervical spinal cord 3 weeks after treatment with AAV serotypes 7, 8, and 9, but not with AAV2, 6, or rhesus-10. Overall, AAV7 produced the most consistent GFP expression in phrenic motoneurons. SH was performed 3 weeks after intrapleural injection of AAV7 expressing human TrkB.FL-FLAG or saline. Delivery of TrkB.FL-FLAG to phrenic motoneurons was confirmed by FLAG protein expression in the phrenic motor nucleus and human TrkB.FL mRNA expression in microdissected phrenic motoneurons. In all SH rats, absence of ipsilateral diaphragm EMG activity was confirmed at 3 days post-SH, verifying complete interruption of ipsilateral descending drive to phrenic motoneurons. At 14 days post-SH, all AAV7-TrkB.FL treated rats (n = 11) displayed recovery of ipsilateral diaphragm EMG activity compared to 3 out of 8 untreated SH rats (p<0.01). During eupnea, AAV7-TrkB.FL treated rats exhibited 73±7% of pre-SH root mean squared EMG vs. only 31±11% in untreated SH rats displaying recovery (p<0.01). This study provides direct evidence that increased TrkB.FL expression in phrenic motoneurons is sufficient to enhance recovery of ipsilateral rhythmic phrenic activity after SH, indicating that selectively targeting gene expression in spared motoneurons below the level of spinal cord injury may promote functional recovery. PMID:23724091

Primary Spinal OPC Culture System from Adult Zebrafish to Study Oligodendrocyte Differentiation In Vitro.

PubMed

Kroehne, Volker; Tsata, Vasiliki; Marrone, Lara; Froeb, Claudia; Reinhardt, Susanne; Gompf, Anne; Dahl, Andreas; Sterneckert, Jared; Reimer, Michell M

2017-01-01

Endogenous oligodendrocyte progenitor cells (OPCs) are a promising target to improve functional recovery after spinal cord injury (SCI) by remyelinating denuded, and therefore vulnerable, axons. Demyelination is the result of a primary insult and secondary injury, leading to conduction blocks and long-term degeneration of the axons, which subsequently can lead to the loss of their neurons. In response to SCI, dormant OPCs can be activated and subsequently start to proliferate and differentiate into mature myelinating oligodendrocytes (OLs). Therefore, researchers strive to control OPC responses, and utilize small molecule screening approaches in order to identify mechanisms of OPC activation, proliferation, migration and differentiation. In zebrafish, OPCs remyelinate axons of the optic tract after lysophosphatidylcholine (LPC)-induced demyelination back to full thickness myelin sheaths. In contrast to zebrafish, mammalian OPCs are highly vulnerable to excitotoxic stress, a cause of secondary injury, and remyelination remains insufficient. Generally, injury induced remyelination leads to shorter internodes and thinner myelin sheaths in mammals. In this study, we show that myelin sheaths are lost early after a complete spinal transection injury, but are re-established within 14 days after lesion. We introduce a novel, easy-to-use, inexpensive and highly reproducible OPC culture system based on dormant spinal OPCs from adult zebrafish that enables in vitro analysis. Zebrafish OPCs are robust, can easily be purified with high viability and taken into cell culture. This method enables to examine why zebrafish OPCs remyelinate better than their mammalian counterparts, identify cell intrinsic responses, which could lead to pro-proliferating or pro-differentiating strategies, and to test small molecule approaches. In this methodology paper, we show efficient isolation of OPCs from adult zebrafish spinal cord and describe culture conditions that enable analysis up to 10 days in vitro . Finally, we demonstrate that zebrafish OPCs differentiate into Myelin Basic Protein (MBP)-expressing OLs when co-cultured with human motor neurons differentiated from induced pluripotent stem cells (iPSCs). This shows that the basic mechanisms of oligodendrocyte differentiation are conserved across species and that understanding the regulation of zebrafish OPCs can contribute to the development of new treatments to human diseases.

Chondroprotective effects of zoledronic acid on articular cartilage in dogs with experimentally induced osteoarthritis.

PubMed

Dearmin, Michael G; Trumble, Troy N; García, Anapatricia; Chambers, Jon N; Budsberg, Steven C

2014-04-01

To assess effects of zoledronic acid on biomarkers, radiographic scores, and gross articular cartilage changes in dogs with induced osteoarthritis. 21 purpose-bred hound-type dogs. The left stifle joint of each dog was examined arthroscopically to determine initial articular cartilage status, which was followed by cranial cruciate ligament (CrCL) transection to induce osteoarthritis. Dogs were assigned to 3 groups (control group, low dose [10 μg of zoledronic acid/kg], or high dose [25 μg of zoledronic acid/kg). Treatments were administered SC every 3 months for 1 year beginning the day after CrCL transection. Serum and synovial fluid samples and radiographs were obtained 0, 1, 3, 6, 9, and 12 months after transection. At 12 months, each joint was scored for cartilage defects. Serum and synovial fluid biomarkers of bone and cartilage turnover (bone-specific alkaline phosphatase, type I and II collagen, carboxy-propeptide of type II collagen, and chondroitin sulfate 846) were analyzed with ELISAs. The high-dose group had fewer total articular defects and lower severity scores in CrCL-transected stifle joints than did the control group. In addition, the high-dose group had significantly less change in collagenase cleavage of type I or II collagen in the synovial fluid at 1 and 3 months after CrCL transection than did the control group and also had greater changes in bone-specific alkaline phosphatase in synovial fluid at 3 months after CrCL transection than did the control group. Zoledronic acid had a chondroprotective effect in dogs with a transected CrCL.

Swimming behaviour and calcium incorporation into inner ear otoliths of fish after vestibular nerve transection

NASA Astrophysics Data System (ADS)

Edelmann, E.; Anken, R. H.; Rahmann, H.

2004-01-01

Previous investigations on neonate swordtail fish (Xiphophorus helleri) revealed that otolithic calcium incorporation (visualized using the calcium tracer alizarin complexone) and thus otolith growth had ceased after nerve transection, supporting a hypothesis according to which the gravity-dependent otolith growth is regulated neuronally. Subsequent investigations on larval cichlid fish (Oreochromis mossambicus) yielded contrasting results, repeatedly depending on the particular batch of cichlids investigated. Like most neonate swordtails, Type I cichlids revealed a stop of calcium incorporation after unilateral vestibular nerve transection. Their behaviour after transection was normal, and the otolithic calcium incorporation in controls of the same batch was symmetric. In Type II cichlids, however, vestibular nerve transection had no effect on otolithic calcium incorporation. They behaved kinetotically after transection (this kind of kinetosis was qualitatively similar to the swimming behaviour exhibited by larval cichlids during microgravity in the course of parabolic aircraft flights). The otolithic calcium incorporation in control animals was asymmetric. These results show that the effects of vestibular nerve transection as well as the efficacy of the mechanism, which regulates otolith growth/otolithic calcium incorporation, are - depending on the particular batch of animals - genetically predispositioned. In conclusion, the regulation of otolithic calcium incorporation is guided neuronally, in part via the vestibular nerve and, in part, via a further pathway, which remains to be addressed in the course of future investigations.

Swimming Behavior and Calcium Incorporation into inner Ear Otoliths of Fish after vestibular Nerve Transection

NASA Astrophysics Data System (ADS)

Edelmann, E.; Anken, R.; Rahmann, H.

Previous investigations on neonate swordtail fish (Xiphophorus helleri) revealed that otolithic calcium incorporation (visualized using the calcium-tracer alizarin- complexone) and thus otolith growth had ceased after nerve transection, supporting a hypothesis according to which the gravity-dependent otolith growth is regulated neuronally. Subsequent investigations on larval cichlid fish (Oreochromis mossambicus) yielded contrasting results, repeatedly depending on the particular batch of cichlids investigated: Like neonate swordtails, type I cichlids revealed a stop of calcium incorporation after unilateral vestibular nerve transection. Their behaviour after transection was normal and the otolithic calcium incorporation in controls of the same batch was symmetrical. In type II cichlids, however, vestibular nerve transection had no effect on otolithic calcium incorporation. They behaved kinetotically after transection (this kind of kinetosis was qualitatively similar to the swimming behaviour exhibited by larval cichlids during microgravity in the course of parabolic aircraft flights). The otolithic calcium incorporation in control animals was asymmetrical. These results stongly suggest that the effects of vestibular nerve transection as well as the efficacy of the mechanism, which regulates otolith growth/otolithic calcium incorporation, are - depending on the particular batch of animals - genetically predispositioned. Thus, it is assumed that the mechanisms regulating otolith growth and equlibibrium differ in the two types of cichlid fish. This work was financially supported by the German Aerospace Center (DLR) e.V. (FKZ: 50 WB 9997).

Ulinastatin attenuates neuropathic pain induced by L5-VRT via the calcineurin/IL-10 pathway.

PubMed

Ouyang, Handong; Nie, Bilin; Wang, Peizong; Li, Qiang; Huang, Wan; Xin, Wenjun; Zeng, Weian; Liu, Xianguo

2016-01-01

Previous studies have shown that ulinastatin, an effective inhibitor of the inflammatory response in clinical applications, can attenuate hyperalgesia in rodents. However, the underlying mechanism remains unclear. In the present study, we first examined the change in the calcineurin level, which plays an important role in regulating cytokine release in the nervous system, following lumbar 5 ventral root transection in the rat. Furthermore, we determined whether intraperitoneal (i.p.) injection of ulinastatin attenuated pain behavior via inhibition of the calcineurin-mediated inflammatory response induced by lumbar 5 ventral root transection. The results showed that the paw withdrawal threshold and paw withdrawal latency were significantly decreased following lumbar 5 ventral root transection compared to the sham group. Neuropathic pain induced by lumbar 5 ventral root transection significantly decreased the expression of calcineurin in the DRG, and calcineurin was mostly located with NF-200-positive cells, IB4-positive cells, and CGRP-positive cells and less with GFAP-positive satellite cells. Furthermore, intrathecal (i.t.) injection of exogenous calcineurin attenuated the pain behavior induced by lumbar 5 ventral root transection. Importantly, intraperitoneal injection of ulinastatin alleviated the pain behavior and calcineurin downregulation induced by lumbar 5 ventral root transection. Lastly, the cytokine IL-10 was significantly decreased following lumbar 5 ventral root transection, and application of calcineurin (intrathecal) or ulinastatin (intraperitoneal) inhibited the IL-10 downregulation induced by lumbar 5 ventral root transection. These results suggested that ulinastatin, by acting on the CN/IL-10 pathway, might be a novel and effective drug for the treatment of neuropathic pain. © The Author(s) 2016.

Ulinastatin attenuates neuropathic pain induced by L5-VRT via the calcineurin/IL-10 pathway

PubMed Central

Ouyang, Handong; Nie, Bilin; Wang, Peizong; Li, Qiang; Huang, Wan; Xin, Wenjun; Liu, Xianguo

2016-01-01

Previous studies have shown that ulinastatin, an effective inhibitor of the inflammatory response in clinical applications, can attenuate hyperalgesia in rodents. However, the underlying mechanism remains unclear. In the present study, we first examined the change in the calcineurin level, which plays an important role in regulating cytokine release in the nervous system, following lumbar 5 ventral root transection in the rat. Furthermore, we determined whether intraperitoneal (i.p.) injection of ulinastatin attenuated pain behavior via inhibition of the calcineurin-mediated inflammatory response induced by lumbar 5 ventral root transection. The results showed that the paw withdrawal threshold and paw withdrawal latency were significantly decreased following lumbar 5 ventral root transection compared to the sham group. Neuropathic pain induced by lumbar 5 ventral root transection significantly decreased the expression of calcineurin in the DRG, and calcineurin was mostly located with NF-200-positive cells, IB4-positive cells, and CGRP-positive cells and less with GFAP-positive satellite cells. Furthermore, intrathecal (i.t.) injection of exogenous calcineurin attenuated the pain behavior induced by lumbar 5 ventral root transection. Importantly, intraperitoneal injection of ulinastatin alleviated the pain behavior and calcineurin downregulation induced by lumbar 5 ventral root transection. Lastly, the cytokine IL-10 was significantly decreased following lumbar 5 ventral root transection, and application of calcineurin (intrathecal) or ulinastatin (intraperitoneal) inhibited the IL-10 downregulation induced by lumbar 5 ventral root transection. These results suggested that ulinastatin, by acting on the CN/IL-10 pathway, might be a novel and effective drug for the treatment of neuropathic pain. PMID:27175013

Methylxanthines do not affect rhythmogenic preBötC inspiratory network activity but impair bursting of preBötC-driven motoneurons.

PubMed

Panaitescu, B; Kuribayashi, J; Ruangkittisakul, A; Leung, V; Iizuka, M; Ballanyi, K

2013-01-01

Clinical stimulation of preterm infant breathing with methylxanthines like caffeine and theophylline can evoke seizures. It is unknown whether underlying neuronal hyperexcitability involves the rhythmogenic inspiratory active pre-Bötzinger complex (preBötC) in the brainstem or preBötC-driven motor networks. Inspiratory-related preBötC interneuronal plus spinal (cervical/phrenic) or cranial hypoglossal (XII) motoneuronal bursting was studied in newborn rat en bloc brainstem-spinal cords and brainstem slices, respectively. Non-respiratory bursting perturbed inspiratory cervical nerve activity in en bloc models at >0.25mM theophylline or caffeine. Rhythm in the exposed preBötC of transected en bloc preparations was less perturbed by 10mM theophylline than cervical root bursting which was more affected than phrenic nerve activity. In the preBötC of slices, even 10mM methylxanthine did not evoke seizure-like bursting whereas >1mM masked XII rhythm via large amplitude 1-10Hz oscillations. Blocking A-type γ-aminobutyric (GABAA) receptors evoked seizure-like cervical activity whereas in slices neither XII nor preBötC rhythm was disrupted. Methylxanthines (2.5-10mM), but not blockade of adenosine receptors, phosphodiesterase-4 or the sarcoplasmatic/endoplasmatic reticulum ATPase countered inspiratory depression by muscimol-evoked GABAA receptor activation that was associated with a hyperpolarization and input resistance decrease silencing preBötC neurons in slices. The latter blockers did neither affect preBötC or cranial/spinal motor network bursting nor evoke seizure-like activity or mask corresponding methylxanthine-evoked discharges. Our findings show that methylxanthine-evoked hyperexcitability originates from motor networks, leaving preBötC activity largely unaffected, and suggest that GABAA receptors contribute to methylxanthine-evoked seizure-like perturbation of spinal motoneurons whereas non-respiratory XII motoneuron oscillations are of different origin. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Evaluation of radio-tracking and strip transect methods for determining foraging ranges of Black-Legged Kittiwakes

USGS Publications Warehouse

Ostrand, William D.; Drew, G.S.; Suryan, R.M.; McDonald, L.L.

1998-01-01

We compared strip transect and radio-tracking methods of determining foraging range of Black-legged Kittiwakes (Rissa tridactyla). The mean distance birds were observed from their colony determined by radio-tracking was significantly greater than the mean value calculated from strip transects. We determined that this difference was due to two sources of bias: (1) as distance from the colony increased, the area of available habitat also increased resulting in decreasing bird densities (bird spreading). Consequently, the probability of detecting birds during transect surveys also would decrease as distance from the colony increased, and (2) the maximum distance birds were observed from the colony during radio-tracking exceeded the extent of the strip transect survey. We compared the observed number of birds seen on the strip transect survey to the predictions of a model of the decreasing probability of detection due to bird spreading. Strip transect data were significantly different from modeled data; however, the field data were consistently equal to or below the model predictions, indicating a general conformity to the concept of declining detection at increasing distance. We conclude that radio-tracking data gave a more representative indication of foraging distances than did strip transect sampling. Previous studies of seabirds that have used strip transect sampling without accounting for bird spreading or the effects of study-area limitations probably underestimated foraging range.

A line transect model for aerial surveys

USGS Publications Warehouse

Quang, Pham Xuan; Lanctot, Richard B.

1991-01-01

We employ a line transect method to estimate the density of the common and Pacific loon in the Yukon Flats National Wildlife Refuge from aerial survey data. Line transect methods have the advantage of automatically taking into account “visibility bias” due to detectability difference of animals at different distances from the transect line. However, line transect methods must overcome two difficulties when applied to inaccurate recording of sighting distances due to high travel speeds, so that in fact only a few reliable distance class counts are available. We propose a unimodal detection function that provides an estimate of the effective area lost due to the blind strip, under the assumption that a line of perfect detection exists parallel to the transect line. The unimodal detection function can also be applied when a blind strip is absent, and in certain instances when the maximum probability of detection is less than 100%. A simple bootstrap procedure to estimate standard error is illustrated. Finally, we present results from a small set of Monte Carlo experiments.

Should Body Weight–Supported Treadmill Training and Robotic-Assistive Steppers for Locomotor Training Trot Back to the Starting Gate?

PubMed Central

Dobkin, Bruce H.; Duncan, Pamela W.

2014-01-01

Body weight–supported treadmill training (BWSTT) and robotic-assisted step training (RAST) have not, so far, led to better outcomes than a comparable dose of progressive over-ground training (OGT) for disabled persons with stroke, spinal cord injury, multiple sclerosis, Parkinson’s disease, or cerebral palsy. The conceptual bases for these promising rehabilitation interventions had once seemed quite plausible, but the results of well-designed, randomized clinical trials have been disappointing. The authors reassess the underpinning concepts for BWSTT and RAST, which were derived from mammalian studies of treadmill-induced hind-limb stepping associated with central pattern generation after low thoracic spinal cord transection, as well as human studies of the triple crown icons of task-oriented locomotor training, massed practice, and activity-induced neuroplasticity. The authors retrospectively consider where theory and practice may have fallen short in the pilot studies that aimed to produce thoroughbred interventions. Based on these shortcomings, the authors move forward with recommendations for the future development of workhorse interventions for walking. In the absence of evidence for physical therapists to employ these strategies, however, BWSTT and RAST should not be provided routinely to disabled, vulnerable persons in place of OGT outside of a scientifically conducted efficacy trial. PMID:22412172

Infrared neural stimulation of human spinal nerve roots in vivo.

PubMed

Cayce, Jonathan M; Wells, Jonathon D; Malphrus, Jonathan D; Kao, Chris; Thomsen, Sharon; Tulipan, Noel B; Konrad, Peter E; Jansen, E Duco; Mahadevan-Jansen, Anita

2015-01-01

Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients ([Formula: see text]) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and [Formula: see text]. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at [Formula: see text] and a [Formula: see text] safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans.

Should body weight-supported treadmill training and robotic-assistive steppers for locomotor training trot back to the starting gate?

PubMed

Dobkin, Bruce H; Duncan, Pamela W

2012-05-01

Body weight-supported treadmill training (BWSTT) and robotic-assisted step training (RAST) have not, so far, led to better outcomes than a comparable dose of progressive over-ground training (OGT) for disabled persons with stroke, spinal cord injury, multiple sclerosis, Parkinson's disease, or cerebral palsy. The conceptual bases for these promising rehabilitation interventions had once seemed quite plausible, but the results of well-designed, randomized clinical trials have been disappointing. The authors reassess the underpinning concepts for BWSTT and RAST, which were derived from mammalian studies of treadmill-induced hind-limb stepping associated with central pattern generation after low thoracic spinal cord transection, as well as human studies of the triple crown icons of task-oriented locomotor training, massed practice, and activity-induced neuroplasticity. The authors retrospectively consider where theory and practice may have fallen short in the pilot studies that aimed to produce thoroughbred interventions. Based on these shortcomings, the authors move forward with recommendations for the future development of workhorse interventions for walking. In the absence of evidence for physical therapists to employ these strategies, however, BWSTT and RAST should not be provided routinely to disabled, vulnerable persons in place of OGT outside of a scientifically conducted efficacy trial.

A comprehensive review with potential significance during skull base and neck operations, Part II: glossopharyngeal, vagus, accessory, and hypoglossal nerves and cervical spinal nerves 1-4.

PubMed

Shoja, Mohammadali M; Oyesiku, Nelson M; Shokouhi, Ghaffar; Griessenauer, Christoph J; Chern, Joshua J; Rizk, Elias B; Loukas, Marios; Miller, Joseph H; Tubbs, R Shane

2014-01-01

Knowledge of the possible neural interconnections found between the lower cranial and upper cervical nerves may prove useful to surgeons who operate on the skull base and upper neck regions in order to avoid inadvertent traction or transection. We review the literature regarding the anatomy, function, and clinical implications of the complex neural networks formed by interconnections between the lower cranial and upper cervical nerves. A review of germane anatomic and clinical literature was performed. The review is organized into two parts. Part I discusses the anastomoses between the trigeminal, facial, and vestibulocochlear nerves or their branches and other nerve trunks or branches in the vicinity. Part II deals with the anastomoses between the glossopharyngeal, vagus, accessory and hypoglossal nerves and their branches or between these nerves and the first four cervical spinal nerves; the contribution of the autonomic nervous system to these neural plexuses is also briefly reviewed. Part II is presented in this article. Extensive and variable neural anastomoses exist between the lower cranial nerves and between the upper cervical nerves in such a way that these nerves with their extra-axial communications can be collectively considered a plexus. Copyright © 2013 Wiley Periodicals, Inc.

Mobile acoustic transects miss rare bat species: implications of survey method and spatio-temporal sampling for monitoring bats

PubMed Central

Wallrichs, Megan A.; Ober, Holly K.; McCleery, Robert A.

2017-01-01

Due to increasing threats facing bats, long-term monitoring protocols are needed to inform conservation strategies. Effective monitoring should be easily repeatable while capturing spatio-temporal variation. Mobile acoustic driving transect surveys (‘mobile transects’) have been touted as a robust, cost-effective method to monitor bats; however, it is not clear how well mobile transects represent dynamic bat communities, especially when used as the sole survey approach. To assist biologists who must select a single survey method due to resource limitations, we assessed the effectiveness of three acoustic survey methods at detecting species richness in a vast protected area (Everglades National Park): (1) mobile transects, (2) stationary surveys that were strategically located by sources of open water and (3) stationary surveys that were replicated spatially across the landscape. We found that mobile transects underrepresented bat species richness compared to stationary surveys across all major vegetation communities and in two distinct seasons (dry/cool and wet/warm). Most critically, mobile transects failed to detect three rare bat species, one of which is federally endangered. Spatially replicated stationary surveys did not estimate higher species richness than strategically located stationary surveys, but increased the rate at which species were detected in one vegetation community. The survey strategy that detected maximum species richness and the highest mean nightly species richness with minimal effort was a strategically located stationary detector in each of two major vegetation communities during the wet/warm season. PMID:29134138

Global and segmental kinematic changes following sequential resection of posterior osteoligamentous structures in the lumbar spine: An in vitro biomechanical investigation using pure moment testing protocols.

PubMed

Chamoli, Uphar; Korkusuz, Mert H; Sabnis, Ashutosh B; Manolescu, Andrei R; Tsafnat, Naomi; Diwan, Ashish D

2015-11-01

Lumbar spinal surgeries may compromise the integrity of posterior osteoligamentous structures implicating mechanical stability. Circumstances necessitating a concomitant surgery to achieve restabilisation are not well understood. The main objective of this in vitro study was to quantify global and segmental (index and adjacent levels) kinematic changes in the lumbar spine following sequential resection of the posterior osteoligamentous structures using pure moment testing protocols. Six fresh frozen cadaveric kangaroo lumbar spines (T12-S1) were tested under a bending moment in flexion-extension, bilateral bending, and axial torsion in a 6-degree-of-freedom Kinematic Spine Simulator. Specimens were tested in the following order: intact state (D0), after interspinous and supraspinous ligaments transection between L4 and L5 (D1), further after a total bilateral facetectomy between L4 and L5 (D2). Segmental motions at the cephalad, damaged, and caudal levels were recorded using an infrared-based motion tracking device. Following D1, no significant change in the global range of motion was observed in any of the bending planes. Following D2, a significant increase in the global range of motion from the baseline (D0) was observed in axial torsion (median normalised change +20%). At the damaged level, D2 resulted in a significant increase in the segmental range of motion in flexion-extension (+77%) and axial torsion (+492%). Additionally, a significant decrease in the segmental range of motion in axial torsion (-35%) was observed at the caudal level following D2. These results suggest that a multi-segment lumbar spine acts as a mechanism for transmitting motions, and that a compromised joint may significantly alter motion transfer to adjacent segments. We conclude that the interspinous and supraspinous ligaments play a modest role in restricting global spinal motions within physiologic limits. Following interspinous and supraspinous ligaments transection, a total bilateral facetectomy resulted in a significant increase in axial torsion motion, both at global and damaged levels, accompanied with a compensatory decrease in motion at the caudal level. © IMechE 2015.

Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

PubMed Central

Sahin, Murat; Gullu, Huriye; Peker, Kemal; Sayar, Ilyas; Binici, Orhan; Yildiz, Huseyin

2015-01-01

The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia. PMID:26807119

Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

PubMed

Sahin, Murat; Gullu, Huriye; Peker, Kemal; Sayar, Ilyas; Binici, Orhan; Yildiz, Huseyin

2015-11-01

The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia.

Hypothalamic network for thermoregulatory shivering.

PubMed

Kanosue, K; Zhang, Y H; Yanase-Fujiwara, M; Hosono, T

1994-07-01

Warming one side of a rat's preoptic area and anterior hypothalamus (POAH) suppresses shivering on both sides of the body, and the present study evaluated the extent to which signals mediating this suppression cross the midline within and below the POAH. Hind paw shivering during unilateral POAH thermal stimulation was measured for rats in which the POAH had been midsagittally transected and for rats in which one side of the hypothalamus had been coronally transected just caudal to the POAH. In midsagittally transected rats, unilateral warming on either side of the POAH suppressed shivering equally on both sides of the body. In unilaterally transected rats, POAH warming on the transected side did not affect shivering, but warming the intact side suppressed shivering equally on both sides of the body. When a unilateral transection of only the lateral part of the hypothalamus included the medial forebrain bundle, the effect was the same as that of a unilateral transection of the whole hypothalamus. These results indicate that no information controlling shivering is exchanged between the left and right POAH and that efferent signals from the POAH, descending through the medial forebrain bundle, cross the midline somewhere below the hypothalamus to innervate both sides of the body equally.

Measure of pancreas transection and postoperative pancreatic fistula.

PubMed

Takahashi, Shinichiro; Gotohda, Naoto; Kato, Yuichiro; Konishi, Masaru

2016-05-15

In pancreaticoduodenectomy (PD), a standard protocol for pancreas transection has not been established although the method of pancreas transection might be involved in the occurrence of postoperative pancreatic fistula (POPF). This study aimed to compare whether pancreas transection by ultrasonically activated shears (UAS) or that by scalpel contributed more to POPF development. A prospective database of 171 patients who underwent PD for periampullary tumor at National Cancer Center Hospital East between January 2010 and June 2013 was reviewed. Among the 171 patients, 93 patients with soft pancreas were specifically included in this study. Surgical results and background were compared between patients with pancreas transection by UAS and scalpel to evaluate the effectiveness of UAS on reducing POPF. Body mass index, main pancreatic duct diameter, or other clinicopathologic factors that have been reported as predictive factors for POPF were not significantly different between the two groups. The incidence of all grades of POPF and that of grade B were significantly lower in the scalpel group (52%, 4%) than in the UAS group (74%, 42%). Postoperative complications ≥ grade III were also significantly fewer in the scalpel group. Scalpel transection was less associated with POPF than UAS transection in patients who underwent PD for soft pancreas. The method of pancreas transection plays an important role in the prevention of clinical POPF. Copyright © 2016 Elsevier Inc. All rights reserved.

Collagen/heparin sulfate scaffolds fabricated by a 3D bioprinter improved mechanical properties and neurological function after spinal cord injury in rats.

PubMed

Chen, Chong; Zhao, Ming-Liang; Zhang, Ren-Kun; Lu, Gang; Zhao, Chang-Yu; Fu, Feng; Sun, Hong-Tao; Zhang, Sai; Tu, Yue; Li, Xiao-Hong

2017-05-01

Effective treatments promoting axonal regeneration and functional recovery for spinal cord injury (SCI) are still in the early stages of development. Most approaches have been focused on providing supportive substrates for guiding neurons and overcoming the physical and chemical barriers to healing that arise after SCI. Although collagen has become a promising natural substrate with good compatibility, its low mechanical properties restrict its potential applications. The mechanical properties mainly rely on the composition and pore structure of scaffolds. For the composition of a scaffold, we used heparin sulfate to react with collagen by crosslinking. For the structure, we adopted a three-dimensional (3D) printing technology to fabricate a scaffold with a uniform pore distributions. We observed that the internal structure of the scaffold printed with a 3D bioprinter was regular and porous. We also found that both the compression modulus and strengths of the scaffold were significantly enhanced by the collagen/heparin sulfate composition compared to a collagen scaffold. Meanwhile, the collagen/heparin sulfate scaffold presented good biocompatibility when it was co-cultured with neural stem cells in vitro. We also demonstrated that heparin sulfate modification significantly improved bFGF immobilization and absorption to the collagen by examining the release kinetics of bFGF from scaffolds. Two months after implantating the scaffold into transection lesions in T10 of the spinal cord in rats, the collagen/heparin sulfate group demonstrated significant recovery of locomotor function and according to electrophysiological examinations. Parallel to functional recovery, collagen/heparin sulfate treatment further ameliorated the pathological process and markedly increased the number of neurofilament (NF) positive cells compared to collagen treatment alone. These data suggested that a collagen/heparin sulfate scaffold fabricated by a 3D bioprinter could enhance the mechanical properties of collagen and provide continuous guidance channels for axons, which would improve the neurological function after SCI. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1324-1332, 2017. © 2017 Wiley Periodicals, Inc.

[Urethroplasty with transection of urethral orifice and preservation and lengthening of urethral plate: highly applicable to the treatment of hypospadias].

PubMed

Wang, Wen-Min; Qiu, Wei-Feng; Qian, Chong

2010-07-01

To explore the feasibility of urethroplasty with transection of the urethral orifice and preservation and lengthening of the urethral plate in the treatment of hypospadias. Forty-eight patients with hypospadias (18 of the coronal type, 21 the penile type, 8 the penoscrotal type and 1 the perineal type) underwent urethroplasty with transection of the urethral orifice and preservation and lengthening of the urethral plate. The surgical effects were observed by following up the patients for 3-27 months. One-stage surgical success was achieved in 44 of the cases, with satisfactory functional and cosmetic results but no complications. Two cases developed urinary fistula and another 2 urethral stricture, but all cured by the second surgery. Urethroplasty with transection of the urethral orifice and preservation and lengthening of the urethral plate is a simple, safe and effective surgical procedure for the treatment of hypospadias.

Restoration of Hindlimb Movements after Complete Spinal Cord Injury Using Brain-Controlled Functional Electrical Stimulation.

PubMed

Knudsen, Eric B; Moxon, Karen A

2017-01-01

Single neuron and local field potential signals recorded in the primary motor cortex have been repeatedly demonstrated as viable control signals for multi-degree-of-freedom actuators. Although the primary source of these signals has been fore/upper limb motor regions, recent evidence suggests that neural adaptation underlying neuroprosthetic control is generalizable across cortex, including hindlimb sensorimotor cortex. Here, adult rats underwent a longitudinal study that included a hindlimb pedal press task in response to cues for specific durations, followed by brain machine interface (BMI) tasks in healthy rats, after rats received a complete spinal transection and after the BMI signal controls epidural stimulation (BMI-FES). Over the course of the transition from learned behavior to BMI task, fewer neurons were responsive after the cue, the proportion of neurons selective for press duration increased and these neurons carried more information. After a complete, mid-thoracic spinal lesion that completely severed both ascending and descending connections to the lower limbs, there was a reduction in task-responsive neurons followed by a reacquisition of task selectivity in recorded populations. This occurred due to a change in pattern of neuronal responses not simple changes in firing rate. Finally, during BMI-FES, additional information about the intended press duration was produced. This information was not dependent on the stimulation, which was the same for short and long duration presses during the early phase of stimulation, but instead was likely due to sensory feedback to sensorimotor cortex in response to movement along the trunk during the restored pedal press. This post-cue signal could be used as an error signal in a continuous decoder providing information about the position of the limb to optimally control a neuroprosthetic device.

Effect of partial and complete posterior cruciate ligament transection on medial meniscus: A biomechanical evaluation in a cadaveric model.

PubMed

Gao, Shu-Guang; Zhang, Can; Zhao, Rui-Bo; Liao, Zhan; Li, Yu-Sheng; Yu, Fang; Zeng, Chao; Luo, Wei; Li, Kang-Hua; Lei, Guang-Hua

2013-09-01

The relationship between medial meniscus tear and posterior cruciate ligament (PCL) injury has not been exactly explained. We studied to investigate the biomechanical effect of partial and complete PCL transection on different parts of medial meniscus at different flexion angles under static loading conditions. TWELVE FRESH HUMAN CADAVERIC KNEE SPECIMENS WERE DIVIDED INTO FOUR GROUPS: PCL intact (PCL-I), anterolateral bundle transection (ALB-T), posteromedial bundle transection (PMB-T) and PCL complete transection (PCL-T) group. Strain on the anterior horn, body part and posterior horn of medial meniscus were measured under different axial compressive tibial loads (200-800 N) at 0°, 30°, 60° and 90° knee flexion in each groups respectively. Compared with the PCL-I group, the PCL-T group had a higher strain on whole medial meniscus at 30°, 60° and 90° flexion in all loading conditions and at 0° flexion with 400, 600 and 800 N loads. In ALB-T group, strain on whole meniscus increased at 30°, 60° and 90° flexion under all loading conditions and at 0° flexion with 800 N only. PMB-T exihibited higher strain at 0° flexion with 400 N, 600 N and 800 N, while at 30° and 60° flexion with 800 N and at 90° flexion under all loading conditions. Partial PCL transection triggers strain concentration on medial meniscus and the effect is more pronounced with higher loading conditions at higher flexion angles.

Can roads be used as transects for primate population surveys?.

PubMed

Hilário, Renato R; Rodrigues, Flávio H G; Chiarello, Adriano G; Mourthé, Italo

2012-01-01

Line transect distance sampling (LTDS) can be applied to either trails or roads. However, it is likely that sampling along roads might result in biased density estimates. In this paper, we compared the results obtained with LTDS applied on trails and roads for two primate species (Callithrix penicillata and Callicebus nigrifrons) to clarify whether roads are appropriate transects to estimate densities. We performed standard LTDS surveys in two nature reserves in south-eastern Brazil. Effective strip width and population density were different between trails and roads for C. penicillata, but not for C. nigrifrons. The results suggest that roads are not appropriate for use as transects in primate surveys, at least for some species. Further work is required to fully understand this issue, but in the meantime we recommend that researchers avoid using roads as transects or treat roads and trails as covariates when sampling on roads is unavoidable. Copyright © 2012 S. Karger AG, Basel.

Enhancing fish Underwater Visual Census to move forward assessment of fish assemblages: An application in three Mediterranean Marine Protected Areas

PubMed Central

Thiriet, Pierre; Di Franco, Antonio; Francour, Patrice

2017-01-01

Monitoring fish assemblages is needed to assess whether Marine Protected Areas (MPAs) are meeting their conservation and fisheries management goals, as it allows one to track the progress of recovery of exploited species and associated communities. Underwater Visual Census techniques (UVC) are used to monitor fish assemblages in MPAs. UVCs should be adapted to fish abundance, body-size and behaviour, which can strongly affect fish detectability. In Mediterranean subtidal habitats, however, UVC strip transects of one surface area (25x5 m2) are commonly used to survey the whole fish assemblage, from large shy fish to small crypto-benthic fish. Most high trophic level predators (HTLPs) are large shy fish which rarely swim close to divers and, consequently, their abundance may be under-estimated with commonly used transects. Here, we propose an improvement to traditional transect surveys to better account for differences in behaviour among and within species. First, we compared the effectiveness of combining two transect surface areas (large: 35x20 m2; medium: 25x5 m2) in quantifying large, shy fish within and outside Mediterranean MPAs. We identified species-specific body-size thresholds defining a smaller and a larger size class better sampled by medium and large transects respectively. Combining large and medium transects provided more accurate biomass and species richness estimates for large, shy species than using medium transects alone. We thus combined the new approach with two other transect surface areas commonly used to survey crypto-benthic (10x1 m2) and necto-benthic (25x5 m2) species in order to assess how effectively MPAs protection the whole fish assemblage. We verified that MPAs offer significant protection for HTLPs, their response in terms of biomass and density increase in MPAs was always higher in magnitude than other functional groups. Inside MPAs, the contribution of HTLP reached >25% of total fish biomass, against < 2% outside MPAs. Surveys with multiple transect surface areas allow for a more realistic assessment of the structure of the whole fish assemblage and better assessment of potential recovery of HTLPs within reserves of HTLP. PMID:28594836

Enhancing fish Underwater Visual Census to move forward assessment of fish assemblages: An application in three Mediterranean Marine Protected Areas.

PubMed

Prato, Giulia; Thiriet, Pierre; Di Franco, Antonio; Francour, Patrice

2017-01-01

Monitoring fish assemblages is needed to assess whether Marine Protected Areas (MPAs) are meeting their conservation and fisheries management goals, as it allows one to track the progress of recovery of exploited species and associated communities. Underwater Visual Census techniques (UVC) are used to monitor fish assemblages in MPAs. UVCs should be adapted to fish abundance, body-size and behaviour, which can strongly affect fish detectability. In Mediterranean subtidal habitats, however, UVC strip transects of one surface area (25x5 m2) are commonly used to survey the whole fish assemblage, from large shy fish to small crypto-benthic fish. Most high trophic level predators (HTLPs) are large shy fish which rarely swim close to divers and, consequently, their abundance may be under-estimated with commonly used transects. Here, we propose an improvement to traditional transect surveys to better account for differences in behaviour among and within species. First, we compared the effectiveness of combining two transect surface areas (large: 35x20 m2; medium: 25x5 m2) in quantifying large, shy fish within and outside Mediterranean MPAs. We identified species-specific body-size thresholds defining a smaller and a larger size class better sampled by medium and large transects respectively. Combining large and medium transects provided more accurate biomass and species richness estimates for large, shy species than using medium transects alone. We thus combined the new approach with two other transect surface areas commonly used to survey crypto-benthic (10x1 m2) and necto-benthic (25x5 m2) species in order to assess how effectively MPAs protection the whole fish assemblage. We verified that MPAs offer significant protection for HTLPs, their response in terms of biomass and density increase in MPAs was always higher in magnitude than other functional groups. Inside MPAs, the contribution of HTLP reached >25% of total fish biomass, against < 2% outside MPAs. Surveys with multiple transect surface areas allow for a more realistic assessment of the structure of the whole fish assemblage and better assessment of potential recovery of HTLPs within reserves of HTLP.

Musashi and Plasticity of Xenopus and Axolotl Spinal Cord Ependymal Cells

PubMed Central

Chernoff, Ellen A. G.; Sato, Kazuna; Salfity, Hai V. N.; Sarria, Deborah A.; Belecky-Adams, Teri

2018-01-01

The differentiated state of spinal cord ependymal cells in regeneration-competent amphibians varies between a constitutively active state in what is essentially a developing organism, the tadpole of the frog Xenopus laevis, and a quiescent, activatable state in a slowly growing adult salamander Ambystoma mexicanum, the Axolotl. Ependymal cells are epithelial in intact spinal cord of all vertebrates. After transection, body region ependymal epithelium in both Xenopus and the Axolotl disorganizes for regenerative outgrowth (gap replacement). Injury-reactive ependymal cells serve as a stem/progenitor cell population in regeneration and reconstruct the central canal. Expression patterns of mRNA and protein for the stem/progenitor cell-maintenance Notch signaling pathway mRNA-binding protein Musashi (msi) change with life stage and regeneration competence. Msi-1 is missing (immunohistochemistry), or at very low levels (polymerase chain reaction, PCR), in both intact regeneration-competent adult Axolotl cord and intact non-regeneration-competent Xenopus tadpole (Nieuwkoop and Faber stage 62+, NF 62+). The critical correlation for successful regeneration is msi-1 expression/upregulation after injury in the ependymal outgrowth and stump-region ependymal cells. msi-1 and msi-2 isoforms were cloned for the Axolotl as well as previously unknown isoforms of Xenopus msi-2. Intact Xenopus spinal cord ependymal cells show a loss of msi-1 expression between regeneration-competent (NF 50–53) and non-regenerating stages (NF 62+) and in post-metamorphosis froglets, while msi-2 displays a lower molecular weight isoform in non-regenerating cord. In the Axolotl, embryos and juveniles maintain Msi-1 expression in the intact cord. In the adult Axolotl, Msi-1 is absent, but upregulates after injury. Msi-2 levels are more variable among Axolotl life stages: rising between late tailbud embryos and juveniles and decreasing in adult cord. Cultures of regeneration-competent Xenopus tadpole cord and injury-responsive adult Axolotl cord ependymal cells showed an identical growth factor response. Epidermal growth factor (EGF) maintains mesenchymal outgrowth in vitro, the cells are proliferative and maintain msi-1 expression. Non-regeneration competent Xenopus ependymal cells, NF 62+, failed to attach or grow well in EGF+ medium. Ependymal Msi-1 expression in vivo and in vitro is a strong indicator of regeneration competence in the amphibian spinal cord. PMID:29535610

Effect of Hurricane Hugo on molluscan skeletal distributions,Salt River Bay, St. Croix, U.S. Virgin Islands

NASA Astrophysics Data System (ADS)

Miller, Arnold I.; Llewellyn, Ghislaine; Parsons, Karla M.; Cummins, Hays; Boardman, Mark R.; Greenstein, Benjamin J.; Jacobs, David K.

1992-01-01

Just prior to the passage of Hurricane Hugo over St. Croix, U.S. Virgin Islands, 35 molluscan skeletal samples were collected at 30 m intervals along a sampling transect in Salt River Bay, on the north-central coast. Three months after the hurricane, the transect was resampled to permit direct assessment of storm effects on skeletal distributions. Results indicate that spatial zonation of molluscan accumulations, associated with environmental transitions along the transect, was maintained in the wake of the hurricane. However, limited transport was diagnosed by comparing the compositions of prestorm and poststorm samples from the deepest, mud-rich subenvironment on the transect. In aggregate, the species richness of samples from the southern half of this zone increased from 16 to 40, and the abundance of species that were not among the characteristic molluscs of this subenvironment increased from 11% to 26%. These storm effects could probably not have been recognized, and attributed directly to Hugo, had there been no prestorm samples with which to compare directly the poststorm samples.

Effect of Chorda Tympani Nerve Transection on Salt Taste Perception in Mice

PubMed Central

Ishiwatari, Yutaka; Theodorides, Maria L.; Bachmanov, Alexander A.

2011-01-01

Effects of gustatory nerve transection on salt taste have been studied extensively in rats and hamsters but have not been well explored in the mouse. We examined the effects of chorda tympani (CT) nerve transection on NaCl taste preferences and thresholds in outbred CD-1 mice using a high-throughput phenotyping method developed in our laboratory. To measure taste thresholds, mice were conditioned by oral self-administration of LiCl or NaCl and then presented with NaCl concentration series in 2-bottle preference tests. LiCl-conditioned and control NaCl-exposed mice were given bilateral transections of the CT nerve (LiCl-CTX, NaCl-CTX) or were left intact as controls (LiCl-CNT, NaCl-CNT). After recovery from surgery, mice received a concentration series of NaCl (0–300 mM) in 48-h 2-bottle tests. CT transection increased NaCl taste thresholds in LiCl-conditioned mice and eliminated avoidance of concentrated NaCl in control NaCl-exposed mice. This demonstrates that in mice, the CT nerve is important for detection and recognition of NaCl taste and is necessary for the normal avoidance of high concentrations of NaCl. The results of this experiment also show that the method of high-throughput phenotyping of salt taste thresholds is suitable for detecting changes in the taste periphery in mouse genetic studies. PMID:21743094

The central nervous system (CNS)-independent anti-bone-resorptive activity of muscle contraction and the underlying molecular and cellular signatures.

PubMed

Qin, Weiping; Sun, Li; Cao, Jay; Peng, Yuanzhen; Collier, Lauren; Wu, Yong; Creasey, Graham; Li, Jianhua; Qin, Yiwen; Jarvis, Jonathan; Bauman, William A; Zaidi, Mone; Cardozo, Christopher

2013-05-10

Mechanisms by which muscle regulates bone are poorly understood. Electrically stimulated muscle contraction reversed elevations in bone resorption and increased Wnt signaling in bone-derived cells after spinal cord transection. Muscle contraction reduced resorption of unloaded bone independently of the CNS, through mechanical effects and, potentially, nonmechanical signals (e.g. myokines). The study provides new insights regarding muscle-bone interactions. Muscle and bone work as a functional unit. Cellular and molecular mechanisms underlying effects of muscle activity on bone mass are largely unknown. Spinal cord injury (SCI) causes muscle paralysis and extensive sublesional bone loss and disrupts neural connections between the central nervous system (CNS) and bone. Muscle contraction elicited by electrical stimulation (ES) of nerves partially protects against SCI-related bone loss. Thus, application of ES after SCI provides an opportunity to study the effects of muscle activity on bone and roles of the CNS in this interaction, as well as the underlying mechanisms. Using a rat model of SCI, the effects on bone of ES-induced muscle contraction were characterized. The SCI-mediated increase in serum C-terminal telopeptide of type I collagen (CTX) was completely reversed by ES. In ex vivo bone marrow cell cultures, SCI increased the number of osteoclasts and their expression of mRNA for several osteoclast differentiation markers, whereas ES significantly reduced these changes; SCI decreased osteoblast numbers, but increased expression in these cells of receptor activator of NF-κB ligand (RANKL) mRNA, whereas ES increased expression of osteoprotegerin (OPG) and the OPG/RANKL ratio. A microarray analysis revealed that ES partially reversed SCI-induced alterations in expression of genes involved in signaling through Wnt, FSH, parathyroid hormone (PTH), oxytocin, and calcineurin/nuclear factor of activated T-cells (NFAT) pathways. ES mitigated SCI-mediated increases in mRNA levels for the Wnt inhibitors DKK1, sFRP2, and sclerostin in ex vivo cultured osteoblasts. Our results demonstrate an anti-bone-resorptive activity of muscle contraction by ES that develops rapidly and is independent of the CNS. The pathways involved, particularly Wnt signaling, suggest future strategies to minimize bone loss after immobilization.

The effect of changes to the method of estimating the pollen count from aerobiological samples.

PubMed

Sikoparija, Branko; Pejak-Šikoparija, Tatjana; Radišić, Predrag; Smith, Matt; Soldevilla, Carmen Galán

2011-02-01

Pollen data have been recorded at Novi Sad in Serbia since 2000. The adopted method of producing pollen counts has been the use of five longitudinal transects that examine 19.64% of total sample surface. However, counting five transects is time consuming and so the main objective of this study is to investigate whether reducing the number to three or even two transects would have a significant effect on daily average and bi-hourly pollen concentrations, as well as the main characteristics of the pollen season and long-term trends. This study has shown that there is a loss of accuracy in daily average and bi-hourly pollen concentrations (an increase in % ERROR) as the sub-sampling area is reduced from five to three or two longitudinal transects. However, this loss of accuracy does not impact on the main characteristics of the season or long-term trends. As a result, this study can be used to justify changing the sub-sampling method used at Novi Sad from five to three longitudinal transects. The use of two longitudinal transects has been ruled out because, although quicker, the counts produced: (a) had the greatest amount of % ERROR, (b) altered the amount of influence of the independent variable on the dependent variable (the slope in regression analysis) and (c) the total sampled surface (7.86%) was less than the minimum requirement recommended by the European Aerobiology Society working group on Quality Control (at least 10% of total slide area).

Gene Therapy for Neuropathic Pain by Silencing of TNF-α Expression with Lentiviral Vectors Targeting the Dorsal Root Ganglion in Mice

PubMed Central

Ogawa, Nobuhiro; Kawai, Hiromichi; Terashima, Tomoya; Kojima, Hideto; Oka, Kazuhiro; Chan, Lawrence; Maegawa, Hiroshi

2014-01-01

Neuropathic pain can be a debilitating condition. Many types of drugs that have been used to treat neuropathic pain have only limited efficacy. Recent studies indicate that pro-inflammatory mediators including tumor necrosis factor α (TNF-α) are involved in the pathogenesis of neuropathic pain. In the present study, we engineered a gene therapy strategy to relieve neuropathic pain by silencing TNF-α expression in the dorsal root ganglion (DRG) using lentiviral vectors expressing TNF short hairpin RNA1-4 (LV-TNF-shRNA1-4) in mice. First, based on its efficacy in silencing TNF-α in vitro, we selected shRNA3 to construct LV-TNF-shRNA3 for in vivo study. We used L5 spinal nerve transection (SNT) mice as a neuropathic pain model. These animals were found to display up-regulated mRNA expression of activating transcription factor 3 (ATF3) and neuropeptide Y (NPY), injury markers, and interleukin (IL)-6, an inflammatory cytokine in the ipsilateral L5 DRG. Injection of LV-TNF-shRNA3 onto the proximal transected site suppressed significantly the mRNA levels of ATF3, NPY and IL-6, reduced mechanical allodynia and neuronal cell death of DRG neurons. These results suggest that lentiviral-mediated silencing of TNF-α in DRG relieves neuropathic pain and reduces neuronal cell death, and may constitute a novel therapeutic option for neuropathic pain. PMID:24642694

Infrared neural stimulation of human spinal nerve roots in vivo

PubMed Central

Cayce, Jonathan M.; Wells, Jonathon D.; Malphrus, Jonathan D.; Kao, Chris; Thomsen, Sharon; Tulipan, Noel B.; Konrad, Peter E.; Jansen, E. Duco; Mahadevan-Jansen, Anita

2015-01-01

Abstract. Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients (n=7) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and 1.23  J/cm2. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at 1.09  J/cm2 and a 2∶1 safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans. PMID:26157986

Properties and connections of cat fastigiospinal neurons.

PubMed

Wilson, V J; Uchino, Y; Maunz, R A; Susswein, A; Fukushima, K

1978-05-12

1. Neurons in the cat fastigial nucleus that project to the upper cervical spinal segments (fastigiospinal neurons) were fired by antidromic stimulation of the contralateral spinal cord. Dye ejection from the recording electrode was used to show that most neurons were in the rostral half of the fastigial nucleus. 2. Fastigiospinal neurons can be excited and/or inhibited by stimulation of forelimb and hindlimb nerves and by stimulation of the vestibular nerve. These inputs converge on many neurons. 3. Antidromic microstimulation was used to trace fastigiospinal axons to the vicinity of motor nuclei in in C2-C3. 4. The rostral fastigial nucleus was stimulated in preparations with the medial longitudinal fasciculus transected by a wide lesion that impinged on the medial reticular formation in the caudal medulla, to eliminate some potential axon reflexes. Short-latency EPSPs were recorded in some trapezius and biventer-cervicis motoneurons. In many cases there was little or no occlusion between these EPSPs and others evoked by stimulation of the vestibular nerve ipsilateral to the motoneurons. 5. Movement of the stimulating electrode and placement of this electrode lateral to the fastigial nucleus show that the zone from which low threshold EPSPs can be evoked is localized. 6. Latency measurements and lack of temporal facilitation with double shocks suggest that the EPSPs are monosynaptic. The evidence suggests that they are caused by fastigiospinal fibers terminating on motoneurons.

Use of the transect method in satellite survey missions with application to the infrared astronomical satellite /IRAS/

NASA Technical Reports Server (NTRS)

Mclaughlin, W. I.; Lundy, S. A.; Ling, H. Y.; Stroberg, M. W.

1980-01-01

The coverage of the celestial sphere or the surface of the earth with a narrow-field instrument onboard a satellite can be described by a set of swaths on the sphere. A transect is a curve on this sphere constructed to sample the coverage. At each point on the transect the number of times that the field-of-view of the instrument has passed over the point is recorded. This information is conveniently displayed as an integer-valued histogram over the length of the transect. The effectiveness of the transect method for a particular observing plan and the best placement of the transects depends upon the structure of the set of observations. Survey missions are usually characterized by a somewhat parallel alignment of the instrument swaths. Using autocorrelation and cross-correlation functions among the histograms the structure of a survey has been analyzed into two components, and each is illustrated by a simple mathematical model. The complex, all-sky survey to be performed by the Infrared Astronomical Satellite (IRAS) is synthesized in some detail utilizing the objectives and constraints of that mission. It is seen that this survey possesses the components predicted by the simple models and this information is useful in characterizing the properties of the IRAS survey and the placement of the transects as a function of celestial latitude and certain structural properties of the coverage.

Long-Term Effects of Beach Nourishment on the Benthic Fauna of Panama City Beach, Florida.

DTIC Science & Technology

1982-01-01

gradual. The continental shelf in this area is not nearly as wide as it is in most areas of the Gulf of Mexico. i0 - ------ The segment of gulf...Lookout Street and Spyglass Street; transect 4 is offshore of the Holiday Inn West; transect 5 is offshore of the Fiesta Motel; transect 6 is off- shore...Region, Puerto Rico and the Virgin Islands," Atlanta, Ga., 1971. WHITTAKER, R.H., "Gradient Analysis of Vegetation," Biological Review, Vol. 49, 1967

Evaluating the effects of check dams on channel geometry, bed sediment size and riparian vegetation in Mediterranean mountain torrents.

PubMed

Zema, Demetrio Antonio; Bombino, Giuseppe; Denisi, Pietro; Lucas-Borja, Manuel Esteban; Zimbone, Santo Marcello

2018-06-12

In mountain streams possible negative impacts of check dams on soil, water and riparian vegetation due to check dam installation can be noticed. In spite of the ample literature on the qualitative effects of engineering works on channel hydrology, morphology, sedimentary effects and riparian vegetation characteristics, quantitative evaluations of the changes induced by check dams on headwater characteristics are rare. In order to fill this gap, this study has evaluated the effects of check dams located in headwaters of Calabria (Southern Italy) on hydrological and geomorphological processes and on the response of riparian vegetation to these actions. The analysis has compared physical and vegetation indicators in transects identified around check dams (upstream and downstream) and far from their direct influence (control transects). Check dams were found to influence significantly unit discharge, surface and subsurface sediments (both upstream and downstream), channel shape and transverse distribution of riparian vegetation (upstream) as well as cover and structure of riparian complexes (downstream). The actions of the structures on torrent longitudinal slope and biodiversity of vegetation were less significant. The differences on bed profile slope were significant only between upstream and downstream transects. The results of the Agglomerative Hierarchical Cluster analysis confirmed the substantial similarity between upstream and control transects, thus highlighting that the construction of check dams, needed to mitigate the hydro-geological risks, has not strongly influenced the torrent functioning and ecology before check dam construction. Moreover, simple and quantitative linkages between torrent hydraulics, geomorphology and vegetation characteristics exist in the analysed headwaters; these relationships among physical adjustments of channels and most of the resulting characteristics of the riparian vegetation are specific for the transect locations with respect of check dams. Conversely, the biodiversity of the riparian vegetation basically eludes any quantitative relations with the physical and other vegetal characteristics of the torrent transects. Copyright © 2018 Elsevier B.V. All rights reserved.

Altered spinal microRNA-146a and the microRNA-183 cluster contribute to osteoarthritic pain in knee joints.

PubMed

Li, Xin; Kroin, Jeffrey S; Kc, Ranjan; Gibson, Gary; Chen, Di; Corbett, Grant T; Pahan, Kalipada; Fayyaz, Sana; Kim, Jae-Sung; van Wijnen, Andre J; Suh, Joon; Kim, Su-Gwan; Im, Hee-Jeong

2013-12-01

The objective of this study was to examine whether altered expression of microRNAs in central nervous system components is pathologically linked to chronic knee joint pain in osteoarthritis. A surgical animal model for knee joint OA was generated by medial meniscus transection in rats followed by behavioral pain tests. Relationships between pathological changes in knee joint and development of chronic joint pain were examined by histology and imaging analyses. Alterations in microRNAs associated with OA-evoked pain sensation were determined in bilateral lumbar dorsal root ganglia (DRG) and the spinal dorsal horn by microRNA array followed by individual microRNA analyses. Gain- and loss-of-function studies of selected microRNAs (miR-146a and miR-183 cluster) were conducted to identify target pain mediators regulated by these selective microRNAs in glial cells. The ipsilateral hind leg displayed significantly increased hyperalgesia after 4 weeks of surgery, and sensitivity was sustained for the remainder of the 8-week experimental period (F = 341, p < 0.001). The development of OA-induced chronic pain was correlated with pathological changes in the knee joints as assessed by histological and imaging analyses. MicroRNA analyses showed that miR-146a and the miR-183 cluster were markedly reduced in the sensory neurons in DRG (L4/L5) and spinal cord from animals experiencing knee joint OA pain. The downregulation of miR-146a and/or the miR-183 cluster in the central compartments (DRG and spinal cord) are closely associated with the upregulation of inflammatory pain mediators. The corroboration between decreases in these signature microRNAs and their specific target pain mediators were further confirmed by gain- and loss-of-function analyses in glia, the major cellular component of the central nervous system (CNS). MicroRNA therapy using miR-146a and the miR-183 cluster could be powerful therapeutic intervention for OA in alleviating joint pain and concomitantly regenerating peripheral knee joint cartilage. © 2013 American Society for Bone and Mineral Research.

Identifying motor and sensory myelinated axons in rabbit peripheral nerves by histochemical staining for carbonic anhydrase and cholinesterase activities

NASA Technical Reports Server (NTRS)

Riley, Danny A.; Sanger, James R.; Matloub, Hani S.; Yousif, N. John; Bain, James L. W.

1988-01-01

Carbonic anhydrase (CA) and cholinesterase (CE) histochemical staining of rabbit spinal nerve roots and dorsal root ganglia demonstrated that among the reactive myeliated axons, with minor exceptions, sensory axons were CA positive and CE negative whereas motor axons were CA negative and CE positive. The high specificity was achieved by adjusting reaction conditions to stain subpopulations of myelinated axons selectively while leaving 50 percent or so unstained. Fixation with glutaraldehyde appeared necessary for achieving selectivity. Following sciatic nerve transection, the reciprocal staining pattern persisted in damaged axons and their regenerating processes which formed neuromas within the proximal nerve stump. Within the neuromas, CA-stained sensory processes were elaborated earlier and in greater numbers than CE-stained regenerating motor processes. The present results indicate that histochemical axon typing can be exploited to reveal heterogeneous responses of motor and sensory axons to injury.

Spinal anesthesia in infants: recent developments.

PubMed

Tirmizi, Henna

2015-06-01

Spinal anesthesia has long been described as a well-tolerated and effective means of providing anesthesia for infants undergoing lower abdominal surgery. Now, spinal anesthetics are being used for an increasing variety of surgeries previously believed to require a general anesthetic. This, along with increasing concerns over the neurocognitive effects of general anesthetics on developing brains, suggests that further exploration into this technique and its effects is essential. Exposure to spinal anesthesia in infancy has not shown the same suggestions of neurocognitive detriment as those resulting from general anesthesia. Ultrasound guidance has enhanced spinal technique by providing real-time guidance into the intrathecal space and confirming medication administration location, as well as helping avoid adverse outcomes by identifying aberrant anatomy. Spinal anesthesia provides benefits over general anesthesia, including cardiorespiratory stability, shorter postoperative recovery, and faster return of gastrointestinal function. Early findings of spinal anesthesia exposure in infancy have shown it to have no independent effect on neurocognitive delay as well as to provide sound cardiorespiratory stability. With safer means of administering a spinal anesthetic, such as with ultrasound guidance, it is a readily available and desirable tool for those providing anesthesia to infants.

Statistical and Multifractal Evaluation of Soil Compaction in a Vineyard

NASA Astrophysics Data System (ADS)

Marinho, M.; Raposo, J. R.; Mirás Avalos, J. M.; Paz González, A.

2012-04-01

One of the detrimental effects caused by agricultural machines is soil compaction, which can be defined by an increase in soil bulk density. Soil compaction often has a negative impact on plant growth, since it reduces the macroporosity and soil permeability and increases resistance to penetration. Our research explored the effect of the agricultural machinery on soil when trafficking through a vineyard at a small spatial scale, based on the evaluation of the soil compaction status. The objectives of this study were: i) to quantify soil bulk density along transects following wine row, wheel track and outside track, and, ii) to characterize the variability of the bulk density along these transects using multifractal analysis. The field work was conducted at the experimental farm of EVEGA (Viticulture and Enology Centre of Galicia) located in Ponte San Clodio, Leiro, Orense, Spain. Three parallel transects were marked on positions with contrasting machine traffic effects, i.e. vine row, wheel-track and outside-track. Undisturbed samples were collected in 16 points of each transect, spaced 0.50 m apart, for bulk density determination using the cylinder method. Samples were taken in autumn 2011, after grape harvest. Since soil between vine rows was tilled and homogenized beginning spring 2011, cumulative effects of traffic during the vine growth period could be evaluated. The distribution patterns of soil bulk density were characterized by multifractal analysis carried out by the method of moments. Multifractality was assessed by several indexes derived from the mass exponent, τq, the generalized dimension, Dq, and the singularity spectrum, f(α), curves. Mean soil bulk density values determined for vine row, outside-track and wheel-track transects were 1.212 kg dm-3, 1.259 kg dm-3and 1.582 kg dm-3, respectively. The respective coefficients of variation (CV) for these three transects were 7.76%, 4.82% and 2.03%. Therefore mean bulk density under wheel-track was 30.5% higher than along the vine row. Vine row and outside-track positions showed not significant differences between means. The bulk density of the wheel-track transect also showed the lowest CV. The multifractal spectra of the three transects were asymmetric curves, rather short toward the left and much longer toward the right. The width of the right deviating shaped multifractal spectra was ranked as: wine row > outside-track ≈ wheel-track. Entropy dimension, D1, was 0.998, 0.992 and 0.992 for vine row, outside-track and track transects, respectively. These results show different patterns of variability of bulk density for parallel transects. They also suggest that multifractal parameters may be useful in assessing the variability of other soil properties such as soil particle density, soil porosity or soil water content, at different spatial scales as well. Acknowledgments. This work was funded in part by Spanish Ministry of Science and Innovation (MICINN) in the frame of project CGL2009-13700-C02. Financial support from CAPES/GOV., Brazil, is also acknowledged by Prof. M. Marinho.

Edge Effects in Line Intersect Sampling With

Treesearch

David L. R. Affleck; Timothy G. Gregoire; Harry T. Valentine

2005-01-01

Transects consisting of multiple, connected segments with a prescribed configuration are commonly used in ecological applications of line intersect sampling. The transect configuration has implications for the probability with which population elements are selected and for how the selection probabilities can be modified by the boundary of the tract being sampled. As...

Lycopene ameliorates neuropathic pain by upregulating spinal astrocytic connexin 43 expression.

PubMed

Zhang, Fang Fang; Morioka, Norimitsu; Kitamura, Tomoya; Fujii, Shiori; Miyauchi, Kazuki; Nakamura, Yoki; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

2016-06-15

Peripheral nerve injury upregulates tumor necrosis factor (TNF) expression. In turn, connexin 43 (Cx43) expression in spinal astrocytes is downregulated by TNF. Therefore, restoration of spinal astrocyte Cx43 expression to normal level could lead to the reduction of nerve injury-induced pain. While the non-provitaminic carotenoid lycopene reverses thermal hyperalgesia in mice with painful diabetic neuropathy, the antinociceptive mechanism is not entirely clear. The current study evaluated whether the antinociceptive effect of lycopene is mediated through the modulation of Cx43 expression in spinal astrocytes. The effect of lycopene on Cx43 expression was examined in cultured rat spinal astrocytes. The effect of intrathecal lycopene on Cx43 expression and neuropathic pain were evaluated in mice with partial sciatic nerve ligation (PSNL). Treatment of cultured rat spinal astrocytes with lycopene reversed TNF-induced downregulation of Cx43 protein expression through a transcription-independent mechanism. By contrast, treatment of cultured spinal astrocytes with either pro-vitamin A carotenoid β-carotene or antioxidant N-acetyl cysteine had no effect on TNF-induced downregulation of Cx43 protein expression. In addition, repeated, but not single, intrathecal treatment with lycopene of mice with a partial sciatic nerve ligation significantly prevented not only the downregulation of Cx43 expression in spinal dorsal horn but mechanical hypersensitivity as well. The current findings suggest a significant spinal mechanism that mediates the analgesic effect of lycopene, through the restoration of normal spinal Cx43 expression. Copyright © 2016 Elsevier Inc. All rights reserved.

Passive immunization of fetal rats with antiserum to luteinizing hormone-releasing hormone (LHRH) or transection of the central roots of the nervus terminalis does not affect rat pups' preference for home nest.

PubMed

Schwanzel-Fukuda, M; Pfaff, D W

1987-01-01

Luteinizing hormone-releasing hormone (LHRH) is found immunocytochemically in cell bodies and fibers of the nervus terminalis, a cranial nerve which courses from the nasal septum through the cribriform plate of the ethmoid bone (medial to the olfactory and vomeronasal nerves) and enters the forebrain, caudal to the olfactory bulbs. Immunoreactive LHRH is first detected in the nervus terminalis of the fetal rat at 15 days of gestation, preceding its detection by immunocytochemistry in any other area of the brain, including the median eminence, and preceding detection of immunoreactive luteinizing hormone (LH) in the anterior pituitary. During development of the rat fetus, the nervus terminalis is the principal source of LHRH in the nervous system from days 15 through 19 of a 21 day gestation period. We tested the notion that the LHRH system of the nervus terminalis is important for olfactory performance by examining the effects of administration of antisera to LHRH during fetal development (versus saline controls), or medial olfactory peduncle transections, in the neonatal rat, which would sever the central projections of the nervus terminalis (versus lateral peduncle transection, complete transection of the olfactory peduncles and the central nervus terminalis or controls) on preferences of rat pups for home nest. The hypothesis that LHRH is important for this chemosensory response was not confirmed. Neither antisera to LHRH nor medical olfactory peduncle transection disrupted preference for home shavings. Only complete olfactory peduncle transection had a significant effect compared to unoperated and sham-operated controls.

Inhibition of spinal astrocytic c-Jun N-terminal kinase (JNK) activation correlates with the analgesic effects of ketamine in neuropathic pain

PubMed Central

2011-01-01

Background We have previously reported that inhibition of astrocytic activation contributes to the analgesic effects of intrathecal ketamine on spinal nerve ligation (SNL)-induced neuropathic pain. However, the underlying mechanisms are still unclear. c-Jun N-terminal kinase (JNK), a member of mitogen-activated protein kinase (MAPK) family, has been reported to be critical for spinal astrocytic activation and neuropathic pain development after SNL. Ketamine can decrease lipopolysaccharide (LPS)-induced phosphorylated JNK (pJNK) expression and could thus exert its anti-inflammatory effect. We hypothesized that inhibition of astrocytic JNK activation might be involved in the suppressive effect of ketamine on SNL-induced spinal astrocytic activation. Methods Immunofluorescence histochemical staining was used to detect SNL-induced spinal pJNK expression and localization. The effects of ketamine on SNL-induced mechanical allodynia were confirmed by behavioral testing. Immunofluorescence histochemistry and Western blot were used to quantify the SNL-induced spinal pJNK expression after ketamine administration. Results The present study showed that SNL induced ipsilateral pJNK up-regulation in astrocytes but not microglia or neurons within the spinal dorsal horn. Intrathecal ketamine relieved SNL-induced mechanical allodynia without interfering with motor performance. Additionally, intrathecal administration of ketamine attenuated SNL-induced spinal astrocytic JNK activation in a dose-dependent manner, but not JNK protein expression. Conclusions The present results suggest that inhibition of JNK activation may be involved in the suppressive effects of ketamine on SNL-induced spinal astrocyte activation. Therefore, inhibition of spinal JNK activation may be involved in the analgesic effects of ketamine on SNL-induced neuropathic pain. PMID:21255465

Effects of excluding goat herbivory on Acacia tortilis woodland around pastoralist settlements in northwest Kenya

NASA Astrophysics Data System (ADS)

Oba, Gufu

1998-08-01

Browsing by goats is considered to cause poor tree regeneration and reduced tree growth around settlements throughout the arid zones of sub-Saharan Africa. This study investigated whether excluding goats from Acacia tortilis woodlands increased tree regeneration, current season's shoot growth rates and browse production over a period of 52 months between 1986 and 1990. The study also investigated the effects of climatic variability on tree growth and browse production. Excluding goat herbivory provided no advantage over continuous browsing for juvenile A. tortilis. Trees on the unbrowsed and on browsed transects increased by 22.2 (standard error [SE] ± 0.53) cm·yr -1 and 25.0 (SE ± 0.58) cm·yr -1, respectively. Fewer but longer shoots were produced by trees on the unbrowsed transects, while trees on the browsed transects invested more in shorter shoots. Net total browse production was lower on unbrowsed (1.73 [standard deviation (SD) ± 4.3] t·ha -1·yr -1) than on the browsed (3.03 [SD ± 3.6] t·ha -1 ·yr -1) transects. Biomass production on unbrowsed and browsed transects was closely correlated with rainfall and presumably soil moisture during wet seasons. Relative growth rates (RGR) of current season's shoots in the two treatments did not differ, implying goat herbivory at moderate stocking density (i.e. 13.0 tropical livestock units [TLU]·km -2) stimulated shoot growth. RGR remained positive except on the browsed transects during 1990, a dry year. Goat browsing pressure was moderate. Total biomass loss on unbrowsed transects was 15.5 %·yr -1 compared with 27.7 %·yr -1 on the browsed transects. These findings do not support the notion that goats always destroy young trees around settlements. Goat herbivory at moderate intensity stimulated shoot productivity. However, the results should not be used to generalize all conditions throughout sub-Saharan Africa, let alone the arid zones of northern Kenya. Rather, there is a need to emphasize individual case studies that ultimately can be used for managing degraded woodlands near pastoralist settlements.

State-space modeling of population sizes and trends in Nihoa Finch and Millerbird

USGS Publications Warehouse

Gorresen, P. Marcos; Brinck, Kevin W.; Camp, Richard J.; Farmer, Chris; Plentovich, Sheldon M.; Banko, Paul C.

2016-01-01

Both of the 2 passerines endemic to Nihoa Island, Hawai‘i, USA—the Nihoa Millerbird (Acrocephalus familiaris kingi) and Nihoa Finch (Telespiza ultima)—are listed as endangered by federal and state agencies. Their abundances have been estimated by irregularly implemented fixed-width strip-transect sampling from 1967 to 2012, from which area-based extrapolation of the raw counts produced highly variable abundance estimates for both species. To evaluate an alternative survey method and improve abundance estimates, we conducted variable-distance point-transect sampling between 2010 and 2014. We compared our results to those obtained from strip-transect samples. In addition, we applied state-space models to derive improved estimates of population size and trends from the legacy time series of strip-transect counts. Both species were fairly evenly distributed across Nihoa and occurred in all or nearly all available habitat. Population trends for Nihoa Millerbird were inconclusive because of high within-year variance. Trends for Nihoa Finch were positive, particularly since the early 1990s. Distance-based analysis of point-transect counts produced mean estimates of abundance similar to those from strip-transects but was generally more precise. However, both survey methods produced biologically unrealistic variability between years. State-space modeling of the long-term time series of abundances obtained from strip-transect counts effectively reduced uncertainty in both within- and between-year estimates of population size, and allowed short-term changes in abundance trajectories to be smoothed into a long-term trend.

Laparoscopic repair of hernia in children: Comparison between ligation and nonligation of sac.

PubMed

Pant, Nitin; Aggarwal, Satish Kumar; Ratan, Simmi K

2014-04-01

The essence of the current techniques of laparoscopic hernia repair in children is suture ligation of the neck of the hernia sac at the deep ring with or without its transection. Some studies show that during open hernia repair, after transection at the neck it can be left unsutured without any consequence. This study was aimed to see if the same holds true for laparoscopic hernia repair. Sixty patients (52 boys and eight girls, 12-144 months) with indirect inguinal hernia were randomized for laparoscopic repair either by transection of the sac alone (Group I) or transection plus suture ligation of sac at the neck (Group II). Outcome was assessed in terms of time taken for surgery, recurrence, and other complications. Thirty-eight hernia units in 28 patients were repaired by transection alone (Group I) and 34 hernia units in 29 patients were repaired by transection and suture ligation (Group II). Three patients were found to have no hernia on laparoscopy. Recurrence rate and other complications were not significantly different in the two groups. All recurrences occurred in hernias with ring size more than 10 mm. Laparoscopic repair of hernia by circumferential incision of the peritoneum at the deep ring is as effective as incision plus ligation of the sac.

ANNUAL CYCLE OF PERIPHYTON, ZOOPLANKTON, AND WATER QUALITY PARAMETERS ALONG A 5 STATION TRANSECT OF ESCAMBIA BAY, FL

EPA Science Inventory

Phytoplankton, zooplankton and water quality parameters were monitored monthly along a 5-station transect in Escambia Bay (Pensacola, FL) from fall 1999 to fall 2000. To provide insight into nutrient processing in Escambia Bay and effects of grazers on phytoplankton community st...

Spinal Reflexes and Windup In Vitro: Effects of Analgesics and Anesthetics.

PubMed

Rivera-Arconada, Ivan; Roza, Carolina; Lopez-Garcia, Jose A

2016-02-01

The spinal cord is the first relay center for nociceptive information. Following peripheral injury, the spinal cord sensitizes. A sign of spinal sensitization is the hyper-reflexia which develops shortly after injury and can be detected in the isolated spinal cord as a "memory of pain." In this context, it is easy to understand that many analgesic compounds target spinally located sites of action to attain analgesia. In vitro isolated spinal cord preparations have been used for a number of years, and experience on the effects of compounds of diverse pharmacological families on spinal function has accumulated. Recently, we have proposed that the detailed study of spinal segmental reflexes in vitro may produce data relevant to the evaluation of the analgesic potential of novel compounds. In this review, we describe the main features of segmental reflexes obtained in vitro and discuss the effects of compounds of diverse chemical nature and pharmacological properties on such reflexes. Our aim was to compare the different profiles of action of the compounds on segmental reflexes in order to extract clues that may be helpful for pharmacological characterization of novel analgesics. © 2015 John Wiley & Sons Ltd.

Effects of selective lingual gustatory deafferentation on suprathreshold taste intensity discrimination of NaCl in rats.

PubMed

Colbert, Connie L; Garcea, Mircea; Spector, Alan C

2004-12-01

In rats, chorda tympani nerve transection (CTX) greatly increases the detection threshold of sodium chloride (NaCl) and severely disrupts salt discriminability. Here it is shown that CTX has surprisingly little effect, if any, on suprathreshold intensity discrimination. Glossopharyngeal nerve transection (GLX), which has no reported effect on salt sensibility, also did not affect performance. Rats were tested in a 2-response, operant taste intensity discrimination task. Difference thresholds for CTX rats were only slightly higher (-0.15 log/10 unit) than those for GLX and sham-transected rats, when 0.05 M served as the standard, and did not significantly differ when 0.1 M NaCl was the standard. Although the perceived intensity of NaCl might be reduced by CTX, input from remaining taste nerves sufficiently maintains the relative discriminability of suprathreshold NaCl concentrations.

Organization, development, and effects of infraorbital nerve transection on galanin binding sites in the trigeminal brainstem complex.

PubMed

Bodie, D; Bennett-Clarke, C A; Davis, K; Postelwaite, J P; Chiaia, N L; Rhoades, R W

1997-01-01

Previous experiments from this laboratory have indicated that transection of the infraorbital nerve (ION, the trigeminal [V] branch that supplies the mystacial vibrissae follicles) at birth and in adulthood has markedly different effects on galanin immunoreactivity in the V brainstem complex. Adult nerve transection increases galanin immunoreactivity in the superficial layers of V subnucleus caudalis (SpC) only, while neonatal nerve transection results in increased galanin expression in vibrissae-related primary afferents throughout the V brainstem complex. The present study describes the distribution of binding sites for this peptide in the mature and developing V ganglion and brainstem complex and determines the effects of neonatal and adult ION damage and the associated changes in galanin levels upon their distribution and density. Galanin binding sites are densely distributed in all V brainstem subnuclei and are particularly dense in V subnucleus interpolaris and the superficial layers of SpC. They are present at birth (P-0) and their distribution is similar to that in adult animals. Transection of the ION in adulthood and examination of brainstem 7 days later indicated marked reductions in the density of galanin binding sites in the V brainstem complex. With the exception of the superficial laminae of SpC, the same reduction in density remained apparent in rats that survived > 45 days after nerve cuts. Transection of the ION on P-0 resulted in no change in the density of galanin binding sites in the brainstem after either 7 or > 60 days survival. These results indicate that densely distributed galanin binding sites are present in the V brainstem complex of both neonatal and adult rats, that they are located in regions not innervated by galanin-positive axons, and that their density is not significantly influenced by large lesion-induced changes in the primary afferent content of their natural ligand.

Location and description of transects for ecological studies in floodplain forests of the lower Suwannee River, Florida

USGS Publications Warehouse

Lewis, L.J.; Light, H.M.; Darst, M.R.

2001-01-01

Twelve transects were established in floodplain forests along the lower Suwannee River, Florida, as the principal data collection sites for a comprehensive study conducted by the U.S. Geological Survey and the Suwannee River Water Management District from 1996 to 2001. Data collected along the 12 transects included hydrologic conditions, land-surface elevations, soils, and vegetation of floodplain forests in relation to river flow. Transect locations are marked in the field with permanent markers at approximately 30 meter intervals. Detailed descriptions of the 12 transects and their locations are provided so that they can be used for future ecological studies. Descriptions of the transects include contact information necessary for access to the property on which the transects are located, maps showing transect locations and routes from the nearest city or major road, small scale maps of each transect showing marker locations, latitude and longitude of each marker, compass bearings of each transect line and graphs showing land-surface elevations of the transect with marker locations.

Osthole attenuates spinal cord ischemia-reperfusion injury through mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction in rats.

PubMed

Zhou, Yue-fei; Li, Liang; Feng, Feng; Yuan, Hua; Gao, Da-kuan; Fu, Luo-an; Fei, Zhou

2013-12-01

Osthole, the main bioactive compounds isolated from the traditional Chinese medical herb broad Cnidium monnieri (L.) cusson, has been shown to exert spectrum of pharmacologic activities. The aim of this study was to investigate the potential neuroprotective effects of osthole against spinal cord ischemia-reperfusion injury in rats. Osthole was administrated at the concentration of 0.1, 1, 10, 50, or 200 mg/kg (intraperitoneally) 1 h before spinal cord ischemia. The effects on spinal cord injury were measured by spinal cord water content, infarct volume, hematoxylin and eosin staining, and neurologic assessment. Mitochondria were purified from injured spinal cord tissue to determine mitochondrial function. We found that treatment with osthole (10 and 50 mg/kg) significantly decreased spinal cord water content and infarct volume, preserved normal motor neurons, and improved neurologic functions. These protective effects can be also observed even if the treatment was delayed to 4 h after reperfusion. Osthole treatment preserved mitochondrial membrane potential level, reduced reactive oxygen species production, increased adenosine triphosphate generation, and inhibited cytochrome c release in mitochondrial samples. Moreover, osthole increased mitochondria respiratory chain complex activities in spinal cord tissue, with no effect on mitochondrial DNA content and the expression of mitochondrial-specific transcription factors. All these findings demonstrate the neuroprotective effect of osthole in spinal cord ischemia-reperfusion injury model and suggest that oshtole-induced neuroprotection was mediated by mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

Shock Wave Treatment Protects From Neuronal Degeneration via a Toll-Like Receptor 3 Dependent Mechanism: Implications of a First-Ever Causal Treatment for Ischemic Spinal Cord Injury.

PubMed

Lobenwein, Daniela; Tepeköylü, Can; Kozaryn, Radoslaw; Pechriggl, Elisabeth J; Bitsche, Mario; Graber, Michael; Fritsch, Helga; Semsroth, Severin; Stefanova, Nadia; Paulus, Patrick; Czerny, Martin; Grimm, Michael; Holfeld, Johannes

2015-10-27

Paraplegia following spinal cord ischemia represents a devastating complication of both aortic surgery and endovascular aortic repair. Shock wave treatment was shown to induce angiogenesis and regeneration in ischemic tissue by modulation of early inflammatory response via Toll-like receptor (TLR) 3 signaling. In preclinical and clinical studies, shock wave treatment had a favorable effect on ischemic myocardium. We hypothesized that shock wave treatment also may have a beneficial effect on spinal cord ischemia. A spinal cord ischemia model in mice and spinal slice cultures ex vivo were performed. Treatment groups received immediate shock wave therapy, which resulted in decreased neuronal degeneration and improved motor function. In spinal slice cultures, the activation of TLR3 could be observed. Shock wave effects were abolished in spinal slice cultures from TLR3(-/-) mice, whereas the effect was still present in TLR4(-/-) mice. TLR4 protein was found to be downregulated parallel to TLR3 signaling. Shock wave-treated animals showed significantly better functional outcome and survival. The protective effect on neurons could be reproduced in human spinal slices. Shock wave treatment protects from neuronal degeneration via TLR3 signaling and subsequent TLR4 downregulation. Consequently, it represents a promising treatment option for the devastating complication of spinal cord ischemia after aortic repair. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Elevational Ranges of Montane Birds and Deforestation in the Western Andes of Colombia.

PubMed

Ocampo-Peñuela, Natalia; Pimm, Stuart L

2015-01-01

Deforestation causes habitat loss, fragmentation, degradation, and can ultimately cause extinction of the remnant species. Tropical montane birds face these threats with the added natural vulnerability of narrower elevational ranges and higher specialization than lowland species. Recent studies assess the impact of present and future global climate change on species' ranges, but only a few of these evaluate the potentially confounding effect of lowland deforestation on species elevational distributions. In the Western Andes of Colombia, an important biodiversity hotspot, we evaluated the effects of deforestation on the elevational ranges of montane birds along altitudinal transects. Using point counts and mist-nets, we surveyed six altitudinal transects spanning 2200 to 2800 m. Three transects were forested from 2200 to 2800 m, and three were partially deforested with forest cover only above 2400 m. We compared abundance-weighted mean elevation, minimum elevation, and elevational range width. In addition to analysing the effect of deforestation on 134 species, we tested its impact within trophic guilds and habitat preference groups. Abundance-weighted mean and minimum elevations were not significantly different between forested and partially deforested transects. Range width was marginally different: as expected, ranges were larger in forested transects. Species in different trophic guilds and habitat preference categories showed different trends. These results suggest that deforestation may affect species' elevational ranges, even within the forest that remains. Climate change will likely exacerbate harmful impacts of deforestation on species' elevational distributions. Future conservation strategies need to account for this by protecting connected forest tracts across a wide range of elevations.

Elevational Ranges of Montane Birds and Deforestation in the Western Andes of Colombia

PubMed Central

2015-01-01

Deforestation causes habitat loss, fragmentation, degradation, and can ultimately cause extinction of the remnant species. Tropical montane birds face these threats with the added natural vulnerability of narrower elevational ranges and higher specialization than lowland species. Recent studies assess the impact of present and future global climate change on species’ ranges, but only a few of these evaluate the potentially confounding effect of lowland deforestation on species elevational distributions. In the Western Andes of Colombia, an important biodiversity hotspot, we evaluated the effects of deforestation on the elevational ranges of montane birds along altitudinal transects. Using point counts and mist-nets, we surveyed six altitudinal transects spanning 2200 to 2800m. Three transects were forested from 2200 to 2800m, and three were partially deforested with forest cover only above 2400m. We compared abundance-weighted mean elevation, minimum elevation, and elevational range width. In addition to analysing the effect of deforestation on 134 species, we tested its impact within trophic guilds and habitat preference groups. Abundance-weighted mean and minimum elevations were not significantly different between forested and partially deforested transects. Range width was marginally different: as expected, ranges were larger in forested transects. Species in different trophic guilds and habitat preference categories showed different trends. These results suggest that deforestation may affect species’ elevational ranges, even within the forest that remains. Climate change will likely exacerbate harmful impacts of deforestation on species’ elevational distributions. Future conservation strategies need to account for this by protecting connected forest tracts across a wide range of elevations. PMID:26641477

Effectiveness of backpack electrofishing for removal of non-native fishes from a small warm-water stream

USGS Publications Warehouse

Ward, David L.; O'neill, Matthew W.; Ka'apu-Lyons, Cassie

2015-01-01

Electrofishing is commonly used when renovating small streams to remove nuisance fishes but the likelihood of complete eradication of unwanted species, particularly warm-water fishes, is unknown. In October of 2008, we electrofished Bonita Creek, a small stream with base flows (<0.56 m3/s) in southern Arizona, and then treated the stream with rotenone to kill all of the remaining fish and quantify the effectiveness of single and multiple-pass electro fishing. Six, 100-m transects were electro fished on three consecutive days followed by a single treatment with rotenone. Fish caught using electrofishing were identified, counted and removed from each transect daily and then compared to numbers of dead fish collected during the subsequent rotenone application. Electrofishing effectiveness was highly variable among transects. Single-pass electrofishing caught an average of 23% (95% CI=5 to 40%) of the fish present, and three-pass electrofishing on consecutive days caught on average 55% (95% CI=28 to 83%) of the fish in each transect. Native Arizona fishes were more susceptible to electrofishing (77 % captured) than non-native species (54% captured), though native fish were rare. Transects in Bonita Creek averaged 3.6±1.5 m wide and 0.25±0.20 m deep (max depth 1.2 m). Bonita Creek is a small first-order stream which exhibits ideal conditions for backpack electrofishing, yet we captured a relatively small percentage of the fish present. This suggests that complete removal of non-native warm-water fishes using backpack electrofishing is not likely to be successful, especially in larger more complex streams.

Developing accurate survey methods for estimating population sizes and trends of the critically endangered Nihoa Millerbird and Nihoa Finch.

USGS Publications Warehouse

Gorresen, P. Marcos; Camp, Richard J.; Brinck, Kevin W.; Farmer, Chris

2012-01-01

Point-transect surveys indicated that millerbirds were more abundant than shown by the striptransect method, and were estimated at 802 birds in 2010 (95%CI = 652 – 964) and 704 birds in 2011 (95%CI = 579 – 837). Point-transect surveys yielded population estimates with improved precision which will permit trends to be detected in shorter time periods and with greater statistical power than is available from strip-transect survey methods. Mean finch population estimates and associated uncertainty were not markedly different among the three survey methods, but the performance of models used to estimate density and population size are expected to improve as the data from additional surveys are incorporated. Using the pointtransect survey, the mean finch population size was estimated at 2,917 birds in 2010 (95%CI = 2,037 – 3,965) and 2,461 birds in 2011 (95%CI = 1,682 – 3,348). Preliminary testing of the line-transect method in 2011 showed that it would not generate sufficient detections to effectively model bird density, and consequently, relatively precise population size estimates. Both species were fairly evenly distributed across Nihoa and appear to occur in all or nearly all available habitat. The time expended and area traversed by observers was similar among survey methods; however, point-transect surveys do not require that observers walk a straight transect line, thereby allowing them to avoid culturally or biologically sensitive areas and minimize the adverse effects of recurrent travel to any particular area. In general, pointtransect surveys detect more birds than strip-survey methods, thereby improving precision and resulting population size and trend estimation. The method is also better suited for the steep and uneven terrain of Nihoa

Simulation of Anterior Cruciate Ligament Deficiency in a Musculoskeletal Model with Anatomical Knees

PubMed Central

Guess, Trent M; Stylianou, Antonis

2012-01-01

Abnormal knee kinematics and meniscus injury resulting from anterior cruciate ligament (ACL) deficiency are often implicated in joint degeneration even though changes in tibio-femoral contact location after injury are small, typically only a few millimeters. Ligament reconstruction surgery does not significantly reduce the incidence of early onset osteoarthritis. Increased knowledge of knee contact mechanics would increase our understanding of the effects of ACL injury and help guide ACL reconstruction methods. Presented here is a cadaver specific computational knee model combined with a body-level musculoskeletal model from a subject of similar height and weight as the cadaver donor. The knee model was developed in the multi-body framework and includes representation of the menisci. Experimental body-level measurements provided input to the musculoskeletal model. The location of tibio-menisco-femoral contact as well as contact pressures were compared for models with an intact ACL, partial ACL transection (posterolateral bundle transection), and full ACL transection during a muscle driven forward dynamics simulation of a dual limb squat. During the squat, small changes in femur motion relative to the tibia for both partial and full ACL transection push the lateral meniscus in the posterior direction at extension. The central-anterior region of the lateral meniscus then becomes “wedged” between the tibia and femur during knee flexion. This “wedging” effect does not occur for the intact knee. Peak contact pressure and contact locations are similar for the partial tear and complete ACL transection during the deep flexion portion of the squat, particularly on the lateral side. The tibio-femoral contact location on the tibia plateau shifts slightly to the posterior and lateral direction with ACL transection. PMID:22470411

Scar modulation in subacute and chronic CNS lesions: Effects on axonal regeneration.

PubMed

Stichel, Christine C.; Lausberg, Friederike; Hermanns, Susanne; Müller, Hans Werner

1999-01-01

After injury of the adult mammalian CNS axonal regeneration across or around the lesion scar is negligible. Previously, we have shown that the lesion-induced basal membrane (BM) within the lesion center participates in a growth barrier for axon regeneration and that its reduction by means of pharmacological or immunochemical treatment is a prerequisite and sufficient condition for regrowing axons to cross the lesion site. The present study was designed to further investigate this observation by analyzing the effect of a delayed treatment on the regeneration of both subacutely and chronically lesioned axons.Adult rats underwent unilateral transection of the postcommissural fornix. At one to five days after transection one group of animals received a local injection of 2, 2'-dipyridyl (DPY), an inhibitor of collagen triple helix formation and synthesis. Another group received a second transection within the former lesion site followed by an immediate DPY-injection at five days or 4 weeks after transection. Six weeks after the last surgery BM deposition and axonal regeneration were analysed using immunocytochemical methods.A local injection of DPY clearly reduced the lesion-induced BM deposition when applied within the first 3 days after transection. Under these conditions regrowing axons still crossed the former impermeable lesion site and regenerated within their normal pathway up to their former target, the mammillary body. However, in late subacute (5 d) and chronic stages (4 w) the double transection+injection paradigm failed to reduce BM deposition and, in consequence, also to induce axonal regeneration.These results demonstrate the potential of the collagen IV-reducing strategy to promote axonal regeneration across the lesion scar not only in acute but also in early subacute traumatic injuries.

Improving Aquatic Warbler Population Assessments by Accounting for Imperfect Detection

PubMed Central

Oppel, Steffen; Marczakiewicz, Piotr; Lachmann, Lars; Grzywaczewski, Grzegorz

2014-01-01

Monitoring programs designed to assess changes in population size over time need to account for imperfect detection and provide estimates of precision around annual abundance estimates. Especially for species dependent on conservation management, robust monitoring is essential to evaluate the effectiveness of management. Many bird species of temperate grasslands depend on specific conservation management to maintain suitable breeding habitat. One such species is the Aquatic Warbler (Acrocephalus paludicola), which breeds in open fen mires in Central Europe. Aquatic Warbler populations have so far been assessed using a complete survey that aims to enumerate all singing males over a large area. Because this approach provides no estimate of precision and does not account for observation error, detecting moderate population changes is challenging. From 2011 to 2013 we trialled a new line transect sampling monitoring design in the Biebrza valley, Poland, to estimate abundance of singing male Aquatic Warblers. We surveyed Aquatic Warblers repeatedly along 50 randomly placed 1-km transects, and used binomial mixture models to estimate abundances per transect. The repeated line transect sampling required 150 observer days, and thus less effort than the traditional ‘full count’ approach (175 observer days). Aquatic Warbler abundance was highest at intermediate water levels, and detection probability varied between years and was influenced by vegetation height. A power analysis indicated that our line transect sampling design had a power of 68% to detect a 20% population change over 10 years, whereas raw count data had a 9% power to detect the same trend. Thus, by accounting for imperfect detection we increased the power to detect population changes. We recommend to adopt the repeated line transect sampling approach for monitoring Aquatic Warblers in Poland and in other important breeding areas to monitor changes in population size and the effects of habitat management. PMID:24713994

Effects of pacing-induced myocardial stress and spinal cord stimulation on whole body and cardiac norepinephrine spillover.

PubMed

Norrsell, H; Eliasson, T; Mannheimer, C; Augustinsson, L E; Bergh, C H; Andersson, B; Waagstein, F; Friberg, P

1997-12-01

Spinal cord stimulation has been used in the treatment of intractable angina pectoris since the beginning of the 1980s. This study was designed to investigate whether the documented anti-ischaemic effects of spinal cord stimulation are mediated through a decrease in sympathetic activity. Ten patients with a spinal cord stimulator implanted as anti-anginal treatment were included in the study. Atrial pacing until the patient experienced moderate angina was performed and after 50 min rest the procedure was repeated during spinal cord stimulation. Total body and cardiac norepinephrine spillover was calculated and the former was found to have increased during pacing (47%, P = 0.02). When spinal cord stimulation was applied, total body norepinephrine spillover decreased at a comparable pacing rate (18%, P = 0.02). Cardiac norepinephrine spillover was not affected during the procedure. The results of this study indicate that the anti-ischaemic effect of spinal cord stimulation is not due to reduced cardiac sympathetic activity. However, spinal cord stimulation decreases overall sympathetic activity which may benefit the heart, possibly by reducing oxygen demand.

Does trans‐spinal and local DC polarization affect presynaptic inhibition and post‐activation depression?

PubMed Central

Kaczmarek, D.; Ristikankare, J.

2017-01-01

Key points Trans‐spinal polarization was recently introduced as a means to improve deficient spinal functions. However, only a few attempts have been made to examine the mechanisms underlying DC actions. We have now examined the effects of DC on two spinal modulatory systems, presynaptic inhibition and post‐activation depression, considering whether they might weaken exaggerated spinal reflexes and enhance excessively weakened ones.Direct current effects were evoked by using local intraspinal DC application (0.3–0.4 μA) in deeply anaesthetized rats and were compared with the effects of trans‐spinal polarization (0.8–1.0 mA).Effects of local intraspinal DC were found to be polarity dependent, as locally applied cathodal polarization enhanced presynaptic inhibition and post‐activation depression, whereas anodal polarization weakened them. In contrast, both cathodal and anodal trans‐spinal polarization facilitated them.The results suggest some common DC‐sensitive mechanisms of presynaptic inhibition and post‐activation depression, because both were facilitated or depressed by DC in parallel. Abstract Direct current (DC) polarization has been demonstrated to alleviate the effects of various deficits in the operation of the central nervous system. However, the effects of trans‐spinal DC stimulation (tsDCS) have been investigated less extensively than the effects of transcranial DC stimulation, and their cellular mechanisms have not been elucidated. The main objectives of this study were, therefore, to extend our previous analysis of DC effects on the excitability of primary afferents and synaptic transmission by examining the effects of DC on two spinal modulatory feedback systems, presynaptic inhibition and post‐activation depression, in an anaesthetized rat preparation. Other objectives were to compare the effects of locally and trans‐spinally applied DC (locDC and tsDCS). Local polarization at the sites of terminal branching of afferent fibres was found to induce polarity‐dependent actions on presynaptic inhibition and post‐activation depression, as cathodal locDC enhanced them and anodal locDC depressed them. In contrast, tsDCS modulated presynaptic inhibition and post‐activation depression in a polarity‐independent fashion because both cathodal and anodal tsDCS facilitated them. The results show that the local presynaptic actions of DC might counteract both excessively strong and excessively weak monosynaptic actions of group Ia and cutaneous afferents. However, they indicate that trans‐spinally applied DC might counteract the exaggerated spinal reflexes but have an adverse effect on pathologically weakened spinal activity by additional presynaptic weakening. The results are also relevant for the analysis of the basic properties of presynaptic inhibition and post‐activation depression because they indicate that some common DC‐sensitive mechanisms contribute to them. PMID:27891626

N-methyl-D-aspartate receptor antagonist MK-801 prevents apoptosis in rats that have undergone fetal spinal cord transplantation following spinal hemisection.

PubMed

Zhang, Qiang; Shao, Yang; Zhao, Changsong; Cai, Juan; Sun, Sheng

2014-12-01

Spinal cord injury is the main cause of paraplegia, but effective therapies for it are lacking. Embryonic spinal cord transplantation is able to repair spinal cord injury, albeit with a large amount of neuronal apoptosis remaining in the spinal cord. MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, is able to reduce cell death by decreasing the concentration of excitatory amino acids and preventing extracellular calcium ion influx. In this study, the effect of MK-801 on the apoptosis of spinal cord neurons in rats that have received a fetal spinal cord (FSC) transplant following spinal hemisection was investigated. Wistar rats were divided into three groups: Spinal cord hemisection injury with a combination of FSC transplantation and MK-801 treatment (group A); spinal cord hemisection injury with FSC transplantation (group B); and spinal cord injury with insertion of a Gelfoam pledget (group C). The rats were sacrificed 1, 3, 7 and 14 days after the surgery. Apoptosis in spinal slices from the injured spinal cord was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling reaction, and the expression of B-cell lymphoma-2 (Bcl-2) was measured by immunohistochemistry. The positive cells were quantitatively analyzed using a computer image analysis system. The rate of apoptosis and the positive expression of Bcl-2 protein in the spinal cord neurons in the three groups decreased in the following order: C>B>A (P<0.05) and A>B>C (P<0.05), respectively. This indicates that treatment with the NMDA receptor antagonist MK-801 prevents apoptosis in the spinal cord neurons of rats that have undergone FSC transplantation following spinal hemisection.

N-methyl-D-aspartate receptor antagonist MK-801 prevents apoptosis in rats that have undergone fetal spinal cord transplantation following spinal hemisection

PubMed Central

ZHANG, QIANG; SHAO, YANG; ZHAO, CHANGSONG; CAI, JUAN; SUN, SHENG

2014-01-01

Spinal cord injury is the main cause of paraplegia, but effective therapies for it are lacking. Embryonic spinal cord transplantation is able to repair spinal cord injury, albeit with a large amount of neuronal apoptosis remaining in the spinal cord. MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, is able to reduce cell death by decreasing the concentration of excitatory amino acids and preventing extracellular calcium ion influx. In this study, the effect of MK-801 on the apoptosis of spinal cord neurons in rats that have received a fetal spinal cord (FSC) transplant following spinal hemisection was investigated. Wistar rats were divided into three groups: Spinal cord hemisection injury with a combination of FSC transplantation and MK-801 treatment (group A); spinal cord hemisection injury with FSC transplantation (group B); and spinal cord injury with insertion of a Gelfoam pledget (group C). The rats were sacrificed 1, 3, 7 and 14 days after the surgery. Apoptosis in spinal slices from the injured spinal cord was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling reaction, and the expression of B-cell lymphoma-2 (Bcl-2) was measured by immunohistochemistry. The positive cells were quantitatively analyzed using a computer image analysis system. The rate of apoptosis and the positive expression of Bcl-2 protein in the spinal cord neurons in the three groups decreased in the following order: C>B>A (P<0.05) and A>B>C (P<0.05), respectively. This indicates that treatment with the NMDA receptor antagonist MK-801 prevents apoptosis in the spinal cord neurons of rats that have undergone FSC transplantation following spinal hemisection. PMID:25371724

Early Versus Delayed Surgical Decompression of Spinal Cord after Traumatic Cervical Spinal Cord Injury: A Cost-Utility Analysis.

PubMed

Furlan, Julio C; Craven, B Catharine; Massicotte, Eric M; Fehlings, Michael G

2016-04-01

This cost-utility analysis was undertaken to compare early (≤24 hours since trauma) versus delayed surgical decompression of spinal cord to determine which approach is more cost effective in the management of patients with acute traumatic cervical spinal cord injury (SCI). This study includes the patients enrolled into the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS) and admitted at Toronto Western Hospital. Cases were grouped into patients with motor complete SCI and individuals with motor incomplete SCI. A cost-utility analysis was performed for each group of patients by the use of data for the first 6 months after SCI. The perspective of a public health care insurer was adopted. Costs were estimated in 2014 U.S. dollars. Utilities were estimated from the STASCIS. The baseline analysis indicates early spinal decompression is more cost-effective approach compared with the delayed spinal decompression. When we considered the delayed spinal decompression as the baseline strategy, the incremental cost-effectiveness ratio analysis revealed a saving of US$ 58,368,024.12 per quality-adjusted life years gained for patients with complete SCI and a saving of US$ 536,217.33 per quality-adjusted life years gained in patients with incomplete SCI for the early spinal decompression. The probabilistic analysis confirmed the early-decompression strategy as more cost effective than the delayed-decompression approach, even though there is no clearly dominant strategy. The results of this economic analysis suggests that early decompression of spinal cord was more cost effective than delayed surgical decompression in the management of patients with motor complete and incomplete SCI, even though no strategy was clearly dominant. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of two spinal needle types to achieve a unilateral spinal block.

PubMed

Kuusniemi, Kristiina; Leino, Kari; Lertola, Kaarlo; Pihlajamäki, Kalevi; Pitkänen, Mikko

2013-04-01

Unilateral spinal anesthesia is beneficial in patients undergoing unilateral leg surgery. The direction and the shape of the spinal needle are thought to influence the unilateral distribution of the local anesthetic in the intrathecal space. Therefore, to study the effects of different spinal needles we compared the effects of the Whitacre and Quincke spinal needles. This was a prospective, randomized, double-blind study of 60 consecutive outpatients scheduled for unilateral lower-limb surgery. The patients were randomized to receive spinal anesthesia with 1.2 ml of 0.5 % plain bupivacaine using either a 27-G Whitacre or a Quincke needle. One half of the local anesthetic was injected towards the nondependent side and the other half was directed cranially. The spread of spinal anesthesia, both sensory and motor blocks, was defined as the primary endpoint and was recorded at 10, 20, and 30 min after the spinal injection, at the end of the operation, 2 h after the spinal injection, and every 30 min thereafter until there was no motor block. Secondary endpoints included patient satisfaction and adverse effects. There was no difference in the spread of sensory or motor blocks between the Whitacre and the Quincke groups. However, the sensory and motor blocks on the operated and the nonoperated sides were significantly different at all testing times, as expected. There was no difference in the incidence of adverse effects or patient satisfaction scores between the Whitacre and the Quincke groups. Unilateral spinal block for outpatient surgery can be achieved with both pencil-point (Whitacre) and Quincke needles using 6.0 mg of plain bupivacaine. Neither the spread of sensory and motor blocks nor the corresponding recovery times appeared to be different between the groups. Nor was there any difference in patient satisfaction.

A structured review of spinal stiffness as a kinesiological outcome of manipulation: its measurement and utility in diagnosis, prognosis and treatment decision-making.

PubMed

Snodgrass, Suzanne J; Haskins, Robin; Rivett, Darren A

2012-10-01

To review and discuss the methods used for measuring spinal stiffness and factors associated with stiffness, how stiffness is used in diagnosis, prognosis, and treatment decision-making and the effects of manipulative techniques on stiffness. A systematic search of MEDLINE, EMBASE, CINAHL, AMED and ICL databases was conducted. Included studies addressed one of four constructs related to stiffness: measurement, diagnosis, prognosis and/or treatment decision-making, and the effects of manipulation on stiffness. Spinal stiffness was defined as the relationship between force and displacement. One hundred and four studies are discussed in this review, with the majority of studies focused on the measurement of stiffness, most often in asymptomatic persons. Eight studies investigated spinal stiffness in diagnosis, providing limited evidence that practitioner-judged stiffness is associated with radiographic findings of sagittal rotational mobility. Fifteen studies investigated spinal stiffness in prognosis or treatment decision-making, providing limited evidence that spinal stiffness is unlikely to independently predict patient outcomes, though stiffness may influence a practitioner's application of non-thrust manipulative techniques. Nine studies investigating the effects of manipulative techniques on spinal stiffness provide very limited evidence that there is no change in spinal stiffness following thrust or non-thrust manipulation in asymptomatic individuals and non-thrust techniques in symptomatic persons, with only one study supporting an immediate, but not sustained, stiffness decrease following thrust manipulation in symptomatic individuals. The existing limited evidence does not support an association between spinal stiffness and manipulative treatment outcomes. There is a need for additional research investigating the effects of manipulation on spinal stiffness in persons with spinal pain. Copyright © 2012 Elsevier Ltd. All rights reserved.

Roads as edges: Effects on birds in forested landscapes

Treesearch

Yvette K. Ortega; David E. Capen

2002-01-01

Numerous studies have documented that forest edges affect habitat use and reproductive success of forest birds, but few studies have considered edges created by narrow breaks in the forest canopy. We compared predation rates on artificial nests placed within forest habitat along edge transects, 10 m from unpaved roads, and along interior transects, 300 m from forest-...

Combined Effects of Acrobatic Exercise and Magnetic Stimulation on the Functional Recovery after Spinal Cord Lesions

PubMed Central

Wieraszko, Andrzej

2008-01-01

Abstract The objective of the study was to determine whether physical exercise combined with epidural spinal cord magnetic stimulation could improve recovery after injury of the spinal cord. Spinal cord lesioning in mice resulted in reduced locomotor function and negatively affected the muscle strength tested in vitro. Acrobatic exercise attenuated the behavioral effects of spinal cord injury. The exposure to magnetic fields facilitated further this improvement. The progress in behavioral recovery was correlated with reduced muscle degeneration and enhanced muscle contraction. The acrobatic exercise combined with stimulation with magnetic fields significantly facilitates behavioral recovery and muscle physiology in mice following spinal cord injury. PMID:18986227

Characterization of bulbospongiosus muscle reflexes activated by urethral distension in male rats.

PubMed

Tanahashi, Masayuki; Karicheti, Venkateswarlu; Thor, Karl B; Marson, Lesley

2012-10-01

The urethrogenital reflex (UGR) is used as a surrogate model of the autonomic and somatic nerve and muscle activity that accompanies ejaculation. The UGR is evoked by distension of the urethra and activation of penile afferents. The current study compares two methods of elevating urethral intraluminal pressure in spinalized, anesthetized male Sprague-Dawley rats (n = 60). The first method, penile extension UGR, involves extracting the penis from the foreskin, so that urethral pressure rises due to a natural anatomical flexure in the penis. The second method, penile clamping UGR, involves penile extension UGR with the addition of clamping of the glans penis. Groups of animals were prepared that either received no additional treatment, surgical shams, or received bilateral nerve cuts (4 nerve cut groups): either the pudendal sensory nerve branch (SbPN), the pelvic nerves, the hypogastric nerves, or all three nerves. Penile clamping UGR was characterized by multiple bursts, monitored by electromyography (EMG) of the bulbospongiosus muscle (BSM) accompanied by elevations in urethral pressure. The penile clamping UGR activity declined across multiple trials and eventually resulted in only a single BSM burst, indicating desensitization. In contrast, the penile extension UGR, without penile clamping, evoked only a single BSM EMG burst that showed no desensitization. Thus, the UGR is composed of two BSM patterns: an initial single burst, termed urethrobulbospongiosus (UBS) reflex and a subsequent multiple bursting pattern (termed ejaculation-like response, ELR) that was only induced with penile clamping urethral occlusion. Transection of the SbPN eliminated the ELR in the penile clamping model, but the single UBS reflex remained in both the clamping and extension models. Pelvic nerve (PelN) transection increased the threshold for inducing BSM activation with both methods of occlusion but actually unmasked an ELR in the penile extension method. Hypogastric nerve (HgN) cuts did not significantly alter any parameter. Transection of all three nerves eliminated BSM activation completely. In conclusion, penile clamping occlusion recruits penile and urethral primary afferent fibers that are necessary for an ELR. Urethral distension without significant penile afferent activation recruits urethral primary afferent fibers carried in either the pelvic or pudendal nerve that are necessary for the single-burst UBS reflex.

Effects of spinal health educational programs for elementary school children.

PubMed

Park, Jeong-hwan; Kim, Jin-Sun

2011-04-01

This study examined the effects of spinal health educational programs. A nonequivalent control-group pretest-posttest design was used. Participants were 88 fifth-grade elementary schoolchildren. Three groups were compared: a Web-based program group, a traditional face-to-face program group, and a control group. In both intervention groups, the changes for spinal health knowledge and self-efficacy were significantly higher than those of the control group. However, the changes of spinal health practices were not significantly different. A Web-based spinal health education program is a convenient and flexible health educational approach that was as effective in this study as traditional face-to-face instruction. © 2011, Wiley Periodicals, Inc.

Plasticity of non-adrenergic non-cholinergic bladder contractions in rats after chronic spinal cord injury

PubMed Central

Lai, H. Henry; Munoz, Alvaro; Smith, Christopher P.; Boone, Timothy B.; Somogyi, George T.

2011-01-01

The purpose of this study was to examine the pharmacologic plasticity of cholinergic, non-adrenergic non-cholinergic (NANC), and purinergic contractions in neurogenic bladder strips from spinal cord injured (SCI) rats. Bladder strips were harvested from female rats three to four weeks after T9–T10 spinal cord transection. The strips were electrically stimulated using two experimental protocols to compare the contribution of muscarinic and NANC/purinergic contractions in the presence and the absence of carbachol or muscarine. The endpoints of the study were: (1) percent NANC contraction that was unmasked by the muscarinic antagonist 4-DAMP, and (2) P2X purinergic contraction that was evoked by α,β–methylene ATP. NANC contraction accounted for 78.5% of the neurally evoked contraction in SCI bladders. When SCI bladder strips were treated with carbachol (10 µM) prior to 4-DAMP (500 nM), the percent NANC contraction decreased dramatically to only 13.1% of the neurally evoked contraction (p=0.041). This was accompanied by a substantial decrease in α,β–methylene ATP evoked P2X contraction, and desensitization of purinergic receptors (the ratio of subsequent over initial P2X contraction decreased from 97.2% to 42.1%, p=0.0017). Sequential activation of the cholinergic receptors with carbachol (or with muscarine in neurally intact bladders) and unmasking of the NANC response with 4-DAMP switched the neurally evoked bladder contraction from predominantly NANC to predominantly cholinergic. We conclude that activation of muscarinic receptors (with carbachol or muscarine) blocks NANC and purinergic contractions in neurally intact or in SCI rat bladders. The carbachol-induced inhibition of the NANC contraction is expressed more in SCI bladders compared to neurally intact bladders. Along with receptor plasticity, this change in bladder function may involve P2X-independent mechanisms. PMID:21689735

Brown-Séquard syndrome without vascular injury associated with Horner's syndrome after a stab injury to the neck

PubMed Central

Jones, Margaret; Zumsteg, Jennifer

2016-01-01

Case Description This case reviews the acute care and rehabilitation course of a 44-year-old right-handed woman after an assault with a pocketknife. She suffered multiple stab wounds including penetrating injury to the left side of her neck. Physical examination revealed left hemiplegia (motor score = 57), impaired pinprick sensation on the right caudal to the C5 dermatome, impaired joint position sense on the left, and left ptosis and miosis. Initially she was unable to stand without maximum assistance. MR imaging revealed transection of the left hemicord at the C5 level without cord hemorrhage. CTA of the neck was negative for vascular injury. She completed 18 days of acute inpatient rehabilitation. She used forearm crutches for ambulation at time of discharge. Prior to discharge the patient provided written permission for a case report. Discussion Stab wounds are the most common cause of traumatic Brown-Séquard syndrome. Horner's syndrome is common in spinal cord lesions occurring in the cervical or thoracic region, however the combination of Horner's and Brown-Séquard syndromes is less commonly reported. In this case report, we review recommendations regarding initial imaging following cervical stab wounds, discuss anatomy and associated neurological findings in Brown-Séquard and Horner's syndromes, and review the expected temporal course of motor recovery. Conclusions Facilitating motor recovery and optimizing function after Brown-Séquard spinal cord injury are important roles for the rehabilitation team. Imaging is necessary to rule out cord hemorrhage or vascular injury and to clinically correlate cord damage with physical examination findings and expected functional impairments. Documenting associated anisocoria and explaining this finding to the patient is an important element of spinal cord injury education. Commonly, patients with Brown-Séquard injuries demonstrate remarkable motor recovery and regain voluntary motor strength and functional ambulation. PMID:25659820

The Effects of Ketorolac Injected via Patient Controlled Analgesia Postoperatively on Spinal Fusion

PubMed Central

Park, Si-Young; Moon, Seong-Hwan; Park, Moon-Soo; Oh, Kyung-Soo

2005-01-01

Lumbar spinal fusions have been performed for spinal stability, pain relief and improved function in spinal stenosis, scoliosis, spinal fractures, infectious conditions and other lumbar spinal problems. The success of lumbar spinal fusion depends on multifactors, such as types of bone graft materials, levels and numbers of fusion, spinal instrumentation, electrical stimulation, smoking and some drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs). From January 2000 to December 2001, 88 consecutive patients, who were diagnosed with spinal stenosis or spondylolisthesis, were retrospectively enrolled in this study. One surgeon performed all 88 posterolateral spinal fusions with instrumentation and autoiliac bone graft. The patients were divided into two groups. The first group (n=30) was infused with ketorolac and fentanyl intravenously via patient controlled analgesia (PCA) postoperatively and the second group (n=58) was infused only with fentanyl. The spinal fusion rates and clinical outcomes of the two groups were compared. The incidence of incomplete union or nonunion was much higher in the ketorolac group, and the relative risk was approximately 6 times higher than control group (odds ratio: 5.64). The clinical outcomes, which were checked at least 1 year after surgery, showed strong correlations with the spinal fusion status. The control group (93.1%) showed significantly better clinical results than the ketorolac group (77.6%). Smoking had no effect on the spinal fusion outcome in this study. Even though the use of ketorolac after spinal fusion can reduce the need for morphine, thereby decreasing morphine related complications, ketorolac used via PCA at the immediate postoperative state inhibits spinal fusion resulting in a poorer clinical outcome. Therefore, NSAIDs such as ketorolac, should be avoided after posterolateral spinal fusion. PMID:15861498

Hemorrhagic thoracic schwannoma presenting with intradural hematoma and acute paraplegia after spinal manipulation therapy.

PubMed

Hdeib, Alia; Goodwin, C Rory; Sciubba, Daniel; Bydon, Ali; Wolinsky, Jean-Paul; Witham, Timothy; Gokaslan, Ziya L

2016-01-01

Hemorrhagic conversion of spinal schwannomas represents a rare occurrence; also rare is the development of a spinal intradural hematoma after spinal manipulation therapy. We report a unique presentation of paraplegia in a patient who underwent spinal manipulation therapy and was found to have a hemorrhagic thoracic schwannoma at time of surgery in the setting of anti-platelet therapy use. In patients with spinal schwannomas, tumor hemorrhage is a rare occasion, which can be considered in the setting of additive effects of spinal manipulation therapy and antiplatelet therapy.

"Low-intensity laser therapy effect on the recovery of traumatic spinal cord injury".

PubMed

Paula, Alecsandra Araujo; Nicolau, Renata Amadei; Lima, Mario de Oliveira; Salgado, Miguel Angel Castillo; Cogo, José Carlos

2014-11-01

Scientific advances have been made to optimize the healing process in spinal cord injury. Studies have been developed to obtain effective treatments in controlling the secondary injury that occurs after spinal cord injury, which substantially changes the prognosis. Low-intensity laser therapy (LILT) has been applied in neuroscience due to its anti-inflammatory effects on biological tissue in the repairing process. Few studies have been made associating LILT to the spinal cord injury. The objective of this study was to investigate the effect of the LILT (GaAlAs laser-780 nm) on the locomotor functional recovery, histomorphometric, and histopathological changes of the spinal cord after moderate traumatic injury in rats (spinal cord injury at T9 and T10). Thirty-one adult Wistar rats were used, which were divided into seven groups: control without surgery (n = 3), control surgery (n = 3), laser 6 h after surgery (n = 5), laser 48 h after surgery (n = 5), medullar lesion (n = 5) without phototherapy, medullar lesion + laser 6 h after surgery (n = 5), and medullar lesion + laser 48 h after surgery (n = 5). The assessment of the motor function was performed using Basso, Beattie, and Bresnahan (BBB) scale and adapted Sciatic Functional Index (aSFI). The assessment of urinary dysfunction was clinically performed. After 21 days postoperative, the animals were euthanized for histological and histomorphometric analysis of the spinal cord. The results showed faster motor evolution in rats with spinal contusion treated with LILT, maintenance of the effectiveness of the urinary system, and preservation of nerve tissue in the lesion area, with a notorious inflammation control and increased number of nerve cells and connections. In conclusion, positive effects on spinal cord recovery after moderate traumatic spinal cord injury were shown after LILT.

Neural effects of muscle stretching on the spinal reflexes in multiple lower-limb muscles.

PubMed

Masugi, Yohei; Obata, Hiroki; Inoue, Daisuke; Kawashima, Noritaka; Nakazawa, Kimitaka

2017-01-01

While previous studies have shown that muscle stretching suppresses monosynaptic spinal reflex excitability in stretched muscles, its effects on non-stretched muscles is still largely unknown. The purpose of this study was to examine the effects of muscle stretching on monosynaptic spinal reflex in non-stretched muscles. Ten healthy male subjects participated in this study. Muscle stretching of the right triceps surae muscle was performed using a motor torque device for 1 minute. Three different dorsiflexion torques (at approximately 5, 10, and 15 Nm) were applied during muscle stretching. Spinal reflexes evoked by transcutaneous spinal cord stimulation were recorded in both the lower-limb muscles before, during, and at 0 and 5 min following muscle stretching. The amplitudes of the spinal reflexes in both the stretched and non-stretched muscles in the right (ipsilateral) leg were smaller during stretching compared to before, and at 0 and 5 min after stretching. Furthermore, the degree of reduction in the amplitude of the spinal reflexes in the right (ipsilateral) leg muscles increased significantly as the dorsiflexion torque (i.e., stretching of the right triceps surae muscles) increased. In contrast, reduction in the amplitude of the spinal reflexes with increasing dorsiflexion torque was not seen in the left (contralateral) leg muscles. Our results clearly indicate that muscle stretching has inhibitory effects on monosynaptic spinal reflexes, not only in stretched muscles, but also in non-stretched muscles of the ipsilateral leg.

Neural effects of muscle stretching on the spinal reflexes in multiple lower-limb muscles

PubMed Central

Obata, Hiroki; Inoue, Daisuke; Kawashima, Noritaka; Nakazawa, Kimitaka

2017-01-01

While previous studies have shown that muscle stretching suppresses monosynaptic spinal reflex excitability in stretched muscles, its effects on non-stretched muscles is still largely unknown. The purpose of this study was to examine the effects of muscle stretching on monosynaptic spinal reflex in non-stretched muscles. Ten healthy male subjects participated in this study. Muscle stretching of the right triceps surae muscle was performed using a motor torque device for 1 minute. Three different dorsiflexion torques (at approximately 5, 10, and 15 Nm) were applied during muscle stretching. Spinal reflexes evoked by transcutaneous spinal cord stimulation were recorded in both the lower-limb muscles before, during, and at 0 and 5 min following muscle stretching. The amplitudes of the spinal reflexes in both the stretched and non-stretched muscles in the right (ipsilateral) leg were smaller during stretching compared to before, and at 0 and 5 min after stretching. Furthermore, the degree of reduction in the amplitude of the spinal reflexes in the right (ipsilateral) leg muscles increased significantly as the dorsiflexion torque (i.e., stretching of the right triceps surae muscles) increased. In contrast, reduction in the amplitude of the spinal reflexes with increasing dorsiflexion torque was not seen in the left (contralateral) leg muscles. Our results clearly indicate that muscle stretching has inhibitory effects on monosynaptic spinal reflexes, not only in stretched muscles, but also in non-stretched muscles of the ipsilateral leg. PMID:28662201

The "Tracked Roaming Transect" and distance sampling methods increase the efficiency of underwater visual censuses.

PubMed

Irigoyen, Alejo J; Rojo, Irene; Calò, Antonio; Trobbiani, Gastón; Sánchez-Carnero, Noela; García-Charton, José A

2018-01-01

Underwater visual census (UVC) is the most common approach for estimating diversity, abundance and size of reef fishes in shallow and clear waters. Abundance estimation through UVC is particularly problematic in species occurring at low densities and/or highly aggregated because of their high variability at both spatial and temporal scales. The statistical power of experiments involving UVC techniques may be increased by augmenting the number of replicates or the area surveyed. In this work we present and test the efficiency of an UVC method based on diver towed GPS, the Tracked Roaming Transect (TRT), designed to maximize transect length (and thus the surveyed area) with respect to diving time invested in monitoring, as compared to Conventional Strip Transects (CST). Additionally, we analyze the effect of increasing transect width and length on the precision of density estimates by comparing TRT vs. CST methods using different fixed widths of 6 and 20 m (FW3 and FW10, respectively) and the Distance Sampling (DS) method, in which perpendicular distance of each fish or group of fishes to the transect line is estimated by divers up to 20 m from the transect line. The TRT was 74% more time and cost efficient than the CST (all transect widths considered together) and, for a given time, the use of TRT and/or increasing the transect width increased the precision of density estimates. In addition, since with the DS method distances of fishes to the transect line have to be estimated, and not measured directly as in terrestrial environments, errors in estimations of perpendicular distances can seriously affect DS density estimations. To assess the occurrence of distance estimation errors and their dependence on the observer's experience, a field experiment using wooden fish models was performed. We tested the precision and accuracy of density estimators based on fixed widths and the DS method. The accuracy of the estimates was measured comparing the actual total abundance with those estimated by divers using FW3, FW10, and DS estimators. Density estimates differed by 13% (range 0.1-31%) from the actual values (average = 13.09%; median = 14.16%). Based on our results we encourage the use of the Tracked Roaming Transect with Distance Sampling (TRT+DS) method for improving density estimates of species occurring at low densities and/or highly aggregated, as well as for exploratory rapid-assessment surveys in which divers could gather spatial ecological and ecosystem information on large areas during UVC.

The "Tracked Roaming Transect" and distance sampling methods increase the efficiency of underwater visual censuses

PubMed Central

2018-01-01

Underwater visual census (UVC) is the most common approach for estimating diversity, abundance and size of reef fishes in shallow and clear waters. Abundance estimation through UVC is particularly problematic in species occurring at low densities and/or highly aggregated because of their high variability at both spatial and temporal scales. The statistical power of experiments involving UVC techniques may be increased by augmenting the number of replicates or the area surveyed. In this work we present and test the efficiency of an UVC method based on diver towed GPS, the Tracked Roaming Transect (TRT), designed to maximize transect length (and thus the surveyed area) with respect to diving time invested in monitoring, as compared to Conventional Strip Transects (CST). Additionally, we analyze the effect of increasing transect width and length on the precision of density estimates by comparing TRT vs. CST methods using different fixed widths of 6 and 20 m (FW3 and FW10, respectively) and the Distance Sampling (DS) method, in which perpendicular distance of each fish or group of fishes to the transect line is estimated by divers up to 20 m from the transect line. The TRT was 74% more time and cost efficient than the CST (all transect widths considered together) and, for a given time, the use of TRT and/or increasing the transect width increased the precision of density estimates. In addition, since with the DS method distances of fishes to the transect line have to be estimated, and not measured directly as in terrestrial environments, errors in estimations of perpendicular distances can seriously affect DS density estimations. To assess the occurrence of distance estimation errors and their dependence on the observer’s experience, a field experiment using wooden fish models was performed. We tested the precision and accuracy of density estimators based on fixed widths and the DS method. The accuracy of the estimates was measured comparing the actual total abundance with those estimated by divers using FW3, FW10, and DS estimators. Density estimates differed by 13% (range 0.1–31%) from the actual values (average = 13.09%; median = 14.16%). Based on our results we encourage the use of the Tracked Roaming Transect with Distance Sampling (TRT+DS) method for improving density estimates of species occurring at low densities and/or highly aggregated, as well as for exploratory rapid-assessment surveys in which divers could gather spatial ecological and ecosystem information on large areas during UVC. PMID:29324887

Instrumentation and fusion for congenital spine deformities.

PubMed

Hedequist, Daniel J

2009-08-01

A retrospective clinical review. To review the use of modern instrumentation of the spine for congenital spinal deformities. Spinal instrumentation has evolved since the advent of the Harrington rod. There is a paucity of literature, which discusses the use of modern spinal instrumentation in congenital spine deformity cases. This review focuses on modern instrumentation techniques for congenital scoliosis and kyphosis. A systematic review was performed of the literature to discuss spinal implant use for congenital deformities. Spinal instrumentation may be safely and effectively used in cases of congenital spinal deformity. Spinal surgeons taking care of children with congenital spine deformities need to be trained in all aspects of modern spinal instrumentation.

Effect of ramosetron on shivering during spinal anesthesia

PubMed Central

Kim, Min Soo; Kim, Dong Won; Woo, Seung-Hoon; Yon, Jun Heum

2010-01-01

Background Shivering associated with spinal anesthesia is uncomfortable and may interfere with monitoring. The aim of this study is to evaluate the effect of ramosetron, a serotonin-3 receptor antagonist, on the prevention of shivering during spinal anesthesia. Methods We enrolled 52 patients who were ASA I or II and who had undergone knee arthroscopy under spinal anesthesia. Warmed (37°) lactated Ringer's solution was infused over 15 minutes before spinal anesthesia. Patients were randomly allocated to a control group (group S, N = 26) or study group (group R, N = 26). Spinal anesthesia was performed with a 25-G Quincke-type spinal needle between the lumbar 3-4 interspace with 2.2 ml 0.5% hyperbaric bupivacaine. For patients allocated in groups S and R, 2 ml 0.9% saline and 0.3 mg ramosetron, respectively, was intravenously injected immediately before intrathecal injection at identical times. Shivering and spinal block levels were assessed immediately after the completion of subarachnoid injection, as well as 5, 10, 15, 20, 25, 30, 60, and 120 minutes after spinal anesthesia. Systolic and diastolic blood pressures, heart rate, and peripheral oxygen saturation were also recorded. Core temperatures were measured by tympanic thermometer and recorded before and during spinal anesthesia at 30-minute intervals. Results Shivering was observed in 2 patients in group R and 9 patients in group S (P = 0.038, odds ratio = 6.14, 95% C.I. = 1.08-65.5). The difference in core temperature between the groups was not significant. Conclusions Compared to control, ramosetron is an effective way to prevent shivering during spinal anesthesia. PMID:20498774

A standardized safe hepatectomy; selective Glissonean transection using endolinear stapling devices.

PubMed

Fujii, Masahiko; Shimada, Mitsuo; Satoru, Imura; Morine, Yuji; Ikemoto, Tetsuya; Soejima, Yuji

2007-01-01

Selective clamping of Glisson's pedicle at the hilum is effective for systematized hepatectomy. Because of the development of stapling devices, a Glissonean transection using a surgical stapler has been used widely. However, the risk of accidental stapling of the biliary confluence still remains. In this paper we report about a case that underwent selective Glissonean transection using an endolinear stapling device. We used this standardized technique in five patients without any major complications. The particular case to which we refer was a 71-year-old woman with hepatocellular carcinoma in the right lobe. The anterior and posterior branches of Glisson's pedicle were independently divided using an endolinear stapling device. The right hepatic lobectomy was achieved with little bleeding and in addition there was a shortened operation time and the postoperative course was uneventful. In the patient with liver cirrhosis, postoperative complications often related to liver failure. We herein advocate a standardized safe hepatectomy using endolinear stapling devices. We believe that the shortened operative time and decreased risk of complications by selective Glissonean transection as well as hepatic vein transection using stapling devices contribute to the improved short-term outcome.

Healing process of vascular cutting edge using an Nd:YAG laser bipolar dissector.

PubMed

Morita, T; Ishida, K; Ookubo, K; Tanaka, K; Nakamura, H; Daikuzono, N

1995-08-01

The wound healing process was histopathologically investigated in a rabbit femoral artery (n = 48) after transection using a laser bipolar dissector (LBD, 1064nm the Nd:YAG bipolar contact laser) with laser power of 13W in 0.5-sec pulses. The cutting edges were harvested immediately (n = 6) and at 1 (n = 6), 4 (n = 6), and 7 (n = 6) days, 2 (n = 6), 3 (n = 6), and 4 (n = 6) weeks, and 6 months (n = 6), and evaluated by light microscopy. During the postoperative period, no perforation was seen in the 48 transected sites with the LBD. The healing process after LBD transection was accomplished within 2 weeks by organization of the intraluminal thrombus and by the formation of granulation tissue outside the adventitia of vessels. Characteristic morphological changes after LBD transection were recognized in the tapering area, i.e., cartilage and bone formation. Cartilaginous foci (n = 6) were observed in the media at 4 weeks after transection, and osseous foci (n = 3) in subendothelial space at 6 months. These observations may suggest that the heterotopic cartilaginous and osseous metaplasia of a vessel wall may be a result of the biostimulative effects of the Nd:YAG laser.

Effects of even-aged management on forest birds at northern hardwood stand interfaces

Treesearch

Richard M. DeGraaf

1992-01-01

Breeding birds were counted along transects across edges of even-aged northern hardwood stands in the White Mountain National Forest, New Hampshire, U.S.A. Two replicate transects across each of 7 edge types representing 3 classes of contrast (abrupt, intermediate, and subtle) were sampled during June 1983-1985 to define species assemblages at stand edges and estimate...

Axonal Regeneration after Sciatic Nerve Lesion Is Delayed but Complete in GFAP- and Vimentin-Deficient Mice

PubMed Central

Berg, Alexander; Zelano, Johan; Pekna, Marcela; Wilhelmsson, Ulrika; Pekny, Milos; Cullheim, Staffan

2013-01-01

Peripheral axotomy of motoneurons triggers Wallerian degeneration of injured axons distal to the lesion, followed by axon regeneration. Centrally, axotomy induces loss of synapses (synaptic stripping) from the surface of lesioned motoneurons in the spinal cord. At the lesion site, reactive Schwann cells provide trophic support and guidance for outgrowing axons. The mechanisms of synaptic stripping remain elusive, but reactive astrocytes and microglia appear to be important in this process. We studied axonal regeneration and synaptic stripping of motoneurons after a sciatic nerve lesion in mice lacking the intermediate filament (nanofilament) proteins glial fibrillary acidic protein (GFAP) and vimentin, which are upregulated in reactive astrocytes and Schwann cells. Seven days after sciatic nerve transection, ultrastructural analysis of synaptic density on the somata of injured motoneurons revealed more remaining boutons covering injured somata in GFAP–/–Vim–/– mice. After sciatic nerve crush in GFAP–/–Vim–/– mice, the fraction of reinnervated motor endplates on muscle fibers of the gastrocnemius muscle was reduced 13 days after the injury, and axonal regeneration and functional recovery were delayed but complete. Thus, the absence of GFAP and vimentin in glial cells does not seem to affect the outcome after peripheral motoneuron injury but may have an important effect on the response dynamics. PMID:24223940

Effects of fluid structure interaction in a three dimensional model of the spinal subarachnoid space.

PubMed

Cheng, Shaokoon; Fletcher, David; Hemley, Sarah; Stoodley, Marcus; Bilston, Lynne

2014-08-22

It is unknown whether spinal cord motion has a significant effect on cerebrospinal fluid (CSF) pressure and therefore the importance of including fluid structure interaction (FSI) in computational fluid dynamics models (CFD) of the spinal subarachnoid space (SAS) is unclear. This study aims to determine the effects of FSI on CSF pressure and spinal cord motion in a normal and in a stenosis model of the SAS. A three-dimensional patient specific model of the SAS and spinal cord were constructed from MR anatomical images and CSF flow rate measurements obtained from a healthy human being. The area of SAS at spinal level T4 was constricted by 20% to represent the stenosis model. FSI simulations in both models were performed by running ANSYS CFX and ANSYS Mechanical in tandem. Results from this study show that the effect of FSI on CSF pressure is only about 1% in both the normal and stenosis models and therefore show that FSI has a negligible effect on CSF pressure. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Numerical simulations to assess the tracer dilution method for measurement of landfill methane emissions.

PubMed

Taylor, Diane M; Chow, Fotini K; Delkash, Madjid; Imhoff, Paul T

2016-10-01

Landfills are a significant contributor to anthropogenic methane emissions, but measuring these emissions can be challenging. This work uses numerical simulations to assess the accuracy of the tracer dilution method, which is used to estimate landfill emissions. Atmospheric dispersion simulations with the Weather Research and Forecast model (WRF) are run over Sandtown Landfill in Delaware, USA, using observation data to validate the meteorological model output. A steady landfill methane emissions rate is used in the model, and methane and tracer gas concentrations are collected along various transects downwind from the landfill for use in the tracer dilution method. The calculated methane emissions are compared to the methane emissions rate used in the model to find the percent error of the tracer dilution method for each simulation. The roles of different factors are examined: measurement distance from the landfill, transect angle relative to the wind direction, speed of the transect vehicle, tracer placement relative to the hot spot of methane emissions, complexity of topography, and wind direction. Results show that percent error generally decreases with distance from the landfill, where the tracer and methane plumes become well mixed. Tracer placement has the largest effect on percent error, and topography and wind direction both have significant effects, with measurement errors ranging from -12% to 42% over all simulations. Transect angle and transect speed have small to negligible effects on the accuracy of the tracer dilution method. These tracer dilution method simulations provide insight into measurement errors that might occur in the field, enhance understanding of the method's limitations, and aid interpretation of field data. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Local Administration of Boric Acid on Posterolateral Spinal Fusion with Autogenous Bone Grafting in a Rodent Model.

PubMed

Kömürcü, Erkam; Özyalvaçlı, Gülzade; Kaymaz, Burak; Gölge, Umut Hatay; Göksel, Ferdi; Cevizci, Sibel; Adam, Gürhan; Ozden, Raif

2015-09-01

Spinal fusion is among the most frequently applied spinal surgical procedures. The goal of the present study was to evaluate whether the local administration of boric acid (BA) improves spinal fusion in an experimental spinal fusion model in rats. Currently, there is no published data that evaluates the possible positive effects if the local administration of BA on posterolateral spinal fusion. Thirty-two rats were randomly divided into four independent groups: no material was added at the fusion area for group 1; an autogenous morselized corticocancellous bone graft was used for group 2; an autogenous morselized corticocancellous bone graft with boric acid (8.7 mg/kg) for group 3; and only boric acid was placed into the fusion area for group 4. The L4-L6 spinal segments were collected at week 6, and the assessments included radiography, manual palpation, and histomorphometry. A statistically significant difference was determined between the groups with regard to the mean histopathological scores (p = 0.002), and a paired comparison was made with the Mann-Whitney U test to detect the group/groups from which the difference originated. It was determined that only the graft + BA practice increased the histopathological score significantly with regard to the control group (p = 0.002). Whereas, there was no statistically significant difference between the groups in terms of the manual assessment of fusion and radiographic analysis (respectively p = 0.328 and p = 0.196). This preliminary study suggests that BA may clearly be useful as a therapeutic agent in spinal fusion. However, further research is required to show the most effective dosage of BA on spinal fusion, and should indicate whether BA effects spinal fusion in the human body.

Comparison of subarachnoid anesthetic effect of emulsified volatile anesthetics in rats.

PubMed

Guo, Jiao; Zhou, Cheng; Liang, Peng; Huang, Han; Li, Fengshan; Chen, Xiangdong; Liu, Jin

2014-01-01

Spinal cord is an important target of volatile anesthetics in particular for the effect of immobility. Intrathecal injection of volatile anesthetics has been found to produce subarachnoid anesthesia. The present study was designed to compare spinal anesthetic effects of emulsified volatile anesthetics, and to investigate the correlation between their spinal effects and general effect of immobility. In this study, halothane, isoflurane, enflurane and sevoflurane were emulsified by 30% Intralipid. These emulsified volatile anesthetics were intravenously and intrathecally injected, respectively. ED50 of general anesthesia and EC50 of spinal anesthesia were determined. The durations of general and spinal anesthesia were recorded. Correlation analysis was applied to evaluate the anesthetic potency of volatile anesthetics between their spinal and general effects. ED50 of general anesthesia induced by emulsified halothane, isoflurane, enflurane and sevoflurane were 0.41 ± 0.07, 0.54 ± 0.07, 0.74 ± 0.11 and 0.78 ± 0.08 mmol/kg, respectively, with significant correlation to their inhaled MAC (R(2) = 0.8620, P = 0.047). For intrathecal injection, EC50 of spinal anesthesia induced by emulsified halothane, isoflurane, enflurane and sevoflurane were 0.35, 0.27, 0.33 and 0.26 mol/L, respectively, which could be predicted by the product of inhaled MAC and olive oil/gas partition coefficients (R(2) = 0.9627, P = 0.013). In conclusion, potency and efficacy of the four emulsified volatile anesthetics in spinal anesthesia were similar and could be predicted by the product of inhaled MAC and olive oil/gas partition coefficients (MAC × olive oil/gas partition coefficients).

Comparison of subarachnoid anesthetic effect of emulsified volatile anesthetics in rats

PubMed Central

Guo, Jiao; Zhou, Cheng; Liang, Peng; Huang, Han; Li, Fengshan; Chen, Xiangdong; Liu, Jin

2014-01-01

Spinal cord is an important target of volatile anesthetics in particular for the effect of immobility. Intrathecal injection of volatile anesthetics has been found to produce subarachnoid anesthesia. The present study was designed to compare spinal anesthetic effects of emulsified volatile anesthetics, and to investigate the correlation between their spinal effects and general effect of immobility. In this study, halothane, isoflurane, enflurane and sevoflurane were emulsified by 30% Intralipid. These emulsified volatile anesthetics were intravenously and intrathecally injected, respectively. ED50 of general anesthesia and EC50 of spinal anesthesia were determined. The durations of general and spinal anesthesia were recorded. Correlation analysis was applied to evaluate the anesthetic potency of volatile anesthetics between their spinal and general effects. ED50 of general anesthesia induced by emulsified halothane, isoflurane, enflurane and sevoflurane were 0.41 ± 0.07, 0.54 ± 0.07, 0.74 ± 0.11 and 0.78 ± 0.08 mmol/kg, respectively, with significant correlation to their inhaled MAC (R2 = 0.8620, P = 0.047). For intrathecal injection, EC50 of spinal anesthesia induced by emulsified halothane, isoflurane, enflurane and sevoflurane were 0.35, 0.27, 0.33 and 0.26 mol/L, respectively, which could be predicted by the product of inhaled MAC and olive oil/gas partition coefficients (R2 = 0.9627, P = 0.013). In conclusion, potency and efficacy of the four emulsified volatile anesthetics in spinal anesthesia were similar and could be predicted by the product of inhaled MAC and olive oil/gas partition coefficients (MAC × olive oil/gas partition coefficients). PMID:25674241

Effects of whole spine alignment patterns on neck responses in rear end impact.

PubMed

Sato, Fusako; Odani, Mamiko; Miyazaki, Yusuke; Yamazaki, Kunio; Östh, Jonas; Svensson, Mats

2017-02-17

The aim of this study was to investigate the whole spine alignment in automotive seated postures for both genders and the effects of the spinal alignment patterns on cervical vertebral motion in rear impact using a human finite element (FE) model. Image data for 8 female and 7 male subjects in a seated posture acquired by an upright open magnetic resonance imaging (MRI) system were utilized. Spinal alignment was determined from the centers of the vertebrae and average spinal alignment patterns for both genders were estimated by multidimensional scaling (MDS). An occupant FE model of female average size (162 cm, 62 kg; the AF 50 size model) was developed by scaling THUMS AF 05. The average spinal alignment pattern for females was implemented in the model, and model validation was made with respect to female volunteer sled test data from rear end impacts. Thereafter, the average spinal alignment pattern for males and representative spinal alignments for all subjects were implemented in the validated female model, and additional FE simulations of the sled test were conducted to investigate effects of spinal alignment patterns on cervical vertebral motion. The estimated average spinal alignment pattern was slight kyphotic, or almost straight cervical and less-kyphotic thoracic spine for the females and lordotic cervical and more pronounced kyphotic thoracic spine for the males. The AF 50 size model with the female average spinal alignment exhibited spine straightening from upper thoracic vertebra level and showed larger intervertebral angular displacements in the cervical spine than the one with the male average spinal alignment. The cervical spine alignment is continuous with the thoracic spine, and a trend of the relationship between cervical spine and thoracic spinal alignment was shown in this study. Simulation results suggested that variations in thoracic spinal alignment had a potential impact on cervical spine motion as well as cervical spinal alignment in rear end impact condition.

Effects of core body temperature on changes in spinal somatosensory-evoked potential in acute spinal cord compression injury: an experimental study in the rat.

PubMed

Jou, I M

2000-08-01

Acute spinal cord injury was induced by a clip compression model in rats to approximate spinal cord injury encountered in spinal surgery. Spinal somatosensory-evoked potential neuromonitoring was used to study the electrophysiologic change. To compare and correlate changes in evoked potential after acute compression at different core temperatures with postoperative neurologic function and histologic change, to evaluate current intraoperative neuromonitoring warning criteria for neural damage, and to confirm the protective effect of hypothermia in acute spinal cord compression injury by electrophysiologic, histologic, and clinical observation. With the increase in aggressive correction of spinal deformities, and the invasiveness of surgical instruments, the incidence of neurologic complication appears to have increased despite the availability of sensitive intraoperative neuromonitoring techniques designed to alert surgeons to impending neural damage. Many reasons have been given for the frequent failures of neuromonitoring, but the influence of temperature-a very important and frequently encountered factor-on evoked potential has not been well documented. Specifically, decrease in amplitude and elongation of latency seem not to have been sufficiently taken into account when intraoperative neuromonitoring levels were interpreted and when acceptable intraoperative warning criteria were determined. Experimental acute spinal cord injury was induced in rats by clip compression for two different intervals and at three different core temperatures. Spinal somatosensory-evoked potential, elicited by stimulating the median nerve and recorded from the cervical interspinous C2-C3, was monitored immediately before and after compression, and at 15-minute intervals for 1 hour. Spinal somatosensory-evoked potential change is almost parallel to temperature-based amplitude reduction and latency elongation. Significant neurologic damage induced by acute compression of the cervical spinal cord produced a degree of effect on the amplitude of spinal somatosensory-evoked potential in normothermic conditions that differed from the effect in moderately hypothermic conditions. Using the same electromonitoring criteria,moderately hypothermic groups showed a significantly higher false-negative rate statistically (35%) than normothermic groups (10%). Systemic cooling may protect against the detrimental effects of aggressive spinal surgical procedures. There is still not enough published information available to establish statistically and ethically acceptable intraoperative neuromonitoring warning and intervention criteria conclusively. Therefore, an urgent need exists for further investigation. Although a reduction of more than 50% in evoked potential still seems acceptable as an indicator of impending neural function loss, maintenance of more than 50% of baseline evoked potential is no guarantee of normal postoperative neural function, especially at lower than normal temperatures.

Modeling trans-spinal direct current stimulation for the modulation of the lumbar spinal motor pathways

NASA Astrophysics Data System (ADS)

Kuck, A.; Stegeman, D. F.; van Asseldonk, E. H. F.

2017-10-01

Objective. Trans-spinal direct current stimulation (tsDCS) is a potential new technique for the treatment of spinal cord injury (SCI). TsDCS aims to facilitate plastic changes in the neural pathways of the spinal cord with a positive effect on SCI recovery. To establish tsDCS as a possible treatment option for SCI, it is essential to gain a better understanding of its cause and effects. We seek to understand the acute effect of tsDCS, including the generated electric field (EF) and its polarization effect on the spinal circuits, to determine a cellular target. We further ask how these findings can be interpreted to explain published experimental results. Approach. We use a realistic full body finite element volume conductor model to calculate the EF of a 2.5 mA direct current for three different electrode configurations. We apply the calculated electric field to realistic motoneuron models to investigate static changes in membrane resting potential. The results are combined with existing knowledge about the theoretical effect on a neuronal level and implemented into an existing lumbar spinal network model to simulate the resulting changes on a network level. Main results. Across electrode configurations, the maximum EF inside the spinal cord ranged from 0.47 V m-1 to 0.82 V m-1. Axon terminal polarization was identified to be the dominant cellular target. Also, differences in electrode placement have a large influence on axon terminal polarization. Comparison between the simulated acute effects and the electrophysiological long-term changes observed in human tsDCS studies suggest an inverse relationship between the two. Significance. We provide methods and knowledge for better understanding the effects of tsDCS and serve as a basis for a more targeted and optimized application of tsDCS.

Primary non-transecting bulbar urethroplasty long-term success rates are similar to transecting urethroplasty.

PubMed

Anderson, Kirk M; Blakely, Stephen A; O'Donnell, Colin I; Nikolavsky, Dmitriy; Flynn, Brian J

2017-01-01

To review the long-term outcomes of transecting versus non-transecting urethroplasty to repair bulbar urethral strictures. A retrospective review was conducted of 342 patients who underwent anterior urethroplasty performed by a single surgeon from 2003 to 2014. Patients were excluded from further analysis if there had been prior urethroplasty, stricture location outside the bulbous urethra, or age <18 years. In the transecting group, surgical techniques used included excision and primary anastomosis and augmented anastomotic urethroplasty. In the non-transecting group, surgical techniques used included non-transecting anastomotic urethroplasty and dorsal and/or ventral buccal grafting. The primary endpoint was stricture resolution in transecting vs. non-transecting bulbar urethroplasty. Success was defined as freedom from secondary procedures including dilation, urethrotomy, or repeat urethroplasty. One hundred and fifty-two patients met inclusion criteria. At a mean follow-up of 65 months (range: 10-138 months), stricture-free recurrence in the transecting and non-transecting groups was similar, 83% (n = 85/102) and 82% (n = 41/50), respectively (p = 0.84). Surgical technique (p = 0.91), stricture length (p = 0.8), and etiology (p = 0.6) did not affect stricture recurrence rate on multivariate analysis. There was no difference detected in time to stricture recurrence (p = 0.21). In this retrospective series, transecting and non-transecting primary bulbar urethroplasty resulted in similar long-term stricture resolution rate. Prospective studies are needed to determine what differences may present in outcomes related to sexual function and long-term success.

A Combination of Ex vivo Diffusion MRI and Multiphoton to Study Microglia/Monocytes Alterations after Spinal Cord Injury

PubMed Central

Noristani, Harun N.; Boukhaddaoui, Hassan; Saint-Martin, Guillaume; Auzer, Pauline; Sidiboulenouar, Rahima; Lonjon, Nicolas; Alibert, Eric; Tricaud, Nicolas; Goze-Bac, Christophe; Coillot, Christophe; Perrin, Florence E.

2017-01-01

Central nervous system (CNS) injury has been observed to lead to microglia activation and monocytes infiltration at the lesion site. Ex vivo diffusion magnetic resonance imaging (diffusion MRI or DWI) allows detailed examination of CNS tissues, and recent advances in clearing procedures allow detailed imaging of fluorescent-labeled cells at high resolution. No study has yet combined ex vivo diffusion MRI and clearing procedures to establish a possible link between microglia/monocytes response and diffusion coefficient in the context of spinal cord injury (SCI). We carried out ex vivo MRI of the spinal cord at different time-points after spinal cord transection followed by tetrahydrofuran based clearing and examined the density and morphology of microglia/monocytes using two-photon microscopy. Quantitative analysis revealed an early marked increase in microglial/monocytes density that is associated with an increase in the extension of the lesion measured using diffusion MRI. Morphological examination of microglia/monocytes somata at the lesion site revealed a significant increase in their surface area and volume as early as 72 hours post-injury. Time-course analysis showed differential microglial/monocytes response rostral and caudal to the lesion site. Microglia/monocytes showed a decrease in reactivity over time caudal to the lesion site, but an increase was observed rostrally. Direct comparison of microglia/monocytes morphology, obtained through multiphoton, and the longitudinal apparent diffusion coefficient (ADC), measured with diffusion MRI, highlighted that axonal integrity does not correlate with the density of microglia/monocytes or their somata morphology. We emphasize that differential microglial/monocytes reactivity rostral and caudal to the lesion site may thus coincide, at least partially, with reported temporal differences in debris clearance. Our study demonstrates that the combination of ex vivo diffusion MRI and two-photon microscopy may be used to follow structural tissue alteration. Lesion extension coincides with microglia/monocytes density; however, a direct relationship between ADC and microglia/monocytes density and morphology was not observed. We highlighted a differential rostro-caudal microglia/monocytes reactivity that may correspond to a temporal difference in debris clearance and axonal integrity. Thus, potential therapeutic strategies targeting microglia/monocytes after SCI may need to be adjusted not only with the time after injury but also relative to the location to the lesion site. PMID:28769787

Expression of the vesicular glutamate transporters-1 and -2 in adult mouse dorsal root ganglia and spinal cord and their regulation by nerve injury.

PubMed

Brumovsky, P; Watanabe, M; Hökfelt, T

2007-06-29

The expression of two vesicular glutamate transporters (VGLUTs), VGLUT1 and VGLUT2, was studied with immunohistochemistry in lumbar dorsal root ganglia (DRGs), the lumbar spinal cord and the skin of the adult mouse. About 12% and 65% of the total number of DRG neuron profiles (NPs) expressed VGLUT1 and VGLUT2, respectively. VGLUT1-immunoreactive (IR) NPs were usually medium- to large-sized, in contrast to a majority of small- or medium-sized VGLUT2-IR NPs. Most VGLUT1-IR NPs did not coexpress calcitonin gene-related peptide (CGRP) or bound isolectin B4 (IB4). In contrast, approximately 31% and approximately 42% of the VGLUT2-IR DRG NPs were also CGRP-IR or bound IB4, respectively. Conversely, virtually all CGRP-IR and IB4-binding NPs coexpressed VGLUT2. Moderate colocalization between VGLUT1 and VGLUT2 was also observed. Sciatic nerve transection induced a decrease in the overall number of VGLUT1- and VGLUT2-IR NPs (both ipsi- and contralaterally) and, in addition, a parallel, unilateral increase of VGLUT2-like immunoreactivity (LI) in a subpopulation of mostly small NPs. In the dorsal horn of the spinal cord, strong VGLUT1-LI was detected, particularly in deep dorsal horn layers and in the ventral horns. VGLUT2-LI was abundant throughout the gray spinal matter, 'radiating' into/from the white matter. A unilateral dorsal rhizotomy reduced VGLUT1-LI, while apparently leaving unaffected the VGLUT2-LI. Transport through axons for both VGLUTs was confirmed by their accumulation after compression of the sciatic nerve or dorsal roots. In the hind paw skin, abundant VGLUT2-IR nerve fibers were observed, sometimes associated with Merkel cells. Lower numbers of VGLUT1-IR fibers were also detected in the skin. Some VGLUT1-IR and VGLUT2-IR fibers were associated with hair follicles. Based on these data and those by Morris et al. [Morris JL, Konig P, Shimizu T, Jobling P, Gibbins IL (2005) Most peptide-containing sensory neurons lack proteins for exocytotic release and vesicular transport of glutamate. J Comp Neurol 483:1-16], we speculate that virtually all DRG neurons in adult mouse express VGLUTs and use glutamate as transmitter.

Reinforcement of spinal anesthesia by epidural injection of saline: a comparison of hyperbaric and isobaric tetracaine.

PubMed

Yamazaki, Y; Mimura, M; Hazama, K; Namiki, A

2000-04-25

An epidural injection of saline was reported to extend spinal anesthesia because of a volume effect. The aim of this study was to evaluate the influence of the baricity of spinal local anesthetics upon the extension of spinal anesthesia by epidural injection of saline. Forty patients undergoing elective lower-limb surgery were randomly allocated to four groups of 10 patients each. Group A received no epidural injection after the spinal administration of hyperbaric tetracaine (dissolved in 10% glucose). Group B received an epidural injection of 8 ml of physiological saline 20 min after spinal hyperbaric tetracaine. Group C received no epidural injection after spinal isobaric tetracaine (dissolved in physiological saline). Group D received an epidural injection of 8 ml of saline 20 min after spinal isobaric tetracaine. The level of analgesia was examined by the pinprick method at 5-min intervals. The levels of analgesia 20 min after spinal anesthesia were significantly higher in hyperbaric groups than in isobaric groups [T5 (T2-L2) vs. T7 (T3-12)]. After epidural injection of saline, the levels of analgesia in groups B and D were significantly higher than in groups A and C. The segmental increases after epidural saline injection were 2 (0-3) in group B and 2 (1-7) in group D. Sensation in the sacral area remained 20 min after spinal block in one patient in group D; however, it disappeared after epidural saline injection. In this study, 8 ml of epidural saline extended spinal analgesia. However, there was no difference between the augmenting effect in isobaric and hyperbaric spinal anesthesia. We conclude that the reinforcement of spinal anesthesia by epidural injection of saline is not affected by the baricity of the spinal anesthetic solution used.

Subdural Thoracolumbar Spine Hematoma after Spinal Anesthesia: A Rare Occurrence and Literature Review of Spinal Hematomas after Spinal Anesthesia.

PubMed

Maddali, Prasanthi; Walker, Blake; Fisahn, Christian; Page, Jeni; Diaz, Vicki; Zwillman, Michael E; Oskouian, Rod J; Tubbs, R Shane; Moisi, Marc

2017-02-16

Spinal hematomas are a rare but serious complication of spinal epidural anesthesia and are typically seen in the epidural space; however, they have been documented in the subdural space. Spinal subdural hematomas likely exist within a traumatically induced space within the dural border cell layer, rather than an anatomical subdural space. Spinal subdural hematomas present a dangerous clinical situation as they have the potential to cause significant compression of neural elements and can be easily mistaken for spinal epidural hematomas. Ultrasound can be an effective modality to diagnose subdural hematoma when no epidural blood is visualized. We have reviewed the literature and present a full literature review and a case presentation of an 82-year-old male who developed a thoracolumbar spinal subdural hematoma after spinal epidural anesthesia. Anticoagulant therapy is an important predisposing risk factor for spinal epidural hematomas and likely also predispose to spinal subdural hematomas. It is important to consider spinal subdural hematomas in addition to spinal epidural hematomas in patients who develop weakness after spinal epidural anesthesia, especially in patients who have received anticoagulation.

Batrachochytrium dendrobatidis infection patterns among Panamanian amphibian species, habitats and elevations during epizootic and enzootic stages.

PubMed

Brem, Forrest M R; Lips, Karen R

2008-09-24

The pathogenic fungus Batrachochytrium dendrobatidis (Bd) has caused declines of many amphibian populations, yet the full course of the epizootic has rarely been observed in wild populations. We determined effects of elevation, habitat, and aquatic index (AI) on prevalence of infection among Panamanian amphibians sampled along 2 elevational transects. Amphibian populations on the Santa Fé transect (SFT) had declined in 2002, while those on the El Copé transect (ECT) were healthy until September 2004. In 2004 we sampled Bd along both transects, surveying the SFT 2 yr after decline, and surveying the ECT 4 mo prior to the arrival of Bd, during the epizootic, and 2 mo later. Overall prevalence of Bd along the ECT increased from 0.0 (95% CI 0.00-0.0003) to 0.51 (95% CI 0.48-0.55) over a 3 mo period, accompanied by significant decreases in amphibian abundance and species richness in all habitats. Prevalence of infection on the ECT was highest along riparian transects and at higher elevations, but not among levels of AI. Prevalence of infection on the SFT was highest in pool transects, and at higher elevations, but not among levels of AI. Riparian amphibian abundance and species richness also declined at SFT following detection of Bd in 2002. Variation among species, microenvironmental conditions, and the length of coexistence with Bd may contribute to observed differences in prevalence of Bd and in population response.

Correction for slope in point and transect relascope sampling of downed coarse woody debris

Treesearch

Goran Stahl; Anna Ringvall; Jeffrey H. Gove; Mark J. Ducey

2002-01-01

In this article, the effect of sloping terrain on estimates in point and transect relascope sampling (PRS and TRS, respectively) is studied. With these inventory methods, a wide angle relascope is used either from sample points (PRS) or along survey lines (TRS). Characteristics associated with line-shaped objects on the ground are assessed, e.g., the length or volume...

Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses

PubMed Central

Mishra, Asht M.; Pal, Ajay; Gupta, Disha

2017-01-01

Key points Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord.The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone.Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal.Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Abstract Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this protocol and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensorimotor function after injury to the central nervous system. PMID:28752624

Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses.

PubMed

Mishra, Asht M; Pal, Ajay; Gupta, Disha; Carmel, Jason B

2017-11-15

Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord. The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone. Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal. Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this protocol and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensorimotor function after injury to the central nervous system. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Remarkable recovery in an infant presenting with extensive perinatal cervical cord injury.

PubMed

Ul Haq, Israr; Gururaj, A K

2012-12-10

Cervical-cord damage is a complication of a difficult delivery, and results in spinal shock with flaccidity progressing to spastic paralysis. Conventionally, outlook for such patients is extremely poor and most will recover only slightly from quadriplegia and autonomic dysfunction. Here, we report a case in which the extent of damage considerably contrasted with the outcome and recovery. A full-term baby girl born by difficult vaginal delivery displayed bilateral flaccid paralysis of the lower limbs with absent spontaneous movements, weakness of both upper limbs, hyporeflexia in all limbs and axial hypotonia. MRI of cervicothoracic spine exhibited raised signal intensity in the dorsal aspects of C7 to T1 signifying myelopathy. MRI at 4 months revealed a near-total transection of the cervical cord. However, at 6 months, the child could move all lower limbs independently with a marked increase in power. There was no spasticity, wasting or incontinence. Reflexes had also returned.

Suicidal Decapitation by Hanging-A Population-based Study.

PubMed

Byard, Roger W; Gilbert, John D

2018-05-01

A prospective study was undertaken at Forensic Science SA over a 15-year period from July 2002 to June 2017 for all cases of adult (>18 years) suicidal hangings with decapitation. A total of 1446 cases of suicidal hangings were identified from a general population of approximately 1.5 million (1206 males-age range 18-97 years, average 42.6; and 240 females-age range 18-96 years, average 40.1). Only three cases of decapitation were found, all from long-drop hangings; these consisted of three males (ages 32-55 years; average 45 years). Spinal transections had occurred between the first and second, second and third, and third and fourth cervical vertebrae, respectively. In this study, the number of suicidal hangings with decapitation represented only 0.2% of the total number of hangings. These events are therefore extremely rare, most likely due to most suicidal hangings occurring from relatively low levels in a domestic environment. © 2017 American Academy of Forensic Sciences.

Effects of glycine on motor performance in rats after traumatic spinal cord injury.

PubMed

Gonzalez-Piña, Rigoberto; Nuño-Licona, Alberto

2007-01-01

It has been reported that glycine improves some functions lost after spinal cord injury (SCI). In order to assess the effects of glycine administration on motor performance after SCI, we used fifteen male Wistar rats distributed into three groups: sham (n = 3), spinal-cord injury (n = 6,) and spinal cord injury + glycine (n = 6). Motor performance was assessed using the beam-walking paradigm and footprint analysis. Results showed that for all animals with spinal-cord injury, scores in the beam-walking increased, which is an indication of increased motor deficit. In addition, footprint analysis showed a decrease in stride length and an increase in stride angle, additional indicators of motor deficit. These effects trended towards recovery after 8 weeks of recording and trended toward improvement by glycine administration; the effect was not significant. These results suggest that glycine replacement alone is not sufficient to improve the motor deficits that occur after SCI.

The retrograde delivery of adenovirus vector carrying the gene for brain-derived neurotrophic factor protects neurons and oligodendrocytes from apoptosis in the chronically compressed spinal cord of twy/twy mice.

PubMed

Uchida, Kenzo; Nakajima, Hideaki; Hirai, Takayuki; Yayama, Takafumi; Chen, Kebing; Guerrero, Alexander Rodriguez; Johnson, William Eustace; Baba, Hisatoshi

2012-12-15

The twy/twy mouse undergoes spontaneous chronic mechanical compression of the spinal cord; this in vivo model system was used to examine the effects of retrograde adenovirus (adenoviral vector [AdV])-mediated brain-derived neurotrophic factor (BDNF) gene delivery to spinal neural cells. To investigate the targeting and potential neuroprotective effect of retrograde AdV-mediated BDNF gene transfection in the chronically compressed spinal cord in terms of prevention of apoptosis of neurons and oligodendrocytes. Several studies have investigated the neuroprotective effects of neurotrophins, including BDNF, in spinal cord injury. However, no report has described the effects of retrograde neurotrophic factor gene delivery in compressed spinal cords, including gene targeting and the potential to prevent neural cell apoptosis. AdV-BDNF or AdV-LacZ (as a control gene) was injected into the bilateral sternomastoid muscles of 18-week old twy/twy mice for retrograde gene delivery via the spinal accessory motor neurons. Heterozygous Institute of Cancer Research mice (+/twy), which do not undergo spontaneous spinal compression, were used as a control for the effects of such compression on gene delivery. The localization and cell specificity of β-galactosidase expression (produced by LacZ gene transfection) and BDNF expression in the spinal cord were examined by coimmunofluorescence staining for neural cell markers (NeuN, neurons; reactive immunology protein, oligodendrocytes; glial fibrillary acidic protein, astrocytes; OX-42, microglia) 4 weeks after gene injection. The possible neuroprotection afforded by retrograde AdV-BDNF gene delivery versus AdV-LacZ-transfected control mice was assessed by scoring the prevalence of apoptotic cells (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells) and immunoreactivity to active caspases -3, -8, and -9, p75, neurofilament 200 kD (NF), and for the oligodendroglial progenitor marker, NG2. RESULTS.: Four weeks after injection, the retrograde delivery of the LacZ marker gene was identified in cervical spinal neurons and some glial cells, including oligodendrocytes in the white matter of the spinal cord, in both the twy/twy mouse and the heterozygous Institute of Cancer Research mouse (+/twy). In the compressed spinal cord of twy/twy mouse, AdV-BDNF gene transfection resulted in a significant decrease in the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells present in the spinal cord and a downregulation in the caspase apoptotic pathway compared with AdV-LacZ (control) gene transfection. There was a marked and significant increase in the areas of the spinal cord of AdV-BDNF-injected mice that were NF- and NG2-immunopositive compared with AdV-LacZ-injected mice, indicating the increased presence of neurons and oligodendrocytes in response to BDNF transfection. Our results demonstrate that targeted retrograde BDNF gene delivery suppresses apoptosis in neurons and oligodendrocytes in the chronically compressed spinal cord of twy/twy mouse. Further work is required to establish whether this method of gene delivery may provide neuroprotective effects in other situations of compressive spinal cord injury.

Spatial and temporal variability of soil hydraulic properties of topsoil affected by soil erosion

NASA Astrophysics Data System (ADS)

Nikodem, Antonin; Kodesova, Radka; Jaksik, Ondrej; Jirku, Veronika; Klement, Ales; Fer, Miroslav

2014-05-01

This study is focused on the comparison of soil hydraulic properties of topsoil that is affected by erosion processes. In order to include variable morphological and soil properties along the slope three sites - Brumovice, Vidim and Sedlčany were selected. Two transects (A, B) and five sampling sites along each one were chosen. Soil samples were taken in Brumovice after the tillage and sowing of winter wheat in October 2010 and after the wheat harvest in August 2011. At locality Vidim and Sedlčany samples were collected in May and August 2012. Soil hydraulic properties were studied in the laboratory on the undisturbed 100-cm3 soil samples placed in Tempe cells using the multi-step outflow test. Soil water retention data points were obtained by calculating water balance in the soil sample at each pressure head step of the experiment. The single-porosity model in HYDRUS-1D was applied to analyze the multi-step outflow and to obtain the parameters of soil hydraulic properties using the numerical inversion. The saturated hydraulic conductivities (Ks) and unsaturated hydraulic conductivities (Kw) for the pressure head of -2 cm of topsoil were also measured after the harvest using Guelph permeameter and Minidisk tensiometer, respectively. In general soil water retention curves measured before and after vegetation period apparently differed, which indicated soil material consolidation and soil-porous system rearrangement. Soil water retention curves obtained on the soil samples and hydraulic conductivities measured in the field reflected the position at the elevation transect and the effect of erosion/accumulation processes on soil structure and consequently on the soil hydraulic properties. The highest Ks values in Brumovice were obtained at the steepest parts of the elevation transects, that have been the most eroded. The Ks values at the bottom parts decreased due to the sedimentation of eroded soil particles. The change of the Kw values along transects didn't show similar trends. However, the variability of values within both transects was low. Higher values were obtained in transect B, where the soil was more affected by erosion. The highest values of Ks as well as the value of Kw were also obtained in the steepest part of transect A in Vidim. This trend was not observed in transect B. The results corresponded with measured retention curves. Two different trends were shown in Sedlčany. While the highest values of Ks and Kw were found in the upper part of transect A, in the case of transect B the highest values were measured at the bottom of transect. Differences observed at both localities were caused by the different terrain attributes of both transects and extent of soil erosion. Acknowledgement: Authors acknowledge the financial support of the Ministry of Agriculture of the Czech Republic (QJ1230319).

Saugus River and Tributaries, Lynn Malden, Revere and Saugus, Massachusetts. Flood Damage Reduction. Volume 8. Appendix K. Environmental

DTIC Science & Technology

1989-06-01

K10 Summary of Soil Analyses for the Salt Marsh Transects K32 KI1 Plant Community Composition Data Along Compartment K33 B Transect K12 Plant...Community Composition Data Along Compartment K33 I Transect K13 Plant Community Composition Data Along Compartment K33 K1 Transect K14 Plant Community... Composition Data Along Compartment K34 K3 Transect K15 Plant Community Composition Data Along Compartment K34 L2 Transect K16 Plant Community Composition

Inhibitory effects of aspirin-triggered resolvin D1 on spinal nociceptive processing in rat pain models.

PubMed

Meesawatsom, Pongsatorn; Burston, James; Hathway, Gareth; Bennett, Andrew; Chapman, Victoria

2016-09-02

Harnessing the actions of the resolvin pathways has the potential for the treatment of a wide range of conditions associated with overt inflammatory signalling. Aspirin-triggered resolvin D1 (AT-RvD1) has robust analgesic effects in behavioural models of pain; however, the potential underlying spinal neurophysiological mechanisms contributing to these inhibitory effects in vivo are yet to be determined. This study investigated the acute effects of spinal AT-RvD1 on evoked responses of spinal neurones in vivo in a model of acute inflammatory pain and chronic osteoarthritic (OA) pain and the relevance of alterations in spinal gene expression to these neurophysiological effects. Pain behaviour was assessed in rats with established carrageenan-induced inflammatory or monosodium iodoacetate (MIA)-induced OA pain, and changes in spinal gene expression of resolvin receptors and relevant enzymatic pathways were examined. At timepoints of established pain behaviour, responses of deep dorsal horn wide dynamic range (WDR) neurones to transcutaneous electrical stimulation of the hind paw were recorded pre- and post direct spinal administration of AT-RvD1 (15 and 150 ng/50 μl). AT-RvD1 (15 ng/50 μl) significantly inhibited WDR neurone responses to electrical stimuli at C- (29 % inhibition) and Aδ-fibre (27 % inhibition) intensities. Both wind-up (53 %) and post-discharge (46 %) responses of WDR neurones in carrageenan-treated animals were significantly inhibited by AT-RvD1, compared to pre-drug response (p < 0.05). These effects were abolished by spinal pre-administration of a formyl peptide receptor 2 (FPR2/ALX) antagonist, butoxy carbonyl-Phe-Leu-Phe-Leu-Phe (BOC-2) (50 μg/50 μl). AT-RvD1 did not alter evoked WDR neurone responses in non-inflamed or MIA-treated rats. Electrophysiological effects in carrageenan-inflamed rats were accompanied by a significant increase in messenger RNA (mRNA) for chemerin (ChemR23) receptor and 5-lipoxygenase-activating protein (FLAP) and a decrease in 15-lipoxygenase (15-LOX) mRNA in the ipsilateral spinal cord of the carrageenan group, compared to controls. Our data suggest that peripheral inflammation-mediated changes in spinal FLAP expression may contribute to the novel inhibitory effects of spinal AT-RvD1 on WDR neuronal excitability, which are mediated by FPR2/ALX receptors. Inflammatory-driven changes in this pathway may offer novel targets for inflammatory pain treatment.

Descending serotonergic facilitation mediated by spinal 5-HT3 receptors engages spinal rapamycin-sensitive pathways in the rat

PubMed Central

Asante, Curtis O.; Dickenson, Anthony H.

2010-01-01

We have recently reported the importance of spinal rapamycin-sensitive pathways in maintaining persistent pain-like states. A descending facilitatory drive mediated through spinal 5-HT3 receptors (5-HT3Rs) originating from superficial dorsal horn NK1-expressing neurons and that relays through the parabrachial nucleus and the rostroventral medial medulla to act on deep dorsal horn neurons is known be important in maintaining these pain-like states. To determine if spinal rapamycin-sensitive pathways are activated by a descending serotonergic drive, we investigated the effects of spinally administered rapamycin on responses of deep dorsal horn neurons that had been pre-treated with the selective 5-HT3R antagonist ondansetron. We also investigated the effects of spinally administered cell cycle inhibitor (CCI)-779 (a rapamycin ester analogue) on deep dorsal horn neurons from rats with carrageenan-induced inflammation of the hind paw. Unlike some other models of persistent pain, this model does not involve an altered 5-HT3R-mediated descending serotonergic drive. We found that the inhibitory effects of rapamycin were significantly reduced for neuronal responses to mechanical and thermal stimuli when the spinal cord was pre-treated with ondansetron. Furthermore, CCI-779 was found to be ineffective in attenuating spinal neuronal responses to peripheral stimuli in carrageenan-treated rats. Therefore, we conclude that 5-HT3R-mediated descending facilitation is one requirement for activation of rapamycin-sensitive pathways that contribute to persistent pain-like states. PMID:20709148

Comparison of rangeland vegetation sampling techniques in the Central Grasslands

USGS Publications Warehouse

Stohlgren, T.J.; Bull, K.A.; Otsuki, Yuka

1998-01-01

Maintaining native plant diversity, detecting exotic species, and monitoring rare species are becoming important objectives in rangeland conservation. Four rangeland vegetation sampling techniques were compared to see how well they captured local pant diversity. The methods tested included the commonly used Parker transects, Daubenmire transects as modified by the USDA Forest Service, a new transect and 'large quadrat' design proposed by the USDA Agricultural Research Service, and the Modified-Whittaker multi-scale vegetation plot. The 4 methods were superimposed in shortgrass steppe, mixed grass prairie, northern mixed prairie, and tallgrass prairie in the Central Grasslands of the United States with 4 replicates in each prairie type. Analysis of variance tests showed significant method effects and prairie type effects, but no significant method X type interactions for total species richness, the number of native species, the number of species with less than 1 % cover, and the time required for sampling. The methods behaved similarly in each prairie type under a wide variety of grazing regimens. The Parker, large quadrat, and Daubenmire transects significantly underestimated the total species richness and the number of native species in each prairie type, and the number of species with less than 1 % cover in all but the tallgrass prairie type. The transect techniques also consistently missed half the exotic species, including noxious weeds, in each prairie type. The Modified-Whittaker method, which included an exhaustive search for plant species in a 20 x 50 m plot, served as the baseline for species richeness comparisons. For all prairie types, the Modified-Whittaker plot captured an average of 42. (?? 2.4; 1 S.E.) plant species per site compared to 15.9 (?? 1.3), 18.9 (?? 1.2), and 22.8 (?? 1.6) plant species per site using the Parker, large quadrat, and Daubenmire transect methods, respectively. The 4 methods captured most of the dominant species at each site and thus produced similar results for total foliar cover and soil cover. The detection and measurement of exotic plant species were greatly enhanced by using ten 1 m2 subplots in a multi-scale sampling design and searching a larger area (1,000 m2) at each site. Even with 4 replicate sites, the transect methods usually captured, and thus would monitor, 36 to 66 % of the plant species at each site. To evaluate the status and trends of common, rare, and exotic plant species at local, regional, and national scales, innovative, multi-scale methods must replace the commonly used transect methods to the past.

Effects of wheelchair propulsion on neuropathic pain and resting electroencephalography after spinal cord injury.

PubMed

Sato, Gosuke; Osumi, Michihiro; Morioka, Shu

2017-01-31

To investigate the effects of wheelchair propulsion on neuropathic pain and to examine resting electroencephalography pre- and post-wheelchair propulsion after spinal cord injury. Cross-sectional study. Eleven individuals with spinal cord injury and pain and 10 healthy controls. Single-session 15-min wheelchair propulsion and measurement of resting electroence-phalography. Effects of wheelchair propulsion were investigated using numerical rating scale (NRS) for neuropathic pain and short-form Profile of Mood States-Brief for mood. Peak alpha frequency on electroencephalography was calculated in 4 regions of interest; frontal, central, parietal and occipital areas. These outcomes were compared between pre- and post-wheelchair propulsion. Ten participants with spinal cord injury and all healthy controls completed the wheelchair propulsion exercise. NRS scores and negative mood were significantly improved following the wheelchair propulsion exercise. Pre-wheelchair propulsion, parietal and occipital peak alpha frequencies were significantly lower in the spinal cord injury group compared with the healthy controls group. Post-wheelchair propulsion, central peak alpha frequency increased in the spinal cord injury group. Wheelchair propulsion exercise temporarily decreased neuropathic pain intensity, improved negative mood, and modified alpha activity in spinal cord injury.

Subdural Thoracolumbar Spine Hematoma after Spinal Anesthesia: A Rare Occurrence and Literature Review of Spinal Hematomas after Spinal Anesthesia

PubMed Central

Maddali, Prasanthi; Walker, Blake; Fisahn, Christian; Page, Jeni; Diaz, Vicki; Zwillman, Michael E; Oskouian, Rod J; Tubbs, R. Shane

2017-01-01

Spinal hematomas are a rare but serious complication of spinal epidural anesthesia and are typically seen in the epidural space; however, they have been documented in the subdural space. Spinal subdural hematomas likely exist within a traumatically induced space within the dural border cell layer, rather than an anatomical subdural space. Spinal subdural hematomas present a dangerous clinical situation as they have the potential to cause significant compression of neural elements and can be easily mistaken for spinal epidural hematomas. Ultrasound can be an effective modality to diagnose subdural hematoma when no epidural blood is visualized. We have reviewed the literature and present a full literature review and a case presentation of an 82-year-old male who developed a thoracolumbar spinal subdural hematoma after spinal epidural anesthesia. Anticoagulant therapy is an important predisposing risk factor for spinal epidural hematomas and likely also predispose to spinal subdural hematomas. It is important to consider spinal subdural hematomas in addition to spinal epidural hematomas in patients who develop weakness after spinal epidural anesthesia, especially in patients who have received anticoagulation. PMID:28357164

Intraoperative electroacupuncture relieves remifentanil-induced postoperative hyperalgesia via inhibiting spinal glial activation in rats.

PubMed

Shi, Changxi; Liu, Yue; Zhang, Wei; Lei, Yishan; Lu, Cui'e; Sun, Rao; Sun, Yu'e; Jiang, Ming; Gu, Xiaoping; Ma, Zhengliang

2017-01-01

Background Accumulating studies have suggested that remifentanil, the widely-used opioid analgesic in clinical anesthesia, can activate the pronociceptive systems and enhance postoperative pain. Glial cells are thought to be implicated in remifentanil-induced hyperalgesia. Electroacupuncture is a complementary therapy to relieve various pain conditions with few side effects, and glial cells may be involved in its antinociceptive effect. In this study, we investigated whether intraoperative electroacupuncture could relieve remifentanil-induced postoperative hyperalgesia by inhibiting the activation of spinal glial cells, the production of spinal proinflammatory cytokines, and the activation of spinal mitogen-activated protein kinases. Methods A rat model of remifentanil-induced postoperative hyperalgesia was used in this study. Electroacupuncture during surgery was conducted at bilateral Zusanli (ST36) acupoints. Behavior tests, including mechanical allodynia and thermal hyperalgesia, were performed at different time points. Astrocytic marker glial fibrillary acidic protein, microglial marker Iba1, proinflammatory cytokines, and phosphorylated mitogen-activated protein kinases in the spinal cord were detected by Western blot and/or immunofluorescence. Results Mechanical allodynia and thermal hyperalgesia were induced by both surgical incision and remifentanil infusion, and remifentanil infusion significantly exaggerated and prolonged incision-induced pronociceptive effects. Glial fibrillary acidic protein, Iba1, proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α), and phosphorylated mitogen-activated protein kinases (p-p38, p-JNK, and p-ERK1/2) were upregulated after surgical incision, remifentanil infusion, and especially after their combination. Intraoperative electroacupuncture significantly attenuated incision- and/or remifentanil-induced pronociceptive effects, spinal glial activation, proinflammatory cytokine upregulation, and phosphorylated mitogen-activated protein kinase upregulation. Conclusions Our study suggests that remifentanil-induced postoperative hyperalgesia can be relieved by intraoperative electroacupuncture via inhibiting the activation of spinal glial cells, the upregulation of spinal proinflammatory cytokines, and the activation of spinal mitogen-activated protein kinases.

Effects of spinal cord stimulation in angina pectoris induced by pacing and possible mechanisms of action.

PubMed Central

Mannheimer, C; Eliasson, T; Andersson, B; Bergh, C H; Augustinsson, L E; Emanuelsson, H; Waagstein, F

1993-01-01

OBJECTIVE--To investigate the effects of spinal cord stimulation on myocardial ischaemia, coronary blood flow, and myocardial oxygen consumption in angina pectoris induced by atrial pacing. DESIGN--The heart was paced to angina during a control phase and treatment with spinal cord stimulation. Blood samples were drawn from a peripheral artery and the coronary sinus. SETTING--Multidisciplinary pain centre, department of medicine, Ostra Hospital, and Wallenberg Research Laboratory, Sahlgrenska Hospital, Gothenburg, Sweden. SUBJECTS--Twenty patients with intractable angina pectoris, all with a spinal cord stimulator implanted before the study. RESULTS--Spinal cord stimulation increased patients' tolerance to pacing (p < 0.001). At the pacing rate comparable to that producing angina during the control recording, myocardial lactate production during control session turned into extraction (p = 0.003) and, on the electrocardiogram, ST segment depression decreased, time to ST depression increased, and time to recovery from ST depression decreased (p = 0.01; p < 0.05, and p < 0.05, respectively). Spinal cord stimulation also reduced coronary sinus blood flow (p = 0.01) and myocardial oxygen consumption (p = 0.02). At the maximum pacing rate during treatment, all patients experienced anginal pain. Myocardial lactate extraction reverted to production (p < 0.01) and the magnitude and duration of ST segment depression increased to the same values as during control pacing, indicating that myocardial ischaemia during treatment with spinal cord stimulation gives rise to anginal pain. CONCLUSIONS--Spinal cord stimulation has an anti-anginal and anti-ischaemic effect in severe coronary artery disease. These effects seem to be secondary to a decrease in myocardial oxygen consumption. Furthermore, myocardial ischemia during treatment gives rise to anginal pain. Thus, spinal cord stimulation does not deprive the patient of a warning signal. PMID:8400930

Systemic effects induced by intralesional injection of ω-conotoxin MVIIC after spinal cord injury in rats

PubMed Central

2014-01-01

Background Calcium channel blockers such as conotoxins have shown a great potential to reduce brain and spinal cord injury. MVIIC neuroprotective effects analyzed in in vitro models of brain and spinal cord ischemia suggest a potential role of this toxin in preventing injury after spinal cord trauma. However, previous clinical studies with MVIIC demonstrated that clinical side effects might limit the usefulness of this drug and there is no research on its systemic effects. Therefore, the present study aimed to investigate the potential toxic effects of MVIIC on organs and to evaluate clinical and blood profiles of rats submitted to spinal cord injury and treated with this marine toxin. Rats were treated with placebo or MVIIC (at doses of 15, 30, 60 or 120 pmol) intralesionally following spinal cord injury. Seven days after the toxin administration, kidney, brain, lung, heart, liver, adrenal, muscles, pancreas, spleen, stomach, and intestine were histopathologically investigated. In addition, blood samples collected from the rats were tested for any hematologic or biochemical changes. Results The clinical, hematologic and biochemical evaluation revealed no significant abnormalities in all groups, even in high doses. There was no significant alteration in organs, except for degenerative changes in kidneys at a dose of 120 pmol. Conclusions These findings suggest that MVIIC at 15, 30 and 60 pmol are safe for intralesional administration after spinal cord injury and could be further investigated in relation to its neuroprotective effects. However, 120 pmol doses of MVIIC may provoke adverse effects on kidney tissue. PMID:24739121

Spinal Stiffness in Prone and Upright Postures During 0-1.8 g Induced by Parabolic Flight.

PubMed

Swanenburg, Jaap; Meier, Michael L; Langenfeld, Anke; Schweinhardt, Petra; Humphreys, B Kim

2018-06-01

The purpose of this study was to analyze posterior-to-anterior spinal stiffness in Earth, hyper-, and microgravity conditions during both prone and upright postures. During parabolic flight, the spinal stiffness of the L3 vertebra of a healthy 37-yr-old man was measured in normal Earth gravity (1.0 g), hypergravity (1.8 g), and microgravity (0.0 g) conditions induced in the prone and upright positions. Differences in spinal stiffness were significant across all three gravity conditions in the prone and upright positions. Most effect sizes were large; however, in the upright posture, the effect size between Earth gravity and microgravity was medium. Significant differences in spinal stiffness between the prone and upright positions were found during Earth gravity and hypergravity conditions. No difference was found between the two postures during microgravity conditions. Based on repeated measurements of a single individual, our results showed detectable changes in posterior-to-anterior spinal stiffness. Spinal stiffness increased during microgravity and decreased during hypergravity conditions. In microgravity conditions, posture did not impact spinal stiffness. More data on spinal stiffness in variable gravitational conditions is needed to confirm these results.Swanenburg J, Meier ML, Langenfeld A, Schweinhardt P, Humphreys BK. Spinal stiffness in prone and upright postures during 0-1.8 g induced by parabolic flight. Aerosp Med Hum Perform. 2018; 89(6):563-567.

Status Report of Environmental Evaluations Trinity River Project Texas. Appendix B. Biological Inventory with Effect Evaluation

DTIC Science & Technology

1975-06-01

wet depressions and sloughs present on the floodplain; heavy black clay soil ; no Spanish moss. Transect No. 4 Location: Henderson County, Bruce Smith...cattle except when too wet; sticky black clay soil ; the transect parallels the river for most of its length, touching the bank at one point. Transect No. 5...4 414 4 4-4. ’ 41-M na USC CA’ 0 nS : N41~ rmO O n4o 1 0’O 1* CC M 0 0a V)S Lj LA LJ USL . a) W WUS >5 0 C) i C n -0- ’D ’A a) __ fig- C tn ’a 0 O

Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat.

PubMed

Cerovecki, Tomislav; Bojanic, Ivan; Brcic, Luka; Radic, Bozo; Vukoja, Ivan; Seiwerth, Sven; Sikiric, Predrag

2010-09-01

We improved medial collateral ligament (MCL) healing throughout 90 days after surgical transection. We introduced intraperitoneal, per-oral (in drinking water) and topical (thin cream layer) peptide therapy always given alone, without a carrier. Previously, as an effective peptide therapy, stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, an anti-ulcer peptide effective in inflammatory bowel disease therapy (PL 14736)) particularly improved healing of transected tendon and muscle and wound healing effect including the expression of the early growth response 1 (egr-1) gene. After MCL transection BPC 157 was effective in rats when given once daily intraperitoneally (10 microg or 10 ng/kg) or locally as a thin layer (1.0 microg dissolved in distilled water/g commercial neutral cream) at the site of injury, first application 30 min after surgery and the final application 24 h before sacrifice. Likewise, BPC 157 was effective given per-orally (0.16 microg/ml in the drinking water (12 ml/day/rat)) until sacrifice. Commonly, BPC 157 microg-ng-rats exhibited consistent functional, biomechanical, macroscopic and histological healing improvements. Thus, we suggest BPC 157 improved healing of acute ligament injuries in further ligament therapy. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Transplantation of embryonic stem cells improves nerve repair and functional recovery after severe sciatic nerve axotomy in rats.

PubMed

Cui, Lin; Jiang, Jun; Wei, Ling; Zhou, Xin; Fraser, Jamie L; Snider, B Joy; Yu, Shan Ping

2008-05-01

Extensive research has focused on transplantation of pluripotent stem cells for the treatment of central nervous system disorders, the therapeutic potential of stem cell therapy for injured peripheral nerves is largely unknown. We used a rat sciatic nerve transection model to test the ability of implanted embryonic stem (ES) cell-derived neural progenitor cells (ES-NPCs) in promoting repair of a severely injured peripheral nerve. Mouse ES cells were neurally induced in vitro; enhanced expression and/or secretion of growth factors were detected in differentiating ES cells. One hour after removal of a 1-cm segment of the left sciatic nerve, ES-NPCs were implanted into the gap between the nerve stumps with the surrounding epineurium as a natural conduit. The transplantation resulted in substantial axonal regrowth and nerve repair, which were not seen in culture medium controls. One to 3 months after axotomy, co-immunostaining with the mouse neural cell membrane specific antibody M2/M6 and the Schwann cell marker S100 suggested that transplanted ES-NPCs had survived and differentiated into myelinating cells. Regenerated axons were myelinated and showed a uniform connection between proximal and distal stumps. Nerve stumps had near normal diameter with longitudinally oriented, densely packed Schwann cell-like phenotype. Fluoro-Gold retrogradely labeled neurons were found in the spinal cord (T12-13) and DRG (L4-L6), suggesting reconnection of axons across the transection. Electrophysiological recordings showed functional activity recovered across the injury gap. These data suggest that transplanted neurally induced ES cells differentiate into myelin-forming cells and provide a potential therapy for severely injured peripheral nerves.

A geostatistical approach for quantification of contaminant mass discharge uncertainty using multilevel sampler measurements

NASA Astrophysics Data System (ADS)

Li, K. Betty; Goovaerts, Pierre; Abriola, Linda M.

2007-06-01

Contaminant mass discharge across a control plane downstream of a dense nonaqueous phase liquid (DNAPL) source zone has great potential to serve as a metric for the assessment of the effectiveness of source zone treatment technologies and for the development of risk-based source-plume remediation strategies. However, too often the uncertainty of mass discharge estimated in the field is not accounted for in the analysis. In this paper, a geostatistical approach is proposed to estimate mass discharge and to quantify its associated uncertainty using multilevel transect measurements of contaminant concentration (C) and hydraulic conductivity (K). The approach adapts the p-field simulation algorithm to propagate and upscale the uncertainty of mass discharge from the local uncertainty models of C and K. Application of this methodology to numerically simulated transects shows that, with a regular sampling pattern, geostatistics can provide an accurate model of uncertainty for the transects that are associated with low levels of source mass removal (i.e., transects that have a large percentage of contaminated area). For high levels of mass removal (i.e., transects with a few hot spots and large areas of near-zero concentration), a total sampling area equivalent to 6˜7% of the transect is required to achieve accurate uncertainty modeling. A comparison of the results for different measurement supports indicates that samples taken with longer screen lengths may lead to less accurate models of mass discharge uncertainty. The quantification of mass discharge uncertainty, in the form of a probability distribution, will facilitate risk assessment associated with various remediation strategies.

Fungiform taste bud degeneration in C57BL/6J mice following chorda-lingual nerve transection.

PubMed

Guagliardo, Nick A; Hill, David L

2007-09-10

Taste buds are dependent on innervation for normal morphology and function. Fungiform taste bud degeneration after chorda tympani nerve injury has been well documented in rats, hamsters, and gerbils. The current study examines fungiform taste bud distribution and structure in adult C57BL/6J mice from both intact taste systems and after unilateral chorda-lingual nerve transection. Fungiform taste buds were visualized and measured with the aid of cytokeratin 8. In control mice, taste buds were smaller and more abundant on the anterior tip (<1 mm) of the tongue. By 5 days after nerve transection taste buds were smaller and fewer on the side of the tongue ipsilateral to the transection and continued to decrease in both size and number until 15 days posttransection. Degenerating fungiform taste buds were smaller due to a loss of taste bud cells rather than changes in taste bud morphology. While almost all taste buds disappeared in more posterior fungiform papillae by 15 days posttransection, the anterior tip of the tongue retained nearly half of its taste buds compared to intact mice. Surviving taste buds could not be explained by an apparent innervation from the remaining intact nerves. Contralateral effects of nerve transection were also observed; taste buds were larger due to an increase in the number of taste bud cells. These data are the first to characterize adult mouse fungiform taste buds and subsequent degeneration after unilateral nerve transection. They provide the basis for more mechanistic studies in which genetically engineered mice can be used. (c) 2007 Wiley-Liss, Inc.

Multiple hippocampal transections for intractable hippocampal epilepsy: Seizure outcome.

PubMed

Koubeissi, Mohamad Z; Kahriman, Emine; Fastenau, Philip; Bailey, Christopher; Syed, Tanvir; Amina, Shahram; Miller, Jonathan; Munyon, Charles; Tanner, Adriana; Karanec, Kristina; Tuxhorn, Ingrid; Lüders, Hans

2016-05-01

The purpose of this study was to evaluate the seizure outcomes after transverse multiple hippocampal transections (MHTs) in 13 patients with intractable TLE. Thirteen patients with normal memory scores, including 8 with nonlesional hippocampi on MRI, had temporal lobe epilepsy (TLE) necessitating depth electrode implantation. After confirming hippocampal seizure onset, they underwent MHT. Intraoperative monitoring was done with 5-6 hippocampal electrodes spaced at approximately 1-cm intervals and spike counting for 5-8min before each cut. The number of transections ranged between 4 and 7. Neuropsychological assessment was completed preoperatively and postoperatively for all patients and will be reported separately. Duration of epilepsy ranged between 5 and 55years. There were no complications. Intraoperatively, MHT resulted in marked spike reduction (p=0.003, paired t-test). Ten patients (77%) are seizure-free (average follow-up was 33months, range 20-65months) without medication changes. One of the 3 patients with persistent seizures had an MRI revealing incomplete transections, another had an additional neocortical seizure focus (as suggested by pure aphasic seizures), and the third had only 2 seizures in 4years, one of which occurred during antiseizure medication withdrawal. Verbal and visual memory outcomes will be reported separately. Right and left hippocampal volumes were not different preoperatively (n=12, p=0.64, Wilcoxon signed-rank test), but the transected hippocampal volume decreased postoperatively (p=0.0173). Multiple hippocampal transections provide an effective intervention and a safe alternative to temporal lobectomy in patients with hippocampal epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced Neuropathic Pain in Rats: Mediation by Spinal α2-Adrenergic Receptor

PubMed Central

Choi, Jiho; Jeon, Changhoon; Jang, Jo Ung; Quan, Fu Shi; Lee, Kyungjin; Kim, Woojin

2017-01-01

Paclitaxel, a chemotherapy drug for solid tumors, induces peripheral painful neuropathy. Bee venom acupuncture (BVA) has been reported to have potent analgesic effects, which are known to be mediated by activation of spinal α-adrenergic receptor. Here, we investigated the effect of BVA on mechanical hyperalgesia and spinal neuronal hyperexcitation induced by paclitaxel. The role of spinal α-adrenergic receptor subtypes in the analgesic effect of BVA was also observed. Administration of paclitaxel (total 8 mg/kg, intraperitoneal) on four alternate days (days 0, 2, 4, and 6) induced significant mechanical hyperalgesic signs, measured using a von Frey filament. BVA (1 mg/kg, ST36) relieved this mechanical hyperalgesia for at least two hours, and suppressed the hyperexcitation in spinal wide dynamic range neurons evoked by press or pinch stimulation. Both melittin (0.5 mg/kg, ST36) and phospholipase A2 (0.12 mg/kg, ST36) were shown to play an important part in this analgesic effect of the BVA, as they significantly attenuated the pain. Intrathecal pretreatment with the α2-adrenergic receptor antagonist (idazoxan, 50 µg), but not α1-adrenergic receptor antagonist (prazosin, 30 µg), blocked the analgesic effect of BVA. These results suggest that BVA has potent suppressive effects against paclitaxel-induced neuropathic pain, which were mediated by spinal α2-adrenergic receptor. PMID:29088102

Preferential Enhancement of Sensory and Motor Axon Regeneration by Combining Extracellular Matrix Components with Neurotrophic Factors

PubMed Central

Santos, Daniel; González-Pérez, Francisco; Giudetti, Guido; Micera, Silvestro; Udina, Esther; Del Valle, Jaume; Navarro, Xavier

2016-01-01

After peripheral nerve injury, motor and sensory axons are able to regenerate but inaccuracy of target reinnervation leads to poor functional recovery. Extracellular matrix (ECM) components and neurotrophic factors (NTFs) exert their effect on different neuronal populations creating a suitable environment to promote axonal growth. Here, we assessed in vitro and in vivo the selective effects of combining different ECM components with NTFs on motor and sensory axons regeneration and target reinnervation. Organotypic cultures with collagen, laminin and nerve growth factor (NGF)/neurotrophin-3 (NT3) or collagen, fibronectin and brain-derived neurotrophic factor (BDNF) selectively enhanced sensory neurite outgrowth of DRG neurons and motor neurite outgrowth from spinal cord slices respectively. For in vivo studies, the rat sciatic nerve was transected and repaired with a silicone tube filled with a collagen and laminin matrix with NGF/NT3 encapsulated in poly(lactic-co-glycolic acid) (PLGA) microspheres (MP) (LM + MP.NGF/NT3), or a collagen and fibronectin matrix with BDNF in PLGA MPs (FN + MP.BDNF). Retrograde labeling and functional tests showed that LM + MP.NGF/NT3 increased the number of regenerated sensory neurons and improved sensory functional recovery, whereas FN + MP.BDNF preferentially increased regenerated motoneurons and enhanced motor functional recovery. Therefore, combination of ECM molecules with NTFs may be a good approach to selectively enhance motor and sensory axons regeneration and promote appropriate target reinnervation. PMID:28036084

[Research progress in the role of aquaproin-4 and inward rectifying potassium channel 4.1 in spinal cord edema].

PubMed

Chen, Tiege; Dang, Yuexiu; Wang, Ming; Zhang, Dongliang; Guo, Yongqiang; Zhang, Haihong

2018-05-28

Spinal edema is a very important pathophysiological basis for secondary spinal cord injury, which affects the repair and prognosis of spinal cord injury. Aquaporin-4 is widely distributed in various organs of the body, and is highly expressed in the brain and spinal cord. Inward rectifying potassium channel 4.1 is a protein found in astrocytes of central nervous system. It interacts with aquaporins in function. Aquaporin-4 and inward rectifying potassium channel 4.1 play an important role in the formation and elimination of spinal cord edema, inhibition of glial scar formation and promotion of excitotoxic agents exclusion. The distribution and function of aquaporin-4 and inward rectifying potassium channel 4.1 in the central nervous system and their expression after spinal cord injury have multiple effects on spinal edema. Studies of aquaporin-4 and inward rectifying potassium channel 4.1 in the spinal cord may provide new ideas for the elimination and treatment of spinal edema.

Cumulative effective dose associated with radiography and CT of adolescents with spinal injuries.

PubMed

Lemburg, Stefan P; Peters, Soeren A; Roggenland, Daniela; Nicolas, Volkmar; Heyer, Christoph M

2010-12-01

The purpose of this study was to analyze the quantity and distribution of cumulative effective doses in diagnostic imaging of adolescents with spinal injuries. At a level 1 trauma center from July 2003 through June 2009, imaging procedures during initial evaluation and hospitalization and after discharge of all patients 10-20 years old with spinal fractures were retrospectively analyzed. The cumulative effective doses for all imaging studies were calculated, and the doses to patients with spinal injuries who had multiple traumatic injuries were compared with the doses to patients with spinal injuries but without multiple injuries. The significance level was set at 5%. Imaging studies of 72 patients (32 with multiple injuries; average age, 17.5 years) entailed a median cumulative effective dose of 18.89 mSv. Patients with multiple injuries had a significantly higher total cumulative effective dose (29.70 versus 10.86 mSv, p < 0.001) mainly owing to the significantly higher CT-related cumulative effective dose to multiple injury patients during the initial evaluation (18.39 versus 2.83 mSv, p < 0.001). Overall, CT accounted for 86% of the total cumulative effective dose. Adolescents with spinal injuries receive a cumulative effective dose equal to that of adult trauma patients and nearly three times that of pediatric trauma patients. Areas of focus in lowering cumulative effective dose should be appropriate initial estimation of trauma severity and careful selection of CT scan parameters.

Low-Grade Inflammation and Spinal Cord Injury: Exercise as Therapy?

PubMed Central

da Silva Alves, Eduardo; de Aquino Lemos, Valdir; Ruiz da Silva, Francieli; Lira, Fabio Santos; dos Santos, Ronaldo Vagner Thomathieli; Rosa, João Paulo Pereira; Caperuto, Erico; Tufik, Sergio; de Mello, Marco Tulio

2013-01-01

An increase in the prevalence of obesity in people with spinal cord injury can contribute to low-grade chronic inflammation and increase the risk of infection in this population. A decrease in sympathetic activity contributes to immunosuppression due to the lower activation of immune cells in the blood. The effects of physical exercise on inflammatory parameters in individuals with spinal cord injury have not been well described. We conducted a review of the literature published from 1974 to 2012. This review explored the relationships between low-grade inflammation, spinal cord injury, and exercise to discuss a novel mechanism that might explain the beneficial effects of exercise involving an increase in catecholamines and cytokines in people with spinal cord injury. PMID:23533315

Transplantation of neurotrophin-3-transfected bone marrow mesenchymal stem cells for the repair of spinal cord injury.

PubMed

Dong, Yuzhen; Yang, Libin; Yang, Lin; Zhao, Hongxing; Zhang, Chao; Wu, Dapeng

2014-08-15

Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury.

Involvement of peripheral and spinal tumor necrosis factor α in spinal cord hyperexcitability during knee joint inflammation in rats.

PubMed

König, Christian; Zharsky, Maxim; Möller, Christian; Schaible, Hans-Georg; Ebersberger, Andrea

2014-03-01

Tumor necrosis factor α (TNFα) is produced not only in peripheral tissues, but also in the spinal cord. The purpose of this study was to address the potential of peripheral and spinal TNFα to induce and maintain spinal hyperexcitability, which is a hallmark of pain states in the joints during rheumatoid arthritis and osteoarthritis. In vivo recordings of the responses of spinal cord neurons to nociceptive knee input under normal conditions and in the presence of experimental knee joint inflammation were obtained in anesthetized rats. TNFα, etanercept, or antibodies to TNF receptors were applied to either the knee joint or the spinal cord surface. Injection of TNFα into the knee joint cavity increased the responses of spinal cord neurons to mechanical joint stimulation, and injection of etanercept into the knee joint reduced the inflammation-evoked spinal activity. These spinal effects closely mirrored the induction and reduction of peripheral sensitization. Responses to joint stimulation were also enhanced by spinal application of TNFα, and spinal application of either etanercept or anti-TNF receptor type I significantly attenuated the generation of inflammation-evoked spinal hyperexcitability, which is characterized by widespread pain sensitization beyond the inflamed joint. Spinally applied etanercept did not reduce established hyperexcitability in the acute kaolin/carrageenan model. In antigen-induced arthritis, etanercept decreased spinal responses on day 1, but not on day 3. While peripheral TNFα increases spinal responses to joint stimulation, spinal TNFα supports the generation of the full pattern of spinal hyperexcitability. However, established spinal hyperexcitability may be maintained by downstream mechanisms that are independent of spinal TNFα. Copyright © 2014 by the American College of Rheumatology.

Human spinal cord injury: motor unit properties and behaviour.

PubMed

Thomas, C K; Bakels, R; Klein, C S; Zijdewind, I

2014-01-01

Spinal cord injury (SCI) results in widespread variation in muscle function. Review of motor unit data shows that changes in the amount and balance of excitatory and inhibitory inputs after SCI alter management of motoneurons. Not only are units recruited up to higher than usual relative forces when SCI leaves few units under voluntary control, the force contribution from recruitment increases due to elevation of twitch/tetanic force ratios. Force gradation and precision are also coarser with reduced unit numbers. Maximal unit firing rates are low in hand muscles, limiting voluntary strength, but are low, normal or high in limb muscles. Unit firing rates during spasms can exceed voluntary rates, emphasizing that deficits in descending drive limit force production. SCI also changes muscle properties. Motor unit weakness and fatigability seem universal across muscles and species, increasing the muscle weakness that arises from paralysis of units, motoneuron death and sensory impairment. Motor axon conduction velocity decreases after human SCI. Muscle contractile speed is also reduced, which lowers the stimulation frequencies needed to grade force when paralysed muscles are activated with patterned electrical stimulation. This slowing does not necessarily occur in hind limb muscles after cord transection in cats and rats. The nature, duration and level of SCI underlie some of these species differences, as do variations in muscle function, daily usage, tract control and fibre-type composition. Exploring this diversity is important to promote recovery of the hand, bowel, bladder and locomotor function most wanted by people with SCI. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Geomorphological and ecological effects of check dams in mountain torrents of Southern Italy

NASA Astrophysics Data System (ADS)

Zema, Demetrio Antonio; Bombino, Giuseppe; Denisi, Pietro; Tamburino, Vincenzo; Marcello Zimbone, Santo

2017-04-01

It is known that installation of check dams noticeably influences torrent morphology and ecology. However, the effects of check dams on channel section and riparian vegetation of torrents are not yet completely understood. This paper provides a further contribution to a better comprehension of the actions played by check dams on hydrological and geomorphological processes in headwaters and their effects on riparian ecosystem. Field surveys on channel morphology, bed material and riparian vegetation were carried out close to five check dams in each of four mountain reaches of Calabria (Southern Italy). For each check dam three transects (one upstream, one downstream and one far from the check dam, located in the undisturbed zone and adopted as control) were identified; at each transect, a set of geomorphological and ecological indicators were surveyed as follows. Channel section morphology was assessed by the width/depth ratio (w/d); the median particle size (D50) and the finer sediment fraction (%fines) were chosen to characterize channel bed material; the specific discharge (q, the discharge per channel unit width) was assumed as measure of the flow regime. Vegetation cover and structure were evaluated by Global Canopy Cover (GCC) and Weighted Canopy Height (WCH) respectively (Bombino et al., 2008); the index of alpha-diversity (H-alpha, Hill, 1973) and the ratio between the number of alien species and the number of native species (NSA/NSN) were chosen as indicators of species richness/abundance and degree of vegetation integrity, respectively. Compared to the control transects, the values of w/d were higher upstream of check dams and lower downstream; conversely, q was lower upstream and higher in downstream sites. Upstream of the check dams D50 of bed material was lower and %fines was higher compared to the control transects; vice versa, the downstream transects showed higher D50 and lower %fines. The differences in the riparian vegetation among transects were found as the torrent ecological response to the strong contrasts surveyed in hydrological (q) and geomorphological (w/d, D50 and %fines) characteristics. Compared to control transects, vegetation was more extensive (higher GCC) and developed (higher WCH) in the upstream zones; the reverse pattern was noticed in the downstream transects (lower GCC and WCH). The indexes H-alpha and NSA/NSN were higher upstream of check dams: the presence of the check dams induced higher species richness and evenness, with alien species prevailing over native ones in the sedimentation wedge. Conversely, downstream of check dams H-alpha and NSA/NSN were lower: here, riparian vegetation lost some herbaceous species and assumed a terrestrial character. Overall, this study confirms on a quantitative approach that check dams have far reaching effects on geomorphology and ecology of mountain torrent channels; as a consequence, important and complex changes occur not only in the extent and development of riparian vegetation, but also in the species diversity and distribution. REFERENCES - Bombino G., Gurnell A.M., Tamburino V., Zema D.A., Zimbone S.M. 2008. Sediment size variation in torrents with check-dams: effects on riparian vegetation. Ecological Engineering 32(2), 166-177. - Hill MO. 1973. Diversity and evenness: a unifying notation and its consequences. Ecology 54: 427-431.

Image analysis of open-door laminoplasty for cervical spondylotic myelopathy: comparing the influence of cord morphology and spine alignment.

PubMed

Lin, Bon-Jour; Lin, Meng-Chi; Lin, Chin; Lee, Meei-Shyuan; Feng, Shao-Wei; Ju, Da-Tong; Ma, Hsin-I; Liu, Ming-Ying; Hueng, Dueng-Yuan

2015-10-01

Previous studies have identified the factors affecting the surgical outcome of cervical spondylotic myelopathy (CSM) following laminoplasty. Nonetheless, the effect of these factors remains controversial. It is unknown about the association between pre-operative cervical spinal cord morphology and post-operative imaging result following laminoplasty. The goal of this study is to analyze the impact of pre-operative cervical spinal cord morphology on post-operative imaging in patients with CSM. Twenty-six patients with CSM undergoing open-door laminoplasty were classified according to pre-operative cervical spine bony alignment and cervical spinal cord morphology, and the results were evaluated in terms of post-operative spinal cord posterior drift, and post-operative expansion of the antero-posterior dura diameter. By the result of study, pre-operative spinal cord morphology was an effective classification in predicting surgical outcome - patients with anterior convexity type, description of cervical spinal cord morphology, had more spinal cord posterior migration than those with neutral or posterior convexity type after open-door laminoplasty. Otherwise, the interesting finding was that cervical spine Cobb's angle had an impact on post-operative spinal cord posterior drift in patients with neutral or posterior convexity type spinal cord morphology - the degree of kyphosis was inversely proportional to the distance of post-operative spinal cord posterior drift, but not in the anterior convexity type. These findings supported that pre-operative cervical spinal cord morphology may be used as screening for patients undergoing laminoplasty. Patients having neutral or posterior convexity type spinal cord morphology accompanied with kyphotic deformity were not suitable candidates for laminoplasty. Copyright © 2015 Elsevier B.V. All rights reserved.

Transcranial cerebellar direct current stimulation and transcutaneous spinal cord direct current stimulation as innovative tools for neuroscientists

PubMed Central

Priori, Alberto; Ciocca, Matteo; Parazzini, Marta; Vergari, Maurizio; Ferrucci, Roberta

2014-01-01

Two neuromodulatory techniques based on applying direct current (DC) non-invasively through the skin, transcranial cerebellar direct current stimulation (tDCS) and transcutaneous spinal DCS, can induce prolonged functional changes consistent with a direct influence on the human cerebellum and spinal cord. In this article we review the major experimental works on cerebellar tDCS and on spinal tDCS, and their preliminary clinical applications. Cerebellar tDCS modulates cerebellar motor cortical inhibition, gait adaptation, motor behaviour, and cognition (learning, language, memory, attention). Spinal tDCS influences the ascending and descending spinal pathways, and spinal reflex excitability. In the anaesthetised mouse, DC stimulation applied under the skin along the entire spinal cord may affect GABAergic and glutamatergic systems. Preliminary clinical studies in patients with cerebellar disorders, and in animals and patients with spinal cord injuries, have reported beneficial effects. Overall the available data show that cerebellar tDCS and spinal tDCS are two novel approaches for inducing prolonged functional changes and neuroplasticity in the human cerebellum and spinal cord, and both are new tools for experimental and clinical neuroscientists. PMID:24907311

Effects of pelvic, pudendal, or hypogastric nerve cuts on Fos induction in the rat brain following vaginocervical stimulation.

PubMed

Pfaus, James G; Manitt, Colleen; Coopersmith, Carol B

2006-12-30

In the female rat, genitosensory input is conveyed to the central nervous system predominantly through the pelvic, pudendal, and hypogastric nerves. The present study examined the relative contribution of those three nerves in the expression of Fos immunoreactivity within brain regions previously shown to be activated by vaginocervical stimulation (VCS). Bilateral transection of those nerves, or sham neurectomy, was conducted in separate groups of ovariectomized, sexually-experienced females. After recovery, females were primed with estrogen and progesterone and given either 50 manual VCSs with a lubricated glass rod over the course of 1 h. VCS increased the number of neurons expressing Fos immunoreactivity in the medial preoptic area, lateral septum, bed nucleus of the stria terminalis, ventromedial hypothalamus, and medial amygdala of sham neurectomized females. Transection of the pelvic nerve reduced Fos immunoreactivity in the medial preoptic area, bed nucleus of the stria terminalis, ventromedial hypothalamus, and medial amygdala, whereas transection of the pudendal nerve had no effect. In contrast, transection of the hypogastric nerve increased Fos immunoreactivity in the medial preoptic area and lateral septum, whereas transaction of the pelvic nerve increased Fos immunoreactivity in the lateral septum, following VCS. All females given VCS, except those with pelvic neurectomy, displayed a characteristic immobility during each application. These data confirm that the pelvic nerve is largely responsible for the neural and behavioral effects of VCS, and support a separate function for the hypogastric nerve.

Involvement of melatonin metabolites in the long-term inhibitory effect of the hormone on rat spinal nociceptive transmission.

PubMed

Mondaca, Mauricio; Hernández, Alejandro; Valladares, Luis; Sierralta, Walter; Noseda, Rodrigo; Soto-Moyano, Rubén

2004-02-01

There is evidence that melatonin and its metabolites could bind to nuclear sites in neurones, suggesting that this hormone is able to exert long-term functional effects in the central nervous system via genomic mechanisms. This study was designed to investigate (i) whether systemically administered melatonin can exert long-term effects on spinal cord windup activity, and (ii) whether blockade of melatonin degradation with eserine could prevent this effect. Rats receiving melatonin (10 mg/kg ip), the same dose of melatonin plus eserine (0.5 mg/kg ip), or saline were studied. Seven days after administration of the drugs or saline, spinal windup of rats was assessed in a C-fiber reflex response paradigm. Results show that rats receiving melatonin exhibited a reduction in spinal windup activity. This was not observed in the animals receiving melatonin plus eserine or saline, suggesting a role for melatonin metabolites in long-term changes of nociceptive transmission in the rat spinal cord.

Changes in vegetative cover on Western Arctic Herd winter range from 1981 to 2005: potential effects of grazing and climate change

Treesearch

Kyle Joly; Randi R. Jandt; Cynthia R. Meyers; Martha J. Cole

2007-01-01

The population of the Western Arctic Herd, estimated at 490,000 caribou (Rangifer tarandus granti) in 2003, is at its highest level in 30 years. Twenty permanent range transects were established in the winter range of the Western Arctic Herd in 1981 to assess the impacts of grazing. These transects were revisited in 1995 and 1996 (1995/96). Only 18...

Effects of submarine power transmission cables on a glass sponge reef and associated megafaunal community.

PubMed

Dunham, A; Pegg, J R; Carolsfeld, W; Davies, S; Murfitt, I; Boutillier, J

2015-06-01

We examined the effects of submarine power transmission cable installation and operation on glass sponge reef condition and associated megafauna. Video and still imagery were collected using a Remotely Operated Vehicle twice a year for 4 years following cable installation. The effects of cables on glass sponges were assessed by comparing sponge cover along fixed transects and at marked index sites. Megafauna counts along transects were used to explore the effects on associated community. We found no evidence of cable movement across the sponge reef surface. Live sponge cover was found to be consistently lower along cable transects and at cable index sites compared to controls. Live sponge cover was the lowest (55 ± 1.1% decrease) at cable index sites 1.5 years after installation and recovered to 85 ± 30.6% of the original size over the following 2 years. Our data suggest 100% glass sponge mortality along the direct cable footprint and 15% mortality in the surrounding 1.5 m corridor 3.5 years after cable installation. Growth rate of a new glass sponge was 1 and 3 cm/year in first and second year, respectively, and appeared to be seasonal. We observed a diverse megafaunal community with representatives from 7 phyla and 14 classes. Total megafauna, spot prawn, and other Arthropoda abundances were slightly lower along cable transects although the effect of cable presence was not statistically significant. The following measures could be taken to reduce the amount of damage to glass sponge reefs and associated fauna: routing the cable around reefs, whenever possible, minimizing cable movement across the surface of the reef at installation and routine operation, and assessing potential damage to glass sponges prior to decommissioning. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

The Animal Model of Spinal Cord Injury as an Experimental Pain Model

PubMed Central

Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

2011-01-01

Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models. PMID:21436995

Metaplasticity and behavior: how training and inflammation affect plastic potential within the spinal cord and recovery after injury

PubMed Central

Grau, James W.; Huie, J. Russell; Lee, Kuan H.; Hoy, Kevin C.; Huang, Yung-Jen; Turtle, Joel D.; Strain, Misty M.; Baumbauer, Kyle M.; Miranda, Rajesh M.; Hook, Michelle A.; Ferguson, Adam R.; Garraway, Sandra M.

2014-01-01

Research has shown that spinal circuits have the capacity to adapt in response to training, nociceptive stimulation and peripheral inflammation. These changes in neural function are mediated by physiological and neurochemical systems analogous to those that support plasticity within the hippocampus (e.g., long-term potentiation and the NMDA receptor). As observed in the hippocampus, engaging spinal circuits can have a lasting impact on plastic potential, enabling or inhibiting the capacity to learn. These effects are related to the concept of metaplasticity. Behavioral paradigms are described that induce metaplastic effects within the spinal cord. Uncontrollable/unpredictable stimulation, and peripheral inflammation, induce a form of maladaptive plasticity that inhibits spinal learning. Conversely, exposure to controllable or predictable stimulation engages a form of adaptive plasticity that counters these maladaptive effects and enables learning. Adaptive plasticity is tied to an up-regulation of brain derived neurotrophic factor (BDNF). Maladaptive plasticity is linked to processes that involve kappa opioids, the metabotropic glutamate (mGlu) receptor, glia, and the cytokine tumor necrosis factor (TNF). Uncontrollable nociceptive stimulation also impairs recovery after a spinal contusion injury and fosters the development of pain (allodynia). These adverse effects are related to an up-regulation of TNF and a down-regulation of BDNF and its receptor (TrkB). In the absence of injury, brain systems quell the sensitization of spinal circuits through descending serotonergic fibers and the serotonin 1A (5HT 1A) receptor. This protective effect is blocked by surgical anesthesia. Disconnected from the brain, intracellular Cl- concentrations increase (due to a down-regulation of the cotransporter KCC2), which causes GABA to have an excitatory effect. It is suggested that BDNF has a restorative effect because it up-regulates KCC2 and re-establishes GABA-mediated inhibition. PMID:25249941

The effects of nicotine exposure and PFC transection on the time-frequency distribution of VTA DA neurons' firing activities.

PubMed

Chen, Ting Y; Zhang, Die; Dragomir, Andrei; Akay, Yasemin; Akay, Metin

2011-05-01

We investigated the influence of nicotine exposure and prefrontal cortex (PFC) transections on ventral tegmental areas (VTA) dopamine (DA) neurons' firing activities using a time-frequency method based on the continuous wavelet transform (CWT). Extracellular single-unit neural activity was recorded from DA neurons in the VTA area of rats. One group had their PFC inputs to the VTA intact, while the other group had the inputs to VTA bilaterally transected immediate caudal to the PFC. We hypothesized that the systemic nicotine exposure will significantly change the energy distribution in the recorded neural activity. Additionally, we investigated whether the loss of inputs to the VTA caused by the PFC transection resulted in the cancellation of the nicotine' effect on the neurons' firing patterns. The time-frequency representations of VTA DA neurons firing activity were estimated from the reconstructed firing rate histogram. The energy contents were estimated from three frequency bands, which are known to encompass the significant modes of operation of DA neurons. Our results show that systemic nicotine exposure disrupts the energy distribution in PFC-intact rats. Particularly, there is a significant increase in energy contents of the 1-1.5 Hz frequency band. This corresponds to an observed increase in the firing rate of VTA DA neurons following nicotine exposure. Additionally, our results from PFC-transected rats show that there is no change in the energy distribution of the recordings after systemic nicotine exposure. These results indicate that the PFC plays an important role in affecting the activities of VTA DA neurons and that the CWT is a useful method for monitoring the changes in neural activity patterns in both time and frequency domains.

Humidification of the Arctic: Effects of more open ocean water on land temperatures and tundra productivity along continental and maritime bioclimate transects

NASA Astrophysics Data System (ADS)

Bhatt, U. S.; Walker, D. A.; Raynolds, M. K.; Epstein, H. E.

2017-12-01

Amplified Arctic warming linked to declining sea-ice extent led to generally enhanced productivity of the tundra biome during the period 1982-2008. After about 2002, coinciding with a recent precipitous decline in sea ice, large areas of the Arctic began showing reversals of previous positive productivity trends. To better understand these recent vegetation productivity declines and whether they are associated with differences in a general humidification of portions of the Arctic, we focus analysis on two transects with ground information: the more continental North America Arctic Transect (NAAT) and the more maritime Eurasia Arctic Transect (EAT). We compare ground information with satellite-derived trends in open water, summer terrestrial temperatures, and vegetation greenness and changes in continentality of the two transects, as indicated by the differences in the annual maximum and minimum mean monthly temperatures. Areas adjacent to perennial sea ice along in the northern parts of the NAAT exhibit climates with positive trends in summer warmth, but negative greening trends, possibly due to soil drying. Southern parts of the NAAT in the vicinity of more open water show positive greenness trends. Along the EAT, cooling midsummer conditions and reduced greenness appear to be caused by cloudier conditions, and possibly later snow melt during the period of maximum potential photosynthesis. Ground-based environmental and vegetation data indicate that biomass, particularly moss biomass is much greater along the more maritime EAT, indicating a buffering effect of the vegetation that will act to damp productivity as humidification of the Arctic proceeds. This multi-scale analysis is one step in the direction of understanding the drivers of tundra vegetation productivity in the Arctic.

[Lumbar spinal anesthesia with cervical nociceptive blockade. Critical review of a series of 1,330 procedures].

PubMed

Benitez, Percio Ramón Becker; Nogueira, Celso Schmalfuss; Holanda, Ana Cristina Carvalho de; Santos, Jose Caio

2016-01-01

The manufacture of minimally traumatic needles and synthesis of pharmacological adjuncts with safe and effective action on inhibitory and neuromodulatory synapses distributed along the nociceptive pathways were crucial for a new expansion phase of spinal anesthesia. The objectives of this paper are present our clinical experience with 1,330 lumbar spinal anesthesia performed with purposeful nociceptive blockade of the thoracic and cervical spinal nerves corresponding to dermatomes C4 or C3; warn about the method pathophysiological risks, and emphasize preventive standards for the safe application of the technique. Review of the historical background and anatomical spinal anesthesia with cervical levels of analgesia. Description of the technique used in our institution; population anesthetized; and surgery performed with the described method. Critical exposition of the physiological, pathophysiological, and clinical effects occurred and registered during anesthesia-surgery and postoperative period. Spinal anesthesia with nociceptive blockade to dermatome C4, or C3, is an effective option for surgery on somatic structures distal to the metamer of the third cervical spinal nerve, lasting no more than four or five hours. The method safety depends on the unrestricted respect for the essential rules of proper anesthesia. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Lumbar spinal anesthesia with cervical nociceptive blockade. Critical review of a series of 1,330 procedures.

PubMed

Benitez, Percio Ramón Becker; Nogueira, Celso Schmalfuss; de Holanda, Ana Cristina Carvalho; Santos, José Caio

2016-01-01

The manufacture of minimally traumatic needles and synthesis of pharmacological adjuncts with safe and effective action on inhibitory and neuromodulatory synapses distributed along the nociceptive pathways were crucial for a new expansion phase of spinal anesthesia. The objectives of this paper are present our clinical experience with 1330 lumbar spinal anesthesia performed with purposeful nociceptive blockade of the thoracic and cervical spinal nerves corresponding to dermatomes C4 or C3; warn about the method pathophysiological risks, and emphasize preventive standards for the safe application of the technique. Review of the historical background and anatomical spinal anesthesia with cervical levels of analgesia. Description of the technique used in our institution; population anesthetized; and surgery performed with the described method. Critical exposition of the physiological, pathophysiological, and clinical effects occurred and registered during anesthesia-surgery and postoperative period. Spinal anesthesia with nociceptive blockade to dermatome C4, or C3, is an effective option for surgery on somatic structures distal to the metamer of the third cervical spinal nerve, lasting no more than four or five hours. The method safety depends on the unrestricted respect for the essential rules of proper anesthesia. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Spinal Manipulative Therapy for Adolescent Idiopathic Scoliosis: A Systematic Review.

PubMed

Théroux, Jean; Stomski, Norman; Losco, Christine Dominique; Khadra, Christelle; Labelle, Hubert; Le May, Sylvie

The purpose of this study was to perform a systematic review of clinical trials of spinal manipulative therapy for adolescent idiopathic scoliosis. Search strategies were developed for PubMed, CINHAL, and CENTRAL databases. Studies were included through June 2016 if they were prospective trials that evaluated spinal manipulative therapy (eg, chiropractic, osteopathic, physical therapy) for adolescent idiopathic scoliosis. Data were extracted and assessed by 2 independent reviewers. Cochrane risk of bias tools were used to assess the quality of the included studies. Data were reported qualitatively because heterogeneity prevented statistical pooling. Four studies satisfied the inclusion criteria and were critically appraised. The findings of the included studies indicated that spinal manipulative therapy might be effective for preventing curve progression or reducing Cobb angle. However, the lack of controls and small sample sizes precluded robust estimation of the interventions' effect sizes. There is currently insufficient evidence to establish whether spinal manipulative therapy may be beneficial for adolescent idiopathic scoliosis. The results of the included studies suggest that spinal manipulative therapy may be a promising treatment, but these studies were all at substantial risk of bias. Further high-quality studies are warranted to conclusively determine if spinal manipulative therapy may be effective in the management of adolescent idiopathic scoliosis. Copyright © 2017. Published by Elsevier Inc.

Analgesic effects of the COX-2 inhibitor parecoxib on surgical pain through suppression of spinal ERK signaling.

PubMed

Guo, Ya-Jing; Shi, Xu-Dan; Fu, DI; Yang, Yong; Wang, Ya-Ping; Dai, Ru-Ping

2013-07-01

Cyclooxygenase (COX)-2 inhibitors are widely used for postoperative pain control in clinical practice. However, it is unknown whether spinal sensitization is involved in the analgesic effects of COX-2 inhibitors on surgical pain. Extracellular signal-regulated kinase (ERK) in the spinal cord is implicated in various types of pain, including surgical pain. The present study investigated the role of spinal ERK signaling in the analgesic effect of the COX-2 inhibitor parecoxib on surgical pain. Surgical pain was produced in rats by surgical incision of the hind paw. Phosphorylated (p)-ERK1/2 expression was determined by immunohistochemistry. Pain hypersensitivity was evaluated by measuring the paw withdrawal threshold using the von Frey test. The selective COX-2 inhibitor parecoxib was delivered 20 min before or 20 min after the incision by intraperitoneal injection. Pretreatment with parecoxib markedly attenuated the pain hypersensitivity induced by incision. However, post-treatment with parecoxib produced minimal analgesic effects. Parecoxib inhibited the increase in spinal p-ERK expression following surgical incision. The present study thus suggests that the COX-2 inhibitor parecoxib exerts its analgesic effect on surgical pain through the inhibition of neuronal ERK activation in the spinal cord. COX-2 inhibitor delivery prior to surgery has more potent analgesic effects, suggesting the advantage of preventive analgesia for post-operative pain control.

Effect of spinal manipulation on the development of history-dependent responsiveness of lumbar paraspinal muscle spindles in the cat

PubMed Central

Cao, Dong-Yuan; Pickar, Joel G.

2014-01-01

We determined whether spinal manipulation could prevent and/or reverse the decrease and increase in paraspinal muscle spindle responsiveness caused respectively by lengthening and shortening histories of the lumbar muscles. Single unit spindle activity from multifidus and longissimus muscles was recorded in the L6 dorsal root in anesthetized cats. Muscle history was created and spinal manipulation delivered (thrust amplitude: 1.0mm, duration: 100ms) using a feedback-controlled motor attached to the L6 spinous process. Muscle spindle discharge to a fixed vertebral position (static test) and to vertebral movement (dynamic test) was evaluated following the lengthening and shortening histories. For the static test, changes in muscle spindle responsiveness were significantly less when spinal manipulation followed muscle history (p<0.01), but not when spinal manipulation preceded it (p>0.05). For the dynamic test, spinal manipulation did not significantly affect the history-induced change in muscle spindle responsiveness. Spinal manipulation may partially reverse the effects of muscle history on muscle spindle signaling of vertebral position. PMID:24932019

Comparison of the effect of intrathecal administration of clonidine and yohimbine on the locomotion of intact and spinal cats.

PubMed

Giroux, N; Reader, T A; Rossignol, S

2001-06-01

Several studies have shown that noradrenergic mechanisms are important for locomotion. For instance, L-dihydroxyphenylalanine (L-DOPA) can initiate "fictive" locomotion in immobilized acutely spinalized cats and alpha(2)-noradrenergic agonists, such as 2,6,-dichloro-N-2-imidazolidinylid-enebenzenamine (clonidine), can induce treadmill locomotion soon after spinalization. However, the activation of noradrenergic receptors may be not essential for the basic locomotor rhythmicity because chronic spinal cats can walk with the hindlimbs on a treadmill in the absence of noradrenergic stimulation because the descending pathways are completely severed. This suggests that locomotion, in intact and spinal conditions, is probably expressed and controlled through different neurotransmitter mechanisms. To test this hypothesis, we compared the effect of the alpha(2) agonist, clonidine, and the antagonist (16 alpha, 17 alpha)-17-hydroxy yohimbine-16-carboxylic acid methyl ester hydrochloride (yohimbine), injected intrathecally at L(3)--L(4) before and after spinalization in the same cats chronically implanted with electrodes to record electromyograms (EMGs). In intact cats, clonidine (50-150 microg/100 microl) modulated the locomotor pattern slightly causing a decrease in duration of the step cycle accompanied with some variation of EMG burst amplitude and duration. In the spinal state, clonidine could trigger robust and sustained hind limb locomotion in the first week after the spinalization at a time when the cats were paraplegic. Later, after the spontaneous recovery of a stable locomotor pattern, clonidine prolonged the cycle duration, increased the amplitude and duration of flexor and extensor bursts, and augmented the foot drag at the onset of swing. In intact cats, yohimbine at high doses (800--1600 microg/100 microl) caused major walking difficulties characterized by asymmetric stepping, stumbling with poor lateral stability, and, at smaller doses (400 microg/100 microl), only had slight effects such as abduction of one of the hindlimbs and the turning of the hindquarters to one side. After spinalization, yohimbine had no effect even at the largest doses. These results indicate that, in the intact state, noradrenergic mechanisms probably play an important role in the control of locomotion since blocking the receptors results in a marked disruption of walking. In the spinal state, although the receptors are still present and functional since they can be activated by clonidine, they are seemingly not critical for the spontaneous expression of spinal locomotion since their blockade by yohimbine does not impair spinal locomotion. It is postulated therefore that the expression of spinal locomotion must depend on the activation of other types of receptors, probably related to excitatory amino acids.

Transspinal direct current stimulation modulates migration and proliferation of adult newly born spinal cells in mice.

PubMed

Samaddar, Sreyashi; Vazquez, Kizzy; Ponkia, Dipen; Toruno, Pedro; Sahbani, Karim; Begum, Sultana; Abouelela, Ahmed; Mekhael, Wagdy; Ahmed, Zaghloul

2017-02-01

Direct current electrical fields have been shown to be a major factor in the regulation of cell proliferation, differentiation, migration, and survival, as well as in the maturation of dividing cells during development. During adulthood, spinal cord cells are continuously produced in both animals and humans, and they hold great potential for neural restoration following spinal cord injury. While the effects of direct current electrical fields on adult-born spinal cells cultured ex vivo have recently been reported, the effects of direct current electrical fields on adult-born spinal cells in vivo have not been characterized. Here, we provide convincing findings that a therapeutic form of transspinal direct current stimulation (tsDCS) affects the migration and proliferation of adult-born spinal cells in mice. Specifically, cathodal tsDCS attracted the adult-born spinal cells, while anodal tsDCS repulsed them. In addition, both tsDCS polarities caused a significant increase in cell number. Regarding the potential mechanisms involved, both cathodal and anodal tsDCS caused significant increases in expression of brain-derived neurotrophic factor, while expression of nerve growth factor increased and decreased, respectively. In the spinal cord, both anodal and cathodal tsDCS increased blood flow. Since blood flow and angiogenesis are associated with the proliferation of neural stem cells, increased blood flow may represent a major factor in the modulation of newly born spinal cells by tsDCS. Consequently, we propose that the method and novel findings presented in the current study have the potential to facilitate cellular, molecular, and/or bioengineering strategies to repair injured spinal cords. NEW & NOTEWORTHY Our results indicate that transspinal direct current stimulation (tsDCS) affects the migratory pattern and proliferation of adult newly born spinal cells, a cell population which has been implicated in learning and memory. In addition, our results suggest a potential mechanism of action regarding the functional effects of applying direct current. Thus tsDCS may represent a novel method by which to manipulate the migration and cell number of adult newly born cells and restore functions following brain or spinal cord injury. Copyright © 2017 the American Physiological Society.

p53 participates in the protective effects of ischemic post-conditioning against OGD-reperfusion injury in primary cultured spinal cord neurons.

PubMed

Li, Jinquan; Chen, Gong; Gao, Xinjie; Shen, Chao; Zhou, Ping; Wu, Xing; Che, Xiaoming; Xie, Rong

2017-01-18

Spinal cord ischemia-reperfusion (I/R) injury is a severe clinical condition, while the mechanism is still not clarified and the therapeutic approach is limited. Ischemia post-conditioning (PC) has been found to have the protective effects against I/R injury in brain. Recently p53 has been reported to take part in the regulation and protection of I/R injury. We hypothesize that PC has the protective effects in primary cultured spinal cord neurons against ischemia-reperfusion injury, and MDM2-p53 signaling pathway may involve in its protective mechanism. In this study, we used an OGD (oxygen and glucose deprivation)-reperfusion model in primary cultured spinal cord neurons to simulate the I/R injury of spinal cord in vitro, and PC was conducted by 3 cycles of 15min restoration of glucose and oxygen with 15min OGD, followed by 6h fully restoration as reperfusion. Lentiviral vectors were used to knock down MDM2 or over-express p53 genes in primary cultured spinal cord neurons. The results showed that 3 cycles of 15min PC generated the most significant protective effects in primary cultured spinal cord neurons against OGD-reperfusion injury. The levels of MDM2 were decreased while p53, Bax, and cleaved Caspase 3 were increased under OGD-reperfusion condition. PC could significantly reverse the down-regulation of MDM2 and up-regulation of p53, Bax, and cleaved Caspase 3 by OGD-reperfusion injury. Moreover, MDM2 knockdown or p53 over-expression could induce the cleaved Caspase 3 expression and blocked the protective effects of PC in primary cultured spinal cord neurons against OGD-reperfusion injury. In conclusion, our work demonstrated that MDM2-p53 pathway plays a pivotal role in the protective effect of PC against OGD-reperfusion injury and PC may be a feasible therapy strategy in the treatment for spinal cord I/R injury. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The "beneficial" effects of locomotor training after various types of spinal lesions in cats and rats.

PubMed

Rossignol, Serge; Martinez, Marina; Escalona, Manuel; Kundu, Aritra; Delivet-Mongrain, Hugo; Alluin, Olivier; Gossard, Jean-Pierre

2015-01-01

This chapter reviews a number of experiments on the recovery of locomotion after various types of spinal lesions and locomotor training mainly in cats. We first recall the major evidence on the recovery of hindlimb locomotion in completely spinalized cats at the T13 level and the role played by the spinal locomotor network, also known as the central pattern generator, as well as the beneficial effects of locomotor training on this recovery. Having established that hindlimb locomotion can recover, we raise the issue as to whether spinal plastic changes could also contribute to the recovery after partial spinal lesions such as unilateral hemisections. We found that after such hemisection at T10, cats could recover quadrupedal locomotion and that deficits could be improved by training. We further showed that, after a complete spinalization a few segments below the first hemisection (at T13, i.e., the level of previous studies on spinalization), cats could readily walk with the hindlimbs within hours of completely severing the remaining spinal tracts and not days as is usually the case with only a single complete spinalization. This suggests that neuroplastic changes occurred below the first hemisection so that the cat was already primed to walk after the spinalization subsequent to the hemispinalization 3 weeks before. Of interest is the fact that some characteristic kinematic features in trained or untrained hemispinalized cats could remain after complete spinalization, suggesting that spinal changes induced by training could also be durable. Other studies on reflexes and on the pattern of "fictive" locomotion recorded after curarization corroborate this view. More recent work deals with training cats in more demanding situations such as ladder treadmill (vs. flat treadmill) to evaluate how the locomotor training regimen can influence the spinal cord. Finally, we report our recent studies in rats using compressive lesions or surgical complete spinalization and find that some principles of locomotor recovery in cats also apply to rats when adequate locomotor training is provided. © 2015 Elsevier B.V. All rights reserved.

Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury

PubMed Central

Ferguson, Adam R.; Huie, J. Russell; Crown, Eric D.; Baumbauer, Kyle M.; Hook, Michelle A.; Garraway, Sandra M.; Lee, Kuan H.; Hoy, Kevin C.; Grau, James W.

2012-01-01

Synaptic plasticity within the spinal cord has great potential to facilitate recovery of function after spinal cord injury (SCI). Spinal plasticity can be induced in an activity-dependent manner even without input from the brain after complete SCI. A mechanistic basis for these effects is provided by research demonstrating that spinal synapses have many of the same plasticity mechanisms that are known to underlie learning and memory in the brain. In addition, the lumbar spinal cord can sustain several forms of learning and memory, including limb-position training. However, not all spinal plasticity promotes recovery of function. Central sensitization of nociceptive (pain) pathways in the spinal cord may emerge in response to various noxious inputs, demonstrating that plasticity within the spinal cord may contribute to maladaptive pain states. In this review we discuss interactions between adaptive and maladaptive forms of activity-dependent plasticity in the spinal cord below the level of SCI. The literature demonstrates that activity-dependent plasticity within the spinal cord must be carefully tuned to promote adaptive spinal training. Prior work from our group has shown that stimulation that is delivered in a limb position-dependent manner or on a fixed interval can induce adaptive plasticity that promotes future spinal cord learning and reduces nociceptive hyper-reactivity. On the other hand, stimulation that is delivered in an unsynchronized fashion, such as randomized electrical stimulation or peripheral skin injuries, can generate maladaptive spinal plasticity that undermines future spinal cord learning, reduces recovery of locomotor function, and promotes nociceptive hyper-reactivity after SCI. We review these basic phenomena, how these findings relate to the broader spinal plasticity literature, discuss the cellular and molecular mechanisms, and finally discuss implications of these and other findings for improved rehabilitative therapies after SCI. PMID:23087647

Line intersect sampling: Ell-shaped transects and multiple intersections

Treesearch

Timothy G. Gregoire; Harry T. Valentine

2003-01-01

The probability of selecting a population element under line intersect sampling depends on the width of the particle in the direction perpendicular to the transect, as is well known. The consequence of this when using ell-shaped transects rather than straight-line transects are explicated, and modifications that preserve design-unbiasedness of Kaiser's (1983)...

The response of tundra springtails (Collembola, Hexapoda) to human activity on the Murman coast of the Kola Penisula, Russia

NASA Astrophysics Data System (ADS)

Olejniczak, Izabella; Boniecki, Paweł; Kaliszewicz, Anita; Panteleeva, Ninel

2018-03-01

This study was carried out in the Dalne Zelentsy settlement (69°07‧N, 36°03‧E) on the Barents Sea of the Kola Penisula in Russia. Three transects were established: the 'new garden transect'; the 'old garden transect'; and the 'settlement transect'. Overall, the number of springtails increased with distance from the 'settlement' and decreased from the 'old garden' towards the tundra. However, in the case of the 'new garden transect' there were no clear trends in springtail abundance. Eleven species of springtail were found, with Parisotoma notabilis being found at each of the studied areas along the transects. Trends in the species diversity of the springtail communities were not clear, and the values of H‧ ranged from 1.36 to 2.08. The springtail communities located 10 m from the 'new garden' and the 'old garden' were characterized by low species diversity compared with the other sites along the transects (H‧ values of 1.36 and 1.67, respectively). There were no differences in species diversity among the springtail communities along the 'settlement transect'.

Rotational stability test for the diagnosis of radial collateral ligament rupture in the fingers: Anatomical study.

PubMed

Lazarus, P; Hidalgo Diaz, J J; Prunières, G; Pire, E; Taleb, C; Honecker, S; Bellemère, P; Fontaine, C; Liverneaux, P A

2017-04-01

Diagnosing rupture of the radial collateral ligament (RCL) of the finger metacarpophalangeal (MCP) joints is difficult. The aim of this cadaver study was to validate a rotational test for the MCP after RCL transection. With the MCP and proximal interphalangeal joints in flexion, rotation along the axis of the proximal phalanx was applied through an extended distal interphalangeal joint to 36 cadaver fingers. Each finger's pulp described an arc of pronation and supination that was noted on the palm. The test was repeated three times: before transection, after transection of the proper collateral ligament (CL) and after transection of both the proper and accessory CLs. Rotational arcs were measured in pronation and supination. Mean length of the pronation arc after transection of the main RCL was 17.53mm, while it was only 12.41mm before transection for the supination arc. Mean length of the pronation arc after transection of both CLs was 22.83mm compared to only 11.93mm before transection. Our results show a significant difference in pronation stability of the MCP joint after transection of the RCL proper. We can conclude that this rotational stability test is a valid test for diagnosing RCL rupture in MCP joints. Copyright © 2017 SFCM. Published by Elsevier Masson SAS. All rights reserved.

Dose-response study of spinal hyperbaric ropivacaine for cesarean section

PubMed Central

Chen, Xin-zhong; Chen, Hong; Lou, Ai-fei; Lü, Chang-cheng

2006-01-01

Background: Spinal hyperbaric ropivacaine may produce more predictable and reliable anesthesia than plain ropivacaine for cesarean section. The dose-response relation for spinal hyperbaric ropivacaine is undetermined. This double-blind, randomized, dose-response study determined the ED50 (50% effective dose) and ED95 (95% effective dose) of spinal hyperbaric ropivacaine for cesarean section anesthesia. Methods: Sixty parturients undergoing elective cesarean section delivery with use of combined spinal-epidural anesthesia were enrolled in this study. An epidural catheter was placed at the L1~L2 vertebral interspace, then lumbar puncture was performed at the L3~L4 vertebral interspace, and parturients were randomized to receive spinal hyperbaric ropivacaine in doses of 10.5 mg, 12 mg, 13.5 mg, or 15 mg in equal volumes of 3 ml. Sensory levels (pinprick) were assessed every 2.5 min until a T7 level was achieved and motor changes were assessed by modified Bromage Score. A dose was considered effective if an upper sensory level to pin prick of T7 or above was achieved and no intraoperative epidural supplement was required. ED50 and ED95 were determined with use of a logistic regression model. Results: ED50 (95% confidence interval) of spinal hyperbaric ropivacaine was determined to be 10.37 (5.23~11.59) mg and ED95 (95% confidence interval) to be 15.39 (13.81~23.59) mg. The maximum sensory block levels and the duration of motor block and the rate of hypotension, but not onset of anesthesia, were significantly related to the ropivacaine dose. Conclusion: The ED50 and ED95 of spinal hyperbaric ropivacaine for cesarean delivery under the conditions of this study were 10.37 mg and 15.39 mg, respectively. Ropivacaine is suitable for spinal anesthesia in cesarean delivery. PMID:17111469

Immediate effects of spinal manipulation on thermal pain sensitivity: an experimental study

PubMed Central

George, Steven Z; Bishop, Mark D; Bialosky, Joel E; Zeppieri, Giorgio; Robinson, Michael E

2006-01-01

Background The underlying causes of spinal manipulation hypoalgesia are largely unknown. The beneficial clinical effects were originally theorized to be due to biomechanical changes, but recent research has suggested spinal manipulation may have a direct neurophysiological effect on pain perception through dorsal horn inhibition. This study added to this literature by investigating whether spinal manipulation hypoalgesia was: a) local to anatomical areas innervated by the lumbar spine; b) correlated with psychological variables; c) greater than hypoalgesia from physical activity; and d) different for A-delta and C-fiber mediated pain perception. Methods Asymptomatic subjects (n = 60) completed baseline psychological questionnaires and underwent thermal quantitative sensory testing for A-delta and C-fiber mediated pain perception. Subjects were then randomized to ride a stationary bicycle, perform lumbar extension exercise, or receive spinal manipulation. Quantitative sensory testing was repeated 5 minutes after the intervention period. Data were analyzed with repeated measures ANOVA and post-hoc testing was performed with Bonferroni correction, as appropriate. Results Subjects in the three intervention groups did not differ on baseline characteristics. Hypoalgesia from spinal manipulation was observed in lumbar innervated areas, but not control (cervical innervated) areas. Hypoalgesic response was not strongly correlated with psychological variables. Spinal manipulation hypoalgesia for A-delta fiber mediated pain perception did not differ from stationary bicycle and lumbar extension (p > 0.05). Spinal manipulation hypoalgesia for C-fiber mediated pain perception was greater than stationary bicycle riding (p = 0.040), but not for lumbar extension (p = 0.105). Conclusion Local dorsal horn mediated inhibition of C-fiber input is a potential hypoalgesic mechanism of spinal manipulation for asymptomatic subjects, but further study is required to replicate this finding in subjects with low back pain. PMID:16911795

Superficial NK1 expressing spinal dorsal horn neurones modulate inhibitory neurotransmission mediated by spinal GABA(A) receptors.

PubMed

Rahman, Wahida; Sikandar, Shafaq; Sikander, Shafaq; Suzuki, Rie; Hunt, Stephen P; Dickenson, Anthony H

2007-06-04

Lamina 1 projection neurones which express the NK1 receptor (NK1R+) drive a descending serotonergic pathway from the brainstem that enhances spinal dorsal horn neuronal activity via the facilitatory spinal 5-HT3 receptor. Selective destruction of these cells via lumbar injection of substance P-saporin (SP-SAP) attenuates pain behaviours, including mechanical and thermal hypersensitivity, which are mirrored by deficits in the evoked responses of lamina V-VI wide dynamic range (WDR) neurones to noxious stimuli. To assess whether removing the origin of this facilitatory spino-bulbo-spinal loop results in alterations in GABAergic spinal inhibitory systems, the effects of spinal bicuculline, a selective GABA(A) receptor antagonist, on the evoked neuronal responses to electrical (Abeta-, Adelta-, C-fibre, post-discharge and Input) and mechanical (brush, prod and von Frey (vF) 8 and 26 g) stimuli were measured in SAP and SP-SAP groups. In the SAP control group, bicuculline produced a significant dose related facilitation of the electrically evoked Adelta-, C-fibre, post-discharge and input neuronal responses. The evoked mechanical (prod, vF8 g and 26 g) responses were also significantly increased. Brush evoked neuronal responses in these animals were enhanced but did not reach significance. This facilitatory effect of bicuculline, however, was lost in the SP-SAP treated group. The generation of intrinsic GABAergic transmission in the spinal cord appears dependent on NK1 bearing neurons, yet despite the loss of GABAergic inhibitory controls after SP-SAP treatment, the net effect is a decrease in spinal cord excitability. Thus activation of these cells predominantly drives facilitation.

Effect of deafferentation from spinal anesthesia on pain sensitivity and resting-state functional brain connectivity in healthy male volunteers.

PubMed

Niesters, Marieke; Sitsen, Elske; Oudejans, Linda; Vuyk, Jaap; Aarts, Leon P H J; Rombouts, Serge A R B; de Rover, Mischa; Khalili-Mahani, Najmeh; Dahan, Albert

2014-08-01

Patients may perceive paradoxical heat sensation during spinal anesthesia. This could be due to deafferentation-related functional changes at cortical, subcortical, or spinal levels. In the current study, the effect of spinal deafferentation on sensory (pain) sensitivity was studied and linked to whole-brain functional connectivity as assessed by resting-state functional magnetic resonance imaging (RS-fMRI) imaging. Deafferentation was induced by sham or spinal anesthesia (15 mg bupivacaine injected at L3-4) in 12 male volunteers. RS-fMRI brain connectivity was determined in relation to eight predefined and seven thalamic resting-state networks (RSNs) and measured before, and 1 and 2 h after spinal/sham injection. To measure the effect of deafferentation on pain sensitivity, responses to heat pain were measured at 15-min intervals on nondeafferented skin and correlated to RS-fMRI connectivity data. Spinal anesthesia altered functional brain connectivity within brain regions involved in the sensory discriminative (i.e., pain intensity related) and affective dimensions of pain perception in relation to somatosensory and thalamic RSNs. A significant enhancement of pain sensitivity on nondeafferented skin was observed after spinal anesthesia compared to sham (area-under-the-curve [mean (SEM)]: 190.4 [33.8] versus 13.7 [7.2]; p<0.001), which significantly correlated to functional connectivity changes observed within the thalamus in relation to the thalamo-prefrontal network, and in the anterior cingulate cortex and insula in relation to the thalamo-parietal network. Enhanced pain sensitivity from spinal deafferentation correlated with functional connectivity changes within brain regions involved in affective and sensory pain processing and areas involved in descending control of pain.

Effects of orally administered OP-1206 alpha-CD with loxoprofen-Na on walking dysfunction in the rat neuropathic intermittent claudication model.

PubMed

Nakai, Katsuhiko; Takenobu, Yoshifumi; Takimizu, Hideyuki; Akimaru, Shinji; Ito, Hidenori; Maegawa, Hitoshi; Marsala, Martin; Katsube, Nobuo

2003-10-01

An orally active prostaglandin E1 analogue, OP-1206 alpha-CD improves walking dysfunction in the rat spinal stenosis model. Loxoprofen-Na, a non-steroidal anti-inflammatory drug, is used to relieve chronic pain in patients with lumbar spinal canal stenosis. To determine whether the OP-1206 alpha-CD in combination with loxoprofen-Na could induce a greater therapeutical effect on walking dysfunction and spinal cord blood flow (SCBF) than OP-1206 alpha-CD treatment alone after chronic spinal stenosis in the rat. Spinal stenosis was induced by placing two pieces of silicon rubber strips in the lumbar (L4 and L6) epidural space of rats. After surgery, walking function was measured using a treadmill apparatus and SCBF was measured using a laser-Doppler flow meter. Drugs were administered orally twice a day for 11 days from the day 3 post-surgery. OP-1206 alpha-CD elicited a significant improvement of walking dysfunction on days 7 and 14 post-surgery and significantly increased spinal cord blood flow on day 15, whereas walking dysfunction and SCBF of rats treated with loxoprofen-Na alone remained unchanged. Combined treatment of OP-1206 alpha-CD with loxoprofen-Na did not provide additive therapeutical effect. These results suggest that a significant improvement seen after OP-1206 alpha-CD treatment is primarily mediated by improvement of the local spinal cord blood flow. This effect is not ameliorated or potentiated by a combined treatment with loxoprofen-Na.

Brain protection by methylprednisolone in rats with spinal cord injury.

PubMed

Chang, Chia-Mao; Lee, Ming-Hsueh; Wang, Ting-Chung; Weng, Hsu-Huei; Chung, Chiu-Yen; Yang, Jen-Tsung

2009-07-01

Traumatic spinal cord injury is clinically treated by high doses of methylprednisolone. However, the effect of methylprednisolone on the brain in spinal cord injury patients has been little investigated. This experimental study examined Bcl-2 and Bax protein expression and Nissl staining to evaluate an apoptosis-related intracellular signaling event and final neuron death, respectively. Spinal cord injury produced a significant apoptotic change and cell death not only in the spinal cord but also in the supraventricular cortex and hippocampal cornu ammonis 1 region in the rat brains. The treatment of methylprednisolone increased the Bcl-2/Bax ratio and prevented neuron death for 1-7 days after spinal cord injury. These findings suggest that rats with spinal cord injury show ascending brain injury that could be restricted through methylprednisolone management.

Involvement of hypoglossal and recurrent laryngeal nerves on swallowing pressure.

PubMed

Tsujimura, Takanori; Suzuki, Taku; Yoshihara, Midori; Sakai, Shogo; Koshi, Naomi; Ashiga, Hirokazu; Shiraishi, Naru; Tsuji, Kojun; Magara, Jin; Inoue, Makoto

2018-05-01

Swallowing pressure generation is important to ensure safe transport of an ingested bolus without aspiration or leaving residue in the pharynx. To clarify the mechanism, we measured swallowing pressure at the oropharynx (OP), upper esophageal sphincter (UES), and cervical esophagus (CE) using a specially designed manometric catheter in anesthetized rats. A swallow, evoked by punctate mechanical stimulation to the larynx, was identified by recording activation of the suprahyoid and thyrohyoid muscles using electromyography (EMG). Areas under the curve of the swallowing pressure at the OP, UES, and CE from two trials indicated high intrasubject reproducibility. Effects of transecting the hypoglossal nerve (12N) and recurrent laryngeal nerve (RLN) on swallowing were investigated. Following bilateral hypoglossal nerve transection (Bi-12Nx), OP pressure was significantly decreased, and time intervals between peaks of thyrohyoid EMG bursts and OP pressure were significantly shorter. Decreased OP pressure and shortened times between peaks of thyrohyoid EMG bursts and OP pressure following Bi-12Nx were significantly increased and longer, respectively, after covering the hard and soft palates with acrylic material. UES pressure was significantly decreased after bilateral RLN transection compared with that before transection. These results suggest that the 12N and RLN play crucial roles in OP and UES pressure during swallowing, respectively. We speculate that covering the palates with a palatal augmentation prosthesis may reverse the reduced swallowing pressure in patients with 12N or tongue damage by the changes of the sensory information and of the contact between the tongue and a palates. NEW & NOTEWORTHY Hypoglossal nerve transection reduced swallowing pressure at the oropharynx. Covering the hard and soft palates with acrylic material may reverse the reduced swallowing function caused by hypoglossal nerve damage. Recurrent laryngeal nerve transection reduced upper esophageal sphincter negative pressure during swallowing.

Water-quality data for the Ohio River from New Cumberland Dam to Pike Island Dam, West Virginia and Ohio, June-November 1992

USGS Publications Warehouse

Miller, Kimberly F.; Faulkenburg, C.W.; Chambers, D.B.; Waldron, M.C.

1995-01-01

This report contains water-quality data for the Ohio River, collected during the summer and fall of 1992, from river mile 51.1 (3.3 miles upstream from New Cumberland Dam) to river mile 84.0 (0.2 miles upstream from Pike Island Dam). The data were collected to assess the effects of hydropower development on water quality. Water quality was determined by a combination of repeated synoptic field measurements and laboratory analyses. Synoptic measurements were made along a longitudinal transect with 18 mid-channel sampling sites; cross-sectional transects of water quality were measured at 5 of these sites. Water-quality measurements also were made at two sites located on the back-channel (Ohio) side of Browns Island. Water temperature, dissolved oxygen concentration, pH, and specific conductance were measured at each longitudinal-transect and back-channel sampling site. Longitudinal-transect and back-channel stations were sampled at three depths (about 3.3 feet below the surface of the water, middle of the water column, and near the bottom of the river). Cross-sectional transects consisted of three or four detailed vertical pro- files of the same characteristics. Water samples were collected from three depths at the mid-channel vertical profile in each cross-sectional transect and were analyzed for concentrations of phyto- plankton photosynthetic pigments chlorophyll a and chlorophyll b. Estimates of the depth of light penetration (Secchi disk transparency) were made at pigment-sampling locations whenever light and river-surface conditions were appropriate. Synoptic sampling usually was completed in 12 hours or less and was repeated seven times between June 25 and November 6, 1992.

Spinal-Exercise Prescription in Sport: Classifying Physical Training and Rehabilitation by Intention and Outcome

PubMed Central

Spencer, Simon; Wolf, Alex; Rushton, Alison

2016-01-01

Context: Identification of strategies to prevent spinal injury, optimize rehabilitation, and enhance performance is a priority for practitioners. Different exercises produce different effects on neuromuscular performance. Clarity of the purpose of a prescribed exercise is central to a successful outcome. Spinal exercises need to be classified according to the objective of the exercise and planned physical outcome. Objective: To define the modifiable spinal abilities that underpin optimal function during skilled athletic performance, clarify the effect of spinal pain and pathologic conditions, and classify spinal exercises according to the objective of the exercise and intended physical outcomes to inform training and rehabilitation. Design: Qualitative study. Data Collection and Analysis: We conducted a qualitative consensus method of 4 iterative phases. An exploratory panel carried out an extended review of the English-language literature using CINAHL, EMBASE, MEDLINE, and PubMed to identify key themes and subthemes to inform the definitions of exercise categories, physical abilities, and physical outcomes. An expert project group reviewed panel findings. A draft classification was discussed with physiotherapists (n = 49) and international experts. Lead physiotherapy and strength and conditioning teams (n = 17) reviewed a revised classification. Consensus was defined as unanimous agreement. Results: After the literature review and subsequent analysis, we defined spinal abilities in 4 categories: mobility, motor control, work capacity, and strength. Exercises were subclassified by functionality as nonfunctional or functional and by spinal displacement as either static (neutral spinal posture with no segmental displacement) or dynamic (dynamic segmental movement). The proposed terminology and classification support commonality of language for practitioners. Conclusions: The spinal-exercise classification will support clinical reasoning through a framework of spinal-exercise objectives that clearly define the nature of the exercise prescription required to deliver intended physical outcomes. PMID:27661792

Influence of Spinal Manipulative Therapy Force Magnitude and Application Site on Spinal Tissue Loading: A Biomechanical Robotic Serial Dissection Study in Porcine Motion Segments.

PubMed

Funabashi, Martha; Nougarou, François; Descarreaux, Martin; Prasad, Narasimha; Kawchuk, Greg

In order to define the relation between spinal manipulative therapy (SMT) input parameters and the distribution of load within spinal tissues, the aim of this study was to determine the influence of force magnitude and application site when SMT is applied to cadaveric spines. In 10 porcine cadavers, a servo-controlled linear actuator motor provided a standardized SMT simulation using 3 different force magnitudes (100N, 300N, and 500N) to 2 different cutaneous locations: L3/L4 facet joint (FJ), and L4 transverse processes (TVP). Vertebral kinematics were tracked optically using indwelling bone pins, the motion segment removed and mounted in a parallel robot equipped with a 6-axis load cell. The kinematics of each SMT application were replicated robotically. Serial dissection of spinal structures was conducted to quantify loading characteristics of discrete spinal tissues. Forces experienced by the L3/L4 segment and spinal structures during SMT replication were recorded and analyzed. Spinal manipulative therapy force magnitude and application site parameters influenced spinal tissues loading. A significant main effect (P < .05) of force magnitude was observed on the loads experienced by the intact specimen and supra- and interspinous ligaments. The main effect of application site was also significant (P < .05), influencing the loading of the intact specimen and facet joints, capsules, and ligamentum flavum (P < .05). Spinal manipulative therapy input parameters of force magnitude and application site significantly influence the distribution of forces within spinal tissues. By controlling these SMT parameters, clinical outcomes may potentially be manipulated. Copyright © 2017. Published by Elsevier Inc.

Effective therapy of transected quadriceps muscle in rat: Gastric pentadecapeptide BPC 157.

PubMed

Staresinic, Mario; Petrovic, Igor; Novinscak, Tomislav; Jukic, Ivana; Pevec, Damira; Suknaic, Slaven; Kokic, Neven; Batelja, Lovorka; Brcic, Luka; Boban-Blagaic, Alenka; Zoric, Zdenka; Ivanovic, Domagoj; Ajduk, Marko; Sebecic, Bozidar; Patrlj, Leonardo; Sosa, Tomislav; Buljat, Gojko; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag

2006-05-01

We report complete transection of major muscle and the systemic peptide treatment that induces healing of quadriceps muscle promptly and then maintains the healing with functional restoration. Initially, stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419, PL-10, PLD-116, PL 14736 Pliva, Croatia; in trials for inflammatory bowel disease; wound treatment; no toxicity reported; effective alone without carrier) also superiorly accelerates the healing of transected Achilles tendon. Regularly, quadriceps muscle completely transected transversely 1.0 cm proximal to patella presents a definitive defect that cannot be compensated in rat. BPC 157 (10 microg, 10 ng, 10 pg/kg) is given intraperitoneally, once daily; the first application 30 min posttransection, the final 24 h before sacrifice. It consistently improves muscle healing throughout the whole 72-day period. Improved are: (i) biomechanic (load of failure increased); (ii) function (walking recovery and extensor postural thrust/motor function index returned toward normal healthy values); (iii) microscopy/immunochemistry [i.e., mostly muscle fibers connect muscle segments; absent gap; significant desmin positivity for ongoing regeneration of muscle; larger myofibril diameters on both sides, distal and proximal (normal healthy rat-values reached)]; (iv) macroscopic presentation (stumps connected; subsequently, atrophy markedly attenuated; finally, presentation close to normal noninjured muscle, no postsurgery leg contracture). Thus, posttransection healing-consistently improved-may suggest this peptide therapeutic application in muscle disorders. Copyright 2006 Orthopaedic Research Society.

Intraoperative electroacupuncture relieves remifentanil-induced postoperative hyperalgesia via inhibiting spinal glial activation in rats

PubMed Central

Shi, Changxi; Liu, Yue; Zhang, Wei; Lei, Yishan; Lu, Cui’e; Sun, Rao; Sun, Yu’e; Jiang, Ming; Gu, Xiaoping; Ma, Zhengliang

2017-01-01

Background Accumulating studies have suggested that remifentanil, the widely-used opioid analgesic in clinical anesthesia, can activate the pronociceptive systems and enhance postoperative pain. Glial cells are thought to be implicated in remifentanil-induced hyperalgesia. Electroacupuncture is a complementary therapy to relieve various pain conditions with few side effects, and glial cells may be involved in its antinociceptive effect. In this study, we investigated whether intraoperative electroacupuncture could relieve remifentanil-induced postoperative hyperalgesia by inhibiting the activation of spinal glial cells, the production of spinal proinflammatory cytokines, and the activation of spinal mitogen-activated protein kinases. Methods A rat model of remifentanil-induced postoperative hyperalgesia was used in this study. Electroacupuncture during surgery was conducted at bilateral Zusanli (ST36) acupoints. Behavior tests, including mechanical allodynia and thermal hyperalgesia, were performed at different time points. Astrocytic marker glial fibrillary acidic protein, microglial marker Iba1, proinflammatory cytokines, and phosphorylated mitogen-activated protein kinases in the spinal cord were detected by Western blot and/or immunofluorescence. Results Mechanical allodynia and thermal hyperalgesia were induced by both surgical incision and remifentanil infusion, and remifentanil infusion significantly exaggerated and prolonged incision-induced pronociceptive effects. Glial fibrillary acidic protein, Iba1, proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α), and phosphorylated mitogen-activated protein kinases (p-p38, p-JNK, and p-ERK1/2) were upregulated after surgical incision, remifentanil infusion, and especially after their combination. Intraoperative electroacupuncture significantly attenuated incision- and/or remifentanil-induced pronociceptive effects, spinal glial activation, proinflammatory cytokine upregulation, and phosphorylated mitogen-activated protein kinase upregulation. Conclusions Our study suggests that remifentanil-induced postoperative hyperalgesia can be relieved by intraoperative electroacupuncture via inhibiting the activation of spinal glial cells, the upregulation of spinal proinflammatory cytokines, and the activation of spinal mitogen-activated protein kinases. PMID:28825338

The Effect of Spinal Tap Test on Different Sensory Modalities of Postural Stability in Idiopathic Normal Pressure Hydrocephalus.

PubMed

Abram, Katrin; Bohne, Silvia; Bublak, Peter; Karvouniari, Panagiota; Klingner, Carsten M; Witte, Otto W; Guntinas-Lichius, Orlando; Axer, Hubertus

2016-01-01

Postural instability in patients with normal pressure hydrocephalus (NPH) is a most crucial symptom leading to falls with secondary complications. The aim of the current study was to evaluate the therapeutic effect of spinal tap on postural stability in these patients. Seventeen patients with clinical symptoms of NPH were examined using gait scale, computerized dynamic posturography (CDP), and neuropsychological assessment. Examinations were done before and after spinal tap test. The gait score showed a significant improvement 24 h after spinal tap test in all subtests and in the sum score (p < 0.003), while neuropsychological assessment did not reveal significant differences 72 h after spinal tap test. CDP showed significant improvements after spinal tap test in the Sensory Organization Tests 2 (p = 0.017), 4 (p = 0.001), and 5 (p = 0.009) and the composite score (p = 0.01). Patients showed best performance in somatosensory and worst performance in vestibular dominated tests. Vestibular dominated tests did not improve significantly after spinal tap test, while somatosensory and visual dominated tests did. Postural stability in NPH is predominantly affected by deficient vestibular functions, which did not improve after spinal tap test. Conditions which improved best were mainly independent from visual control and are based on proprioceptive functions.

Effect of locomotor training in completely spinalized cats previously submitted to a spinal hemisection.

PubMed

Martinez, Marina; Delivet-Mongrain, Hugo; Leblond, Hugues; Rossignol, Serge

2012-08-08

After a spinal hemisection in cats, locomotor plasticity occurring at the spinal level can be revealed by performing, several weeks later, a complete spinalization below the first hemisection. Using this paradigm, we recently demonstrated that the hemisection induces durable changes in the symmetry of locomotor kinematics that persist after spinalization. Can this asymmetry be changed again in the spinal state by interventions such as treadmill locomotor training started within a few days after the spinalization? We performed, in 9 adult cats, a spinal hemisection at thoracic level 10 and then a complete spinalization at T13, 3 weeks later. Cats were not treadmill trained during the hemispinal period. After spinalization, 5 of 9 cats were not trained and served as control while 4 of 9 cats were trained on the treadmill for 20 min, 5 d a week for 3 weeks. Using detailed kinematic analyses, we showed that, without training, the asymmetrical state of locomotion induced by the hemisection was retained durably after the subsequent spinalization. By contrast, training cats after spinalization induced a reversal of the left/right asymmetries, suggesting that new plastic changes occurred within the spinal cord through locomotor training. Moreover, training was shown to improve the kinematic parameters and the performance of the hindlimb on the previously hemisected side. These results indicate that spinal locomotor circuits, previously modified by past experience such as required for adaptation to the hemisection, can remarkably respond to subsequent locomotor training and improve bilateral locomotor kinematics, clearly showing the benefits of locomotor training in the spinal state.

Effects of Enhanced Oxygen Delivery by Perfluorocarbons in Spinal Cord Injury

DTIC Science & Technology

2013-10-01

been established, linking post- traumatic ischemia to axonal dysfunction.8 Decreased oxygen level in severe traumatic injuries appears to be implicated...rodent weight drop traumatic spinal cord injury model; ( 2 ) determine if enhanced oxygen delivery in spinal cord injury spares cellular elements, white...shown that ischemia /hypoxia play crucial role in the devastating effects of the secondary injury following SCI which translates into worse neurological

Three combinations of manual therapy techniques within naprapathy in the treatment of neck and/or back pain: a randomized controlled trial.

PubMed

Paanalahti, Kari; Holm, Lena W; Nordin, Margareta; Höijer, Jonas; Lyander, Jessica; Asker, Martin; Skillgate, Eva

2016-04-23

Manual therapy as spinal manipulation, spinal mobilization, stretching and massage are common treatment methods for neck and back pain. The objective was to compare the treatment effect on pain intensity, pain related disability and perceived recovery from a) naprapathic manual therapy (spinal manipulation, spinal mobilization, stretching and massage) to b) naprapathic manual therapy without spinal manipulation and to c) naprapathic manual therapy without stretching for male and female patients seeking care for back and/or neck pain. Participants were recruited among patients, ages 18-65, seeking care at the educational clinic of Naprapathögskolan - the Scandinavian College of Naprapathic Manual Medicine in Stockholm. The patients (n = 1057) were randomized to one of three treatment arms a) manual therapy (i.e. spinal manipulation, spinal mobilization, stretching and massage), b) manual therapy excluding spinal manipulation and c) manual therapy excluding stretching. The primary outcomes were minimal clinically important improvement in pain intensity and pain related disability. Treatments were provided by naprapath students in the seventh semester of eight total semesters. Generalized estimating equations and logistic regression were used to examine the association between the treatments and the outcomes. At 12 weeks follow-up, 64% had a minimal clinically important improvement in pain intensity and 42% in pain related disability. The corresponding chances to be improved at the 52 weeks follow-up were 58% and 40% respectively. No systematic differences in effect when excluding spinal manipulation and stretching respectively from the treatment were found over 1 year follow-up, concerning minimal clinically important improvement in pain intensity (p = 0.41) and pain related disability (p = 0.85) and perceived recovery (p = 0.98). Neither were there disparities in effect when male and female patients were analyzed separately. The effect of manual therapy for male and female patients seeking care for neck and/or back pain at an educational clinic is similar regardless if spinal manipulation or if stretching is excluded from the treatment option. Current Controlled Trials ISRCTN92249294.

Abolition of lemniscal barrellette patterning in Prrxl1 knockout mice: Effects upon ingestive behavior.

PubMed

Bakalar, Dana; Tamaiev, Jonathan; Zeigler, H Philip; Feinstein, Paul

2015-01-01

Ingestive behaviors in mice are dependent on orosensory cues transmitted via the trigeminal nerve, as confirmed by transection studies. However, these studies cannot differentiate between deficits caused by the loss of the lemniscal pathway vs. the parallel paralemniscal pathway. The paired-like homeodomain protein Prrxl1 is expressed widely in the brain and spinal cord, including the trigeminal system. A knockout of Prrxl1 abolishes somatotopic barrellette patterning in the lemniscal brainstem nucleus, but not in the parallel paralemniscal nucleus. Null animals are significantly smaller than littermates by postnatal day 5, but reach developmental landmarks at appropriate times, and survive to adulthood on liquid diet. A careful analysis of infant and adult ingestive behavior reveals subtle impairments in suckling, increases in time spent feeding and the duration of feeding bouts, feeding during inappropriate times of the day, and difficulties in the mechanics of feeding. During liquid diet feeding, null mice display abnormal behaviors including extensive use of the paws to move food into the mouth, submerging the snout in the diet, changes in licking, and also have difficulty consuming solid chow pellets. We suggest that our Prrxl1(-/-) animal is a valuable model system for examining the genetic assembly and functional role of trigeminal lemniscal circuits in the normal control of eating in mammals and for understanding feeding abnormalities in humans resulting from the abnormal development of these circuits.

Safety and efficacy of cervical laminoplasty using a piezosurgery device compared with a high-speed drill.

PubMed

Li, Kunpeng; Zhang, Wen; Li, Bin; Xu, Hui; Li, Zhong; Luo, Dawei; Zhang, Jingtao; Ma, Jinzhu

2016-09-01

Piezosurgery is a relatively new osteotomy technique using microvibrations of scalpels at ultrasonic frequencies to perform safe and effective osteotomies without damage to adjacent soft tissue, which is widely used in spinal, oral, and maxillofacial surgery. We hypothesized that such a device could also be useful in cervical laminoplasty. The purpose of this study was to compare the safety and efficacy of a piezosurgery device with those of a highspeed drill in cervical laminoplasty. A prospectively randomized clinical study was designed. Forty-two consecutive patients were enrolled in the study. All patients underwent modified expansive open-door laminoplasty and were randomly divided into 2 groups according to the instrument for transection of the lamina, using high-speed drill (drill group) or piezosurgery device (piezosurgery group). The operation time, intraoperative blood loss, and postoperative drainage were recorded. Japanese Orthopedic Association (JOA) score and visual analogue scale (VAS) as clinical assessments were quantified. No significant difference was observed in the operation time between the 2 groups. In the piezosurgery group, there were less loss of the intraoperative blood and postoperative drainage compared with the drill group. However, clinical results (VAS and JOA scores) showed no significant difference between both groups during the all follow-up periods. The piezosurgery is a useful instrument and at least as safe and efficacious as the conventional high-speed drill in cervical laminoplasty.

The transect method: a novel approach to on-farm welfare assessment of commercial turkeys

PubMed Central

Marchewka, Joanna; Estevez, Inma; Vezzoli, Giuseppe; Ferrante, Valentina; Makagon, Maja M.

2015-01-01

Currently, no animal-based protocol for on-farm welfare assessment of commercial turkeys is available. The birds’ size and flighty nature make obtaining a representative sample using traditional methods difficult. The transect walks (TW) approach provides a potential alternative for on-farm assessments of turkey welfare. We compared the TW approach with a traditional method, and data collected as the birds were moved out of the house during the load out process (L). Ten commercial 19- to 20-week-old Hybrid turkey flocks were evaluated (1 flock/house/farm). Half of the flocks were housed on farms deemed as “faring well” by the company, the other half were on “suboptimal” farms. Each house was subdivided longitudinally into 4 transects. Two observers walked the transects in random order, recording the total number of birds per transect that were immobile; lame; aggressive towards a mate; interacting with humans; with visible head, vent, or back wounds; engaging in mounting behaviors; small; featherless; dirty; sick; terminal; or dead. Flocks were re-evaluated on the same day using the individual sampling method (S), where randomly selected birds were scored as they took 10 steps. Flocks were re-assessed within 48 h of the transect evaluation, as birds were funneled out of the house during load out. Using ANOVAs we determined the effects of observers, method, management, and their interactions on proportions of turkeys per house within each category. Outcome parameters were not affected by management (P > 0.05 for all) or observer (P > 0.05 for most), but an assessment method effect was detected (P < 0.05). S differed from the 2 other methods (P < 0.05) for most parameters except aggression towards a mate, back wounds, dirty, sick, and vent wounds. Differences were not detected between data collected using TW and during L, except for dead (P = 0.0007) and immobile (P = 0.007). Results suggest that the TW method is a promising tool for on-farm turkey welfare assessment as it produced results similar to those obtained at L when all birds could be scored individually. PMID:25577791

The transect method: a novel approach to on-farm welfare assessment of commercial turkeys.

PubMed

Marchewka, Joanna; Estevez, Inma; Vezzoli, Giuseppe; Ferrante, Valentina; Makagon, Maja M

2015-01-01

Currently, no animal-based protocol for on-farm welfare assessment of commercial turkeys is available. The birds' size and flighty nature make obtaining a representative sample using traditional methods difficult. The transect walks (TW) approach provides a potential alternative for on-farm assessments of turkey welfare. We compared the TW approach with a traditional method, and data collected as the birds were moved out of the house during the load out process (L). Ten commercial 19- to 20-week-old Hybrid turkey flocks were evaluated (1 flock/house/farm). Half of the flocks were housed on farms deemed as "faring well" by the company, the other half were on "suboptimal" farms. Each house was subdivided longitudinally into 4 transects. Two observers walked the transects in random order, recording the total number of birds per transect that were immobile; lame; aggressive towards a mate; interacting with humans; with visible head, vent, or back wounds; engaging in mounting behaviors; small; featherless; dirty; sick; terminal; or dead. Flocks were re-evaluated on the same day using the individual sampling method (S), where randomly selected birds were scored as they took 10 steps. Flocks were re-assessed within 48 h of the transect evaluation, as birds were funneled out of the house during load out. Using ANOVAs we determined the effects of observers, method, management, and their interactions on proportions of turkeys per house within each category. Outcome parameters were not affected by management (P>0.05 for all) or observer (P>0.05 for most), but an assessment method effect was detected (P<0.05). S differed from the 2 other methods (P<0.05) for most parameters except aggression towards a mate, back wounds, dirty, sick, and vent wounds. Differences were not detected between data collected using TW and during L, except for dead (P=0.0007) and immobile (P=0.007). Results suggest that the TW method is a promising tool for on-farm turkey welfare assessment as it produced results similar to those obtained at L when all birds could be scored individually. © The Author 2015. Published by Oxford University Press on behalf of Poultry Science Association.

Sampling coarse woody debris along spoked transects

Treesearch

Paul C. Van Deusen; Jeffery H. Gove

2011-01-01

Line transects are commonly used for sampling coarse woody debris (CWD). The USDA Forest Service Forest Inventory and Analysis programme uses a variant of this method that involves sampling for CWD along transects that radiate from the centre of a circular plot-like spokes on a wheel. A new approach for analysis of data collected with spoked transects is developed....

Correction of bias in belt transect studies of immotile objects

USGS Publications Warehouse

Anderson, D.R.; Pospahala, R.S.

1970-01-01

Unless a correction is made, population estimates derived from a sample of belt transects will be biased if a fraction of, the individuals on the sample transects are not counted. An approach, useful for correcting this bias when sampling immotile populations using transects of a fixed width, is presented. The method assumes that a searcher's ability to find objects near the center of the transect is nearly perfect. The method utilizes a mathematical equation, estimated from the data, to represent the searcher's inability to find all objects at increasing distances from the center of the transect. An example of the analysis of data, formation of the equation, and application is presented using waterfowl nesting data collected in Colorado.

The impact of forest roads on understory plant diversity in temperate hornbeam-beech forests of Northern Iran.

PubMed

Deljouei, Azade; Abdi, Ehsan; Marcantonio, Matteo; Majnounian, Baris; Amici, Valerio; Sohrabi, Hormoz

2017-08-01

Forest roads alter the biotic and abiotic components of ecosystems, modifying temperature, humidity, wind speed, and light availability that, in turn, cause changes in plant community composition and diversity. We aim at investigating and comparing the diversity of herbaceous species along main and secondary forest roads in a temperate-managed hornbeam-beech forest, north of Iran. Sixteen transects along main and secondary forest roads were established (eight transects along main roads and eight along secondary roads). To eliminate the effect of forest type, all transects were located in Carpinetum-Fagetum forests, the dominant forest type in the study area. The total length of each transect was 200 m (100 m toward up slope and 100 m toward down slope), and plots were established along it at different distances from road edge. The diversity of herbaceous plant species was calculated in each plot using Shannon-Wiener index, species richness, and Pielou's index. The results showed that diversity index decreased when distance from road edge increases. This decreasing trend continued up to 60 m from forest road margin, and after this threshold, the index slightly increased. Depending on the type of road (main or secondary) as well as cut or fill slopes, the area showing a statistical different plant composition and diversity measured through Shannon-Wiener, species richness, and Pielou's index is up to 10 m. The length depth of the road edge effect found in main and secondary forest roads was small, but it could have cumulative effects on forest microclimate and forest-associated biota at the island scale. Forest managers should account for the effect of road buildings on plant communities.

The regional effect of spinal manipulation on the pressure pain threshold in asymptomatic subjects: a systematic literature review.

PubMed

Honoré, Margaux; Leboeuf-Yde, Charlotte; Gagey, Olivier

2018-01-01

Spinal manipulation (SM) has been shown to have an effect on pain perception. More knowledge is needed on this phenomenon and it would be relevant to study its effect in asymptomatic subjects. To compare regional effect of SM on pressure pain threshold (PPT) vs. sham, inactive control, mobilisation, another SM, and some type of physical therapy. In addition, we reported the results for the three different spinal regions. A systematic search of literature was done using PubMed, Embase and Cochrane. Search terms were ((spinal manipulation) AND (experimental pain)); ((spinal manipulative therapy OR spinal manipulation) AND ((experimental pain OR quantitative sensory testing OR pressure pain threshold OR pain threshold)) (Final search: June 13th 2017). The inclusion criteria were SM performed anywhere in the spine; the use of PPT, PPT tested in an asymptomatic region and on the same day as the SM. Studies had to be experimental with at least one external or internal control group. Studies on only spinal motion or tenderness, other reviews, case reports, and less than 15 invited participants in each group were excluded. Evidence tables were constructed with information relevant to each research question and by spinal region. Results were reported in relation to statistical significance and were interpreted taking into account their quality. Only 12 articles of 946 were accepted. The quality of studies was generally good. In 8 sham controlled studies, a psychologically and physiologically "credible" sham was found in only 2 studies. A significant difference was noted between SM vs. Sham, and between SM and an inactive control. No significant difference in PPT was found between SM and another SM, mobilisation or some type of physical therapy. The cervical region more often obtained significant findings as compared to studies in the thoracic or lumbar regions. SM has an effect regionally on pressure pain threshold in asymptomatic subjects. The clinical significance of this must be quantified. More knowledge is needed in relation to the comparison of different spinal regions and different types of interventions.

[Exoskeletons for rehabilitation of patients with spinal cord injuries. Options and limitations].

PubMed

Aach, M; Meindl, R C; Geßmann, J; Schildhauer, T A; Citak, M; Cruciger, O

2015-02-01

Mobile exoskeletons are increasingly being applied in the course of rehabilitation and provision of medical aids to patients with spinal cord injuries. This article gives a description of the currently available exoskeletal systems and the clinical application including scientific and medical evidence, to derive recommendations regarding clinical practice of the various exoskeletons in the rehabilitation of patients with spinal cord injuries. The different systems represent a useful adjunct to the therapeutic regimen depending on the medical objectives. Posture-controlled exoskeletons in particular enable mobilization of patients with neurological gait disorders via direct motion support. In addition the neurologically controlled exoskeleton HAL® leads to functional improvements in patients with residual muscular functions in the chronic phase of spinal cord injury in terms of improved walking abilities subsequent to training. However, beneficial effects on bone density, bladder function and perfusion are conceivable but not yet adequately supported by evidence. Positive effects on spasticity and neuropathic pain are currently based only on case series or small clinical trials. Although exoskeletons are not yet an established tool in the treatment of spinal cord injuries, the systems will play a more important role in rehabilitation of patients with spinal cord injuries in the future. Neurologically controlled exoskeletons show beneficial effects in the treatment of acute and chronic spinal cord injuries and might therefore evolve to be a useful alternative to conventional locomotion training.

Hypobaric bupivacaine spinal anesthesia for cystoscopic intervention: the impact of adding fentanyl.

PubMed

Atallah, Mohamed M; Helal, Mostafa A; Shorrab, Ahmed A

2003-10-01

Addition of fentanyl to hyperbaric bupivacaine spinal anesthesia prolonged the duration of sensory block. This study seeks to test the hypothesis that adding fentanyl to small dose hypobaric spinal anesthesia will improve intraoperative patients and surgeon satisfaction without delay in recovery. Patients (n = 80) subjected to minor cystoscopic surgery were randomly assigned to have spinal anesthesia with either 5 mg bupivacaine 0.1% or 5 mg bupivacaine 0.1% mixed with 20 micrograms fentanyl. The main outcome measures included intraoperative patient and endoscopist satisfaction, sedative/analgesic supplementation, postoperative side effects and time to ambulation. Patients in the bupivacaine group needed more analgesic supplementation. Analgesia was more adequate in the bupivacaine-fentanyl group. Pruritus was the main side effect in the bupivacaine fentanyl group. Ambulation and discharge of patients were nearly the same in both groups. Spinal anesthesia with small dose (5 mg) hypobaric (0.1%) bupivacaine mixed with fentanyl (20 micrograms) produced adequate anesthesia for short cystoscopic procedures with minimal side effects and without delay in ambulation.

Effectiveness of spinal anesthesia combined with obturator nerve blockade in preventing adductor muscle contraction during transurethral resection of bladder tumor

PubMed Central

Alavi, Cyrus Emir; Asgari, Seyed Alaeddin; Falahatkar, Siavash; Rimaz, Siamak; Naghipour, Mohammadreza; Khoshrang, Hossein; Jafari, Mehdi; Herfeh, Nadia

2017-01-01

Objective To determine whether spinal anesthesia combined with obturator nerve blockade (SOB) is effective in preventing obturator nerve stimulation, jerking and bladder perforation during transurethral resection of bladder tumor (TURBT). Material and methods In this clinical trial, 30 patients were randomly divided into two groups: spinal anesthesia (SA) and SOB. In SA group, 2.5 cc of 0.5% bupivacaine was injected intrathecally using a 25-gauge spinal needle and in SOB after spinal anesthesia, a classic obturator nerve blockade was performed by using nerve stimulation technique. Results There was a statistically significant difference between jerking in both groups (p=0.006). During the TURBT, surgeon satisfaction was significantly higher in SOB group compared to SA group (p=0.006). There was no significant correlation between sex, patient age and location of bladder tumor between the groups (p>0.05). Conclusion Obturator nerve blockade by using 15 cc lidocaine 1% is effective in preventing adductor muscle spasms during TURBT. PMID:29201516

Histomorphometric and Ultrastructural Evaluation of Long-Term Alpha Lipoic Acid and Vitamin B12 Use After Experimental Sciatic Nerve Injury in Rats.

PubMed

Arikan, Murat; Togral, Guray; Hasturk, Askin Esen; Horasanli, Bahriye; Helvacioglu, Fatma; Dagdeviren, Atilla; Tekindal, Mustafa Agah; Parpucu, Murat

2016-01-01

To analyze the therapeutic effects of long-term alpha lipoic acid (A-LA) and vitamin B12 use via histomorphometric methods and electron microscopy in the transected sciatic nerves of rats. Forty rats were randomized into five groups (n=8/group). In group I, 1 cm segment of sciatic nerve was resected without any other intervention. In group II (sham), following right sciatic nerve transection, primary epineurial anastomosis was performed by placing the edges of the nerve end-to-end. In group III (saline), after right sciatic nerve transection, the ends of the nerves were brought together and closed after application of intraperitoneal physiologic saline. In group IV, 2 mg/kg of alpha lipoic acid and in group V, 2 mg/kg of vitamin B12 was administered intraperitoneally before surgical intervention. Histomorphometric and electron microscopic analyses revealed that vitamin B12 did not prevent structural changes, abnormal myelination and g-ratio deviations regarding the functional aspects of the sciatic nerve. Alpha lipoic acid was more effective in restructuring the histomorphometric and structural aspects of the nerve with more myelinated fibers with optimal values (0.55-0.68) than vitamin B12 groups, in which the number of myelinated nerve fibers significantly decreased at optimal intervals (0.55-0.68). A-LA administration following peripheral nerve transection injury is more effective in promoting nerve healing regarding the structural aspects of the sciatic nerve compared to vitamin B12 and also myelination of nerve fibers by increasing g-values.

Comparison of segmental spinal movement control in adolescents with and without idiopathic scoliosis using modified pressure biofeedback unit.

PubMed

Luo, Hong-Ji; Lin, Shi-Xiang; Wu, Shyi-Kuen; Tsai, Mei-Wun; Lee, Shwn-Jen

2017-01-01

Postural rehabilitation emphasizing on motor control training of segmental spinal movements has been proposed to effectively reduce the scoliotic spinal deformities in adolescent idiopathic scoliosis (AIS). However, information regarding the impairments of segmental spinal movement control involving segmental spinal stabilizers in adolescent idiopathic scoliosis remains limited. Examination of segmental spinal movement control may provide a window for investigating the features of impaired movement control specific to spinal segments that may assist in the development of physiotherapeutic management of AIS. To compare segmental spinal movement control in adolescents with and without idiopathic scoliosis using modified pressure biofeedback unit. Segmental spinal movement control was assessed in twenty adolescents with idiopathic scoliosis (AISG) and twenty healthy adolescents (CG) using a modified pressure biofeedback unit. Participants performed segmental spinal movements that primarily involved segmental spinal stabilizing muscles with graded and sustained muscle contraction against/off a pressure cuff from baseline to target pressures and then maintained for 1 min. Pressure data during the 1-minute maintenance phase were collected for further analysis. Pressure deviation were calculated and compared between groups. The AISG had significantly greater pressure deviations for all segmental spinal movements of cervical, thoracic, and lumbar spine than the CG. Pressure biofeedback unit was feasible for assessing segmental spinal movement control in AIS. AISG exhibited poorer ability to grade and sustain muscle activities for local movements of cervical, thoracic, and lumbar spine, suggesting motor control training of segmental spinal movements involving segmental spinal stabilizing muscles on frontal, sagittal, and transverse planes were required.

Effect of spinal anaesthesia on the lower urinary tract in continent women.

PubMed

Haeusler, G; Sam, C; Chiari, A; Tempfer, C; Hanzal, E; Koelbl, H

1998-01-01

To evaluate the effect of spinal anaesthesia on the bladder neck position and the urethral closure function in the resting state and during clinical stress test in healthy, continent women. Controlled clinical trial. Department of Gynaecology and Obstetrics, Vienna University Medical School. Fourteen continent women, of which seven were nulliparous and seven parous, underwent minor gynaecological procedures under spinal anaesthesia. Urodynamics and ultrasound investigations were performed before and during spinal anaesthesia. Changes in the bladder neck position and the urethral closure function before and during spinal anaesthesia. Bladder neck position was found to be lower and more posterior during spinal anaesthesia as compared with pre-operative assessment. The posterior urethrovesical angle increased significantly both at rest and during maximum straining. We observed a significant increase in bladder compliance, and all parameters of the urethral pressure profile decreased significantly. While none of the nulliparous women had a positive clinical stress test during spinal anaesthesia, 4/7 parous women demonstrated leakage (Fisher's exact test, P = 0.003). Blockage of nerve supply to the pelvic floor muscles in continent women is associated with a significant loss of support of the bladder neck region confirming the theory of an active mechanism of muscular elements providing continence.

Effects of patterned peripheral nerve stimulation on soleus spinal motor neuron excitability

PubMed Central

Dileone, Michele; Campolo, Michela; Carrasco-Lopez, Carmen; Moitinho-Ferreira, Fabricia; Gallego-Izquierdo, Tomas; Siebner, Hartwig R.; Valls-Solé, Josep; Aguilar, Juan

2018-01-01

Spinal plasticity is thought to contribute to sensorimotor recovery of limb function in several neurological disorders and can be experimentally induced in animals and humans using different stimulation protocols. In healthy individuals, electrical continuous Theta Burst Stimulation (TBS) of the median nerve has been shown to change spinal motoneuron excitability in the cervical spinal cord as indexed by a change in mean H-reflex amplitude in the flexor carpi radialis muscle. It is unknown whether continuous TBS of a peripheral nerve can also shift motoneuron excitability in the lower limb. In 26 healthy subjects, we examined the effects of electrical TBS given to the tibial nerve in the popliteal fossa on the excitability of lumbar spinal motoneurons as measured by H-reflex amplitude of the soleus muscle evoked by tibial nerve stimulation. Continuous TBS was given at 110% of H-reflex threshold intensity and compared to non-patterned regular electrical stimulation at 15 Hz. To disclose any pain-induced effects, we also tested the effects of TBS at individual sensory threshold. Moreover, in a subgroup of subjects we evaluated paired-pulse inhibition of H-reflex. Continuous TBS at 110% of H-reflex threshold intensity induced a short-term reduction of H-reflex amplitude. The other stimulation conditions produced no after effects. Paired-pulse H-reflex inhibition was not modulated by continuous TBS or non-patterned repetitive stimulation at 15 Hz. An effect of pain on the results obtained was discarded, since non-patterned 15 Hz stimulation at 110% HT led to pain scores similar to those induced by EcTBS at 110% HT, but was not able to induce any modulation of the H reflex amplitude. Together, the results provide first time evidence that peripheral continuous TBS induces a short-lasting change in the excitability of spinal motoneurons in lower limb circuitries. Future studies need to investigate how the TBS protocol can be optimized to produce a larger and longer effect on spinal cord physiology and whether this might be a useful intervention in patients with excessive excitability of the spinal motorneurons. PMID:29451889

The effect of high mesencephalic transection (cerveau isolé) and pentobarbital on basal forebrain mechanisms of EEG synchronization.

PubMed

Obál, F; Benedek, G; Szikszay, M; Obál, F

1979-01-01

A study was made of the effects of high mesencephalic transection (cerveau isolé) and low doses of pentobarbital on the cortical synchronizations elicited in acute immobilized cats by (a) low frequency stimulation of the lateral hypothalamus (HL) and nucleus ventralis anterior thalami (VA) and (b) by low and high frequency stimulation of the laterobasal preoptic region (RPO) and olfactory tubercle (TbOf). The results obtained were as follows: (1) The synchronizations induced by basal forebrain stimulations were found to survive in acute cerveau isolé cats, moreover, even a facilitation of the synchronizing effect were observed. (2) A gradual facilitation was observed upon TbOf and RPO stimulation, while in the case of VA and HL stimulations, the facilitation appeared immediately after the transection. (3) Low doses of pentobarbital depressed the cortical effects of TbOf stimulation, while an increase of the synchronizing effect of low frequency VA and HL stimulation was found. The observations suggested that (i) the synchronizing mechanism in the ventral part of the basal forebrain (RPO and TbOf) differs from that of the thalamus and HL; (ii) the basal forebrain synchronizing mechanism is effective without the contribution of the brain stem; (iii) the mechanism responsible for the synchronizing effect of low frequency HL stimulation is similar as that described for the thalamus.

Comparison of line transects and point counts for monitoring spring migration in forested wetlands

USGS Publications Warehouse

Wilson, R.R.; Twedt, D.J.; Elliott, A.B.

2000-01-01

We compared the efficacy of 400-m line transects and sets of three point counts at detecting avian richness and abundance in bottomland hardwood forests and intensively managed cottonwood (Populus deltoides) plantations within the Mississippi Alluvial Valley. We detected more species and more individuals on line transects than on three point counts during 218 paired surveys conducted between 24 March and 3 June, 1996 and 1997. Line transects also yielded more birds per unit of time, even though point counts yielded higher estimates of relative bird density. In structurally more-complex bottomland hardwood forests, we detected more species and individuals on line transects, but in more-open cottonwood plantations, transects surpassed point counts only at detecting species within 50 m of the observer. Species richness and total abundance of Nearctic-Neotropical migrants and temperate migrants were greater on line transects within bottomland hardwood forests. Within cottonwood plantations, however, only species richness of Nearctic-Neotropical migrants and total abundance of temperate migrants were greater on line transects. Because we compared survey techniques using the same observer, within the same forest stand on a given day, we assumed that the technique yielding greater estimates of avian species richness and total abundance per unit of effort is superior. Thus, for monitoring migration within hardwood forests of the Mississippi Alluvial Valley, we recommend using line transects instead of point counts.

Demonstration of line transect methodologies to estimate urban gray squirrel density

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hein, E.W.

1997-11-01

Because studies estimating density of gray squirrels (Sciurus carolinensis) have been labor intensive and costly, I demonstrate the use of line transect surveys to estimate gray squirrel density and determine the costs of conducting surveys to achieve precise estimates. Density estimates are based on four transacts that were surveyed five times from 30 June to 9 July 1994. Using the program DISTANCE, I estimated there were 4.7 (95% Cl = 1.86-11.92) gray squirrels/ha on the Clemson University campus. Eleven additional surveys would have decreased the percent coefficient of variation from 30% to 20% and would have cost approximately $114. Estimatingmore » urban gray squirrel density using line transect surveys is cost effective and can provide unbiased estimates of density, provided that none of the assumptions of distance sampling theory are violated.« less

Comparison between surgical and standing percutaneous contact Nd:YAG laser periosteal transection for potential treatment of equine limb deformities

NASA Astrophysics Data System (ADS)

Tate, Lloyd P.; Baines, Steven J.; Meuten, Donald J.; Stefanacci, J.

1994-09-01

Medial and lateral aspects of both radiuses were subjected to periosteal transection of nine healthy equine foals. One site per foal was subjected to surgical periosteal transection and elevation under general anesthesia. The remaining three sites of each foal after injection of a local anesthetic received Nd:YAG contact percutaneous periosteal transection. All radiuses were evaluated radiographically prior to periosteal transection and immediately prior to euthanasia. Foals were euthanized at 3 days, 31 to 34 days, and 67 days post-periosteal transection and gross postmortem and histologic examination performed on each site. Radiographically, periosteal proliferation occurred at all the conventional surgery sites and a majority of the percutaneous laser sites by 30 days post-treatment and was present at 67 days. No limb angulations were noted to occur in any of the foals. The conclusion of the study was that Nd:YAG percutaneous laser periosteal transection was successful in producing periosteal obliteration but with a different histologic appearance than that produced by conventional surgery.

Non-transecting bulbar urethroplasty

PubMed Central

Andrich, Daniela E.; Mundy, Anthony R.

2015-01-01

Excision and end-to-end anastomosis (EPA) has been the preferred urethroplasty technique for short bulbar strictures and is associated with an excellent functional outcome. Driven by concerns over the potential morbidity associated with dividing the urethra, therefore compromising spongiosal blood flow, as well as spongiofibrosis being superficial in the majority of non-traumatic bulbar strictures, the non-transecting technique for bulbar urethroplasty has been developed with the aim of achieving the same success as EPA without the morbidity associated with transection. This manuscript highlights the fundamental principles underlying the ongoing debate—transection or non-transection of the strictured bulbar urethra? The potential advantages of avoiding dividing the corpus spongiosum of the urethra are discussed. The non-transecting anastomotic procedure together with its various modifications are decribed in detail. Our experience with this technique is presented. Non-transecting excision of spongiofibrosis with preservation of well vascularised underlying spongiosum provides an excellent alternative to dividing the urethra during urethroplasty for short non-traumatic proximal bulbar strictures. PMID:26816808

Effect of DSPE-PEG on compound action potential, injury potential and ion concentration following compression in ex vivo spinal cord.

PubMed

Wang, Aihua; Huo, Xiaolin; Zhang, Guanghao; Wang, Xiaochen; Zhang, Cheng; Wu, Changzhe; Rong, Wei; Xu, Jing; Song, Tao

2016-05-04

It has been shown that polyethylene glycol (PEG) can reseal membrane disruption on the spinal cord, but only high concentrations of PEG have been shown to have this effect. Therefore, the effect of PEG is somewhat limited, and it is necessary to investigate a new approach to repair spinal cord injury. This study assesses the ability of 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly (ethylene glycol)) 2000] (DSPE-PEG) to recover physiological function and attenuate the injury-induced influx of extracellular ions in ex vivo spinal cord injury. Isolated spinal cords were subjected to compression injury and treated with PEG or DSPE-PEG immediately after injury. The compound action potential (CAP) was recorded before and after injury to assess the functional recovery. Furthermore, injury potential, the difference in gap potentials before and after compression, and the concentration of intracellular ions were used to evaluate the effect of DSPE-PEG on reducing ion influx. Data showed that the injury potential and ion concentration of the untreated, PEG and DSPE-PEG group, without significant difference among them, are remarkably higher than those of the intact group. Moreover, the CAP recovery of the DSPE-PEG and PEG treated spinal cords was significantly greater than that of the untreated spinal cords. The level of CAP recovery in the DSPE-PEG and PEG treated groups was the same, but the concentration of DSPE-PEG used was much lower than the concentration of PEG. These results suggest that instant application of DSPE-PEG could effectively repair functional disturbance in SCI at a much lower concentration than PEG. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of anodal transcranial direct current stimulation over the leg motor area on lumbar spinal network excitability in healthy subjects

PubMed Central

Roche, N; Lackmy, A; Achache, V; Bussel, B; Katz, R

2011-01-01

Abstract In recent years, two techniques have become available for the non-invasive stimulation of human motor cortex: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). The effects of TMS and tDCS when applied over motor cortex should be considered with regard not only to cortical circuits but also to spinal motor circuits. The different modes of action and specificity of TMS and tDCS suggest that their effects on spinal network excitability may be different from that in the cortex. Until now, the effects of tDCS on lumbar spinal network excitability have never been studied. In this series of experiments, on healthy subjects, we studied the effects of anodal tDCS over the lower limb motor cortex on (i) reciprocal Ia inhibition projecting from the tibialis anterior muscle (TA) to the soleus (SOL), (ii) presynaptic inhibition of SOL Ia terminals, (iii) homonymous SOL recurrent inhibition, and (iv) SOL H-reflex recruitment curves. The results show that anodal tDCS decreases reciprocal Ia inhibition, increases recurrent inhibition and induces no modification of presynaptic inhibition of SOL Ia terminals and of SOL-H reflex recruitment curves. Our results indicate therefore that the effects of tDCS are the opposite of those previously described for TMS on spinal network excitability. They also indicate that anodal tDCS induces effects on spinal network excitability similar to those observed during co-contraction suggesting that anodal tDCS activates descending corticospinal projections mainly involved in co-contractions. PMID:21502292

Effect of spinal monoaminergic neuronal system dysfunction on pain threshold in rats, and the analgesic effect of serotonin and norepinephrine reuptake inhibitors.

PubMed

Tamano, Ryuta; Ishida, Mitsuhiro; Asaki, Toshiyuki; Hasegawa, Minoru; Shinohara, Shunji

2016-02-26

Dysfunction in the central serotonin (5-HT) and norepinephrine (NE) systems cause depression and pain. Descending spinal pain modulatory pathways are important in the analgesic mechanisms of antidepressants, particularly serotonin and norepinephrine reuptake inhibitors (SNRIs). While many non-clinical studies have demonstrated the roles of central monoaminergic systems in pain, there is little evidence to illuminate the direct contribution of spinal descending pain modulatory systems independently of depressive-like behavior. To examine the effects of dysfunction of spinal monoaminergic systems on pain sensitivity, we established a rat chronic pain model by administering lumbar-intrathecal reserpine to minimize its influence on brain. Lumbar-intrathecal reserpine evoked persistent mechanical hypersensitivity and corresponding reductions in spinal 5-HT and NE concentrations (from 767.2 to 241.6ng/g and from 455.9 to 41.7ng/g, respectively after reserpine 30nmol). Lumbar-intrathecal reserpine did not deplete brain monoamines or bring about depressive-like behavior in the forced swim test. Spinal monoamines depletion-induced pain sensitivity was ameliorated by lumbar-intrathecal administration of the SNRIs (duloxetine and milnacipran) in dose-dependent manners. These suggest that increased pain sensitivity could be induced by dysfunction solely of the descending pain modulatory system, regardless of depressive-like behavior, and lumbar-intrathecal administration of SNRIs could ameliorate the pain sensitivity which might be mediated by affecting the descending pain modulatory system in the spinal cord, not via their antidepressant effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparison of effect of electroacupuncture and nefopam for prevention of postanesthetic shivering in patients undergoing urologic operation under spinal anesthesia

PubMed Central

Hwang, Min-Sub

2016-01-01

Background Shivering during spinal anesthesia is a frequent complication and is induced by the core-to-peripheral redistribution of heat. Nefopam has minimal side effects and prevents shivering by reducing the shivering threshold. Electroacupuncture is known to prevent shivering by preserving the core body temperature. We compared the efficacies of electroacupuncture and nefopam for the prevention of shivering during spinal anesthesia. Methods Ninety patients scheduled for elective urological surgery under spinal anesthesia were enrolled in the study. Patients were randomly divided into the control group (Group C, n = 30), the electroacupuncture group (Group A, n = 30), and the nefopam group (Group N, n = 30). Groups C and A received 100 ml of isotonic saline intravenously for 30 minutes before spinal anesthesia, while Group N received nefopam (0.15 mg/kg) mixed in 100 ml of isotonic saline. Group A received 30 minutes of electroacupuncture before receiving anesthesia. Shivering scores, mean arterial pressure, heart rate, body temperature and side effects were recorded before, and at 5, 15, 30, and 60 minutes after spinal anesthesia. Results The incidence of postanesthetic shivering was significantly lower in Group N (10 of 30) and Group A (4 of 30) compared with that in Group C (18 of 30)(P < 0.017). Body temperature was higher in Group N and Group A than in Group C (P < 0.05). Hemodynamic parameters were not different among the groups. Conclusions By maintaining body temperature during spinal anesthesia, electroacupuncture is as effective as nefopam in preventing postanesthetic shivering. PMID:27924198

Changes in spinal mobility with increasing age in women.

PubMed

Einkauf, D K; Gohdes, M L; Jensen, G M; Jewell, M J

1987-03-01

The purpose of our study was to determine changes in spinal mobility for women aged 20 to 84 years. Anterior flexion, right and left lateral flexion, and extension were measured on 109 healthy women. The modified Schober method was used to measure anterior flexion. Standard goniometry was used to measure lateral flexion and extension. The results of the study indicated that spinal mobility decreases with advancing age. The most significant (p less than .05) differences occurred between the two youngest and the two oldest age categories. Data gathered in this study indicate that physical therapists should consider the effects of age on spinal mobility when assessing spinal range of motion. A simple, objective method for measuring spinal mobility is presented. Suggestions for future research are given.

Experimental spinal cord trauma: a review of mechanically induced spinal cord injury in rat models.

PubMed

Abdullahi, Dauda; Annuar, Azlina Ahmad; Mohamad, Masro; Aziz, Izzuddin; Sanusi, Junedah

2017-01-01

It has been shown that animal spinal cord compression (using methods such as clips, balloons, spinal cord strapping, or calibrated forceps) mimics the persistent spinal canal occlusion that is common in human spinal cord injury (SCI). These methods can be used to investigate the effects of compression or to know the optimal timing of decompression (as duration of compression can affect the outcome of pathology) in acute SCI. Compression models involve prolonged cord compression and are distinct from contusion models, which apply only transient force to inflict an acute injury to the spinal cord. While the use of forceps to compress the spinal cord is a common choice due to it being inexpensive, it has not been critically assessed against the other methods to determine whether it is the best method to use. To date, there is no available review specifically focused on the current compression methods of inducing SCI in rats; thus, we performed a systematic and comprehensive publication search to identify studies on experimental spinalization in rat models, and this review discusses the advantages and limitations of each method.

Multivariate analysis of the geochemistry and mineralogy of soils along two continental-scale transects in North America

USGS Publications Warehouse

Drew, L.J.; Grunsky, E.C.; Sutphin, D.M.; Woodruff, L.G.

2010-01-01

Soils collected in 2004 along two North American continental-scale transects were subjected to geochemical and mineralogical analyses. In previous interpretations of these analyses, data were expressed in weight percent and parts per million, and thus were subject to the effect of the constant-sum phenomenon. In a new approach to the data, this effect was removed by using centered log-ratio transformations to 'open' the mineralogical and geochemical arrays. Multivariate analyses, including principal component and linear discriminant analyses, of the centered log-ratio data reveal the effects of soil-forming processes, including soil parent material, weathering, and soil age, at the continental-scale of the data arrays that were not readily apparent in the more conventionally presented data. Linear discriminant analysis of the data arrays indicates that the majority of the soil samples collected along the transects can be more successfully classified with Level 1 ecological regional-scale classification by the soil geochemistry than soil mineralogy. A primary objective of this study is to discover and describe, in a parsimonious way, geochemical processes that are both independent and inter-dependent and manifested through compositional data including estimates of the elements and corresponding mineralogy. ?? 2010.

Effect of cochlear nerve electrocautery on the adult cochlear nucleus.

PubMed

Iseli, Claire E; Merwin, William H; Klatt-Cromwell, Cristine; Hutson, Kendall A; Ewend, Matthew G; Adunka, Oliver F; Fitzpatrick, Douglas C; Buchman, Craig A

2015-04-01

Electrocauterization and subsequent transection of the cochlear nerve induce greater injury to the cochlear nucleus than sharp transection alone. Some studies show that neurofibromatosis Type 2 (NF2) patients fit with auditory brainstem implants (ABIs) fail to achieve speech perception abilities similar to ABI recipients without NF2. Reasons for these differences remain speculative. One hypothesis posits poorer performance to surgically induced trauma to the cochlear nucleus from electrocautery. Sustained electrosurgical depolarization of the cochlear nerve may cause excitotoxic-induced postsynaptic nuclear injury. Equally plausible is that cautery in the vicinity of the cochlear nucleus induces necrosis. The cochlear nerve was transected in anesthetized adult gerbils sharply with or without bipolar electrocautery at varying intensities. Gerbils were perfused at 1, 3, 5, and 7 days postoperatively; their brainstem and cochleas were embedded in paraffin and sectioned at 10 μm. Alternate sections were stained with flourescent markers for neuronal injury or Nissl substance. In additional experiments, anterograde tracers were applied directly to a sectioned eighth nerve to verify that fluorescent-labeled profiles seen were terminating auditory nerve fibers. Cochlear nerve injury was observed from 72 hours postoperatively and was identical across cases regardless of surgical technique. Postsynaptic cochlear nucleus injury was not seen after distal transection of the nerve. By contrast, proximal transection was associated with trauma to the cochlear nucleus. Distal application of bipolar electrocautery seems safe for the cochlear nucleus. Application near the root entry zone must be used cautiously because this may compromise nuclear viability needed to support ABI stimulation.

Do McKinnon lists provide reliable data in bird species frequency? A comparison with transect-based data

NASA Astrophysics Data System (ADS)

Cento, Michele; Scrocca, Roberto; Coppola, Michele; Rossi, Maurizio; Di Giuseppe, Riccardo; Battisti, Corrado; Luiselli, Luca; Amori, Giovanni

2018-05-01

Although occurrence-based listing methods could provide reliable lists of species composition for a site, the effective reliability of this method to provide more detailed information about species frequency (and abundance) has been rarely tested. In this paper, we compared the species frequencies obtained for the same set of species-rich sites (wetlands of central Italy) from two different methods: McKinnon lists and line transects. In all sites we observed: (i) rapid cumulating curves of line transect abundance frequencies toward the asymptote represented by the maximum value in McKinnon occurrence frequency; (ii) a large amount of species having a low frequency with line transect method showing a high range of variation in frequency obtained by McKinnon lists; (iii) a set of species having a subdominant (>0.02-<0.05) and dominant species (>0.05) frequency with line transect showed all the highest value in McKinnon frequency. McKinnon lists provides only a coarse-grained proxy of species frequency of individuals distinguishing only between common species (having the highest values of McKinnon frequency) and rare species (all the other species). Although McKinnon lists have some points of strength, this method does not discriminate the frequencies inside the subset of common species (sub-dominant and dominant species). Therefore, we suggest a cautionary approach when McKinnon frequencies should be used to obtain complex univariate metrics of diversity.

Beliefs in the population about cracking sounds produced during spinal manipulation.

PubMed

Demoulin, Christophe; Baeri, Damien; Toussaint, Geoffrey; Cagnie, Barbara; Beernaert, Axel; Kaux, Jean-François; Vanderthommen, Marc

2018-03-01

To examine beliefs about cracking sounds heard during high-velocity low-amplitude (HVLA) thrust spinal manipulation in individuals with and without personal experience of this technique. We included 100 individuals. Among them, 60 had no history of spinal manipulation, including 40 who were asymptomatic with or without a past history of spinal pain and 20 who had nonspecific spinal pain. The remaining 40 patients had a history of spinal manipulation; among them, 20 were asymptomatic and 20 had spinal pain. Participants attended a one-on-one interview during which they completed a questionnaire about their history of spinal manipulation and their beliefs regarding sounds heard during spinal manipulation. Mean age was 43.5±15.4years. The sounds were ascribed to vertebral repositioning by 49% of participants and to friction between two vertebras by 23% of participants; only 9% of participants correctly ascribed the sound to the formation of a gas bubble in the joint. The sound was mistakenly considered to indicate successful spinal manipulation by 40% of participants. No differences in beliefs were found between the groups with and without a history of spinal manipulation. Certain beliefs have documented adverse effects. This study showed a high prevalence of unfounded beliefs regarding spinal manipulation. These beliefs deserve greater attention from healthcare providers, particularly those who practice spinal manipulation. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Simultaneous Brain–Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning

PubMed Central

Cohen-Adad, Julien; Marchand-Pauvert, Veronique; Benali, Habib; Doyon, Julien

2015-01-01

The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6–C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain–spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations. PMID:26125597

Simultaneous Brain-Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning.

PubMed

Vahdat, Shahabeddin; Lungu, Ovidiu; Cohen-Adad, Julien; Marchand-Pauvert, Veronique; Benali, Habib; Doyon, Julien

2015-06-01

The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6-C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain-spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations.

Onyx injection by direct puncture for the treatment of hypervascular spinal metastases close to the anterior spinal artery: initial experience.

PubMed

Clarençon, Frédéric; Di Maria, Federico; Cormier, Evelyne; Sourour, Nader-Antoine; Enkaoua, Eric; Sailhan, Frédéric; Iosif, Christina; Le Jean, Lise; Chiras, Jacques

2013-06-01

Presurgical devascularization of hypervascular spinal metastases has been shown to be effective in preventing major blood loss during open surgery. Most often, embolization can be performed using polyvinyl alcohol (PVA) microparticles. However, in some cases, the close relationship between the feeders of the metastases and the feeders of the anterior spinal artery (ASA) poses a risk of spinal cord ischemia when PVA microparticle embolization is performed. The authors present their early experience in the treatment of spinal metastases close to the ASA; in 2 cases they injected Onyx-18, by direct puncture, into hypervascular posterior arch spinal metastases situated close to the ASA. Two women, one 36 and the other 55 years of age, who presented with spinal lesions (at the posterior arch of C-4 and T-6, respectively) from thyroid and a kidney tumors, were sent to the authors' department to undergo presurgical embolization. After having performed a complete spinal digital subtraction angiography study, a regular angiography catheter was positioned at the ostium of the artery that mainly supplied the lesion. Then, with the patient in the left lateral decubitus position, direct puncture with 18-gauge needles of the lesion was performed using roadmap guidance. Onyx-18 was injected through the needles under biplanar fluoroscopy. Satisfactory devascularization of the lesions was obtained; the ASA remained patent in both cases. The metastases were surgically removed in both cases within the 48 hours after the embolization and major blood loss did not occur. Presurgical devascularization of hypervascular spinal metastases close the ASA by direct puncture with Onyx-18 seems to be an effective technique and appears to be safe in terms of the preserving the ASA's patency.

Multifractal analyis of soil invertebrates along a transect under different land uses

NASA Astrophysics Data System (ADS)

Machado Siqueira, Glécio; Alves Silva, Raimunda; Vidal-Vázquez, Eva; Paz-González, Antonio

2017-04-01

Soil fauna play a central role in many essential ecosystem processes. Land use and management can have a dramatic effect upon soil invertebrate community. Indices based on soil invertebrates abundance and diversity are fundamental for soil quality assessment. Many soil properties and attributes have been shown to exhibit spatial variabilityThe aim of this study was to analyze the scaling heterogeneity of the soil invertebrate community sampled using pitfall traps across a transect. The field study was conducted at Mata Roma municipality, Maranhão State, Brazil. Transects were marked under seven different agricultural/forestry land uses (millet, soybean, maize, eucalyptus, pasture, secondary savannah and native savannah). Native vegetation was considered as a reference, whereas the agricultural fields showed a range of soil use intensities. Along these transects 130 pitfall per land use were installed. First, differences in community assemblages and composition under different land use systems were evaluated using classical indices. Then, the spatial distribution of soil fauna trapped by pitfall techniques, characterized through generalized dimension, Dq, and singularity spectra, f(α) - α, showed a well-defined multifractal structure. Differences in scaling heterogeneity and other multifractal characteristics were examined in relation to land use intensification.

Two-surgeon technique for liver transection using precoagulation by a soft-coagulation system and ultrasonic dissection.

PubMed

Yamada, Nobuya; Amano, Ryosuke; Kimura, Kenjiro; Murata, Akihiro; Yashiro, Masakazu; Tanaka, Sayaka; Wakasa, Kenichi; Hirakawa, Kosei

2015-01-01

A soft-coagulation system (SCS) was introduced as an effective device to reduce blood loss in hepatectomy. Here we evaluated the efficacy of a two-surgeon technique using precoagulation by an SCS and the Cavitron Ultrasonic Surgical Aspirator (CUSA) for liver transection. The 163 patients with liver tumors were divided into two groups (conventional group and two-surgeon group). Liver transection was conducted using saline-coupled bipolar electrocautery and CUSA in 102 patients (conventional group). In 61 patients (the two-surgeon group), a two-surgeon technique using precoagulation by an SCS and CUSA for liver resection was performed. The median blood loss was significantly less in the two-surgeon group compared to the conventional group (354.8 mL vs. 557.8 mL, respec tively: p = 0.0011). The postoperative hospital stay was significantly shorter in the two-surgeon group compared to the conventional group (12.7 days vs. 15.5 days, p = 0.0035). The two-surgeon technique using precoagulation by an SCS and CUSA was significantly reduced blood loss during liver transection, and associated with low morbidity and mortality. This technique may be useful for many hepatobiliary surgeons.

Seasonal effects on the population structure of Prochlorococcus in the North Pacific Ocean

NASA Astrophysics Data System (ADS)

Calfee, B. C.; Johnson, Z. I.; Wilhelm, S.; Zinser, E. R.

2016-02-01

Prochlorococcus is one of the most abundant marine phytoplankton and is responsible for a large portion of oceanic primary production. Basin-scale meridional transects and time series studies at fixed stations have established that the Prochlorococcus population in the surface mixed layer is partitioned with respect to temperature, with the eMIT9312 ecotype dominating the warmer, lower latitudes, and eMED4 dominating the colder, higher latitudes. Spatial and temporal resolution of this relationship is however not well characterized particularly in the higher latitudes where the transitions of ecotypic dominance occur. To improve our understanding of Prochlorococcus dynamics in these high latitudes, we performed a pair of research expeditions spanning the Prochlorococcus habitat range north of Hawaii. Winter and summer cruises along a similar transect allowed for assessment of seasonal succession in this region. For the winter transect, trends in ecotype abundances as a function of latitude were consistent with those found in prior studies. Surprisingly, ecotype abundances of the summer transect deviated from these trends, and indicate that seasonal progression in these high latitude waters is not simply a function of temperature dictating relative ecotype abundances. Potential reasons for this observation will be discussed.

Premedication with granisetron reduces shivering during spinal anaesthesia in children.

PubMed

Eldaba, Ahmed A; Amr, Yasser M

2012-01-01

This study evaluates the effect of prophylactic granisetron on the incidence of postoperative shivering after spinal anaesthesia in children. Eighty children, American Society of Anesthesiologists physical status I to II and aged two to five years were scheduled for surgery of the lower limb under spinal anaesthesia. The children were randomised to receive 10 µg/kg granisetron diluted in 10 ml saline 0.9% intravenously (group 1, n=40) or placebo (10 ml 0.9% saline, group 2, n=40) to be given over five minutes just before spinal puncture. Shivering, core temperature and the levels of motor and sensory block were assessed. No patients shivered in group 1. However, six patients shivered in Group 2 (P=0.025). There were no significant differences in the other measured variables between the groups. Granisetron is an effective agent to prevent shivering after spinal anaesthesia in children from two to five years of age.

Neurophysiology of pruritus: interaction of itch and pain.

PubMed

Ikoma, Akihiko; Rukwied, Roman; Ständer, Sonja; Steinhoff, Martin; Miyachi, Yoshiki; Schmelz, Martin

2003-11-01

The discovery of an itch-specific neuronal pathway, which is distinct from the pain-processing pathway, has clarified the neuronal basis for the itch sensation. Albeit being distinct, there are complex interactions between pain and itch. The inhibition of itch by pain is well known and can explain the antipruritic effect of scratching. However, the opposite effect also exists and has major clinical implications: inhibition of pain processing (eg, by spinal opioids) can generate itch. Conversely, blockade of spinal opioid receptors can be used as an antipruritic therapy. Moreover, the spinal processing of pain and itch can be modulated, resulting in a hypersensitivity or hyposensitivity to pain or itch: similar to chronic painful conditions, ongoing activity of pruriceptors can induce a spinal hypersensitivity for itch in patients with chronic pruritus. Therapeutic antipruritic approaches therefore should target both local inflammation and spinal sensitization of itch processing.

Design and criteria of electrospun fibrous scaffolds for the treatment of spinal cord injury

PubMed Central

Vigani, Barbara; Rossi, Silvia; Sandri, Giuseppina; Bonferoni, Maria Cristina; Ferrari, Franca

2017-01-01

The complex pathophysiology of spinal cord injury may explain the current lack of an effective therapeutic approach for the regeneration of damaged neuronal cells and the recovery of motor functions. Many efforts have been performed to design and develop suitable scaffolds for spinal cord regeneration, keeping in mind that the reconstruction of a pro-regenerative environment is the key challenge for an effective neurogenesis. The aim of this review is to outline the main features of an ideal scaffold, based on biomaterials, produced by the electrospinning technique and intended for the spinal cord regeneration. An overview of the polymers more investigated in the production of neural fibrous scaffolds is also provided. PMID:29239316

The influence of transection site on the development of pancreatic fistula in patients undergoing distal pancreatectomy: A review of 294 consecutive cases.

PubMed

Sell, Naomi M; Pucci, Michael J; Gabale, Salil; Leiby, Benjamin E; Rosato, Ernest L; Winter, Jordan M; Yeo, Charles J; Lavu, Harish

2015-06-01

Pancreatic fistula (PF) is a significant cause of morbidity in patients undergoing distal pancreatectomy (DP), with an incidence of 15-40%. It remains unclear if the location of pancreatic transection affects the rate of PF occurrence. This study examines the correlation between the transection site of the pancreas during DP and the incidence of PF. All cases of DP from October 2005 to January 2012 were reviewed retrospectively from an institutional review board-approved database at the Thomas Jefferson University Hospital. Patient demographics and perioperative outcomes were analyzed. The pancreatic transection location was determined by review of operative reports, and then dichotomized into 2 groups: neck/body or tail. PF were graded following the International Study Group on Pancreatic Fistula guidelines. During the study period, 294 DP were performed with 244 pancreas transections at the neck/body and 50 at the tail. Of the 294 patients, 52 (17.7%) developed a postoperative PF. The incidence of PF after transection at the tail of the pancreas was higher (28%) when compared with transection at the neck/body (15.6%; P = .04). When stratified by PF grade, grade A PF occurred more commonly when transection of the gland was at the tail (22% tail vs 8.2% neck/body; P = .007); however, no difference was found for grade B/C PF (6% tail vs 7.4% neck/body; P = 1). Our data suggest that PF occurs more often when the tail is transected during DP, although the majority are low grade and of minimal clinical significance. More severe PF occurred equally between the transection sites. Copyright © 2015 Elsevier Inc. All rights reserved.

Spontaneous regeneration of the corticospinal tract after transection in young rats: a key role of reactive astrocytes in making favorable and unfavorable conditions for regeneration.

PubMed

Iseda, T; Nishio, T; Kawaguchi, S; Yamanoto, M; Kawasaki, T; Wakisaka, S

2004-01-01

We demonstrated the occurrence of marked regeneration of the corticospinal tract (CST) after a single transection and failure of regeneration after a repeated transection in young rats. To provide convincing evidence for the complete transection and regeneration we used retrograde neuronal double labeling. Double-labeled neurons that took up the first tracer from the transection site and the second tracer from the injection site caudal to the transection site were observed in the sensorimotor cortex. The anterograde tracing method revealed various patterns of regeneration. In the most successful cases the vast majority of regenerated fibers descended in the normal tract and terminated normally whereas a trace amount of fibers coursed aberrantly. In the less successful cases fibers descended partly normally and partly aberrantly or totally aberrantly. To clarify the role of astrocytes in determining the success or failure of regeneration we compared expression of glial fibrillary acidic protein (GFAP), vimentin and neurofilament (NF) immunoreactivity (IR) in the lesion between single and repeated transections. In either transection, astrocytes disappeared from the CST near the lesion site as early as 3 h after lesioning. However, by 24 h after a single transection, immature astrocytes coexpressing GFAP- and vimentin-IR appeared in the former astrocyte-free area and NF-positive axons crossed the lesion. By contrast, after a repeated transection the astrocyte-free area spread and NF-positive axons never crossed the lesion. It appears likely that the major sign, and possibly cause of failure of regeneration is the prolonged disappearance of astrocytes in the lesioned tract area. Copyright 2004 IBRO

Ergonomics intervention on an alternative design of a spinal board.

PubMed

Zadry, Hilma Raimona; Susanti, Lusi; Rahmayanti, Dina

2017-09-01

A spinal board is the evacuation tool of first aid to help the injured spinal cord. The existing spinal board has several weaknesses, both in terms of user comfort and the effectiveness and efficiency of the evacuation process. This study designs an ergonomic spinal board using the quality function deployment approach. A preliminary survey was conducted through direct observation and interviews with volunteers from the Indonesian Red Cross. Data gathered were translated into a questionnaire and answered by 47 participants in West Sumatra. The results indicate that the selection of materials, the application of strap systems as well as the addition of features are very important in designing an ergonomic spinal board. The data were used in designing an ergonomic spinal board. The use of anthropometric data ensures that this product can accommodate safety and comfort when immobilized, as well as the flexibility and speed of the rescue evacuation process.

Are there endogenous stem cells in the spinal cord?

PubMed

Ferrucci, Michela; Ryskalin, Larisa; Busceti, Carla L; Gaglione, Anderson; Biagioni, Francesca; Fornai, Francesco

2017-12-01

Neural progenitor cells (NPC) represent the stem-like niche of the central nervous system that maintains a regenerative potential also in the adult life. Despite NPC in the brain are well documented, the presence of NPC in the spinal cord has been controversial for a long time. This is due to a scarce activity of NPC within spinal cord, which also makes difficult their identification. The present review recapitulates the main experimental studies, which provided evidence for the occurrence of NPC within spinal cord, with a special emphasis on spinal cord injury and amyotrophic lateral sclerosis. By using experimental models, here we analyse the site-specificity, the phenotype and the main triggers of spinal cord NPC. Moreover, data are reported on the effect of specific neurogenic stimuli on these spinal cord NPC in an effort to comprehend the endogenous neurogenic potential of this stem cell niche.

Icariin, a flavonoid with anti-cancer effects, alleviated paclitaxel-induced neuropathic pain in a SIRT1-dependent manner.

PubMed

Gui, Yulong; Zhang, Jie; Chen, Liang; Duan, Shunyuan; Tang, Jing; Xu, Wei; Li, Aiyuan

2018-01-01

Background One of the most common side effects of paclitaxel was dosage-dependently painful neuropathy. Various reports indicated that spinal neuroinflammation was involved in paclitaxel-induced neuropathic pain. This study investigated the effect of icariin on paclitaxel-induced neuroinflammation and peripheral neuropathy in rats. Methods Two parts were included in this study. In part one, the effect of icariin on paclitaxel-induced neuropathic pain was investigated. Mechanical thresholds were measured as primary outcomes. Production of proinflammatory factors (tumor necrosis factor-α, interleukin-1 β, and interleukin-6), activation of nuclear factor-κB (NF-κB(p65)) signal, and activation of astrocytes were detected as secondary outcomes. Spinal Sirtuin 1 (SIRT1) expression, H4 acetylation, and NAD + content were measured to investigate the effect of icariin on spinal SIRT1 signal pathway. In part two, the role of SIRT1 signal on icariin-induced effect in rats was investigated, and EX527, a SIRT1 inhibitor, was employed. Results The results showed paclitaxel treatment induced significant decrease in mechanical thresholds. Paclitaxel treatment also induced NF-κB(p65) activation and upregulation of proinflammatory factors (TNF-α, IL-1β, and IL-6). Paclitaxel also induced astrocyte activation in the spinal cord. However, 100 mg/kg icariin treatment significantly alleviated paclitaxel-induced mechanical allodynia and spinal neuroinflammation. Furthermore, icariin treatment dosage-dependently reversed paclitaxel-induced SIRT1 downregulation and H4 acetylation. EX527, a selective SIRT1 inhibitor, completely reversed icariin-induced anti-neuroinflammation and anti-allodynia effects in paclitaxel-induced neuropathic pain rats. Conclusions This meant that spinal SIRT1 activation was involved in icariin-induced effects in paclitaxel-induced neuropathic pain rats. Icariin could be a potential agent for the treatment of paclitaxel-induced neuropathic pain.

Propagation of vent CO2 in a subtropical shallow-water ecosystem assessed by stable carbon isotopes

NASA Astrophysics Data System (ADS)

Cheng, Y. F.; Chen, C. T. A.; Liao, Y. M.; Lin, Y. S.

2016-02-01

Carbon cycle of the ocean plays an important role in the global change associated with the emission of CO2. Anthropogenic CO2 dissolves in seawater, changes carbon chemistry of the ocean, and affects marine life in different and complicated ways. In this study, we investigated stable carbon isotope systematics of a shallow-water hydrothermal field near the Kueishantao Islet off NE Taiwan, which has vent gas composition dominated by CO2 and world record breaking low pH hydrothermal fluids. By studying this natural laboratory of ocean acidification, we aim at clarifying to which extent the high dosage of CO2 propagates in the subtropical shallow-water ecosystem, and how it affects the carbon cycle. Samples of seawater and suspended particles were collected from stations of two nearshore-offshore transects, one with hydrothermal vents at the nearshore end (Transect M, 1230 m long) and the other serving as the baseline (Transect B, 1560 m long). Surface seawater of Transect M showed increasing pH in the offshore direction, from 5.8 at the vent mouths to 7.6 at the most distant station. In contrast, pH of surface water decreased seaward from 8.0 to 7.8 in Transect B. The δ13C values of the vent CO2 averaged -6.4‰, consistent with the range attributed to mantle CO2. Seawater DIC δ13C values of Transect M were 13C-depleted (as negative as -2.5‰) at the vent mouths, and became increasingly 13C-enriched till 0.7‰ at the most distant station. This pattern is in clear contrast to that of Transect B, the DIC δ13C values of which decreased from 0.7 to 0.6 ‰ in the offshore direction. We concluded that the vent CO2 has propagated in the surface ocean at least >700 m away from the hydrothermal field. Our next step is to explore how the vent CO2 affects the stable carbon isotopes of particulate organic matter, and to assess the effect of vent CO2 using quantitative approaches.

Estimating nest detection probabilities for white-winged dove nest transects in Tamaulipas, Mexico

USGS Publications Warehouse

Nichols, J.D.; Tomlinson, R.E.; Waggerman, G.

1986-01-01

Nest transects in nesting colonies provide one source of information on White-winged Dove (Zenaida asiatica asiatica) population status and reproduction. Nests are counted along transects using standardized field methods each year in Texas and northeastern Mexico by personnel associated with Mexico's Office of Flora and Fauna, the Texas Parks and Wildlife Department, and the U.S. Fish and Wildlife Service. Nest counts on transects are combined with information on the size of nesting colonies to estimate total numbers of nests in sampled colonies. Historically, these estimates have been based on the actual nest counts on transects and thus have required the assumption that all nests lying within transect boundaries are detected (seen) with a probability of one. Our objectives were to test the hypothesis that nest detection probability is one and, if rejected, to estimate this probability.

The time course of taste bud regeneration after glossopharyngeal or greater superficial petrosal nerve transection in rats.

PubMed

St John, Steven J; Garcea, Mircea; Spector, Alan C

2003-01-01

We previously have published data detailing the time course of taste bud regeneration in the anterior tongue following transection of the chorda tympani (CT) nerve in the rat. This study extends the prior work by determining the time course of taste bud regeneration in the vallate papilla, soft palate and nasoincisor ducts (NID) following transection of either the glossopharyngeal (GL) or greater superficial petrosal (GSP) nerve. Following GL transection in rats (n = 6 per time point), taste buds reappeared in the vallate papilla between 15 and 28 days after surgery, and returned to 80.3% of control levels (n = 12) of taste buds by 70 days postsurgery. The first appearance and the final percentage of the normal complement of regenerated vallate taste buds after GL transection resembled that seen previously in the anterior tongue after CT transection. However, in the latter case, regenerated taste buds reached asymptotic levels by 42 days after surgery, whereas within the time frame of the present study, a clear asymptotic return of vallate taste buds was not observed. In contrast to the posterior (and anterior) tongue, only 25% of the normal complement of palatal taste buds regenerated by 112 days and 224 days after GSP transection (n = 9). The difference in regenerative capacity might relate to the surgical approach used to transect the GSP. These experiments provide useful parametric data for investigators studying the functional consequences of gustatory nerve transection and regeneration.

Anesthetic effects on fictive locomotion in the rat isolated spinal cord

PubMed Central

Jinks, Steven L.; Andrada, Jason; Satter, Omar

2011-01-01

General anesthetic mechanisms are poorly understood. Anesthetic immobilizing effects occur in the spinal ventral horn. However, a detailed analysis of anesthetic effects on ventral motor networks is lacking. We delivered isoflurane, desflurane, or propofol during NMDA/5-HT-induced, or noxious tail stimulus-evoked, fictive locomotion in neonatal rat isolated spinal cords. Anesthetics changed the frequency, amplitude, and regularity of fictive locomotion with little effect on phase-lag. Isoflurane abolished pharmacologically-induced vs noxious stimulus-induced motor output at similar concentrations. Propofol abolished pharmacologically-induced fictive locomotion via a GABAA-receptor mechanism. Anesthetic effects on pharmacologically-elicted fictive locomotion appear clinically-relevant, and support a ventral horn immobilizing effect on locomotor rhythm generation. PMID:21817927

Skeletal muscle calcineurin: influence of phenotype adaptation and atrophy

NASA Technical Reports Server (NTRS)

Spangenburg, E. E.; Williams, J. H.; Roy, R. R.; Talmadge, R. J.; Spangenberg, E. E. (Principal Investigator)

2001-01-01

Calcineurin (CaN) has been implicated as a signaling molecule that can transduce physiological stimuli (e.g., contractile activity) into molecular signals that initiate slow-fiber phenotypic gene expression and muscle growth. To determine the influence of muscle phenotype and atrophy on CaN levels in muscle, the levels of soluble CaN in rat muscles of varying phenotype, as assessed by myosin heavy chain (MHC)-isoform proportions, were determined by Western blotting. CaN levels were significantly greater in the plantaris muscle containing predominantly fast (IIx and IIb) MHC isoforms, compared with the soleus (predominantly type I MHC) or vastus intermedius (VI, contains all 4 adult MHC isoforms). Three months after a complete spinal cord transection (ST), the CaN levels in the VI muscle were significantly reduced, despite a significant increase in fast MHC isoforms. Surprisingly, the levels of CaN in the VI were highly correlated with muscle mass but not MHC isoform proportions in ST and control rats. These data demonstrate that CaN levels in skeletal muscle are highly correlated to muscle mass and that the normal relationship with phenotype is lost after ST.

Drug therapy in spinal tuberculosis.

PubMed

Rajasekaran, S; Khandelwal, Gaurav

2013-06-01

Although the discovery of effective anti-tuberculosis drugs has made uncomplicated spinal tuberculosis a medical disease, the advent of multi-drug-resistant Mycobacterium tuberculosis and the co-infection of HIV with tuberculosis have led to a resurgence of the disease recently. The principles of drug treatment of spinal tuberculosis are derived from our experience in treating pulmonary tuberculosis. Spinal tuberculosis is classified to be a severe form of extrapulmonary tuberculosis and hence is included in Category I of the WHO classification. The tuberculosis bacilli isolated from patients are of four different types with different growth kinetics and metabolic characteristics. Hence multiple drugs, which act on the different groups of the mycobacteria, are included in each anti-tuberculosis drug regimen. Prolonged and uninterrupted chemotherapy (which may be 'short course' and 'intermittent' but preferably 'directly observed') is effective in controlling the infection. Spinal Multi-drug-resistant TB and spinal TB in HIV-positive patients present unique problems in management and have much poorer prognosis. Failure of chemotherapy and emergence of drug resistance are frequent due to the failure of compliance hence all efforts must be made to improve patient compliance to the prescribed drug regimen.

Neuroprotective effect of curcumin on spinal cord in rabbit model with ischemia/reperfusion.

PubMed

Liu, Zhi-Qiang; Xing, Shan-Shan; Zhang, Wei

2013-03-01

Ischemic/reperfusion (I/R) injury of the spinal cord is a serious complication that can result from thoracoabdominal aortic surgery. To investigate the neuroprotective effect of curcumin against I/R injury in a rabbit model. A total of 36 rabbits were randomly divided into three groups: sham, I/R, and curcumin-treated group. Rabbits were subject to 30-min aortic occlusion to induce transient spinal cord ischemia. Neurological function was observed after reperfusion and spinal cord segment (L3-L5) was collected for histopathological evaluation. Malondialdehyde (MDA) and total superoxide dismutase (SOD) activity were also assayed. Rabbits in I/R group were induced to paraplegia. While after 48-hour treatment, compared with I/R group, curcumin significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05). The results suggest that curcumin, at least in an animal model, can attenuate transient spinal cord ischemic injury potentially via reducing oxidative damage, which may provide a novel approach in the treatment of spinal cord ischemic injury.

Pregnancy outcome using general anesthesia versus spinal anesthesia for in vitro fertilization.

PubMed

Azmude, Azra; Agha'amou, Shahrzad; Yousefshahi, Fardin; Berjis, Katayoun; Mirmohammad'khani, Majid; Sadaat'ahmadi, Farahnaz; Ghods, Kamran; Dabbagh, Ali

2013-09-01

There is a considerable rate of fertility failure and this causes a great burden of untoward effects for patients. Usually a considerable number of these patients undergo anesthesia for their treatment. This study was designed to compare the effects of general and spinal anesthesia on these patients. In a randomized clinical trial, after taking informed written consent from the patients, 200 patients entered the study; 100 in each. During a 2 year period, women aged 20 to 40 years entered the study (one group receiving spinal anesthesia and the other, receiving general anesthesia). Ovum retrieval protocols were the same. Nonparametric and parametric analyses were used for data analysis. P value less than 0.05 was considered significant. There was no difference between the two groups regarding demographic variables. 15 of 100 patients (15%) in the general anesthesia group and 27 of 100 patients (27%) in the spinal anesthesia group had successful pregnancy after IVF; so, spinal anesthesia increased significantly the chance of IVF success (P value < 0.001; Chi Square). The results of this study demonstrated that spinal anesthesia increased the chance of fertilization success.

Occurrence of substance P(1-7) in the metabolism of substance P and its antinociceptive activity at the mouse spinal cord level.

PubMed

Sakurada, C; Watanabe, C; Sakurada, T

2004-04-01

Substance P (SP), which is known as a pain transmitter or modulator in the spinal cord, was degraded by the synaptic membranes of the mouse spinal cord. The major metabolites of SP were phenylalanine, SP(1-6), SP(1-7), SP(1-9), SP(8-9) and SP(10-11). Degradation of SP was inhibited by a metal chelator, o-phenanthroline, and also by specific inhibitors of endopeptidase-24.11, thiorphan and phosphoramidon. In contrast, captopril (a specific inhibitor of angiotensin-converting enzyme), bestatin (a specific inhibitor of aminopeptidase) and Z-321 (a specific inhibitor of prolylendopeptidase) showed little effect on the degradation of SP. The accumulation of the major cleavage products was strongly inhibited by phosphoramidon and thirophan, as well as the initial cleavage of SP. Thus, endopeptidase-24.11 plays a major role in SP degradation in the mouse spinal cord. Additional in vivo experiments were performed to investigate the antinociceptive effect of SP(1-7), a major product of SP that was detected after incubation with spinal synaptic membranes. In the mouse tail-flick test, the intrathecal administration of SP(1-7) (1.0-4.0 pmol) increased tail-flick latency in a dose-dependent manner. These results suggest that degradation of SP by spinal endopeptidase-24.11 may lead to the formation of SP(1-7), which has an ability to produce antinociceptive effects at the mouse spinal cord level.

Cost Analysis of Spinal Versus General Anesthesia for Lumbar Diskectomy and Laminectomy Spine Surgery.

PubMed

Agarwal, Prateek; Pierce, John; Welch, William C

2016-05-01

Lumbar spine surgery can be performed using various anesthetic modalities, most notably general or spinal anesthesia. Because data comparing the cost of these anesthetic modalities in spine surgery are scarce, this study asks whether spinal anesthesia is less costly than general anesthesia. A total of 542 patients who underwent elective lumbar diskectomy or laminectomy spine surgery between 2007 and 2011 were retrospectively identified, with 364 having received spinal anesthesia and 178 having received general anesthesia. Mean direct operating cost, indirect cost (general support staff, insurance, taxes, floor space, facility, and administrative costs), and total cost were compared among patients who received general and spinal anesthesia. Linear multiple regression analysis was used to identify the effect of anesthesia type on cost and determine the factors underlying this effect, while controlling for patient and procedure characteristics. When controlling for patient and procedure characteristics, use of spinal anesthesia was associated with a 41.1% lower direct operating cost (-$3629 ± $343, P < 0.001), 36.6% lower indirect cost (-$1603 ± $168, P < 0.001), and 39.6% lower total cost (-$5232 ± $482, P < 0.001) compared with general anesthesia. Shorter hospital stay, shorter duration of anesthesia, shorter duration of operation, and lower estimated blood loss contributed to lower costs for spinal anesthesia, but other factors beyond these were also responsible for lower direct operating and total costs. When comparing the benefits of spinal and general anesthesia, spinal anesthesia is less costly when used in patients undergoing lumbar diskectomy and laminectomy spine surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Why do spinal manipulation techniques take the form they do? Towards a general model of spinal manipulation.

PubMed

Evans, David W

2010-06-01

For centuries, techniques used to manipulate joints in the spine have been passed down from one generation of manipulators to the next. Today, spinal manipulation is in the curious position that positive clinical effects have now been demonstrated, yet the theoretical base underpinning every aspect of its use is still underdeveloped. An important question is posed in this masterclass: why do spinal manipulation techniques take the form they do? From the available literature, two factors appear to provide an answer: 1. Action of a force upon vertebrae. Any 'direct' spinal manipulation technique requires that the patient be orientated in such a way that force is applied perpendicular to the overlying skin surface so as to act upon the vertebrae beneath. If the vertebral motion produced by 'directly' applied force is insufficient to produce the desired effect (e.g. cavitation), then force must be applied 'indirectly', often through remote body segments such as the head, thorax, abdomen, pelvis, and extremities. 2. Spinal segment morphology. A new hypothesis is presented. Spinal manipulation techniques exploit the morphology of vertebrae by inducing rotation at a spinal segment, about an axis that is always parallel to the articular surfaces of the constituent zygapophysial joints. In doing so, the articular surfaces of one zygapophysial joint appose to the point of contact, resulting in migration of the axis of rotation towards these contacting surfaces, and in turn this facilitates gapping of the other (target) zygapophysial joint. Other variations in the form of spinal manipulation techniques are likely to depend upon the personal style and individual choices of the practitioner.

Neuroprotective effects of Ganoderma lucidum polysaccharides against traumatic spinal cord injury in rats.

PubMed

Gokce, Emre Cemal; Kahveci, Ramazan; Atanur, Osman Malik; Gürer, Bora; Aksoy, Nurkan; Gokce, Aysun; Sargon, Mustafa Fevzi; Cemil, Berker; Erdogan, Bulent; Kahveci, Ozan

2015-11-01

Ganoderma lucidum (G. lucidum) is a mushroom belonging to the polyporaceae family of Basidiomycota and has widely been used as a traditional medicine for thousands of years. G. lucidum has never been studied in traumatic spinal cord injury. The aim of this study is to investigate whether G. lucidum polysaccharides (GLPS) can protect the spinal cord after experimental spinal cord injury. Rats were randomized into five groups of eight animals each: control, sham, trauma, GLPS, and methylprednisolone. In the control group, no surgical intervention was performed. In the sham group, only a laminectomy was performed. In all the other groups, the spinal cord trauma model was created by the occlusion of the spinal cord with an aneurysm clip. In the spinal cord tissue, caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, nitric oxide levels, and superoxide dismutase levels were analysed. Histopathological and ultrastructural evaluations were also performed. Neurological evaluation was performed using the Basso, Beattie, and Bresnahan locomotor scale and the inclined-plane test. After traumatic spinal cord injury, increases in caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels were detected. After the administration of GLPS, decreases were observed in tissue caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels. Furthermore, GLPS treatment showed improved results in histopathological scores, ultrastructural scores, and functional tests. Biochemical, histopathological, and ultrastructural analyses and functional tests reveal that GLPS exhibits meaningful neuroprotective effects against spinal cord injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Neuroprotective Effect of Kefir on Spinal Cord Ischemia/Reperfusion Injury in Rats.

PubMed

Guven, Mustafa; Akman, Tarik; Yener, Ali Umit; Sehitoglu, Muserref Hilal; Yuksel, Yasemin; Cosar, Murat

2015-05-01

The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (p<0.05). Catalase and superoxide dismutase levels of the kefir group were significantly higher than ischemia group (p<0.05). In histopathological samples, the kefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (p<0.05). In immunohistochemical staining, hipoxia-inducible factor-1α and caspase 3 immunopositive neurons were significantly decreased in kefir group compared with ischemia group (p<0.05). The neurological deficit scores of kefir group were significantly higher than ischemia group at 24 h (p<0.05). Our study revealed that kefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.

Ethyl pyruvate attenuates spinal cord ischemic injury with a wide therapeutic window through inhibiting high-mobility group box 1 release in rabbits.

PubMed

Wang, Qiang; Ding, Qian; Zhou, Yiming; Gou, Xingchun; Hou, Lichao; Chen, Shaoyang; Zhu, Zhenghua; Xiong, Lize

2009-06-01

Ethyl pyruvate (EP) has been reported to offer a protective effect against ischemic injury through its antiinflammatory action. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from ischemic cells. This study was designed to investigate the neuroprotective effect of EP against spinal cord ischemic injury and the potential role of HMGB1 in this process. EP was administered at various time points before or after 20 min of spinal cord ischemia in male New Zealand rabbits. All animals were sacrificed at 72 h after reperfusion with modified Tarlov criteria, and the spinal cord segment (L4) was harvested for histopathological examination and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining. The HMGB1 levels in serum and spinal cord tissue were analyzed by enzyme-linked immunosorbent assay. The treatment of EP at 30 min before ischemia or at 6 h after reperfusion significantly improved the hind-limb motor function scores and increased the numbers of normal motor neurons, which was accompanied with reduction of the number of apoptotic neurons and levels of HMGB1 in serum and spinal cord tissue. The HMGB1 contents of spinal cord tissue correlated well with the numbers of apoptotic motor neurons in the anterior spinal cord at 72 h after reperfusion. These results suggest that EP affords a strong protection against the transient spinal cord ischemic injury with a wide therapeutic window through inhibition of HMGB1 release.

Effect of Calendula officinalis cream on achilles tendon healing.

PubMed

Aro, A A; Perez, M O; Vieira, C P; Esquisatto, M A M; Rodrigues, R A F; Gomes, L; Pimentel, E R

2015-02-01

In recent years, the scientific community has undertaken research on plant extracts, searching for compounds with pharmacological activities that can be used in diverse fields of medicine. Calendula officinalis L. is known to have antioxidant, anti-inflammatory, antibacterial, and wound healing properties when used to treat skin burns. Therefore, the purpose of this study was to analyze the effects of C. officinalis on the initial phase of Achilles tendon healing. Wistar rats were separated in three groups: Calendula (Cal)-rats with a transected tendon were treated with topical applications of C. officinalis cream and then euthanized 7 days after injury; Control (C)-rats were treated with only vehicle after transection; and Normal (N)-rats without tenotomy. Higher concentrations of hydroxyproline (an indicator of total collagen) and non-collagenous proteins were observed in the Cal group in relation to the C group. Zymography showed no difference in the amount of the isoforms of metalloproteinase-2 and of metalloproteinase-9, between C and Cal groups. Polarization microscopy images analysis showed that the Cal group presented a slightly higher birefringence compared with the C group. In sections of tendons stained with toluidine blue, the transected groups presented higher metachromasy as compared with the N group. Immunocytochemistry analysis for chondroitin-6-sulfate showed no difference between the C and Cal groups. In conclusion, the topical application of C. officinalis after tendon transection increases the concentrations of collagen and non-collagenous proteins, as well as the collagen organization in the initial phase of healing. © 2014 Wiley Periodicals, Inc.

Respiratory reflexes in response to nasal administration of halothane to anesthetized, spontaneously breathing dogs.

PubMed

Mutoh, T; Kanamaru, A; Tsubone, H; Nishimura, R; Sasaki, N

2000-03-01

To characterize and determine the sensory innervation of respiratory reflexes elicited by nasal administration of halothane to dogs. 10 healthy Beagles. Dogs underwent permanent tracheostomy and, 2 to 3 weeks later, were anesthetized with thiopental and alpha-chloralose administered IV. The nasal passages were functionally isolated so that halothane could be administered to the nasal passages while dogs were breathing 100% O2 via the tracheostomy. Respiratory reflexes in response to administration of halothane at concentrations of 1.25, 1.75, and 2.5 times the minimum alveolar concentration (MAC), and 5% (administered in 100% O2 at a flow rate of 5 L/min) were recorded. Reflexes in response to administration of 5% halothane were also recorded following transection of the infraorbital nerve, transection of the caudal nasal nerve, and nasal administration of lidocaine. Nasal administration of halothane induced an inhibition of breathing characterized by a dose-dependent increase in expiratory time and a resultant decrease in expired volume per unit time. Effects were noticeable immediately after the onset of halothane administration and lasted until its cessation. Reflex responses to halothane administration were attenuated by transection of the caudal nasal nerve and by nasal administration of lidocaine, but transection of the infraorbital nerve had no effect. Nasal administration of halothane at concentrations generally used for mask induction of anesthesia induces reflex inhibition of breathing. Afferent fibers in the caudal nasal nerve appear to play an important role in the reflex inhibition of breathing induced by halothane administration.

Effects of polarization in low-level laser therapy of spinal cord injury in rats

NASA Astrophysics Data System (ADS)

Ando, Takahiro; Sato, Shunichi; Kobayashi, Hiroaki; Nawashiro, Hiroshi; Ashida, Hiroshi; Hamblin, Michael R.; Obara, Minoru

2012-03-01

Low-level laser therapy (LLLT) is a promising approach to treat the spinal cord injury (SCI). Since nerve fibers have optical anisotropy, propagation of light in the spinal tissue might be affected by its polarization direction. However, the effect of polarization on the efficacy of LLLT has not been elucidated. In the present study, we investigated the effect of polarization on the efficacy of near-infrared LLLT for SCI. Rat spinal cord was injured with a weight-drop device. The lesion site was irradiated with an 808-nm diode laser beam that was transmitted through a polarizing filter immediately after injury and daily for five consecutive days. The laser power at the injured spinal cord surface was 25 mW, and the dosage per day was 9.6 J/cm2 (spot diameter, 2 cm; irradiation duration, 1200 s). Functional recovery was assessed daily by an open-field test. The results showed that the functional scores of the SCI rats that were treated with 808-nm laser irradiation were significantly higher than those of the SCI alone group (Group 1) from day 5 after injury, regardless of the polarization direction. Importantly, as compared to the locomotive function of the SCI rats that were treated with the perpendicularly-polarized laser parallel to the spinal column (Group 2), that of the SCI rats that were irradiated with the linearly aligned polarization (Group 3) was significantly improved from day 10 after injury. In addition, the ATP contents in the injured spinal tissue of Group 3, which were measured immediately after laser irradiation, were moderately higher than those of Group 2. These observations are attributable to the deeper penetration of the parallelpolarized light in the anisotropic spinal tissue, suggesting that polarization direction significantly affects the efficacy of LLLT for SCI.

Spinal Tissue Loading Created by Different Methods of Spinal Manipulative Therapy Application

PubMed Central

Funabashi, Martha; Nougarou, François; Descarreaux, Martin; Prasad, Narasimha; Kawchuk, Gregory N.

2017-01-01

Study Design. Comparative study using robotic replication of spinal manipulative therapy (SMT) vertebral kinematics together with serial dissection. Objective. The aim of this study was to quantify loads created in cadaveric spinal tissues arising from three different forms of SMT application. Summary of Background Data. There exist many distinct methods by which to apply SMT. It is not known presently whether different forms of SMT application have different effects on spinal tissues. Should the method of SMT application modulate spinal tissue loading, quantifying this relation may help explain the varied outcomes of SMT in terms of effect and safety. Methods. SMT was applied to the third lumbar vertebra in 12 porcine cadavers using three SMT techniques: a clinical device that applies forces through a hand-held instrument (INST), a manual technique of applying SMT clinically (MAN) and a research device that applies parameters of manual SMT through a servo-controlled linear actuator motor (SERVO). The resulting kinematics from each SMT application were tracked optically via indwelling bone pins. The L3/L4 segment was then removed, mounted in a parallel robot and the resulting kinematics from SMT replayed for each SMT application technique. Serial dissection of spinal structures was conducted to quantify loading characteristics of discrete spinal tissues. Results. In terms of load magnitude, SMT application with MAN and SERVO created greater forces than INST in all conditions (P < 0.05). Additionally, MAN and SERVO created comparable posterior forces in the intact specimen, but MAN created greater posterior forces on IVD structures compared to SERVO (P < 0.05). Conclusion. Specific methods of SMT application create unique vertebral loading characteristics, which may help explain the varied outcomes of SMT in terms of effect and safety. Level of Evidence: N/A PMID:28146021

Brain-derived neurotrophic factor (BDNF) in the rostral anterior cingulate cortex (rACC) contributes to neuropathic spontaneous pain-related aversion via NR2B receptors.

PubMed

Zhang, Le; Wang, Gongming; Ma, Jinben; Liu, Chengxiao; Liu, Xijiang; Zhan, Yufeng; Zhang, Mengyuan

2016-10-01

The rostral anterior cingulate cortex (rACC) plays an important role in pain affect. Previous investigations have reported that the rACC mediates the negative affective component of inflammatory pain and contributed to the aversive state of nerve injury-induced neuropathic pain. Brain-derived neurotrophic factor (BDNF), an activity-dependent neuromodulator in the adult brain, is believed to play a role in the development and maintenance of inflammatory and neuropathic pain in the spinal cord. However, whether and how BDNF in the rACC regulates pain-related aversion due to peripheral nerve injury is largely unknown. Behaviorally, using conditioned place preference (CPP) training in rats, which is thought to reveal spontaneous pain-related aversion, we found that CPP was acquired following spinal clonidine in rats with partial sciatic nerve transection. Importantly, BDNF was upregulated within the rACC in of rats with nerve injury and enhanced the CPP acquisition, while a local injection of a BDNF-tropomyosin receptor kinase B (TrkB) antagonist into the rACC completely blocked this process. Finally, we demonstrated that the BDNF/TrkB pathway exerted its function by activating the NR2B receptor, which is widely accepted to be a crucial factor contributing to pain affect. In conclusion, our results demonstrate that the BDNF/TrkB-mediated signaling pathway in the rACC is involved in the development of neuropathic spontaneous pain-related aversion and that this process is dependent upon activation of NR2B receptors. These findings suggest that suppression of the BDNF-related signaling pathway in the rACC may provide a novel strategy to overcome pain-related aversion. Copyright © 2016 Elsevier Inc. All rights reserved.

Electrical stimulation modulates Wnt signaling and regulates genes for the motor endplate and calcium binding in muscle of rats with spinal cord transection

PubMed Central

2013-01-01

Background Spinal cord injury (SCI) results in muscle atrophy and a shift of slow oxidative to fast glycolytic fibers. Electrical stimulation (ES) at least partially restores muscle mass and fiber type distribution. The objective of this study was to was to characterize the early molecular adaptations that occur in rat soleus muscle after initiating isometric resistance exercise by ES for one hour per day for 1, 3 or 7 days when ES was begun 16 weeks after SCI. Additionally, changes in mRNA levels after ES were compared with those induced in soleus at the same time points after gastrocnemius tenotomy (GA). Results ES increased expression of Hey1 and Pitx2 suggesting increased Notch and Wnt signaling, respectively, but did not normalize RCAN1.4, a measure of calcineurin/NFAT signaling, or PGC-1ß mRNA levels. ES increased PGC-1α expression but not that of slow myofibrillar genes. Microarray analysis showed that after ES, genes coding for calcium binding proteins and nicotinic acetylcholine receptors were increased, and the expression of genes involved in blood vessel formation and morphogenesis was altered. Of the 165 genes altered by ES only 16 were also differentially expressed after GA, of which 12 were altered in the same direction by ES and GA. In contrast to ES, GA induced expression of genes related to oxidative phosphorylation. Conclusions Notch and Wnt signaling may be involved in ES-induced increases in the mass of paralyzed muscle. Molecular adaptations of paralyzed soleus to resistance exercise are delayed or defective compared to normally innervated muscle. PMID:23914941

Ovine model of neuropathic pain for assessing mechanisms of spinal cord stimulation therapy via dorsal horn recordings, von Frey filaments, and gait analysis

PubMed Central

Reddy, Chandan G; Miller, John W; Abode-Iyamah, Kingsley O; Safayi, Sina; Wilson, Saul; Dalm, Brian D; Fredericks, Douglas C; Gillies, George T; Howard, Matthew A; Brennan, Timothy J

2018-01-01

Background It is becoming increasingly important to understand the mechanisms of spinal cord stimulation (SCS) in alleviating neuropathic pain as novel stimulation paradigms arise. Purpose Additionally, the small anatomic scale of current SCS animal models is a barrier to more translational research. Methods Using chronic constriction injury (CCI) of the common peroneal nerve (CPN) in sheep (ovine), we have created a chronic model of neuropathic pain that avoids motor deficits present in prior large animal models. This large animal model has allowed us to implant clinical grade SCS hardware, which enables both acute and chronic testing using von Frey filament thresholds and gait analysis. Furthermore, the larger anatomic scale of the sheep allows for simultaneous single-unit recordings from the dorsal horn and SCS with minimal electrical artifact. Results Detectable tactile hypersensitivity occurred 21 days after nerve injury, with preliminary indications that chronic SCS may reverse it in the painful limb. Gait analysis revealed no hoof drop in the CCI model. Single neurons were identified and discriminated in the dorsal horn, and their activity was modulated via SCS. Unlike previous large animal models that employed a complete transection of the nerve, no motor deficit was observed in the sheep with CCI. Conclusion To our knowledge, this is the first reported large animal model of chronic neuropathic pain which facilitates the study of both acute and chronic SCS using complementary behavioral and electrophysiologic measures. As demonstrated by our successful establishment of these techniques, an ovine model of neuropathic pain is suitable for testing the mechanisms of SCS. PMID:29942150

The history of head transplantation: a review.

PubMed

Lamba, Nayan; Holsgrove, Daniel; Broekman, Marike L

2016-12-01

Since the turn of the last century, the prospect of head transplantation has captured the imagination of scientists and the general public. Recently, head transplant has regained attention in popular media, as neurosurgeons have proposed performing this procedure in 2017. Given the potential impact of such a procedure, we were interested in learning the history of the technical hurdles that need to be overcome, and determine if it is even technically possible to perform such a procedure on humans today. We conducted a historical review of available literature on the technical challenges and developments of head transplantation. The many social, psychological, ethical, religious, cultural, and legal questions of head transplantation were beyond the scope of this review. Our historical review identified the following important technical considerations related to performing a head transplant: maintenance of blood flow to an isolated brain via vessel anastomosis; availability of immunosuppressive agents; spinal anastomosis and fusion following cord transfection; pain control in the recipient. Several animal studies have demonstrated success in maintaining recipient cerebral perfusion and achieving immunosuppression. However, there is currently sparse evidence in favor of successful spinal anastomosis and fusion after transection. While recent publications by an Italian group offer novel approaches to this challenge, research on this topic has been sparse and hinges on procedures performed in animal models in the 1970s. How transferrable these older methods are to the human nervous system is unclear and warrants further exploration. Our review identified several important considerations related to performing a viable head transplantation. Besides the technical challenges that remain, there are important ethical issues to consider, such as exploitation of vulnerable patients and informed consent. Thus, besides the remaining technical challenges, these ethical issues will also need to be addressed before moving these studies to the clinic.

Melatonin Inhibits Neural Cell Apoptosis and Promotes Locomotor Recovery via Activation of the Wnt/β-Catenin Signaling Pathway After Spinal Cord Injury.

PubMed

Shen, Zhaoliang; Zhou, Zipeng; Gao, Shuang; Guo, Yue; Gao, Kai; Wang, Haoyu; Dang, Xiaoqian

2017-08-01

The spinal cord is highly sensitive to spinal cord injury (SCI) by external mechanical damage, resulting in irreversible neurological damage. Activation of the Wnt/β-catenin signaling pathway can effectively reduce apoptosis and protect against SCI. Melatonin, an indoleamine originally isolated from bovine pineal tissue, exerts neuroprotective effects after SCI through activation of the Wnt/β-catenin signaling pathway. In this study, we demonstrated that melatonin exhibited neuroprotective effects on neuronal apoptosis and supported functional recovery in a rat SCI model by activating the Wnt/β-catenin signaling pathway. We found that melatonin administration after SCI significantly upregulated the expression of low-density lipoprotein receptor related protein 6 phosphorylation (p-LRP-6), lymphoid enhancer factor-1 (LEF-1) and β-catenin protein in the spinal cord. Melatonin enhanced motor neuronal survival in the spinal cord ventral horn and improved the locomotor functions of rats after SCI. Melatonin administration after SCI also reduced the expression levels of Bax and cleaved caspase-3 in the spinal cord and the proportion of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) positive cells, but increased the expression level of Bcl-2. These results suggest that melatonin attenuated SCI by activating the Wnt/β-catenin signaling pathway.

Memantine elicits spinal blockades of motor function, proprioception, and nociception in rats.

PubMed

Chen, Yu-Wen; Chiu, Chong-Chi; Liu, Kuo-Sheng; Hung, Ching-Hsia; Wang, Jhi-Joung

2015-12-01

Although memantine blocks sodium currents and produces local skin anesthesia, spinal anesthesia with memantine is unknown. The purpose of the study was to evaluate the local anesthetic effect of memantine in spinal anesthesia and its comparison with a widely used local anesthetic lidocaine. After intrathecally injecting the rats with five doses of each drug, the dose-response curves of memantine and lidocaine were constructed. The potencies of the drugs and durations of spinal anesthetic effects on motor function, proprioception, and nociception were compared with those of lidocaine. We showed that memantine produced dose-dependent spinal blockades in motor function, proprioception, and nociception. On a 50% effective dose (ED50 ) basis, the rank of potency was lidocaine greater than memantine (P < 0.05 for the differences). At the equipotent doses (ED25 , ED50 , ED75 ), the block duration produced by memantine was longer than that produced by lidocaine (P < 0.05 for the differences). Memantine, but not lidocaine, displayed more sensory/nociceptive block than motor block. The preclinical data demonstrated that memantine is less potent than lidocaine, whereas memantine produces longer duration of spinal anesthesia than lidocaine. Memantine shows a more sensory-selective action over motor blockade. © 2015 Société Française de Pharmacologie et de Thérapeutique.