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Sample records for cord transection effects

  1. Unusual cord transection in a patient with traumatic spondylolisthesis

    PubMed Central

    Baliyan, Vinit; Shylendran, Sudhin; Ajay, K. Yadav; Kumar, Atin; Gamanagatti, Shivanand; Sinha, Sumit

    2016-01-01

    Spinal cord injury is one of the most debilitating injuries in patients with spinal trauma. Cord injury may range from simple cord edema to frank transection. Cord transection is the most severe form of cord injury as it results in complete and irreversible loss of all neural functions. Generally, it is a result of unstable spinal fractures with associated spondylolisthesis or spondyloptosis. Generally, the level of cord transection corresponds to the level of spinal fracture/spondylolisthesis. However, here we are presenting a case having a traumatic spinal fracture with spondylolisthesis where the level of cord transection was much higher than the level of the spinal fracture. Due to the traumatic traction, the cord distal to transection is displaced inferior leaving behind a long segment of the empty thecal sac. PMID:26889291

  2. The Morphofunctional Effect of the Transplantation of Bone Marrow Stromal Cells and Predegenerated Peripheral Nerve in Chronic Paraplegic Rat Model via Spinal Cord Transection.

    PubMed

    Buzoianu-Anguiano, Vinnitsa; Orozco-Suárez, Sandra; García-Vences, Elisa; Caballero-Chacón, Sara; Guizar-Sahagún, Gabriel; Chavez-Sanchez, Luis; Grijalva, Israel

    2015-01-01

    Functional recovery following spinal cord injury (SCI) is limited by poor axonal and cellular regeneration as well as the failure to replace damaged myelin. Employed separately, both the transplantation of the predegenerated peripheral nerve (PPN) and the transplantation of bone marrow stromal cells (BMSCs) have been shown to promote the regrowth and remyelination of the damaged central axons in SCI models of hemisection, transection, and contusion injury. With the aim to test the effects of the combined transplantation of PPN and BMSC on regrowth, remyelination, and locomotor function in an adult rat model of spinal cord (SC) transection, 39 Fischer 344 rats underwent SC transection at T9 level. Four weeks later they were randomly assigned to traumatic spinal cord injury (TSCI) without treatment, TSCI + Fibrin Glue (FG), TSCI + FG + PPN, and TSCI + FG + PPN + BMSCs. Eight weeks after, transplantation was carried out on immunofluorescence and electron microscope studies. The results showed greater axonal regrowth and remyelination in experimental groups TSCI + FG + PPN and TSCI + FG + PPN + BMSCs analyzed with GAP-43, neuritin, and myelin basic protein. It is concluded that the combined treatment of PPN and BMSCs is a favorable strategy for axonal regrowth and remyelination in a chronic SC transection model. PMID:26634157

  3. The Morphofunctional Effect of the Transplantation of Bone Marrow Stromal Cells and Predegenerated Peripheral Nerve in Chronic Paraplegic Rat Model via Spinal Cord Transection

    PubMed Central

    Buzoianu-Anguiano, Vinnitsa; Orozco-Suárez, Sandra; García-Vences, Elisa; Caballero-Chacón, Sara; Guizar-Sahagún, Gabriel; Chavez-Sanchez, Luis; Grijalva, Israel

    2015-01-01

    Functional recovery following spinal cord injury (SCI) is limited by poor axonal and cellular regeneration as well as the failure to replace damaged myelin. Employed separately, both the transplantation of the predegenerated peripheral nerve (PPN) and the transplantation of bone marrow stromal cells (BMSCs) have been shown to promote the regrowth and remyelination of the damaged central axons in SCI models of hemisection, transection, and contusion injury. With the aim to test the effects of the combined transplantation of PPN and BMSC on regrowth, remyelination, and locomotor function in an adult rat model of spinal cord (SC) transection, 39 Fischer 344 rats underwent SC transection at T9 level. Four weeks later they were randomly assigned to traumatic spinal cord injury (TSCI) without treatment, TSCI + Fibrin Glue (FG), TSCI + FG + PPN, and TSCI + FG + PPN + BMSCs. Eight weeks after, transplantation was carried out on immunofluorescence and electron microscope studies. The results showed greater axonal regrowth and remyelination in experimental groups TSCI + FG + PPN and TSCI + FG + PPN + BMSCs analyzed with GAP-43, neuritin, and myelin basic protein. It is concluded that the combined treatment of PPN and BMSCs is a favorable strategy for axonal regrowth and remyelination in a chronic SC transection model. PMID:26634157

  4. 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.

  5. Effect of neural stem cell transplantation combined with erythropoietin injection on axon regeneration in adult rats with transected spinal cord injury.

    PubMed

    Zhao, Y; Zuo, Y; Wang, X L; Huo, H J; Jiang, J M; Yan, H B; Xiao, Y L

    2015-01-01

    We investigated the effect of neural stem cells (NSC) and erythropoietin (EPO) on axon regeneration in adult rats with transected spinal cord injury, and provided an experimental basis for clinical treatment. Forty Wistar rats with T10-transected spinal cord injury were randomly divided into four groups of ten rats: a control group (group A), an NSC-transplant group (group B), an NSC-transplant and EPO group (group C), and an EPO group (group D). Biotinylated dextran amines (BDA) anterograde corticospinal cord neuronal tracing and Fluoro-Gold (FG) retrograde tracing were carried out at the 8th week after operation to observe the regeneration of nerve fibers. The Basso, Beattie, and Bresnahan (BBB) locomotor score was used to evaluate restoration. 1) BDA and FG immunofluorescence staining: in group C, a large number of regenerated axons were observed and some penetrated the injured area. In group B, only a small number of regenerated axons were observed and none penetrated the injured area. In group D, only sporadic regenerated nerve fibers were observed occasionally, while in group A, no axonal regeneration was observed. In group C, a small number of cones and axons emitted yellow fluorescence, and no FG-labeled cells were observed in the other groups. 2) The BBB scores for group C were higher than those for the other groups, and the differences were statistically significance (P < 0.05). NSC transplantation combined with EPO intraperitoneal injection may benefit axon regeneration in rats with transected spinal cord injury, and accelerate the functional recovery of the hindlimb locomotor. PMID:26782425

  6. Haemodynamic changes after spinal cord transection are anaesthetic agent dependent.

    PubMed

    Leal, P R; Lima, R C; Lopes, A C; da Graça, J R V; Santos, A A; Rola, F H; Gondim, F de A A

    2007-10-01

    1 To evaluate the effect of high spinal cord transection (SCT), between T4 and T5, on the mean arterial pressure (MAP) and heart rate in animals anaesthetized with different anaesthetic agents: ether (n = 12), 20% urethane, 1.2 g kg(-1) (n = 12), 2% tri-bromide-ethanol, 200 mg kg(-1) (n = 12); chloral hydrate and urethane, 75 and 525 mg kg(-1) respectively (n = 12). 2 In the animals anaesthetized with ether or urethane, SCT caused an immediate major drop in MAP, with hypotension and bradycardia throughout the next 10 min. In the animals anaesthetized with urethane + chloralose or tri-bromide-ethanol, SCT transiently increased MAP with subsequent hypotension and bradycardia. 3 In summary, the haemodynamic changes after complete, high SCT are anaesthetic agent dependent. Further research about the exact mechanisms responsible for these diverse autonomic changes is warranted. PMID:18076477

  7. Effects of sciatic nerve transection on glucose uptake in the presence and absence of lactate in the frog dorsal root ganglia and spinal cord.

    PubMed

    Rigon, F; Horst, A; Kucharski, L C; Silva, R S M; Faccioni-Heuser, M C; Partata, W A

    2014-08-01

    Frogs have been used as an alternative model to study pain mechanisms because the simplicity of their nervous tissue and the phylogenetic aspect of this question. One of these models is the sciatic nerve transection (SNT), which mimics the clinical symptoms of "phantom limb", a condition that arises in humans after amputation or transverse spinal lesions. In mammals, the SNT increases glucose metabolism in the central nervous system, and the lactate generated appears to serve as an energy source for nerve cells. An answerable question is whether there is elevated glucose uptake in the dorsal root ganglia (DRG) after peripheral axotomy. As glucose is the major energy substrate for frog nervous tissue, and these animals accumulate lactic acid under some conditions, bullfrogs Lithobates catesbeianus were used to demonstrate the effect of SNT on DRG and spinal cord 1-[14C] 2-deoxy-D-glucose (14C-2-DG) uptake in the presence and absence of lactate. We also investigated the effect of this condition on the formation of 14CO2 from 14C-glucose and 14C-L-lactate, and plasmatic glucose and lactate levels. The 3-O-[14C] methyl-D-glucose (14C-3-OMG) uptake was used to demonstrate the steady-state tissue/medium glucose distribution ratio under these conditions. Three days after SNT, 14C-2-DG uptake increased, but 14C-3-OMG uptake remained steady. The increase in 14C-2-DG uptake was lower when lactate was added to the incubation medium. No change was found in glucose and lactate oxidation after SNT, but lactate and glucose levels in the blood were reduced. Thus, our results showed that SNT increased the glucose metabolism in the frog DRG and spinal cord. The effect of lactate on this uptake suggests that glucose is used in glycolytic pathways after SNT. PMID:25627385

  8. Complete rat spinal cord transection as a faithful model of spinal cord injury for translational cell transplantation.

    PubMed

    Lukovic, Dunja; Moreno-Manzano, Victoria; Lopez-Mocholi, Eric; Rodriguez-Jiménez, Francisco Javier; Jendelova, Pavla; Sykova, Eva; Oria, Marc; Stojkovic, Miodrag; Erceg, Slaven

    2015-01-01

    Spinal cord injury (SCI) results in neural loss and consequently motor and sensory impairment below the injury. There are currently no effective therapies for the treatment of traumatic SCI in humans. Various animal models have been developed to mimic human SCI. Widely used animal models of SCI are complete or partial transection or experimental contusion and compression, with both bearing controversy as to which one more appropriately reproduces the human SCI functional consequences. Here we present in details the widely used procedure of complete spinal cord transection as a faithful animal model to investigate neural and functional repair of the damaged tissue by exogenous human transplanted cells. This injury model offers the advantage of complete damage to a spinal cord at a defined place and time, is relatively simple to standardize and is highly reproducible. PMID:25860664

  9. Complete rat spinal cord transection as a faithful model of spinal cord injury for translational cell transplantation.

    PubMed

    Lukovic, Dunja; Moreno-Manzano, Victoria; Lopez-Mocholi, Eric; Rodriguez-Jiménez, Francisco Javier; Jendelova, Pavla; Sykova, Eva; Oria, Marc; Stojkovic, Miodrag; Erceg, Slaven

    2015-04-10

    Spinal cord injury (SCI) results in neural loss and consequently motor and sensory impairment below the injury. There are currently no effective therapies for the treatment of traumatic SCI in humans. Various animal models have been developed to mimic human SCI. Widely used animal models of SCI are complete or partial transection or experimental contusion and compression, with both bearing controversy as to which one more appropriately reproduces the human SCI functional consequences. Here we present in details the widely used procedure of complete spinal cord transection as a faithful animal model to investigate neural and functional repair of the damaged tissue by exogenous human transplanted cells. This injury model offers the advantage of complete damage to a spinal cord at a defined place and time, is relatively simple to standardize and is highly reproducible.

  10. Panax notoginseng saponins improve recovery after spinal cord transection by upregulating neurotrophic factors.

    PubMed

    Wang, Bo; Li, Yu; Li, Xuan-Peng; Li, Yang

    2015-08-01

    Saponins extracted from Panax notoginseng are neuroprotective, but the mechanisms underlying this effect remain unclear. In the present study, we established a rat model of thoracic (T10) spinal cord transection, and injected Panax notoginseng saponins (100 mg/kg) or saline 30 minutes after injury. Locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) scale from 1 to 30 days after injury, and immunohistochemistry was carried out in the ventral horn of the spinal cord at 1 and 7 days to determine expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Our results show that at 7-30 days post injury, the BBB score was higher in rats treated with Panax notoginseng saponins than in those that received saline. Furthermore, at 7 days, more NGF- and BDNF-immunoreactive neurons were observed in the ventral horn of the spinal cord of rats that had received Panax notoginseng saponins than in those that received saline. These results indicate that Panax notoginseng saponins caused an upregulation of NGF and BDNF in rats with spinal cord transection, and improved hindlimb motor function. PMID:26487862

  11. Panax notoginseng saponins improve recovery after spinal cord transection by upregulating neurotrophic factors

    PubMed Central

    Wang, Bo; Li, Yu; Li, Xuan-peng; Li, Yang

    2015-01-01

    Saponins extracted from Panax notoginseng are neuroprotective, but the mechanisms underlying this effect remain unclear. In the present study, we established a rat model of thoracic (T10) spinal cord transection, and injected Panax notoginseng saponins (100 mg/kg) or saline 30 minutes after injury. Locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) scale from 1 to 30 days after injury, and immunohistochemistry was carried out in the ventral horn of the spinal cord at 1 and 7 days to determine expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Our results show that at 7–30 days post injury, the BBB score was higher in rats treated with Panax notoginseng saponins than in those that received saline. Furthermore, at 7 days, more NGF- and BDNF-immunoreactive neurons were observed in the ventral horn of the spinal cord of rats that had received Panax notoginseng saponins than in those that received saline. These results indicate that Panax notoginseng saponins caused an upregulation of NGF and BDNF in rats with spinal cord transection, and improved hindlimb motor function. PMID:26487862

  12. Polyethylene glycol enhances axolemmal resealing following transection in cultured cells and in ex vivo spinal cord.

    PubMed

    Nehrt, Ashley; Hamann, Kristin; Ouyang, Hui; Shi, Riyi

    2010-01-01

    The integrity of the neuronal membrane is critical for its function as well as survival, and ineffective repair of damaged membranes may be one of the key factors underlying the neuronal degeneration and overall functional loss that occurs after spinal cord injury and traumatic brain injury. Previously, we showed that polyethylene glycol (PEG) can reseal axonal membranes following compression in isolated guinea pig spinal cord white matter. We now report that 10 mM PEG can also significantly enhance membrane resealing following transection in the clinically relevant conditions of low extracellular Ca(2+) and low temperature. Such beneficial effects were demonstrated both functionally, through membrane potential measured by double sucrose gap apparatus, and anatomically, through horseradish peroxidase and tetramethyl rhodamine dextran dye exclusion assays. We further noted that axons with small diameters preferentially benefited from PEG-mediated axolemmal resealing. Using atomic force microscopy, we further showed that PEG can effectively reduce neuronal membrane surface tension. We hypothesize that PEG may promote axolemmal resealing by increasing membrane line tension and reducing membrane tension, thus creating conditions more favorable to membrane resealing. In summary, these studies suggest that PEG is effective under the clinically relevant conditions of low Ca(2+) and temperature, and thus has the potential to be used in combination with other more established interventions in spinal cord and traumatic brain injury.

  13. 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. PMID:27515203

  14. Transplantation of Human Umbilical Mesenchymal Stem Cells from Wharton's Jelly after Complete Transection of the Rat Spinal Cord

    PubMed Central

    Hsu, Shao-Yun; Cheng, Henrich; Fu, Yu-Show

    2008-01-01

    Background Human umbilical mesenchymal stem cells (HUMSCs) isolated from Wharton's jelly of the umbilical cord can be easily obtained and processed compared with embryonic or bone marrow stem cells. These cells may be a valuable source in the repair of spinal cord injury. Methodology/Principal Findings We examine the effects of HUMSC transplantation after complete spinal cord transection in rats. Approximately 5×105 HUMSCs were transplanted into the lesion site. Three groups of rats were implanted with either untreated HUMSCs (referred to as the stem cell group), or HUMSCs treated with neuronal conditioned medium (NCM) for either three days or six days (referred to as NCM-3 and NCM-6 days, respectively). The control group received no HUMSCs in the transected spinal cord. Three weeks after transplantation, significant improvements in locomotion were observed in all the three groups receiving HUMSCs (stem cell, NCM-3 and NCM-6 days groups). This recovery was accompanied by increased numbers of regenerated axons in the corticospinal tract and neurofilament-positive fibers around the lesion site. There were fewer microglia and reactive astrocytes in both the rostral and caudal stumps of the spinal cord in the stem cell group than in the control group. Transplanted HUMSCs survived for 16 weeks and produced large amounts of human neutrophil-activating protein-2, neurotrophin-3, basic fibroblast growth factor, glucocorticoid induced tumor necrosis factor receptor, and vascular endothelial growth factor receptor 3 in the host spinal cord, which may help spinal cord repair. Conclusions/Significance Transplantation of HUMSCs is beneficial to wound healing after spinal cord injury in rats. PMID:18852872

  15. Further evidence of olfactory ensheathing glia facilitating axonal regeneration after a complete spinal cord transection.

    PubMed

    Ziegler, Matthias D; Hsu, Derek; Takeoka, Aya; Zhong, Hui; Ramón-Cueto, Almudena; Phelps, Patricia E; Roy, Roland R; Edgerton, V Reggie

    2011-05-01

    Spinal Wistar Hannover rats injected with olfactory ensheathing glia (OEG) have been shown to recover some bipedal stepping and climbing abilities. Given the intrinsic ability of the spinal cord to regain stepping with pharmacological agents or epidural stimulation after a complete mid-thoracic transection, we asked if functional recovery after OEG injections is due to changes in the caudal stump or facilitation of functional regeneration of axons across the transection site. OEG were injected rostral and caudal to the transection site immediately after transection. Robotically assisted step training in the presence of intrathecal injections of a 5-HT(2A) receptor agonist (quipazine) was used to facilitate recovery of stepping. Bipedal stepping as well as climbing abilities were tested over a 6-month period post-transection to determine any improvement in hindlimb functional due to OEG injections and/or step training. The ability for OEG to facilitate regeneration was analyzed electrophysiologically by transcranially stimulating the brainstem and recording motor evoked potentials (MEP) with chronically implanted intramuscular EMG electrodes in the soleus and tibalis anterior with and without intrathecal injections of noradrenergic, serotonergic, and glycinergic receptor antagonists. Analyses confirmed that along with improved stepping ability and increased use of the hindlimbs during climbing, only OEG rats showed recovery of MEP. In addition the MEP signals were eliminated after a re-transection of the spinal cord rostral to the original transection and were modified in the presence of receptor antagonists. These data indicate that improved hindlimb function after a complete transection was coupled with OEG-facilitated functional regeneration of axons. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair. PMID:21272578

  16. Traumatic cervical cord transection without facet dislocations--a proposal of combined hyperflexion-hyperextension mechanism: a case report.

    PubMed

    Cha, Yoo-Hyun; Cho, Tai-Hyoung; Suh, Jung-Keun

    2010-08-01

    A patient is presented with a cervical spinal cord transection which occurred after a motor vehicle accident in which the air bag deployed and the seat belt was not in use. The patient had complete quadriplegia below the C5 level and his imaging study showed cervical cord transection at the level of the C5/6 disc space with C5, C6 vertebral bodies and laminar fractures. He underwent a C5 laminectomy and a C4-7 posterior fusion with lateral mass screw fixation. Previous reports have described central cord syndromes occurring in hyperextension injuries, but in adults, acute spinal cord transections have only developed after fracture-dislocations of the spine. A case involving a post-traumatic spinal cord transection without any evidence of radiologic facet dislocations is reported. Also, we propose a combined hyperflexion-hyperextension mechanism to explain this type of injury.

  17. Transplanted Oligodendrocytes and Motoneuron Progenitors Generated from Human Embryonic Stem Cells Promote Locomotor Recovery After Spinal Cord Transection

    PubMed Central

    Erceg, Slaven; Ronaghi, Mohammad; Oria, Marc; García Roselló, Mireia; Aragó, Maria Amparo Pérez; Lopez, Maria Gomez; Radojevic, Ivana; Moreno-Manzano, Victoria; Rodríguez-Jiménez, Francisco-Javier; Shanker Bhattacharya, Shom; Cordoba, Juan; Stojkovic, Miodrag

    2010-01-01

    Human embryonic stem cells (hESC) hold great promise for the treatment of patients with many neurodegenerative diseases particularly those arising from cell loss or neural dysfunction including spinal cord injury. This study evaluates the therapeutic effects of transplanted hESC-derived oligodendrocyte progenitors (OPC) and/or motoneuron progenitors (MP) on axonal remyelination and functional recovery of adult rats after complete spinal cord transection. OPC and/or MP were grafted into the site of injury in the acute phase. Based on Basso-Beattie-Bresnahan scores recovery of locomotor function was significantly enhanced in rats treated with OPC and/or MP when compared with control animals. When transplanted into the spinal cord immediately after complete transection, OPC and MP survived, migrated, and differentiated into mature oligodendrocytes and neurons showing in vivo electrophysiological activity. Taken together, these results indicate that OPC and MP derived from hESC could be a useful therapeutic strategy to repair injured spinal cord. Stem Cells 2010; 28:1541–1549. PMID:20665739

  18. Functional Regeneration Following Spinal Transection Demonstrated in the Isolated Spinal Cord of the Larval Sea Lamprey

    NASA Astrophysics Data System (ADS)

    Cohen, A. H.; Mackler, S. A.; Selzer, M. E.

    1986-04-01

    Axons in the larval sea lamprey can regenerate across the site of a spinal cord transection and form functioning synapses with some of their normal target neurons. The animals recover normal-appearing locomotion, but whether the regenerating axons and their synaptic connections are capable of playing a functional role during this behavior is unknown. To test this, ``fictive'' swimming was induced in the isolated spinal cord by the addition of D-glutamate to the bathing solution. Ventral root discharges of segments above and below a healed transection showed a high degree of phase-locking. This strongly suggests that the behavioral recovery is mediated by regenerated functional synaptic connections subserving intersegmental coordination of the central pattern generator for locomotion.

  19. Characterization of dendritic morphology and neurotransmitter phenotype of thoracic descending propriospinal neurons after complete spinal cord transection and GDNF treatment.

    PubMed

    Deng, Lingxiao; Ruan, Yiwen; Chen, Chen; Frye, Christian Corbin; Xiong, Wenhui; Jin, Xiaoming; Jones, Kathryn; Sengelaub, Dale; Xu, Xiao-Ming

    2016-03-01

    After spinal cord injury (SCI), poor regeneration of damaged axons of the central nervous system (CNS) causes limited functional recovery. This limited spontaneous functional recovery has been attributed, to a large extent, to the plasticity of propriospinal neurons, especially the descending propriospinal neurons (dPSNs). Compared with the supraspinal counterparts, dPSNs have displayed significantly greater regenerative capacity, which can be further enhanced by glial cell line-derived neurotrophic factor (GDNF). In the present study, we applied a G-mutated rabies virus (G-Rabies) co-expressing green fluorescence protein (GFP) to reveal Golgi-like dendritic morphology of dPSNs. We also investigated the neurotransmitters expressed by dPSNs after labeling with a retrograde tracer Fluoro-Gold (FG). dPSNs were examined in animals with sham injuries or complete spinal transections with or without GDNF treatment. Bilateral injections of G-Rabies and FG were made into the 2nd lumbar (L2) spinal cord at 3 days prior to a spinal cord transection performed at the 11th thoracic level (T11). The lesion gap was filled with Gelfoam containing either saline or GDNF in the injury groups. Four days post-injury, the rats were sacrificed for analysis. For those animals receiving G-rabies injection, the GFP signal in the T7-9 spinal cord was visualized via 2-photon microscopy. Dendritic morphology from stack images was traced and analyzed using a Neurolucida software. We found that dPSNs in sham injured animals had a predominantly dorsal-ventral distribution of dendrites. Transection injury resulted in alterations in the dendritic distribution with dorsal-ventral retraction and lateral-medial extension. Treatment with GDNF significantly increased the terminal dendritic length of dPSNs. The density of spine-like structures was increased after injury, and treatment with GDNF enhanced this effect. For the group receiving FG injections, immunohistochemistry for glutamate, choline

  20. Neurogenesis in the lamprey central nervous system following spinal cord transection.

    PubMed

    Zhang, Guixin; Vidal Pizarro, Ivonne; Swain, Gary P; Kang, Shin H; Selzer, Michael E

    2014-04-15

    After spinal cord transection, lampreys recover functionally and axons regenerate. It is not known whether this is accompanied by neurogenesis. Previous studies suggested a baseline level of nonneuronal cell proliferation in the spinal cord and rhombencephalon (where most supraspinal projecting neurons are located). To determine whether cell proliferation increases after injury and whether this includes neurogenesis, larval lampreys were spinally transected and injected with 5-bromo-2&prime-deoxyuridine (BrdU) at 0-3 weeks posttransection. Labeled cells were counted in the lesion site, within 0.5 mm rostral and caudal to the lesion, and in the rhombencephalon. One group of animals was processed in the winter and a second group was processed in the summer. The number of labeled cells was greater in winter than in summer. The lesion site had the most BrdU labeling at all times, correlating with an increase in the number of cells. In the adjacent spinal cord, the percentage of BrdU labeling was higher in the ependymal than in nonependymal regions. This was also true in the rhombencephalon but only in summer. In winter, BrdU labeling was seen primarily in the subventricular and peripheral zones. Some BrdU-labeled cells were also double labeled by antibodies to glial-specific (antikeratin) as well as neuron-specific (anti-Hu) antigens, indicating that both gliogenesis and neurogenesis occurred after spinal cord transection. However, the new neurons were restricted to the ependymal zone, were never labeled by antineurofilament antibodies, and never migrated away from the ependyma even at 5 weeks after BrdU injection. They would appear to be cerebrospinal fluid-contacting neurons.

  1. Hindlimb loading determines stepping quantity and quality following spinal cord transection.

    PubMed

    Timoszyk, Wojciech K; Nessler, Jeff A; Acosta, Cynthia; Roy, Roland R; Edgerton, V Reggie; Reinkensmeyer, David J; de Leon, Ray

    2005-07-19

    We compared the bipedal hindlimb stepping ability of untrained and trained (step-trained 6 min/day) spinal rats (mid-thoracic spinal cord transection at post-natal day 5) at different levels of body weight support on a treadmill over a 40-day period, starting at 69 days of age. A robotic device provided precise levels of body weight support and recorded hindlimb movement. We assessed stepping ability using: (1) step quantity determined from the measured hindlimb movement, (2) ordinal scales of paw placement, weight-bearing, and limb flexion, and (3) the lowest level of body weight support at which stepping was maintained. Stepping quantity and quality depended strongly on the level of support provided. Stepping ability improved with time, but only at the higher levels of weight-bearing, and independently of training. Increasing limb loading by gradually decreasing body weight support altered the spatiotemporal properties of the steps, resulting in an increase in step length and stance duration and a decrease in swing and step cycle duration. The rats progressively improved their ability to support more load before collapsing from a maximum of about 42 g ( approximately 25% of body weight) at Day 1 to 73 g ( approximately 35% of body weight) at Day 40. We conclude that the level of hindlimb loading provided to a spinally transected rat strongly influences the quantity and quality of stepping. Furthermore, the relationship between stepping ability and loading conditions changes with time after spinal cord transection and is unaltered by small amounts of step training. Finally, load-bearing failure point can be a quantitative measure of locomotor recovery following spinal cord injury, especially for severely impaired animals that cannot step unassisted.

  2. Neurogenesis and growth factors expression after complete spinal cord transection in Pleurodeles waltlii

    PubMed Central

    Zaky, Amira Z.; Moftah, Marie Z.

    2015-01-01

    Following spinal lesion, connections between the supra-spinal centers and spinal neuronal networks can be disturbed, which causes the deterioration or even the complete absence of sublesional locomotor activity. In mammals, possibilities of locomotion restoration are much reduced since descending tracts either have very poor regenerative ability or do not regenerate at all. However, in lower vertebrates, there is spontaneous locomotion recuperation after complete spinal cord transection at the mid-trunk level. This phenomenon depends on a translesional descending axon re-growth originating from the brainstem. On the other hand, cellular and molecular mechanisms underlying spinal cord regeneration and in parallel, locomotion restoration of the animal, are not well known. Fibroblast growth factor 2 (FGF-2) plays an important role in different processes such as neural induction, neuronal progenitor proliferation and their differentiation. Studies had shown an over expression of this growth factor after tail amputation. Nestin, a protein specific for intermediate filaments, is considered an early marker for neuronal precursors. It has been recently shown that its expression increases after tail transection in urodeles. Using this marker and western blots, our results show that the number of FGF-2 and FGFR2 mRNAs increases and is correlated with an increase in neurogenesis especially in the central canal lining cells immediately after lesion. This study also confirms that spinal cord re-growth through the lesion site initially follows a rostrocaudal direction. In addition to its role known in neuronal differentiation, FGF-2 could be implicated in the differentiation of ependymal cells into neuronal progenitors. PMID:25628538

  3. NEURAL RECONNECTION IN THE TRANSECTED SPINAL CORD OF THE FRESH-WATER TURTLE Trachemys dorbignyi

    PubMed Central

    Rehermann, María Inés; Marichal, Nicolás; Russo, Raúl E.; Trujillo-Cenóz, Omar

    2009-01-01

    This paper provides the first evidence that fresh water turtles are able to reconnect their completely transected spinal cord leading to some degree of recovery of the motor functions lost after injury. Videographic analysis showed that some turtles (5 out of 11) surviving more than 20 days after injury were able to initiate stepping locomotion. However the stepping movements were slower than those of normal animals and swimming patterns were not restored. Even though just 45% of the injured turtles recovered their stepping patterns, all showed axonal sprouting beyond the lesion site. Immunocytochemical and electron microscope images revealed the occurrence of regrowing axons crossing the severed region. A major contingent of the axons reconnecting the cord originated from sensory neurons lying in dorsal ganglia adjacent to the lesion site. The axons bridging the damaged region traveled on a cellular scaffold consisting of BLBP and GFAP positive cells and processes. Serotonergic varicose nerve fibers and endings were found at early stages of the healing process at the epicenter of the lesion. Interestingly, the glial scar commonly found in the damaged central nervous system of mammals was absent. In contrast GFAP and BLBP positive processes were found running parallel to the main axis of the cord accompanying the crossing axons. PMID:19418545

  4. Passive exercise of the hind limbs after complete thoracic transection of the spinal cord promotes cortical reorganization.

    PubMed

    Graziano, Alessandro; Foffani, Guglielmo; Knudsen, Eric B; Shumsky, Jed; Moxon, Karen A

    2013-01-01

    Physical exercise promotes neural plasticity in the brain of healthy subjects and modulates pathophysiological neural plasticity after sensorimotor loss, but the mechanisms of this action are not fully understood. After spinal cord injury, cortical reorganization can be maximized by exercising the non-affected body or the residual functions of the affected body. However, exercise per se also produces systemic changes - such as increased cardiovascular fitness, improved circulation and neuroendocrine changes - that have a great impact on brain function and plasticity. It is therefore possible that passive exercise therapies typically applied below the level of the lesion in patients with spinal cord injury could put the brain in a more plastic state and promote cortical reorganization. To directly test this hypothesis, we applied passive hindlimb bike exercise after complete thoracic transection of the spinal cord in adult rats. Using western blot analysis, we found that the level of proteins associated with plasticity - specifically ADCY1 and BDNF - increased in the somatosensory cortex of transected animals that received passive bike exercise compared to transected animals that received sham exercise. Using electrophysiological techniques, we then verified that neurons in the deafferented hindlimb cortex increased their responsiveness to tactile stimuli delivered to the forelimb in transected animals that received passive bike exercise compared to transected animals that received sham exercise. Passive exercise below the level of the lesion, therefore, promotes cortical reorganization after spinal cord injury, uncovering a brain-body interaction that does not rely on intact sensorimotor pathways connecting the exercised body parts and the brain. PMID:23349859

  5. In vivo longitudinal Myelin Water Imaging in rat spinal cord following dorsal column transection injury.

    PubMed

    Kozlowski, Piotr; Rosicka, Paulina; Liu, Jie; Yung, Andrew C; Tetzlaff, Wolfram

    2014-04-01

    Longitudinal Myelin Water Imaging was carried out in vivo to characterize white matter damage following dorsal column transection (DC Tx) injury at the lumbar level L1 of rat spinal cords. A transmit-receive implantable coil system was used to acquire multiple spin-echo (MSE) quantitative T2 data from the lumbar spinal cords of 16 rats at one week pre-injury as well as 3 and 8weeks post-injury (117 microns in-plane resolution and 1.5mm slice thickness). In addition, ex vivo MSE and DTI data were acquired from cords fixed and excised at 3 or 8weeks post injury using a solenoid coil. The MSE data were used to generate Myelin Water Fractions (MWFs) as a surrogate measure of myelin content, while DTI data were acquired to study damage to the axons. Myelin damage was assessed histologically with Eriochrome cyanine (EC) and Myelin Basic Protein in degenerated myelin (dgen-MBP) staining, and axonal damage was assessed by neurofilament-H in combination with neuron specific beta-III-tubulin (NF/Tub) staining. These MRI and histological measures of injury were studied in the dorsal column at 5mm cranial and 5mm caudal to injury epicenter. MWF increased significantly at 3weeks post-injury at both the cranial and caudal sites, relative to baseline. The values on the cranial side of injury returned to baseline at 8weeks post-injury but remained elevated on the caudal side. This trend was found in both in vivo and ex vivo data. This MWF increase was likely due to the presence of myelin debris, which were cleared by 8 weeks on the cranial, but not the caudal, side. Both EC and dgen-MBP stains displayed similar trends. MWF showed significant correlation with EC staining (R=0.63, p=0.005 in vivo and R=0.74, p=0.0001 ex vivo). MWF also correlated strongly with the dgen-MBP stain, but only on the cranial side (R=0.64, p=0.05 in vivo; R=0.63, p=0.038 ex vivo). This study demonstrates that longitudinal MWI in vivo can accurately characterize white matter damage in DC Tx model of injury

  6. Structural remodeling of the heart and its premotor cardioinhibitory vagal neurons following T5 spinal cord transection

    PubMed Central

    Lujan, Heidi L.; Janbaih, Hussein

    2014-01-01

    Midthoracic spinal cord injury (SCI) is associated with enhanced cardiac sympathetic activity and reduced cardiac parasympathetic activity. The enhanced cardiac sympathetic activity is associated with sympathetic structural plasticity within the stellate ganglia, spinal cord segments T1–T4, and heart. However, changes to cardiac parasympathetic centers rostral to an experimental SCI are relatively unknown. Importantly, reduced vagal activity is a predictor of high mortality. Furthermore, this autonomic dysregulation promotes progressive left ventricular (LV) structural remodeling. Accordingly, we hypothesized that midthoracic spinal cord injury is associated with structural plasticity in premotor (preganglionic parasympathetic neurons) cardioinhibitory vagal neurons located within the nucleus ambiguus as well as LV structural remodeling. To test this hypothesis, dendritic arborization and morphology (cholera toxin B immunohistochemistry and Sholl analysis) of cardiac projecting premotor cardioinhibitory vagal neurons located within the nucleus ambiguus were determined in intact (sham transected) and thoracic level 5 transected (T5X) rats. In addition, LV chamber size, wall thickness, and collagen content (Masson trichrome stain and structural analysis) were determined. Midthoracic SCI was associated with structural changes within the nucleus ambiguus and heart. Specifically, following T5 spinal cord transection, there was a significant increase in cardiac parasympathetic preganglionic neuron dendritic arborization, soma area, maximum dendritic length, and number of intersections/animal. This parasympathetic structural remodeling was associated with a profound LV structural remodeling. Specifically, T5 spinal cord transection increased LV chamber area, reduced LV wall thickness, and increased collagen content. Accordingly, results document a dynamic interaction between the heart and its parasympathetic innervation. PMID:24610530

  7. Rigid and remodelled: cerebrovascular structure and function after experimental high-thoracic spinal cord transection.

    PubMed

    Phillips, A A; Matin, N; Frias, B; Zheng, M M Z; Jia, M; West, C; Dorrance, A M; Laher, I; Krassioukov, A V

    2016-03-15

    High-thoracic or cervical spinal cord injury (SCI) is associated with several critical clinical conditions related to impaired cerebrovascular health, including: 300-400% increased risk of stroke, cognitive decline and diminished cerebral blood flow regulation. The purpose of this study was to examine the influence of high-thoracic (T3 spinal segment) SCI on cerebrovascular structure and function, as well as molecular markers of profibrosis. Seven weeks after complete T3 spinal cord transection (T3-SCI, n = 15) or sham injury (Sham, n = 10), rats were sacrificed for either middle cerebral artery (MCA) structure and function assessments via ex vivo pressure myography, or immunohistochemical analyses. Myogenic tone was unchanged, but over a range of transmural pressures, inward remodelling occurred after T3-SCI with a 40% reduction in distensibility (both P < 0.05), and a 33% reduction in vasoconstrictive reactivity to 5-HT trending toward significance (P = 0.09). After T3-SCI, the MCA had more collagen I (42%), collagen III (24%), transforming growth factor β (47%) and angiotensin II receptor type 2 (132%), 27% less elastin as well as concurrent increased wall thickness and reduced lumen diameter (all P < 0.05). Sympathetic innervation (tyrosine hydroxylase-positive axon density) and endothelium-dependent dilatation (carbachol) of the MCA were not different between groups. This study demonstrates profibrosis and hypertrophic inward remodelling within the largest cerebral artery after high-thoracic SCI, leading to increased stiffness and possibly impaired reactivity. These deleterious adaptations would substantially undermine the capacity for regulation of cerebral blood flow and probably underlie several cerebrovascular clinical conditions in the SCI population.

  8. Iron oxide nanoparticles and magnetic field exposure promote functional recovery by attenuating free radical-induced damage in rats with spinal cord transection

    PubMed Central

    Pal, Ajay; Singh, Anand; Nag, Tapas C; Chattopadhyay, Parthaprasad; Mathur, Rashmi; Jain, Suman

    2013-01-01

    Background Iron oxide nanoparticles (IONPs) can attenuate oxidative stress in a neutral pH environment in vitro. In combination with an external electromagnetic field, they can also facilitate axon regeneration. The present study demonstrates the in vivo potential of IONPs to recover functional deficits in rats with complete spinal cord injury. Methods The spinal cord was completely transected at the T11 vertebra in male albino Wistar rats. Iron oxide nanoparticle solution (25 μg/mL) embedded in 3% agarose gel was implanted at the site of transection, which was subsequently exposed to an electromagnetic field (50 Hz, 17.96 μT for two hours daily for five weeks). Results Locomotor and sensorimotor assessment as well as histological analysis demonstrated significant functional recovery and a reduction in lesion volume in rats with IONP implantation and exposure to an electromagnetic field. No collagenous scar was observed and IONPs were localized intracellularly in the immediate vicinity of the lesion. Further, in vitro experiments to explore the cytotoxic effects of IONPs showed no effect on cell survival. However, a significant decrease in H2O2-mediated oxidative stress was evident in the medium containing IONPs, indicating their free radical scavenging properties. Conclusion These novel findings indicate a therapeutic role for IONPs in spinal cord injury and other neurodegenerative disorders mediated by reactive oxygen species. PMID:23818782

  9. 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

  10. 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. PMID:11229711

  11. Spontaneous development of full weight-supported stepping after complete spinal cord transection in the neonatal opossum, Monodelphis domestica.

    PubMed

    Wheaton, Benjamin J; Callaway, Jennifer K; Ek, C Joakim; Dziegielewska, Katarzyna M; Saunders, Norman R

    2011-01-01

    Spinal cord trauma in the adult nervous system usually results in permanent loss of function below the injury level. The immature spinal cord has greater capacity for repair and can develop considerable functionality by adulthood. This study used the marsupial laboratory opossum Monodelphis domestica, which is born at a very early stage of neural development. Complete spinal cord transection was made in the lower-thoracic region of pups at postnatal-day 7 (P7) or P28, and the animals grew to adulthood. Injury at P7 resulted in a dense neuronal tissue bridge that connected the two ends of the cord; retrograde neuronal labelling indicated that supraspinal and propriospinal innervation spanned the injury site. This repair was associated with pronounced behavioural recovery, coordinated gait and an ability to use hindlimbs when swimming. Injury at P28 resulted in a cyst-like cavity encased in scar tissue forming at the injury site. Using retrograde labelling, no labelled brainstem or propriospinal neurons were found above the lesion, indicating that detectable neuronal connectivity had not spanned the injury site. However, these animals could use their hindlimbs to take weight-supporting steps but could not use their hindlimbs when swimming. White matter, demonstrated by Luxol Fast Blue staining, was present in the injury site of P7- but not P28-injured animals. Overall, these studies demonstrated that provided spinal injury occurs early in development, regrowth of supraspinal innervation is possible. This repair appears to lead to improved functional outcomes. At older ages, even without detectable axonal growth spanning the injury site, substantial development of locomotion was still possible. This outcome is discussed in conjunction with preliminary findings of differences in the local propriospinal circuits following spinal cord injury (demonstrated with fluororuby labelling), which may underlie the weight bearing locomotion observed in the apparent absence of

  12. The linear-ordered collagen scaffold-BDNF complex significantly promotes functional recovery after completely transected spinal cord injury in canine.

    PubMed

    Han, Sufang; Wang, Bin; Jin, Wei; Xiao, Zhifeng; Li, Xing; Ding, Wenyong; Kapur, Meghan; Chen, Bing; Yuan, Baoyu; Zhu, Tiansheng; Wang, Handong; Wang, Jing; Dong, Qun; Liang, Weibang; Dai, Jianwu

    2015-02-01

    Spinal cord injury (SCI) is still a worldwide clinical challenge for which there is no viable therapeutic method. We focused on developing combinatorial methods targeting the complex pathological process of SCI. In this study, we implanted linear-ordered collagen scaffold (LOCS) fibers with collagen binding brain-derived neurotrophic factor (BDNF) by tagging a collagen-binding domain (CBD) (LOCS + CBD-BDNF) in completely transected canine SCI with multisystem rehabilitation to validate its potential therapeutic effect through a long-term (38 weeks) observation. We found that LOCS + CBD-BDNF implants strikingly promoted locomotion and functional sensory recovery, with some dogs standing unassisted and transiently moving. Further histological analysis showed that administration of LOCS + CBD-BDNF reduced lesion volume, decreased collagen deposits, promoted axon regeneration and improved myelination, leading to functional recovery. Collectively, LOCS + CBD-BDNF showed striking therapeutic effect on completely transected canine SCI model and it is the first time to report such breakthrough in the war with SCI. Undoubtedly, it is a potentially promising therapeutic method for SCI paralysis or other movement disorders caused by neurological diseases in the future.

  13. Accelerated recovery of sensorimotor function in a dog submitted to quasi-total transection of the cervical spinal cord and treated with PEG

    PubMed Central

    Kim, C-Yoon; Hwang, In-Kyu; Kim, Hana; Jang, Se-Woong; Kim, Hong Seog; Lee, Won-Young

    2016-01-01

    Background: A case report on observing the recovery of sensory-motor function after cervical spinal cord transection. Case Description: Laminectomy and transection of cervical spinal cord (C5) was performed on a male beagle weighing 3.5 kg. After applying polyethylene glycol (PEG) on the severed part, reconstruction of cervical spinal cord was confirmed by the restoration of sensorimotor function. Tetraplegia was observed immediately after operation, however, the dog showed stable respiration and survival without any complication. The dog showed fast recovery after 1 week, and recovered approximately 90% of normal sensorimotor function 3 weeks after the operation, although urinary disorder was still present. All recovery stages were recorded by video camera twice a week for behavioral analysis. Conclusion: While current belief holds that functional recovery is impossible after a section greater than 50% at C5-6 in the canine model, this case study shows the possibility of cervical spinal cord reconstruction after near-total transection. Furthermore, this case study also confirms that PEG can truly expedite the recovery of sensorimotor function after cervical spinal cord sections in dogs.

  14. Accelerated recovery of sensorimotor function in a dog submitted to quasi-total transection of the cervical spinal cord and treated with PEG

    PubMed Central

    Kim, C-Yoon; Hwang, In-Kyu; Kim, Hana; Jang, Se-Woong; Kim, Hong Seog; Lee, Won-Young

    2016-01-01

    Background: A case report on observing the recovery of sensory-motor function after cervical spinal cord transection. Case Description: Laminectomy and transection of cervical spinal cord (C5) was performed on a male beagle weighing 3.5 kg. After applying polyethylene glycol (PEG) on the severed part, reconstruction of cervical spinal cord was confirmed by the restoration of sensorimotor function. Tetraplegia was observed immediately after operation, however, the dog showed stable respiration and survival without any complication. The dog showed fast recovery after 1 week, and recovered approximately 90% of normal sensorimotor function 3 weeks after the operation, although urinary disorder was still present. All recovery stages were recorded by video camera twice a week for behavioral analysis. Conclusion: While current belief holds that functional recovery is impossible after a section greater than 50% at C5-6 in the canine model, this case study shows the possibility of cervical spinal cord reconstruction after near-total transection. Furthermore, this case study also confirms that PEG can truly expedite the recovery of sensorimotor function after cervical spinal cord sections in dogs. PMID:27656327

  15. Electro-acupuncture promotes survival, differentiation of the bone marrow mesenchymal stem cells as well as functional recovery in the spinal cord-transected rats

    PubMed Central

    Ding, Ying; Yan, Qing; Ruan, Jing-Wen; Zhang, Yan-Qing; Li, Wen-Jie; Zhang, Yu-Jiao; Li, Yan; Dong, Hongxin; Zeng, Yuan-Shan

    2009-01-01

    Background Bone marrow mesenchymal stem cells (MSCs) are one of the potential tools for treatment of the spinal cord injury; however, the survival and differentiation of MSCs in an injured spinal cord still need to be improved. In the present study, we investigated whether Governor Vessel electro-acupuncture (EA) could efficiently promote bone marrow mesenchymal stem cells (MSCs) survival and differentiation, axonal regeneration and finally, functional recovery in the transected spinal cord. Results The spinal cords of adult Sprague-Dawley (SD) rats were completely transected at T10, five experimental groups were performed: 1. sham operated control (Sham-control); 2. operated control (Op-control); 3. electro-acupuncture treatment (EA); 4. MSCs transplantation (MSCs); and 5. MSCs transplantation combined with electro-acupuncture (MSCs+EA). After 2-8 weeks of MSCs transplantation plus EA treatment, we found that the neurotrophin-3 (NT-3), cAMP level, the differentiation of MSCs, the 5-HT positive and CGRP positive nerve fibers in the lesion site and nearby tissue of injured spinal cord were significantly increased in the MSCs+EA group as compared to the group of the MSCs transplantation or the EA treated alone. Furthermore, behavioral test and spinal cord evoked potentials detection demonstrated a significantly functional recovery in the MSCs +EA group. Conclusion These results suggest that EA treatment may promote grafted MSCs survival and differentiation; MSCs transplantation combined with EA treatment could promote axonal regeneration and partial locomotor functional recovery in the transected spinal cord in rats and indicate a promising avenue of treatment of spinal cord injury. PMID:19374777

  16. MicroRNA-127 targeting of mitoNEET inhibits neurite outgrowth, induces cell apoptosis and contributes to physiological dysfunction after spinal cord transection

    PubMed Central

    He, Qin-Qin; Xiong, Liu-Lin; Liu, Fei; He, Xiang; Feng, Guo-Ying; Shang, Fei-Fei; Xia, Qing-Jie; Wang, You-Cui; Qiu, De-Lu; Luo, Chao-Zhi; Liu, Jia; Wang, Ting-Hua

    2016-01-01

    Neuroregeneration and apoptosis are two important pathophysiologic changes after spinal cord injury (SCI), but their underlying mechanisms remain unclear. MicroRNAs (miRNAs) play a crucial role in the regulation of neuroregeneration and neuronal apoptosis, research areas that have been greatly expanded in recent years. Here, using miRNA arrays to profile miRNA transcriptomes, we demonstrated that miR-127-3p was significantly down-regulated after spinal cord transection (SCT). Then, bioinformatics analyses and experimental detection showed that miR-127-3p exhibited specific effects on the regulation of neurite outgrowth and the induction of neuronal apoptosis by regulating the expression of the mitochondrial membrane protein mitoNEET. Moreover, knockdown of MitoNEET leaded to neuronal loss and apoptosis in primary cultured spinal neurons. This study therefore revealed that miR-127-3p, which targets mitoNEET, plays a vital role in regulating neurite outgrowth and neuronal apoptosis after SCT. Thus, modificatioin of the mitoNEET expression, such as mitoNEET activition may provide a new strategy for the treatment of SCI in preclinical trials. PMID:27748416

  17. Peripheral Nerve Transplantation Combined with Acidic Fibroblast Growth Factor and Chondroitinase Induces Regeneration and Improves Urinary Function in Complete Spinal Cord Transected Adult Mice

    PubMed Central

    DePaul, Marc A.; Lin, Ching-Yi; Silver, Jerry; Lee, Yu-Shang

    2015-01-01

    The loss of lower urinary tract (LUT) control is a ubiquitous consequence of a complete spinal cord injury, attributed to a lack of regeneration of supraspinal pathways controlling the bladder. Previous work in our lab has utilized a combinatorial therapy of peripheral nerve autografts (PNG), acidic fibroblast growth factor (aFGF), and chondroitinase ABC (ChABC) to treat a complete T8 spinal cord transection in the adult rat, resulting in supraspinal control of bladder function. In the present study we extended these findings by examining the use of the combinatorial PNG+aFGF+ChABC treatment in a T8 transected mouse model, which more closely models human urinary deficits following spinal cord injury. Cystometry analysis and external urethral sphincter electromyograms reveal that treatment with PNG+aFGF+ChABC reduced bladder weight, improved bladder and external urethral sphincter histology, and significantly enhanced LUT function, resulting in more efficient voiding. Treated mice’s injured spinal cord also showed a reduction in collagen scaring, and regeneration of serotonergic and tyrosine hydroxylase-positive axons across the lesion and into the distal spinal cord. Regeneration of serotonin axons correlated with LUT recovery. These results suggest that our mouse model of LUT dysfunction recapitulates the results found in the rat model and may be used to further investigate genetic contributions to regeneration failure. PMID:26426529

  18. Effects of roadside transect width on waterfowl and wetland estimates

    USGS Publications Warehouse

    Austin, Jane E.; Sklebar, H. Thomas; Guntenspergen, Glenn R.; Buhl, Thomas K.

    2000-01-01

    Strip transects located along roads are commonly used to estimate waterfowl populations and characterize associated wetland habitat. We used data collected in May and early June, 1995, on forty-five 40-km2 plots in North Dakota to evaluate bias of 800-m and 400-m wide roadside transects for sampling wetlands relative to a larger (40-km2) scale and to compare duck abundance at the two widths. Densities of all basins combined and of seasonal basins considered alone were biased high for both transect widths, but mean bias did not differ from zero for temporary or semipermanent basins. Biases did not occur when excavated seasonal and temporary basins (i.e., road ditches) were excluded from the sample. Mean basin density was higher for the inner (400-m) transect width than for the outer transect width (area remaining of the 800-m transect, outside of center 400-m width) for all basins combined and for seasonal and temporary basins. We detected an area-related bias in the occurrence of basins in transects: smaller basins (0.08–1.6 ha) were over-represented in transect samples by 2.9–6.5%, and larger basins (≥11 ha) were under-represented in 800-m transects by 7.3% and in 400-m transects by 16.3%. We compared the distribution of ducks relative to water conditions in the inner and outer transect widths to evaluate whether they were affected by proximity to the road. Mallards (Anas platyrhynchos L.), northern pintails (A. acuta L.), and gadwall (A. strepera L.) responded to water conditions equally in the inner and outer transect widths, but northern shovelers (A. clypeata L.) and blue-winged teal (A. discors L.) responded more strongly to wetlands on the inner than the outer transect width, indicating that estimates of these species would be higher from a 400-m wide transect than from an 800-m wide transect. Differences in an adjustment index, used to account for the portion of basin obscured from view, were highly variable between inner and outer transect widths but

  19. A Radio-telemetric System to Monitor Cardiovascular Function in Rats with Spinal Cord Transection and Embryonic Neural Stem Cell Grafts

    PubMed Central

    Hou, Shaoping; Blesch, Armin; Lu, Paul

    2014-01-01

    High thoracic or cervical spinal cord injury (SCI) can lead to cardiovascular dysfunction. To monitor cardiovascular parameters, we implanted a catheter connected to a radio transmitter into the femoral artery of rats that underwent a T4 spinal cord transection with or without grafting of embryonic brainstem-derived neural stem cells expressing green fluorescent protein. Compared to other methods such as cannula insertion or tail-cuff, telemetry is advantageous to continuously monitor blood pressure and heart rate in freely moving animals. It is also capable of long term multiple data acquisitions. In spinal cord injured rats, basal cardiovascular data under unrestrained condition and autonomic dysreflexia in response to colorectal distension were successfully recorded. In addition, cardiovascular parameters before and after SCI can be compared in the same rat if a transmitter is implanted before a spinal cord transection. One limitation of the described telemetry procedure is that implantation in the femoral artery may influence the blood supply to the ipsilateral hindlimb. PMID:25350486

  20. Knockdown of α-synuclein in cerebral cortex improves neural behavior associated with apoptotic inhibition and neurotrophin expression in spinal cord transected rats.

    PubMed

    Wang, You-Cui; Feng, Guo-Ying; Xia, Qing-Jie; Hu, Yue; Xu, Yang; Xiong, Liu-Lin; Chen, Zhi-Wei; Wang, Hang-Ping; Wang, Ting-Hua; Zhou, Xue

    2016-04-01

    Spinal cord injury (SCI) often causes severe functional impairment with poor recovery. The treatment, however, is far from satisfaction, and the mechanisms remain unclear. By using proteomics and western blot, we found spinal cord transection (SCT) resulted in a significant down-regulation of α-synuclein (SNCA) in the motor cortex of SCT rats at 3 days post-operation. In order to detect the role of SNCA, we used SNCA-ORF/shRNA lentivirus to upregulate or knockdown SNCA expression. In vivo, SNCA-shRNA lentivirus injection into the cerebral cortex motor area not only inhibited SNCA expression, but also significantly enhanced neurons' survival, and attenuated neuronal apoptosis, as well as promoted motor and sensory function recovery in hind limbs. While, overexpression SNCA exhibited the opposite effects. In vitro, cortical neurons transfected with SNCA-shRNA lentivirus gave rise to an optimal neuronal survival and neurite outgrowth, while it was accompanied by reverse efficiency in SNCA-ORF group. In molecular level, SNCA silence induced the upregulation of Bcl-2 and the downregulation of Bax, and the expression of NGF, BDNF and NT3 was substantially upregulated in cortical neurons. Together, endogenous SNCA play a crucial role in motor and sensory function regulation, in which, the underlying mechanism may be linked to the regulation of apoptosis associated with apoptotic gene (Bax, Bcl2) and neurotrophic factors expression (NGF, BDNF and NT3). These finds provide novel insights to understand the role of SNCA in cerebral cortex after SCT, and it may be as a novel treatment target for SCI repair in future clinic trials. PMID:26822976

  1. Local Delivery of High-Dose Chondroitinase ABC in the Sub-Acute Stage Promotes Axonal Outgrowth and Functional Recovery after Complete Spinal Cord Transection

    PubMed Central

    Cheng, Chu-Hsun; Lin, Chi-Te; Lee, Meng-Jen; Tsai, May-Jywan; Huang, Wen-Hung; Huang, Ming-Chao; Lin, Yi-Lo; Chen, Ching-Jung

    2015-01-01

    Chondroitin sulfate proteoglycans (CSPGs) are glial scar-associated molecules considered axonal regeneration inhibitors and can be digested by chondroitinase ABC (ChABC) to promote axonal regeneration after spinal cord injury (SCI). We previously demonstrated that intrathecal delivery of low-dose ChABC (1 U) in the acute stage of SCI promoted axonal regrowth and functional recovery. In this study, high-dose ChABC (50 U) introduced via intrathecal delivery induced subarachnoid hemorrhage and death within 48 h. However, most SCI patients are treated in the sub-acute or chronic stages, when the dense glial scar has formed and is minimally digested by intrathecal delivery of ChABC at the injury site. The present study investigated whether intraparenchymal delivery of ChABC in the sub-acute stage of complete spinal cord transection would promote axonal outgrowth and improve functional recovery. We observed no functional recovery following the low-dose ChABC (1 U or 5 U) treatments. Furthermore, animals treated with high-dose ChABC (50 U or 100 U) showed decreased CSPGs levels. The extent and area of the lesion were also dramatically decreased after ChABC treatment. The outgrowth of the regenerating axons was significantly increased, and some partially crossed the lesion site in the ChABC-treated groups. In addition, retrograde Fluoro-Gold (FG) labeling showed that the outgrowing axons could cross the lesion site and reach several brain stem nuclei involved in sensory and motor functions. The Basso, Beattie and Bresnahan (BBB) open field locomotor scores revealed that the ChABC treatment significantly improved functional recovery compared to the control group at eight weeks after treatment. Our study demonstrates that high-dose ChABC treatment in the sub-acute stage of SCI effectively improves glial scar digestion by reducing the lesion size and increasing axonal regrowth to the related functional nuclei, which promotes locomotor recovery. Thus, our results will aid in

  2. Age-Dependent Transcriptome and Proteome Following Transection of Neonatal Spinal Cord of Monodelphis domestica (South American Grey Short-Tailed Opossum)

    PubMed Central

    Saunders, Norman R.; Noor, Natassya M.; Dziegielewska, Katarzyna M.; Wheaton, Benjamin J.; Liddelow, Shane A.; Steer, David L.; Ek, C. Joakim; Habgood, Mark D.; Wakefield, Matthew J.; Lindsay, Helen; Truettner, Jessie; Miller, Robert D.; Smith, A. Ian; Dietrich, W. Dalton

    2014-01-01

    This study describes a combined transcriptome and proteome analysis of Monodelphis domestica response to spinal cord injury at two different postnatal ages. Previously we showed that complete transection at postnatal day 7 (P7) is followed by profuse axon growth across the lesion with near-normal locomotion and swimming when adult. In contrast, at P28 there is no axon growth across the lesion, the animals exhibit weight-bearing locomotion, but cannot use hind limbs when swimming. Here we examined changes in gene and protein expression in the segment of spinal cord rostral to the lesion at 24 h after transection at P7 and at P28. Following injury at P7 only forty genes changed (all increased expression); most were immune/inflammatory genes. Following injury at P28 many more genes changed their expression and the magnitude of change for some genes was strikingly greater. Again many were associated with the immune/inflammation response. In functional groups known to be inhibitory to regeneration in adult cords the expression changes were generally muted, in some cases opposite to that required to account for neurite inhibition. For example myelin basic protein expression was reduced following injury at P28 both at the gene and protein levels. Only four genes from families with extracellular matrix functions thought to influence neurite outgrowth in adult injured cords showed substantial changes in expression following injury at P28: Olfactomedin 4 (Olfm4, 480 fold compared to controls), matrix metallopeptidase (Mmp1, 104 fold), papilin (Papln, 152 fold) and integrin α4 (Itga4, 57 fold). These data provide a resource for investigation of a priori hypotheses in future studies of mechanisms of spinal cord regeneration in immature animals compared to lack of regeneration at more mature stages. PMID:24914927

  3. Tissue-engineered regeneration of completely transected spinal cord using induced neural stem cells and gelatin-electrospun poly (lactide-co-glycolide)/polyethylene glycol scaffolds.

    PubMed

    Liu, Chang; Huang, Yong; Pang, Mao; Yang, Yang; Li, Shangfu; Liu, Linshan; Shu, Tao; Zhou, Wei; Wang, Xuan; Rong, Limin; Liu, Bin

    2015-01-01

    Tissue engineering has brought new possibilities for the treatment of spinal cord injury. Two important components for tissue engineering of the spinal cord include a suitable cell source and scaffold. In our study, we investigated induced mouse embryonic fibroblasts (MEFs) directly reprogrammed into neural stem cells (iNSCs), as a cell source. Three-dimensional (3D) electrospun poly (lactide-co-glycolide)/polyethylene glycol (PLGA-PEG) nanofiber scaffolds were used for iNSCs adhesion and growth. Cell growth, survival and proliferation on the scaffolds were investigated. Scanning electron microscopy (SEM) and nuclei staining were used to assess cell growth on the scaffolds. Scaffolds with iNSCs were then transplanted into transected rat spinal cords. Two or 8 weeks following transplantation, immunofluorescence was performed to determine iNSC survival and differentiation within the scaffolds. Functional recovery was assessed using the Basso, Beattie, Bresnahan (BBB) Scale. Results indicated that iNSCs showed similar morphological features with wild-type neural stem cells (wt-NSCs), and expressed a variety of neural stem cell marker genes. Furthermore, iNSCs were shown to survive, with the ability to self-renew and undergo neural differentiation into neurons and glial cells within the 3D scaffolds in vivo. The iNSC-seeded scaffolds restored the continuity of the spinal cord and reduced cavity formation. Additionally, iNSC-seeded scaffolds contributed to functional recovery of the spinal cord. Therefore, PLGA-PEG scaffolds seeded with iNSCs may serve as promising supporting transplants for repairing spinal cord injury (SCI). PMID:25803031

  4. Graft of a Tissue-Engineered Neural Scaffold Serves as a Promising Strategy to Restore Myelination after Rat Spinal Cord Transection

    PubMed Central

    Lai, Bi-Qin; Wang, Jun-Mei; Ling, Eng-Ang; Wu, Jin-Lang

    2014-01-01

    Remyelination remains a challenging issue in spinal cord injury (SCI). In the present study, we cocultured Schwann cells (SCs) and neural stem cells (NSCs) with overexpression of neurotrophin-3 (NT-3) and its high affinity receptor tyrosine kinase receptor type 3 (TrkC), respectively, in a gelatin sponge (GS) scaffold. This was aimed to generate a tissue-engineered neural scaffold and to investigate whether it could enhance myelination after a complete T10 spinal cord transection in adult rats. Indeed, many NT-3 overexpressing SCs (NT-3-SCs) in the GS scaffold assumed the formation of myelin. More strikingly, a higher incidence of NSCs overexpressing TrkC differentiating toward myelinating cells was induced by NT-3-SCs. By transmission electron microscopy, the myelin sheath showed distinct multilayered lamellae formed by the seeded cells. Eighth week after the scaffold was transplanted, some myelin basic protein (MBP)-positive processes were observed within the transplantation area. Remarkably, certain segments of myelin derived from NSC-derived myelinating cells and NT-3-SCs were found to ensheath axons. In conclusion, we show here that transplantation of the GS scaffold promotes exogenous NSC-derived myelinating cells and SCs to form myelins in the injury/transplantation area of spinal cord. These findings thus provide a neurohistological basis for the future application or transplantation using GS neural scaffold to repair SCI. PMID:24325427

  5. Complete sciatic nerve transection induces increase of neuropeptide Y-like immunoreactivity in primary sensory neurons and spinal cord of frogs.

    PubMed

    Guedes, Renata P; Marchi, Melina I; Achaval, Matilde; Partata, Wania A

    2004-12-01

    Neuropeptide Y (NPY) was immunohistochemically investigated in the frog spinal cord and dorsal root ganglia after axotomy. In normal ganglia, moderate NPY-like immunoreactivity (NPY-IR) prevailed in large and medium cells. In the spinal cord, the NPY-IR was densest in the dorsal part of the lateral funiculus. Other fibers and neurons NPY-IR were observed in the dorsal and ventral terminal fields and mediolateral band. NPY-IR fibers were also found in the ventral horn and in the ventral and lateral funiculi. The sciatic nerve transection increased the NPY-IR in large and medium neurons of the ipsilateral and contralateral dorsal root ganglia at 3 and 7 days, but no clear change was found at 15 days. In the spinal cord, there was a bilateral increase in the NPY-IR of the dorsal part of the lateral funiculus. In the ipsilateral side, the NPY-IR was increased at 3 and 7 days but was decreased at 15 days. In the contralateral side, a significant reduction at 15 days occurred. These findings seem to favor the role of NPY in the modulation of pain-related information in frogs, suggesting that this role of NPY may have appeared early in vertebrate evolution.

  6. The effect of brain transection on the response to forced submergence in ducks.

    PubMed

    Gabbott, G R; Jones, D R

    1991-10-01

    The effect of brain transection at two levels on cardiovascular responses to forced submergence has been investigated in ducks. Compared with intact ducks, neither decerebration nor brain stem transection at the rostral mesencephalic (RM) level had any effect on development of diving bradycardia, or heart rate at the end of two-min dives. Arterial blood pressure was maintained in brain transected ducks as well as in intact ducks. Furthermore, end-dive arterial blood gases and pH were also similar in intact and brain transected ducks confirming that the oxygen sparing cardiovascular adjustments, involving a massive increase in total peripheral resistance, were unimpaired by brain transection. In this respect, ducks with RM transections tolerated four-min dives. However, the increase in post-dive VE seen in intact and decerebrated ducks was prevented by RM transection. We conclude that control of the circulatory response to diving resides in the lower brainstem, is reflexogenic in nature, and does not depend on the cognitive perception of 'fearful' stimuli. PMID:1753065

  7. Autocrine fibronectin from differentiating mesenchymal stem cells induces the neurite elongation in vitro and promotes nerve fiber regeneration in transected spinal cord injury.

    PubMed

    Zeng, Xiang; Ma, Yuan-Huan; Chen, Yuan-Feng; Qiu, Xue-Cheng; Wu, Jin-Lang; Ling, Eng-Ang; Zeng, Yuan-Shan

    2016-08-01

    Extracellular matrix (ECM) expression is temporally and spatially regulated during the development of stem cells. We reported previously that fibronectin (FN) secreted by bone marrow mesenchymal stem cells (MSCs) was deposited on the surface of gelatin sponge (GS) soon after culture. In this study, we aimed to assess the function of accumulated FN on neuronal differentiating MSCs as induced by Schwann cells (SCs) in three dimensional transwell co-culture system. The expression pattern and amount of FN of differentiating MSCs was examined by immunofluorescence, Western blot and immunoelectron microscopy. The results showed that FN accumulated inside GS scaffold, although its mRNA expression in MSCs was progressively decreased during neural induction. MSC-derived neuron-like cells showed spindle-shaped cell body and long extending processes on FN-decorated scaffold surface. However, after blocking of FN function by application of monoclonal antibodies, neuron-like cells showed flattened cell body with short and thick neurites, together with decreased expression of integrin β1. In vivo transplantation study revealed that autocrine FN significantly facilitated endogenous nerve fiber regeneration in spinal cord transection model. Taken together, the present results showed that FN secreted by MSCs in the early stage accumulated on the GS scaffold and promoted the neurite elongation of neuronal differentiating MSCs as well as nerve fiber regeneration after spinal cord injury. This suggests that autocrine FN has a dynamic influence on MSCs in a three dimensional culture system and its potential application for treatment of traumatic spinal cord injury. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1902-1911, 2016. PMID:26991461

  8. Effects of glutamine supplementation on muscle function and stress responses in a mouse model of spinal cord injury.

    PubMed

    Chamney, Carissa; Godar, Michelle; Garrigan, Ethan; Huey, Kimberly A

    2013-03-01

    Spinal cord injury (SCI) results in loss of muscle function due to rapid breakdown of contractile proteins. Glutamine supplementation improves clinical outcomes, but its effects on muscle function after SCI are unknown. The benefits of glutamine in non-skeletal muscle tissues involve elevated heat shock protein (Hsp)70 and Hsp25, but the muscle response may differ because it is the largest contributor to plasma glutamine. We tested the hypothesis that glutamine preserves muscle function after SCI and that this is associated with increased heat shock protein and reduced inflammatory factors, interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα). Changes in plantarflexor force, fatigability and total myofibrillar, Hsp70, Hsp25, IL-6 and TNFα muscle protein levels were measured 7 days after sham or spinal cord transection surgery in mice receiving daily placebo or glutamine. Compared with placebo, after SCI glutamine significantly attenuated the reductions in maximal isometric force (0.22 ± 0.01 versus 0.31 ± 0.03 N, respectively) and fatigue resistance (34 ± 4 versus 59 ± 4% of initial force, respectively). Glutamine significantly ameliorated the loss of myofibrillar protein with spinal cord transection. Spinal cord transection was associated with decreased Hsp70 and Hsp25 with glutamine only (45 ± 3 and 44 ± 5% of placebo, respectively). Glutamine significantly reduced spinal cord transection-associated increases in IL-6 and TNFα compared with placebo (38 ± 6 and 37 ± 8% of placebo, respectively). Functionally, early reductions in contractile protein, force and fatigue resistance after SCI were reversed with glutamine. Spinal cord transection-associated reductions in Hsp70, Hsp25, IL-6 and TNFα with glutamine versus placebo suggest lower stress in the muscle, possibly related to a reduced need to produce glutamine. These findings support glutamine as a therapeutic intervention to accelerate recovery of muscle function after SCI.

  9. Retraining the injured spinal cord

    NASA Technical Reports Server (NTRS)

    Edgerton, V. R.; Leon, R. D.; Harkema, S. J.; Hodgson, J. A.; London, N.; Reinkensmeyer, D. J.; Roy, R. R.; Talmadge, R. J.; Tillakaratne, N. J.; Timoszyk, W.; Tobin, A.

    2001-01-01

    The present review presents a series of concepts that may be useful in developing rehabilitative strategies to enhance recovery of posture and locomotion following spinal cord injury. First, the loss of supraspinal input results in a marked change in the functional efficacy of the remaining synapses and neurons of intraspinal and peripheral afferent (dorsal root ganglion) origin. Second, following a complete transection the lumbrosacral spinal cord can recover greater levels of motor performance if it has been exposed to the afferent and intraspinal activation patterns that are associated with standing and stepping. Third, the spinal cord can more readily reacquire the ability to stand and step following spinal cord transection with repetitive exposure to standing and stepping. Fourth, robotic assistive devices can be used to guide the kinematics of the limbs and thus expose the spinal cord to the new normal activity patterns associated with a particular motor task following spinal cord injury. In addition, such robotic assistive devices can provide immediate quantification of the limb kinematics. Fifth, the behavioural and physiological effects of spinal cord transection are reflected in adaptations in most, if not all, neurotransmitter systems in the lumbosacral spinal cord. Evidence is presented that both the GABAergic and glycinergic inhibitory systems are up-regulated following complete spinal cord transection and that step training results in some aspects of these transmitter systems being down-regulated towards control levels. These concepts and observations demonstrate that (a) the spinal cord can interpret complex afferent information and generate the appropriate motor task; and (b) motor ability can be defined to a large degree by training.

  10. Effects of limb exercise after spinal cord injury on motor neuron dendrite structure.

    PubMed

    Gazula, Valeswara-Rao; Roberts, Melinda; Luzzio, Christopher; Jawad, Abbas F; Kalb, Robert Gordon

    2004-08-16

    An integration center subserving locomotor leg movements resides in the upper lumbar spinal cord. If this neuronal network is preserved after a spinal cord injury, it is possible to stimulate this circuitry to initiate and promote walking. The several effective approaches (electrical stimulation, pharmacologic agents, physical therapy training programs) may all share a common modus operandi of altering synaptic activity within segmental spinal cord. To understand the neural substrate for the use-dependent behavioral improvement, we studied the dendritic architecture of spinal motor neurons. In the first experiment, we compared three groups of animals: animals with an intact spinal cord, animals that had a complete spinal cord transection (SCT) and animals with SCT who engaged in a daily exercise program of actively moving paralyzed hindlimbs through the motions of walking. When compared with animals with an intact spinal cord, the motor neurons from animals with SCT displayed marked atrophy, with loss of dendritic membrane and elimination of branching throughout the visible tree within transverse tissue slices. None of these regressive changes were found in the motor neurons from SCT animals that underwent exercise. In a second experiment, we inquired whether exercise of animals with an intact spinal cord influenced dendrite structure. Increased exercise had very modest effects on dendrite morphology, indicating an upper limit of use-dependent dendrite growth. Our findings suggest that the dendritic tree of motor neurons deprived of descending influences is rapidly pruned, and this finding is not observed in motor neurons after SCT if hindlimbs are exercised. The functional benefits of exercise after SCT injury may be subserved, in part, by stabilizing or remodeling the dendritic tree of motor neurons below the injury site.

  11. 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.

  12. 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. PMID:16609979

  13. Volume effects in Rhesus monkey spinal cord

    SciTech Connect

    Schultheiss, T.E. ); Stephens, L.C.; Price, R.E.; Ang, K.K.; Peters, L.J. )

    1994-04-30

    An experiment was conducted to test for the existence of a volume effect in radiation myelopathy using Rhesus monkeys treated with clinically relevant field sizes and fractionation schedules. Five groups of Rhesus monkeys were irradiated using 2.2 Gy per fraction to their spinal cords. Three groups were irradiated with 8 cm fields to total doses of 70.4, 77, and 83.6 Gy. Two additional groups were irradiated to 70.4 Gy using 4 and 16 cm fields. The incidence of paresis expressed within 2 years following the completion of treatment was determined for each group. Maximum likelihood estimation was used to determine parameters of a logistic dose response function. The volume effect was modeled using the probability model in which the probability of producing a lesion in an irradiated volume is governed by the probability of the occurrence of independent events. This is a two parameter model requiring only the estimates of the parameters of the dose-response function for the reference volume, but not needing any additional parameters for describing the volume effect. The probability model using a logistic dose-response function fits the data well with the D[sub 50] = 75.8 Gy for the 8-cm field. No evidence was seen for a difference in sensitivities for different anatomical levels of the spinal cord. Most lesions were type 3, combined white matter parenchymal and vascular lesions. Latent periods did not differ significantly from those of type 3 lesions in humans. The spinal cord exhibits a volume effect that is well described by the probability model. Because the dose response function for radiation myelopathy is steep, the volume effect is modest. The Rhesus monkey remains the animal model most similar to humans in dose response, histopathology, and latency for radiation myelopathy. 22 refs., 3 figs., 1 tab.

  14. The beneficial effects of a thromboxane receptor antagonist on spinal cord perfusion following experimental cord injury.

    PubMed

    Tempel, G E; Martin, H F

    1992-06-01

    The eicosanoids thromboxane A2 and prostacyclin have opposing actions causing vasoconstriction and vasodilation respectively. The ratio of these two eicosanoids is thus an important determinant of circulatory homeostasis. An increase in this ratio occurs in certain inflammatory conditions with dramatic consequences in organ perfusion. In spinal cord trauma, in addition to direct physical perturbation of the spinal cord, it is likely that further structural and functional loss occurs as a result of decreased tissue perfusion precipitated by an increase in the thromboxane/prostacyclin ratio. This study evaluated hemodynamics and organ perfusion, 3 h following 24 g-cm spinal cord trauma in the rat. The role of thromboxane was investigated with an inhibitor of thromboxane synthesis (Dazoxiben) and with a receptor antagonist (13-APT). Cardiac output and blood pressure were unaffected by Dazoxiben, 13-APT, or spinal cord trauma. Injury effected approximately a 40% decrease in spinal cord perfusion from 0.41 to 0.25 ml/min/g which was not improved by the thromboxane synthase inhibitor, Dazoxiben. 13-ATP completely abrogated the decline in spinal cord blood flow flowing injury. Perfusion of other selected organs demonstrated little change as a result of the spinal trauma. Brain flow remained constant at 0.78 ml/min/g brain. Coronary blood flow, however, declined from 3.2 to 2.0 ml/min/g heart tissue. The data suggest consideration of the importance of thromboxane in therapeutic attempts to reduce secondary injury arising in spinal cord trauma. PMID:1386102

  15. Spinal cord effects of antipyretic analgesics.

    PubMed

    Brune, K

    1994-01-01

    Tissue damage results in the release of inflammatory mediators, including prostaglandins, which sensitive fine nerve endings in the periphery to mechanical and thermal changes. Sensitisation of these nerve endings, or nociceptors, contributes to the phenomenon of hyperalgesia, which routinely accompanies tissue damage. It has been shown that the acidic antipyretic analgesics reduce or down-regulate the enhanced nociceptor sensitivity in damaged tissue, an effect probably attributable to inhibition of prostaglandin synthesis. Recent studies suggest that these drugs may have an additional mechanism of action in the spinal cord or higher centres. When enantiomers of flurbiprofen were used in the rat, it was shown that S- and R-flurbiprofen exert differential antinociceptive effects. The R-enantiomer, which is practically devoid of peripheral cyclo-oxygenase inhibitory activity in vitro, showed comparable analgesic potency to the S-enantiomer, which does inhibit cyclo-oxygenase activity, in experimental models of nociception. It is possible that the antinociceptive action of the R-enantiomer is related to a reduction in prostaglandin synthesis in the CNS rather than at the site of tissue damage, although other mechanisms may also contribute to its antinociceptive action. In contrast to earlier indications, it would appear that a significant part of the antinociceptive action of the antipyretic analgesics is exerted in the spinal cord. The observed accumulation of acidic antipyretic analgesics in inflamed tissue may account for the superior anti-inflammatory activity of these latter compounds.

  16. The effect of animal movement on line transect estimates of abundance.

    PubMed

    Glennie, Richard; Buckland, Stephen T; Thomas, Len

    2015-01-01

    Line transect sampling is a distance sampling method for estimating the abundance of wild animal populations. One key assumption of this method is that all animals are detected at their initial location. Animal movement independent of the transect and observer can thus cause substantial bias. We present an analytic expression for this bias when detection within the transect is certain (strip transect sampling) and use simulation to quantify bias when detection falls off with distance from the line (line transect sampling). We also explore the non-linear relationship between bias, detection, and animal movement by varying detectability and movement type. We consider animals that move in randomly orientated straight lines, which provides an upper bound on bias, and animals that are constrained to a home range of random radius. We find that bias is reduced when animal movement is constrained, and bias is considerably smaller in line transect sampling than strip transect sampling provided that mean animal speed is less than observer speed. By contrast, when mean animal speed exceeds observer speed the bias in line transect sampling becomes comparable with, and may exceed, that of strip transect sampling. Bias from independent animal movement is reduced by the observer searching further perpendicular to the transect, searching a shorter distance ahead and by ignoring animals that may overtake the observer from behind. However, when animals move in response to the observer, the standard practice of searching further ahead should continue as the bias from responsive movement is often greater than that from independent movement.

  17. Histopathological Effects of Tissue Adhesives on Experimental Peripheral Nerve Transection Model in Rats

    PubMed Central

    Çıralık, Harun

    2015-01-01

    Objective Our aim was to evaluate the histopathological effects of tissue adhesives on peripheral nerve regeneration after experimental sciatic nerve transection in rats and to search whether these tissue adhesives may possess a therapeutic potential in peripheral nerve injuries. Methods This experimental study was performed using 42 female Wistar-Albino rats distributed in 6 groups subsequent to transection of right sciatic nerves. Group I underwent external circumferential neurolysis; Group II received suture repair; Group III had local polymeric hydrogel based tissue adhesive administration; Group IV received suture repair and polymeric hydrogel based tissue adhesive application together; Group V had gelatin based tissue adhesive application and Group VI had suture repair and gelatin based tissue adhesive together. After a 6-week follow-up period, biopsies were obtained from site of neural injury and groups were compared with respect to histopathological scoring based on inflammatory, degenerative, necrotic and fibrotic changes. Results There were remarkable differences between control group and study groups with respect to inflammation (p=0.001), degeneration (p=0.002), necrosis (p=0.007), fibrosis (p<0.001) and vascularity (p=0.001). Histopathological scores were similar between study groups and the only noteworthy difference was that Group V displayed a lower score for necrosis and higher score in terms of vascularization. Conclusion Our results imply that tissue adhesives can be useful in repair of peripheral nerve injuries by decreasing the surgical trauma and shortening the duration of intervention. Results with gelatin based tissue adhesive are especially promising since more intense vascularity was observed in tissue after application. However, trials on larger series with longer durations of follow-up are essential for reaching more reliable conclusions. PMID:26819683

  18. Curcumin protects against ischemic spinal cord injury: The pathway effect

    PubMed Central

    Zhang, Jinhua; Wei, Hao; Lin, Meimei; Chen, Chunmei; Wang, Chunhua; Liu, Maobai

    2013-01-01

    Inducible nitric oxide synthase and N-methyl-D-aspartate receptors have been shown to participate in nerve cell injury during spinal cord ischemia. This study observed a protective effect of curcumin on ischemic spinal cord injury. Models of spinal cord ischemia were established by ligating the lumbar artery from the left renal artery to the bifurcation of the abdominal aorta. At 24 hours after model establishment, the rats were intraperitoneally injected with curcumin. Reverse transcription-polymerase chain reaction and immunohistochemical results demonstrated that after spinal cord ischemia, inducible nitric oxide synthase and N-methyl-D-aspartate receptor mRNA and protein expression significantly increased. However, curcumin significantly decreased inducible nitric oxide synthase and N-methyl-D-aspartate receptor mRNA and protein expression in the ischemic spinal cord. Tarlov scale results showed that curcumin significantly improved motor function of the rat hind limb after spinal cord ischemia. The results demonstrate that curcumin exerts a neuroprotective fect against ischemic spinal cord injury by decreasing inducible nitric oxide synthase and N-methyl-D-aspartate receptor expression. PMID:25206661

  19. Effect of lycopene on the blood-spinal cord barrier after spinal cord injury in mice.

    PubMed

    Zhang, Qian; Wang, Jianbo; Gu, Zhengsong; Zhang, Qing; Zheng, Hong

    2016-09-01

    The current study aimed to investigate the effect of lycopene on the blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) in a mouse model. Lycopene inhibited lipid peroxidation and oxidative DNA damage as a highly efficient antioxidant and free radical scavenger. Lycopene (4 mg/kg/d) was administrated immediately following SCI. The permeability of the BSCB and water content in the spinal cord tissue were evaluated. Additionally, levels of expression of tight junction proteins and heme oxygenase-1 (HO-1) were determined with Western blotting. An enzyme-linked immunosorbent assay analysis of spinal cord tissue homogenates was performed 48 h after SCI to evaluate the expression of inflammation-related cytokines. In addition, recovery of motor function was assessed 1 d, 2 d, 5 d, 10 d, and 15 d after SCI using the Basso Mouse Scale to score locomotion. Compared to the group with an untreated SCI, mice with an SCI treated with lycopene had significantly reduced spinal cord tissue water content and BSCB permeability. Furthermore, motor function of mice with an SCI was also greatly improved by lycopene administration. The expression of the proinflammatory factors TNF-α and NF-kB increased markedly 48 h after SCI, and their upregulation was significantly attenuated by lycopene treatment. The expression of molecules that protect tight junctions, zonula occluden-1 and claudin-5, was upregulated by lycopene treatment after SCI. Taken together, these results clearly indicate that lycopene attenuated SCI by promoting repair of the damaged BSCB, so lycopene is a novel and promising treatment for SCI in humans. PMID:27357536

  20. Effect of nimodipine on rat spinal cord injury.

    PubMed

    Jia, Y-F; Gao, H-L; Ma, L-J; Li, J

    2015-02-13

    We evaluated the potentially protective effect of nimodipine on rat spinal cord injury. Sprague-Dawley rats received spinal cord injury, and were separated into nimodipine (N = 12) and saline groups (N = 12). Within 1 h of the injury, rats were treated intraperitoneally with nimodipine (1.0 mg/kg) or an equal amount of saline. Treatment was performed 3 times a day for 1 week. Operation BBB score and track experiment were used to measure the physical function of the hind legs 1 and 2 weeks after injury. Two weeks after the injury, malondialdehyde (MDA) content and spinal cord myeloperoxidase (MPO) activity of the injured part were determined, and the glial scar and dead room were studied using the immune tissue chemical test. ED1 was used to observe active gitter cell and macrophages. The physical function of the nimodipine group improved significantly (P < 0.01). Two weeks after injury, spinal cord MDA content in the spinal cord in the nimodipine group (nmol/g, 25.6 ± 9.7 vs 68.5 ± 16.7) and MPO activity (U/g, 252.2 ± 63.9 vs 382.8 ± 108.2) decreased significantly (P < 0.01); nimodipine whole dead space (mm2, 4.45 ± 1.28 vs 6.16 ± 2.65) and ED1 antibody immunity colored positive room (mm2, 1.87 ± 0.42 vs 2.86 ± 1.01) reduced significantly (P < 0.01). Nimodipine treatment could reduce oxidative injury after spinal cord injury, reduce the whole dead space and inflammation, and repair spinal cord injury.

  1. Effect of cord blood processing on transplantation outcomes after single myeloablative umbilical cord blood transplantation.

    PubMed

    Ballen, Karen K; Logan, Brent R; Laughlin, Mary J; He, Wensheng; Ambruso, Daniel R; Armitage, Susan E; Beddard, Rachel L; Bhatla, Deepika; Hwang, William Y K; Kiss, Joseph E; Koegler, Gesine; Kurtzberg, Joanne; Nagler, Arnon; Oh, David; Petz, Lawrence D; Price, Thomas H; Quinones, Ralph R; Ratanatharathorn, Voravit; Rizzo, J Douglas; Sazama, Kathleen; Scaradavou, Andromachi; Schuster, Michael W; Sender, Leonard S; Shpall, Elizabeth J; Spellman, Stephen R; Sutton, Millicent; Weitekamp, Lee Ann; Wingard, John R; Eapen, Mary

    2015-04-01

    Variations in cord blood manufacturing and administration are common, and the optimal practice is not known. We compared processing and banking practices at 16 public cord blood banks (CBB) in the United States and assessed transplantation outcomes on 530 single umbilical cord blood (UCB) myeloablative transplantations for hematologic malignancies facilitated by these banks. UCB banking practices were separated into 3 mutually exclusive groups based on whether processing was automated or manual, units were plasma and red blood cell reduced, or buffy coat production method or plasma reduced. Compared with the automated processing system for units, the day 28 neutrophil recovery was significantly lower after transplantation of units that were manually processed and plasma reduced (red cell replete) (odds ratio, .19; P = .001) or plasma and red cell reduced (odds ratio, .54; P = .05). Day 100 survival did not differ by CBB. However, day 100 survival was better with units that were thawed with the dextran-albumin wash method compared with the "no wash" or "dilution only" techniques (odds ratio, 1.82; P = .04). In conclusion, CBB processing has no significant effect on early (day 100) survival despite differences in kinetics of neutrophil recovery. PMID:25543094

  2. Effect of Cord Blood Processing on Transplant Outcomes after Single Myeloablative Umbilical Cord Blood Transplantation

    PubMed Central

    Ballen, Karen K.; Logan, Brent R.; Laughlin, Mary J.; He, Wensheng; Ambruso, Daniel R.; Armitage, Susan E.; Beddard, Rachel L.; Bhatla, Deepika; Hwang, William Y.K.; Kiss, Joseph E.; Koegler, Gesine; Kurtzberg, Joanne; Nagler, Arnon; Oh, David; Petz, Lawrence D.; Price, Thomas H.; Quinones, Ralph R.; Ratanatharathorn, Voravit; Rizzo, J. Douglas; Sazama, Kathleen; Scaradavou, Andromachi; Schuster, Michael W.; Sender, Leonard S.; Shpall, Elizabeth J.; Spellman, Stephen R.; Sutton, Millicent; Weitekamp, Lee Ann; Wingard, John R.; Eapen, Mary

    2015-01-01

    Variations in cord blood manufacturing and administration are common, and the optimal practice, not known. We compared processing and banking practices at 16 public cord blood banks (CBB) in the United States, and assessed transplant outcomes on 530 single umbilical cord blood (UCB) myeloablative transplantations for hematologic malignancies, facilitated by these banks. UCB banking practices were separated into three mutually exclusive groups based on whether processing was automated or manual; units were plasma and red blood cell reduced or buffy coat production method or plasma reduced. Compared to the automated processing system for units, the day-28 neutrophil recovery was significantly lower after transplantation of units that were manually processed and plasma reduced (red cell replete) (odds ratio [OR] 0.19 p=0.001) or plasma and red cell reduced (OR 0.54, p=0.05). Day-100 survival did not differ by CBB. However, day-100 survival was better with units that were thawed with the dextran-albumin wash method compared to the “no wash” or “dilution only” techniques (OR 1.82, p=0.04). In conclusion, CBB processing has no significant effect on early (day 100) survival despite differences in kinetics of neutrophil recovery. PMID:25543094

  3. Effects of pituitary stalk transection on endocrine function in Pony mares.

    PubMed

    Sharp, D C; Grubaugh, W; Berglund, L A; McDowell, K J; Kilmer, D M; Peck, L S; Seamans, K W; Chen, C L

    1982-01-01

    The pituitary stalk was transected in 10 Pony mares by a surgical approach that involved dorsal reflection of the brain and micro-dissection from the ventro-lateral aspect of the pituitary. Diabetes insipidus was the most immediate and marked result, requiring extensive electrolyte and antidiuretic therapy for approximately 48 h after operation. Fluid stasis then developed and no further supportive measures were necessary. Endocrine challenge tests with GnRH and TRH before and after stalk transection indicated a loss of responsiveness (GnRH) or suppressed responsiveness (TRH) after the operation. This technique permits isolation of the pituitary from its hypothalmic releasing and/or inhibiting hormones and therefore permits more refined study of the hypothalamic-pituitary axis.

  4. [Effect of freezing on cord blood serum proteins].

    PubMed

    Nardid, E O; Rozanova, E D; Tsymbal, L V; Zinchenko, A V; Nardid, O A; Grishchenko, V I

    2009-01-01

    The effect of freezing regimes and storage temperatures on protein conformation and the spectrum of cord blood serum has been investigated. Changes in the parameters of ESR spectra of spin probes in cord blood serum after slow freezing and subsequent thawing were established, indicating protein conformational changes characterized by loosening. This fact is confirmed by an earlier process, the first stage of albumin heat denaturation, as indicated by calorimetric data. It was shown that slow cooling results in the aggregation of serum protein in which serum albumin and immunoglobulins play an important role. It was concluded that, for retaining the properties, of cord blood serum proteins, it is preferable to perform cooling at a rate not lower than 100 degrees C/min and a storage temperature of -80 degrees C and lower. PMID:19894629

  5. 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

  6. Competition effects in the dynamics of tumor cords

    NASA Astrophysics Data System (ADS)

    Scalerandi, M.; Sansone, B. Capogrosso; Benati, C.; Condat, C. A.

    2002-05-01

    A general feature of cancer growth is the cellular competition for available nutrients. This is also the case for tumor cords, neoplasms forming cylindrical structures around blood vessels. Experimental data show that, in their avascular phase, cords grow up to a limit radius of about 100 μm, reaching a quasi-steady-state characterized by a necrotized area separating the tumor from the surrounding healthy tissue. Here we use a set of rules to formulate a model that describes how the dynamics of cord growth is controlled by the competition of tumor cells among themselves and with healthy cells for the acquisition of essential nutrients. The model takes into account the mechanical effects resulting from the interaction between the multiplying cancer cells and the surrounding tissue. We explore the influence of the relevant parameters on the tumor growth and on its final state. The model is also applied to investigate cord deformation in a region containing multiple nutrient sources and to predict the further complex growth of the tumor.

  7. Effects of gustatory nerve transection and/or ovariectomy on oral capsaicin avoidance in rats.

    PubMed

    Boucher, Yves; Simons, Christopher T; Carstens, Mirela Iodi; Carstens, E

    2014-04-01

    The incidence of chronic oral pain such as burning mouth syndrome is greater in peri-menopausal females, and was postulated to be associated with gustatory nerve damage. We investigated whether bilateral transection of the chorda tympani, with or without accompanying ovariectomy, affected oral capsaicin avoidance in rats. Female rats had restricted access to 2 bottles, 1 bottle containing capsaicin (concentration range: 0.33-33 μM/L) and the other vehicle. Percent volume of capsaicin consumption and lick counts were measured. The concentration series was tested before and 0.5, 3, 6, 9, and 12 months after the following surgical procedures: (a) bilateral transection of the chorda tympani (CTx); (b) ovariectomy (OVx); (3) CTx plus OVx; or (4) sham CT surgery. Before surgery there was a concentration-dependent decrease in licks and volume of capsaicin consumed, with a threshold between 0.1 and 0.3 ppm. The majority of drink licks occurred during the first 9 minutes of access. Over the 12-month test period, the CTx group did not exhibit reduced capsaicin consumption, and consumed significantly more capsaicin at 6 and 9 months postsurgery. Rats in the OVx group consistently consumed significantly less capsaicin and exhibited significantly higher counts of capsaicin-evoked Fos-like immunoreactivity in the dorsomedial trigeminal subnucleus caudalis (Vc) compared to all other treatment groups. That CTx, with or without OVx, did not enhance capsaicin avoidance indicates that damage to the gustatory system does not disinhibit trigeminal nociceptive transmission.

  8. Effects of spinal cord stimulation on the flexor reflex and involvement of supraspinal mechanisms: an experimental study in mononeuropathic rats.

    PubMed

    Ren, B; Linderoth, B; Meyerson, B A

    1996-02-01

    The physiological mechanisms responsible for pain relief caused by spinal cord stimulation (SCS) are essentially unknown and recent experimental data are sparse. In the present study the authors explored the possible involvement of supraspinal mechanisms in the effects of SCS applied in rats with experimental mononeuropathy produced by sciatic nerve ligation according to the method of Bennett and Xie or that of Seltzer, et al. Confirming results of a previous study undertaken by the authors, the thresholds of the early component of the flexor reflex (latency 8-12 msec), which is mediated by A fibers, were significantly lower in the nerve-ligated than in the intact leg. In halothane-anesthetized animals the spinal cord was exposed and SCS was applied with parameters similar to those used in clinical SCS. Ten minutes of SCS produced a significant elevation of the lowered threshold of the early flexor component only in the nerve-ligated leg, and this augmentatory effect of SCS persisted for 30 to 40 minutes after cessation of the stimulation. The threshold elevation amounted to between 50% and 80% of the prestimulatory value and it was related to the intensity of SCS. The threshold of the late, C-fiber-mediated component of the flexor reflex was not influenced in either of the legs. After transection of the spinal cord at the T-6 level, there was a moderate threshold increase in both the early and late components in both legs, but the threshold of the early component in the nerve-ligated leg remained lower. Spinal cord stimulation produced an almost identical threshold increase in the early component in the nerve-ligated leg with the same time course as before the transection. There was no effect on the late component of the reflex in either leg. The results indicate that this effect of SCS in mononeuropathic rats does not necessarily involve supraspinal mechanisms; instead SCS is operative at a spinal, segmental level. In view of the similarities between the effects

  9. Neuroprotective Effects of Perflurocarbon (Oxycyte) after Contusive Spinal Cord Injury

    PubMed Central

    Yacoub, Adly; Hajec, Marygrace C.; Stanger, Richard; Wan, Wen; Young, Harold

    2014-01-01

    Abstract Spinal cord injury (SCI) often results in irreversible and permanent neurological deficits and long-term disability. Vasospasm, hemorrhage, and loss of microvessels create an ischemic environment at the site of contusive or compressive SCI and initiate the secondary injury cascades leading to progressive tissue damage and severely decreased functional outcome. Although the initial mechanical destructive events cannot be reversed, secondary injury damage occurs over several hours to weeks, a time frame during which therapeutic intervention could be achieved. One essential component of secondary injury cascade is the reduction in spinal cord blood flow with resultant decrease in oxygen delivery. Our group has recently shown that administration of fluorocarbon (Oxycyte) significantly increased parenchymal tissue oxygen levels during the usual postinjury hypoxic phase, and fluorocarbon has been shown to be effective in stroke and head injury. In the current study, we assessed the beneficial effects of Oxycyte after a moderate-to-severe contusion SCI was simulated in adult Long-Evans hooded rats. Histopathology and immunohistochemical analysis showed that the administration of 5 mL/kg of Oxycyte perfluorocarbon (60% emulsion) after SCI dramatically reduced destruction of spinal cord anatomy and resulted in a marked decrease of lesion area, less cell death, and greater white matter sparing at 7 and 42 days postinjury. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining showed a significant reduced number of apoptotic cells in Oxycyte-treated animals, compared to the saline group. Collectively, these results demonstrate the potential neuroprotective effect of Oxycyte treatment after SCI, and its beneficial effects may be, in part, a result of reducing apoptotic cell death and tissue sparing. Further studies to determine the most efficacious Oxycyte dose and its mechanisms of protection are warranted. PMID:24025081

  10. Neuroprotective effects of human spinal cord-derived neural precursor cells after transplantation to the injured spinal cord.

    PubMed

    Emgård, Mia; Piao, Jinghua; Aineskog, Helena; Liu, Jia; Calzarossa, Cinzia; Odeberg, Jenny; Holmberg, Lena; Samuelsson, Eva-Britt; Bezubik, Bartosz; Vincent, Per Henrik; Falci, Scott P; Seiger, Åke; Åkesson, Elisabet; Sundström, Erik

    2014-03-01

    To validate human neural precursor cells (NPCs) as potential donor cells for transplantation therapy after spinal cord injury (SCI), we investigated the effect of NPCs, transplanted as neurospheres, in two different rat SCI models. Human spinal cord-derived NPCs (SC-NPCs) transplanted 9 days after spinal contusion injury enhanced hindlimb recovery, assessed by the BBB locomotor test. In spinal compression injuries, SC-NPCs transplanted immediately or after 1 week, but not 7 weeks after injury, significantly improved hindlimb recovery compared to controls. We could not detect signs of mechanical allodynia in transplanted rats. Four months after transplantation, we found more human cells in the host spinal cord than were transplanted, irrespective of the time of transplantation. There was no focal tumor growth. In all groups the vast majority of NPCs differentiated into astrocytes. Importantly, the number of surviving rat spinal cord neurons was highest in groups transplanted acutely and subacutely, which also showed the best hindlimb function. This suggests that transplanted SC-NPCs improve the functional outcome by a neuroprotective effect. We conclude that SC-NPCs reliably enhance the functional outcome after SCI if transplanted acutely or subacutely, without causing allodynia. This therapeutic effect is mainly the consequence of a neuroprotective effect of the SC-NPCs.

  11. Effects of different elastic cord assistance levels on vertical jump.

    PubMed

    Tran, Tai T; Brown, Lee E; Coburn, Jared W; Lynn, Scott K; Dabbs, Nicole C; Schick, Monica K; Schick, Evan E; Khamoui, Andy V; Uribe, Brandon P; Noffal, Guillermo J

    2011-12-01

    Tran, TT, Brown, LE, Coburn, JW, Lynn, SK, Dabbs, NC, Schick, MK, Schick, EE, Khamoui, AV, Uribe, BP, and Noffal, GJ. Effects of different elastic cord assistance levels on vertical jump. J Strength Cond Res 25(12): 3472-3478, 2011-Currently, little research has been conducted using body weight reduction (BWR) as a means to enhance vertical jump. The purpose of this study was to determine the effects of different elastic cord assistance levels on vertical jump height (JH), takeoff velocity (TOV), relative ground reaction force (rGRF), relative impact force (RIF), and descent velocity (DV). Thirty recreationally trained college men and women (M = 15, W = 15) completed 3 testing sessions consisting of 5 conditions: 0, 10, 20, 30, and 40% BWR. In all BWR conditions, the subjects wore a full body harness while being attached to 2 elastic cords suspended from the ceiling and a linear velocity transducer. They then performed 3 maximal countermovement jumps with arm swing on a force plate. The results indicated no interaction of condition by sex for any variable; however, there was a significant (p < 0.05) main effect for condition for each variable. The JH significantly increased across all conditions (0%: 43.73 ± 1.62 cm, 40%: 64.77 ± 2.36 cm). The TOV at 30% (2.73 ± 0.34 m·s) was significantly greater than that at 0% (2.59 ± 0.39 m·s) and 10% (2.63 ± 0.34 m·s), whereas that at 40% (2.79 ± 0.43 m·s) was significantly greater than that at >0, 10, and 20%. The rGRF at 30% (18.62 ± 4.35 N·kg) was significantly greater than that at >0, 10, and 20%, whereas that at 40% (21.38 ± 5.21 N·kg) was significantly greater than in all conditions. The RIF at 20, 30, and 40% (40%: 61.60 ± 18.53 N·kg) was significantly greater than that at 0% (44.46 ± 9.12 N·kg). The DV at 20% (2.61 ± 0.31 m·s) was significantly greater than at 10%, whereas those at 30 and 40% (2.8 ± 0.41 m·s) were significantly greater than at 0, 10, and 20%. These results demonstrate that using

  12. Timing of umbilical cord clamping: effect on iron endowment of the newborn and later iron status.

    PubMed

    Chaparro, Camila M

    2011-11-01

    The optimal timing of umbilical cord clamping has been debated in the scientific literature for at least the last century, when cord clamping practices shifted from delayed towards immediate clamping. Recent research provides evidence for the beneficial effect of delayed cord clamping on infant iron status. The present review describes the physiological basis for the impact of cord clamping time on total body iron at birth and the relationship between birth body iron, as affected by cord clamping time, and iron status later in infancy. This research is discussed in the context of current clamping practices, which tend towards early cord clamping in most settings, as well as the high levels of anemia present in young infants in many countries worldwide.

  13. Effect of Anterior Zonule Transection on the Change in Lens Diameter and Power in Cynomolgus Monkeys during Simulated Accommodation

    PubMed Central

    Nankivil, Derek; Manns, Fabrice; Arrieta-Quintero, Esdras; Ziebarth, Noel; Borja, David; Amelinckx, Adriana; Bernal, Andres; Ho, Arthur; Parel, Jean-Marie

    2009-01-01

    Purpose To quantify the role of anterior zonular tension on the optomechanical lens response during simulation of accommodation in primates. Methods Postmortem cynomolgus monkey eyes (n = 14; age range, 3.0 –11.5 years) were dissected leaving intact the lens, zonules, ciliary body, hyaloid membrane, anterior vitreous, and a scleral rim. The lens was mounted in a lens-stretching system and stretched radially in step-wise fashion. The load, and the lens diameter and power were measured at each step and the diameter- and power-load relationships were quantified. The anterior zonular fibers were then transected, and the experiment was repeated. The equatorial lens diameter and lens optical power before and after zonular transection were compared. Results Stretching increased the lens diameter by 0.25 ± 0.09 mm (median ± interquartile range) before and 0.25 ± 0.19 mm after zonular transection. Stretching decreased the lens power by 13.0 ± 6.5 D before and 10.6 ± 8.0 D after zonular transection. The load required to change the diameter of the lens by 1 mm decreased from 18.8 ± 10.7 g before to 15.0 ± 7.8 g after zonular transection. The absolute change in power per gram of loading decreased from 2.5 ± 1.1 before to 2.0 ± 1.2 D after zonular transection. Conclusions The cynomolgus monkey lens retains a significant fraction of its accommodative ability after transection of the anterior zonules in simulated accommodation experiments. PMID:19324840

  14. Some behavioral effects of transecting ventral or dorsal fiber connections of the septum in the rat.

    PubMed

    Ross, J F; Grossman, L; Grossman, S P

    1975-03-01

    The behavioral effects of large electrolytic lesions in the septal area were compared with those of knife cuts that severed the ventral or dorsal connections of this structure. Rats with septal lesions lost weight and were transiently hyperdipsic. Ventral cuts produced similar effects, but dorsal cuts did not. All three operations decreased the latency to eat in a novel environment, increased the intake of sweetened milk, enhanced acquisition of a food-rewarded running response, and facilitated acquisition of a shuttle box avoidance response, The lesion, but neither of the knife cuts, reduced the effects of punishment and impaired the acquisition of a one-way avoidance response. PMID:1150960

  15. Effect of Aspirin on Spinal Cord Injury: An Experimental Study.

    PubMed

    Kermani, Hamed Reihani; Nakhaee, Nouzar; Fatahian, Reza; Najar, Ahmad Gholamhosseinian

    2016-05-01

    Aspirin is an anti-inflammatory drug, peroxyl radical scavenger, and antioxidant agent that inhibits phospholipases, nitric oxide synthetases, and cyclooxygenase enzymes. The existing literature contains no studies on the effects of various doses of aspirin on spinal cord injury (SCI). Therefore, we sought to investigate the putative effects of aspirin on experimental SCI. The weight-drop injury model was used to produce SCI in 100 albino Wistar rats. The animals were allocated to five groups: a control group, where the rats did not undergo any surgical or medical intervention except for anesthesia; a sham-treated group, where laminectomy was performed without SCI and no further therapy was administered; and three other groups, where the rats with SCI received low-dose aspirin [20 mg/kg], high-dose aspirin [80 mg/kg], and a vehicle, respectively. Half of the rats were sacrificed 24 hours later, and their spinal cords were excised for biochemical studies. The other rats were subjected to Basso, Beattie, and Bresnahan (BBB) locomotor rating scale scoring once a week for 6 consecutive weeks. Aspirin decreased lipid peroxidation following SCI as the mean (± standard error) catalase level was significantly higher in the high-dose aspirin group (46.10±12.01) than in the sham-treated group (16.07±2.42) and the vehicle-treated group (15.31±3.20) (P<0.05; P<0.05, respectively). Both of the groups treated with high-dose and low-dose aspirin demonstrated a higher mean BBB score than did the control group (P<0.001) and the sham-treated group (P<0.001). Our data provide evidence in support of the potential effects of aspirin in biochemical and neurobehavioral recovery after SCI. PMID:27217606

  16. Effect of Aspirin on Spinal Cord Injury: An Experimental Study

    PubMed Central

    Kermani, Hamed Reihani; Nakhaee, Nouzar; Fatahian, Reza; Najar, Ahmad Gholamhosseinian

    2016-01-01

    Aspirin is an anti-inflammatory drug, peroxyl radical scavenger, and antioxidant agent that inhibits phospholipases, nitric oxide synthetases, and cyclooxygenase enzymes. The existing literature contains no studies on the effects of various doses of aspirin on spinal cord injury (SCI). Therefore, we sought to investigate the putative effects of aspirin on experimental SCI. The weight-drop injury model was used to produce SCI in 100 albino Wistar rats. The animals were allocated to five groups: a control group, where the rats did not undergo any surgical or medical intervention except for anesthesia; a sham-treated group, where laminectomy was performed without SCI and no further therapy was administered; and three other groups, where the rats with SCI received low-dose aspirin [20 mg/kg], high-dose aspirin [80 mg/kg], and a vehicle, respectively. Half of the rats were sacrificed 24 hours later, and their spinal cords were excised for biochemical studies. The other rats were subjected to Basso, Beattie, and Bresnahan (BBB) locomotor rating scale scoring once a week for 6 consecutive weeks. Aspirin decreased lipid peroxidation following SCI as the mean (± standard error) catalase level was significantly higher in the high-dose aspirin group (46.10±12.01) than in the sham-treated group (16.07±2.42) and the vehicle-treated group (15.31±3.20) (P<0.05; P<0.05, respectively). Both of the groups treated with high-dose and low-dose aspirin demonstrated a higher mean BBB score than did the control group (P<0.001) and the sham-treated group (P<0.001). Our data provide evidence in support of the potential effects of aspirin in biochemical and neurobehavioral recovery after SCI. PMID:27217606

  17. The relative effects of transection of the gustatory branches of the seventh and ninth cranial nerves on NaCl taste detection in rats.

    PubMed

    Blonde, Ginger D; Garcea, Mircea; Spector, Alan C

    2006-06-01

    Chorda tympani nerve (CT) transection in rats severely impairs NaCl taste detection. These rats can detect higher concentrations of NaCl, however, suggesting that remaining oral nerves maintain some salt sensibility. Rats were tested in a gustometer with a 2-response operant taste-detection task before and after sham surgery (n = 5), combined transection of the CT and the greater superficial petrosal nerves (GSP; 7x, n = 6), or transection of the glossopharyngeal nerve (GL; 9x, n = 4). Thresholds did not significantly change after sham surgery. Although the GL responds to NaCl and innervates nearly 60% of total taste buds, 9x surgery had no effect. However, 7x surgery increased NaCl detection threshold by approximately 2.5 log(10) units, greater than that reported for CT transection alone. These results suggest that the GSP contributes to NaCl sensitivity in rats and also demonstrate that the GL and perhaps the superior laryngeal and lingual nerve proper can maintain some NaCl detectability at high concentrations. These findings confirm the primacy of the 7th nerve relative to the 9th nerve in sensibility of NaCl in the rat model.

  18. Abiotic effects on effluent dissolved organic nitrogen along an estuarine transect.

    PubMed

    Funkey, Carolina P; Latour, Robert J; Bronk, Deborah A

    2015-03-01

    Biological nutrient removal is a process commonly used in water resource recovery facilities to reduce dissolved inorganic nitrogen (DIN) concentrations in effluent; this process is less effective at removing all of the effluent dissolved organic nitrogen (EDON). The goal of this study was to investigate the fate of EDON after it undergoes the disinfection process and enters receiving waters. The authors quantified the abiotic effects of effluent exposure to sunlight, increased salinity, and a combination of the two factors. Effluent dissolved organic nitrogen showed significant breakdown during the disinfection process (UV and chlorine) and when exposed to sunlight and increasing salinity. Approximately 7% of the EDON was transformed to DIN and dissolved primary amines after exposure to 9 hours of sunlight and a salinity increase from 0 to 33. The production of DIN and primary amines should be taken into account when considering sources of labile nitrogen to aquatic ecosystems.

  19. 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). 1. 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.

  20. The effects of transection of the anterior cruciate ligament on healing of the medial collateral ligament. A biomechanical study of the knee in dogs.

    PubMed

    Woo, S L; Young, E P; Ohland, K J; Marcin, J P; Horibe, S; Lin, H C

    1990-03-01

    The effect of concurrent injury to the anterior cruciate ligament on the healing of injuries of the medial collateral ligament was studied in dogs. In Group I, isolated transection of the medial collateral ligament was performed; in Group II, transection of the medial collateral ligament with partial transection of the anterior cruciate ligament; and in Group III, complete transection of both the medial collateral ligament and the anterior cruciate ligament. The three groups of animals were examined six and twelve weeks postoperatively with respect to varus-valgus rotation of the knee and tensile properties of the femur-medial collateral ligament-tibia complex. The varus-valgus rotation of the knee was found to be the largest in Group-III specimens at all time-periods and was 3.5 times greater than the control values at twelve weeks. Group-I and Group-II specimens also showed large varus-valgus rotations at time zero, but the rotations returned to the control values by twelve weeks. For the structural properties of the femur-medial collateral ligament-tibia complex, the values for ultimate load for Groups I and II reached the control values by twelve weeks, while that for Group III remained at only 80 per cent of the control value. Both energy absorbed at failure and linear stiffness for all three groups were less than those for the controls at six weeks, and only linear stiffness returned to the control values by twelve weeks. For the mechanical (material) properties of the healed ligament substance, the values for modulus and tensile strength were markedly lower than the control values for all groups at six weeks. By twelve weeks, the tensile strength of Group-I specimens had increased to 52 per cent of the control value, while those of Groups II and III were only 45 and 14 per cent, respectively. Our results demonstrate that healing of the transected medial collateral ligament is adversely affected by concomitant transection of the anterior cruciate ligament

  1. Equal effects of typical environmental and specific social enrichment on posttraumatic cognitive functioning after fimbria-fornix transection in rats.

    PubMed

    Gajhede Gram, Marie; Gade, Louise; Wogensen, Elise; Mogensen, Jesper; Malá, Hana

    2015-12-10

    Enriched environment (EE) has been shown to have beneficial effects on cognitive recovery after brain injury. Typical EE comprises three components: (i) enlarged living area providing physical activation, (ii) sensory stimulation, and (iii) social stimulation. The present study assessed the specific contribution of the social stimulation. Animals were randomly divided into groups of (1) a typical EE, (2) pure social enrichment (SE), or (3) standard housing (SH) and subjected to either a sham operation or transection of the fimbria-fornix (FF). The effect of these conditions on acquisition of a delayed alternation task in a T-maze was assessed. The sham control groups were not affected by housing conditions. In the lesioned groups, both typical EE and SE improved the task acquisition, compared to SH. A baseline one-hour activity measurement confirmed an equal level of physical activity in the EE and SE groups. After delayed alternation testing, pharmacological challenges (muscarinergic antagonist scopolamine and dopaminergic antagonist SKF-83566) were used to assess cholinergic and dopaminergic contributions to task solution. Scopolamine led to a marked impairment in all groups. SKF-83566 significantly enhanced the performance of the lesioned group subjected to SE. The results demonstrate that housing in a typical as well as atypical EE can enhance cognitive recovery after mechanical injury to the hippocampus. The scopolamine challenge revealed a cholinergic dependency during task performance in all groups, regardless of lesion and housing conditions. The dopaminergic challenge revealed a difference in the neural substrates mediating recovery in the lesioned groups exposed to different types of housing.

  2. Combined Effect of Bilateral Ovariectomy and Anterior Cruciate Ligament Transection With Medial Meniscectomy on the Development of Osteoarthritis Model

    PubMed Central

    2016-01-01

    Objective To investigate the combined effect of bilateral ovariectomy (OVX) and anterior cruciate ligament transection (ACLT) with medial meniscectomy (MM) on the development of osteoarthritis (OA). Methods Twenty female 15-week-old Sprague-Dawley rats were used. Five rats in each group underwent bilateral OVX (OVX group), bilateral ACLT with MM (ACLT with MM group), bilateral OVX plus ACLT with MM (OVX plus ACLT with MM group), and sham surgery (SHAM group). All the rats were subjected to treadmill running for 4 weeks. The behavioral evaluation for induction of OA used the number of rears method, and this was conducted at 1, 2, and 4 weeks post-surgery. Bone mineral density (BMD) was calculated with micro-computerized tomography images and the modified Mankin's scoring was used for the histological changes. Results The number of rears in the OVX plus ACLT with MM group decreased gradually and more rapidly in the ACLT with MM group. Histologically, the OVX plus ACLT with MM group had a significantly higher modified Mankin's score than the OVX group (p=0.008) and the SHAM group (p=0.008). BMDs of the OVX plus ACLT with MM group were significantly lower than the SHAM group (p=0.002), and the ACLT with MM group (p=0.003). Conclusion We found that bilateral OVX plus ACLT with MM induced definite OA change in terms of histology and BMD compared to bilateral OVX and ACLT with MM alone. Therefore, OVX and ACLT with MM was an appropriate degenerative OA rat model.

  3. Combined Effect of Bilateral Ovariectomy and Anterior Cruciate Ligament Transection With Medial Meniscectomy on the Development of Osteoarthritis Model

    PubMed Central

    2016-01-01

    Objective To investigate the combined effect of bilateral ovariectomy (OVX) and anterior cruciate ligament transection (ACLT) with medial meniscectomy (MM) on the development of osteoarthritis (OA). Methods Twenty female 15-week-old Sprague-Dawley rats were used. Five rats in each group underwent bilateral OVX (OVX group), bilateral ACLT with MM (ACLT with MM group), bilateral OVX plus ACLT with MM (OVX plus ACLT with MM group), and sham surgery (SHAM group). All the rats were subjected to treadmill running for 4 weeks. The behavioral evaluation for induction of OA used the number of rears method, and this was conducted at 1, 2, and 4 weeks post-surgery. Bone mineral density (BMD) was calculated with micro-computerized tomography images and the modified Mankin's scoring was used for the histological changes. Results The number of rears in the OVX plus ACLT with MM group decreased gradually and more rapidly in the ACLT with MM group. Histologically, the OVX plus ACLT with MM group had a significantly higher modified Mankin's score than the OVX group (p=0.008) and the SHAM group (p=0.008). BMDs of the OVX plus ACLT with MM group were significantly lower than the SHAM group (p=0.002), and the ACLT with MM group (p=0.003). Conclusion We found that bilateral OVX plus ACLT with MM induced definite OA change in terms of histology and BMD compared to bilateral OVX and ACLT with MM alone. Therefore, OVX and ACLT with MM was an appropriate degenerative OA rat model. PMID:27606264

  4. Comments on transect methodology

    SciTech Connect

    Eberhardt, L.L.

    1980-02-01

    One of the outcomes of the recent spate of attention to environmental problems is the realization that we do not have suitable methods to census non-game species. Since marking is expensive and time-consuming, investigators have tended to look for methods that involve only visual techniques. One of the leading candidates thus becomes the line transect method. The purpose here is to briefly describe some of the available transect methods, and to comment on some aspects that may be of particular interest and importance.

  5. Effective repair of traumatically injured spinal cord by nanoscale block copolymer micelles

    NASA Astrophysics Data System (ADS)

    Shi, Yunzhou; Kim, Sungwon; Huff, Terry B.; Borgens, Richard B.; Park, Kinam; Shi, Riyi; Cheng, Ji-Xin

    2010-01-01

    Spinal cord injury results in immediate disruption of neuronal membranes, followed by extensive secondary neurodegenerative processes. A key approach for repairing injured spinal cord is to seal the damaged membranes at an early stage. Here, we show that axonal membranes injured by compression can be effectively repaired using self-assembled monomethoxy poly(ethylene glycol)-poly(D,L-lactic acid) di-block copolymer micelles. Injured spinal tissue incubated with micelles (60 nm diameter) showed rapid restoration of compound action potential and reduced calcium influx into axons for micelle concentrations much lower than the concentrations of polyethylene glycol, a known sealing agent for early-stage spinal cord injury. Intravenously injected micelles effectively recovered locomotor function and reduced the volume and inflammatory response of the lesion in injured rats, without any adverse effects. Our results show that copolymer micelles can interrupt the spread of primary spinal cord injury damage with minimal toxicity.

  6. Effective repair of traumatically injured spinal cord by nanoscale block copolymer micelles.

    PubMed

    Shi, Yunzhou; Kim, Sungwon; Huff, Terry B; Borgens, Richard B; Park, Kinam; Shi, Riyi; Cheng, Ji-Xin

    2010-01-01

    Spinal cord injury results in immediate disruption of neuronal membranes, followed by extensive secondary neurodegenerative processes. A key approach for repairing injured spinal cord is to seal the damaged membranes at an early stage. Here, we show that axonal membranes injured by compression can be effectively repaired using self-assembled monomethoxy poly(ethylene glycol)-poly(d,l-lactic acid) di-block copolymer micelles. Injured spinal tissue incubated with micelles (60 nm diameter) showed rapid restoration of compound action potential and reduced calcium influx into axons for micelle concentrations much lower than the concentrations of polyethylene glycol, a known sealing agent for early-stage spinal cord injury. Intravenously injected micelles effectively recovered locomotor function and reduced the volume and inflammatory response of the lesion in injured rats, without any adverse effects. Our results show that copolymer micelles can interrupt the spread of primary spinal cord injury damage with minimal toxicity.

  7. Effect of local administration of platelet-derived growth factor B on functional recovery of peripheral nerve regeneration: A sciatic nerve transection model

    PubMed Central

    Golzadeh, Atefeh; Mohammadi, Rahim

    2016-01-01

    Background: Effects of platelet-derived growth factor B (PDGF-B) on peripheral nerve regeneration was studied using a rat sciatic nerve transection model. Materials and Methods: Forty-five male, white Wistar rats were divided into three experimental groups (n = 15), randomly: Normal control group (NC), silicon group (SIL), and PDGF-B treated group (SIL/PDGF). In NC group, left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis muscle was sutured. In the SIL group, the left sciatic nerve was exposed in the same way and transected proximal to tibio-peroneal bifurcation leaving a 10-mm gap. Proximal and distal stumps were each inserted into a silicone conduit and filled with 10 μL phosphate buffered solution. In SIL/PDGF group, the silicon conduit was filled with 10 μL PDGF-B (0.5 ng/mL). Each group was subdivided into three subgroups of five and were studied in 4, 8, 12 weeks after surgery. Results: Behavioral testing, sciatic nerve functional study, gastrocnemius muscle mass, and histomorphometric studies showed earlier regeneration of axons in SIL/PDGF than in SIL group (P < 0.05). Conclusion: Local administration of PDGF-B combined with silicon grafting could accelerate functional recovery and may have clinical implications for the surgical management of patients after facial nerve transection. PMID:27274342

  8. The Neuroprotective Effect of Syringic Acid on Spinal Cord Ischemia/Reperfusion Injury in Rats.

    PubMed

    Tokmak, Mehmet; Yuksel, Yasemin; Sehitoglu, Muserref Hilal; Guven, Mustafa; Akman, Tarik; Aras, Adem Bozkurt; Cosar, Murat; Abbed, Khalid M

    2015-10-01

    Acute arterial occlusions via different vascular pathologies are the main causes of spinal cord ischemia. We investigated neuroprotective effects of syringic acid on spinal cord ischemia injury in rats. Rats were divided into four groups: (I) sham-operated control rats, (II) spinal cord ischemia group, (III) spinal cord ischemia group performed syringic acid, and (IV) spinal cord ischemia group performed methylprednisolone intraperitoneally. 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. A significant decrease was seen in malondialdehyde levels in group III as compared to group II (P < 0.05). Besides these, nuclear respiratory factor-1 and superoxide dismutase activity of group III were significantly higher than group II (P < 0.05). In histopathological samples, when group III was compared with group II, there was a significant decrease in numbers of apoptotic neurons (P < 0.05). In immunohistochemical staining, BECN1 and caspase-3-immunopositive neurons were significantly decreased in group III compared with group II (P < 0.05). The neurological deficit scores of group III were significantly higher than group II at twenty-fourth hour of ischemia (P < 0.05). Our study revealed that syringic acid pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required for syringic acid to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.

  9. Radiation Dose-Volume Effects in the Spinal Cord

    SciTech Connect

    Kirkpatrick, John P.; Kogel, Albert J. van der; Schultheiss, Timothy E.

    2010-03-01

    Dose-volume data for myelopathy in humans treated with radiotherapy (RT) to the spine is reviewed, along with pertinent preclinical data. Using conventional fractionation of 1.8-2 Gy/fraction to the full-thickness cord, the estimated risk of myelopathy is <1% and <10% at 54 Gy and 61 Gy, respectively, with a calculated strong dependence on dose/fraction (alpha/beta = 0.87 Gy.) Reirradiation data in animals and humans suggest partial repair of RT-induced subclinical damage becoming evident about 6 months post-RT and increasing over the next 2 years. Reports of myelopathy from stereotactic radiosurgery to spinal lesions appear rare (<1%) when the maximum spinal cord dose is limited to the equivalent of 13 Gy in a single fraction or 20 Gy in three fractions. However, long-term data are insufficient to calculate a dose-volume relationship for myelopathy when the partial cord is treated with a hypofractionated regimen.

  10. Effect of melatonin on the functional recovery from experimental traumatic compression of the spinal cord

    PubMed Central

    Schiaveto-de-Souza, A.; da-Silva, C.A.; Defino, H.L.A.; Bel, E.A.Del

    2013-01-01

    Spinal cord injury is an extremely severe condition with no available effective therapies. We examined the effect of melatonin on traumatic compression of the spinal cord. Sixty male adult Wistar rats were divided into three groups: sham-operated animals and animals with 35 and 50% spinal cord compression with a polycarbonate rod spacer. Each group was divided into two subgroups, each receiving an injection of vehicle or melatonin (2.5 mg/kg, intraperitoneal) 5 min prior to and 1, 2, 3, and 4 h after injury. Functional recovery was monitored weekly by the open-field test, the Basso, Beattie and Bresnahan locomotor scale and the inclined plane test. Histological changes of the spinal cord were examined 35 days after injury. Motor scores were progressively lower as spacer size increased according to the motor scale and inclined plane test evaluation at all times of assessment. The results of the two tests were correlated. The open-field test presented similar results with a less pronounced difference between the 35 and 50% compression groups. The injured groups presented functional recovery that was more evident in the first and second weeks. Animals receiving melatonin treatment presented more pronounced functional recovery than vehicle-treated animals as measured by the motor scale or inclined plane. NADPH-d histochemistry revealed integrity of the spinal cord thoracic segment in sham-operated animals and confirmed the severity of the lesion after spinal cord narrowing. The results obtained after experimental compression of the spinal cord support the hypothesis that melatonin may be considered for use in clinical practice because of its protective effect on the secondary wave of neuronal death following the primary wave after spinal cord injury. PMID:23579633

  11. Ariel's transecting valleys

    NASA Technical Reports Server (NTRS)

    1986-01-01

    This highest-resolution Voyager 2 view of Ariel's terminator shows a complex array of transecting valleys with super-imposed impact craters. Voyager obtained this clear-filter, narrow-angle view from a distance of 130,000 kilometers (80,000 miles) and with a resolution of about 2.4 km (1.5 mi). Particularly striking to Voyager scientists is the fact that the faults that bound the linear valleys are not visible where they transect one another across the valleys. Apparently these valleys were filled with deposits sometime after they were formed by tectonic processes, leaving them flat and smooth. Sinuous rilles (trenches) later formed, probably by some flow process. Some type of fluid flow may well have been involved in their evolution. The Voyager project is managed for NASA by the Jet Propulsion Laboratory.

  12. Effect of oscillating electrical field stimulation on motor function recovery and myelin regeneration after spinal cord injury in rats.

    PubMed

    Tian, Da-Sheng; Jing, Jue-Hua; Qian, Jun; Chen, Lei; Zhu, Bin

    2016-05-01

    [Purpose] The aim of this study was to evaluate the effect of oscillating electrical field stimulation on motor function recovery and myelin regeneration in rats with spinal cord injury. [Subjects and Methods] A rat model of spinal cord injury was constructed by using the Allen weight-drop method. These rats were randomly divided into normal, spinal cord injury, and spinal cord injury + oscillating electrical field stimulation groups. The experimental group received the intervention with oscillating electrical field stimulation, and the control group received the intervention with an electrical field stimulator without oscillating electrical field stimulation. Each group was then randomly divided into seven subgroups according to observation time (1, 2, 4, 6, 8, 10, and 12 weeks). Basso-Beattie-Bresnahan score and inclined plate test score evaluation, motor evoked potential detection, and histological observation were performed. [Results] In the first 2 weeks of oscillating electrical field stimulation, the oscillating electrical field stimulation and inclined plate test scores of spinal cord injury group and spinal cord injury + oscillating electrical field stimulation group were not significantly different. In the fourth week, the scores of the spinal cord injury group were significantly lower than those of the spinal cord injury + oscillating electrical field stimulation group. The motor evoked potential incubation period in the spinal cord injury + oscillating electrical field stimulation group at the various time points was shorter than that in the spinal cord injury group. In the sixth week, the relative area of myelin in the spinal cord injury + oscillating electrical field stimulation group was evidently larger than that in the spinal cord injury group. [Conclusion] Oscillating electrical field stimulation could effectively improve spinal cord conduction function and promote motor function recovery in rats with spinal cord injury, as well as promote myelin

  13. Effect of oscillating electrical field stimulation on motor function recovery and myelin regeneration after spinal cord injury in rats.

    PubMed

    Tian, Da-Sheng; Jing, Jue-Hua; Qian, Jun; Chen, Lei; Zhu, Bin

    2016-05-01

    [Purpose] The aim of this study was to evaluate the effect of oscillating electrical field stimulation on motor function recovery and myelin regeneration in rats with spinal cord injury. [Subjects and Methods] A rat model of spinal cord injury was constructed by using the Allen weight-drop method. These rats were randomly divided into normal, spinal cord injury, and spinal cord injury + oscillating electrical field stimulation groups. The experimental group received the intervention with oscillating electrical field stimulation, and the control group received the intervention with an electrical field stimulator without oscillating electrical field stimulation. Each group was then randomly divided into seven subgroups according to observation time (1, 2, 4, 6, 8, 10, and 12 weeks). Basso-Beattie-Bresnahan score and inclined plate test score evaluation, motor evoked potential detection, and histological observation were performed. [Results] In the first 2 weeks of oscillating electrical field stimulation, the oscillating electrical field stimulation and inclined plate test scores of spinal cord injury group and spinal cord injury + oscillating electrical field stimulation group were not significantly different. In the fourth week, the scores of the spinal cord injury group were significantly lower than those of the spinal cord injury + oscillating electrical field stimulation group. The motor evoked potential incubation period in the spinal cord injury + oscillating electrical field stimulation group at the various time points was shorter than that in the spinal cord injury group. In the sixth week, the relative area of myelin in the spinal cord injury + oscillating electrical field stimulation group was evidently larger than that in the spinal cord injury group. [Conclusion] Oscillating electrical field stimulation could effectively improve spinal cord conduction function and promote motor function recovery in rats with spinal cord injury, as well as promote myelin

  14. Effect of oscillating electrical field stimulation on motor function recovery and myelin regeneration after spinal cord injury in rats

    PubMed Central

    Tian, Da-Sheng; Jing, Jue-Hua; Qian, Jun; Chen, Lei; Zhu, Bin

    2016-01-01

    [Purpose] The aim of this study was to evaluate the effect of oscillating electrical field stimulation on motor function recovery and myelin regeneration in rats with spinal cord injury. [Subjects and Methods] A rat model of spinal cord injury was constructed by using the Allen weight-drop method. These rats were randomly divided into normal, spinal cord injury, and spinal cord injury + oscillating electrical field stimulation groups. The experimental group received the intervention with oscillating electrical field stimulation, and the control group received the intervention with an electrical field stimulator without oscillating electrical field stimulation. Each group was then randomly divided into seven subgroups according to observation time (1, 2, 4, 6, 8, 10, and 12 weeks). Basso-Beattie-Bresnahan score and inclined plate test score evaluation, motor evoked potential detection, and histological observation were performed. [Results] In the first 2 weeks of oscillating electrical field stimulation, the oscillating electrical field stimulation and inclined plate test scores of spinal cord injury group and spinal cord injury + oscillating electrical field stimulation group were not significantly different. In the fourth week, the scores of the spinal cord injury group were significantly lower than those of the spinal cord injury + oscillating electrical field stimulation group. The motor evoked potential incubation period in the spinal cord injury + oscillating electrical field stimulation group at the various time points was shorter than that in the spinal cord injury group. In the sixth week, the relative area of myelin in the spinal cord injury + oscillating electrical field stimulation group was evidently larger than that in the spinal cord injury group. [Conclusion] Oscillating electrical field stimulation could effectively improve spinal cord conduction function and promote motor function recovery in rats with spinal cord injury, as well as promote myelin

  15. The Neuroprotective Effect of Kefir on Spinal Cord Ischemia/Reperfusion Injury in Rats

    PubMed Central

    Akman, Tarik; Yener, Ali Umit; Sehitoglu, Muserref Hilal; Yuksel, Yasemin; Cosar, Murat

    2015-01-01

    Objective 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. Methods 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. Results 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). Conclusion 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. PMID:26113960

  16. Effect of Pregnancy on Vocal Cord Histology: An Animal Experiment

    PubMed Central

    Köybaşı Şanal, Serap; Biçer, Yusuf Özgür; Kükner, Aysel; Tezcan, Erkan

    2016-01-01

    Background: Voice may be affected during the period of pregnancy, especially in the third trimester. However, the exact mechanisms leading to the phonatory changes have not yet uncovered. Aims: The aim of this study is to investigate the possible histological changes in the vocal cords of the pregnant rats in three separate trimesters. Study Design: Animal experiment. Methods: Twenty-five Wistar-Albino female rats were divided into four groups: control group, pregnancy day 7 (Group 1), pregnancy day 14 (Group 2) and pregnancy day 20 (Group 3). The laryngeal specimens were obtained under general anesthesia. Histological assessment was performed using Hematoxylin-eosin and toluidine blue. A stereological analysis of vocal cord tissue was performed using a NIS-Elements D32 Imaging Software. Results: Lamina propria was observed to be edematous, and the lamina propria area was thickened starting from the second trimester. Glycosaminoglycans were observed to increase in the second trimester. Although none was encountered in the control, mast cells were observed in the lamina propria layer of the vocal cord starting in the muscular layer in the first trimester proceed to the subepithelial region as degranulated just before term. The covering epithelium remained unchanged throughout pregnancy. Conclusion: Lamina propria thickening may be attributed to both edema and increased glycosaminoglycans. The presence of mast cells in the cordal tissue may induce edema during pregnancy in rats. PMID:27606142

  17. Effect of Pregnancy on Vocal Cord Histology: An Animal Experiment

    PubMed Central

    Köybaşı Şanal, Serap; Biçer, Yusuf Özgür; Kükner, Aysel; Tezcan, Erkan

    2016-01-01

    Background: Voice may be affected during the period of pregnancy, especially in the third trimester. However, the exact mechanisms leading to the phonatory changes have not yet uncovered. Aims: The aim of this study is to investigate the possible histological changes in the vocal cords of the pregnant rats in three separate trimesters. Study Design: Animal experiment. Methods: Twenty-five Wistar-Albino female rats were divided into four groups: control group, pregnancy day 7 (Group 1), pregnancy day 14 (Group 2) and pregnancy day 20 (Group 3). The laryngeal specimens were obtained under general anesthesia. Histological assessment was performed using Hematoxylin-eosin and toluidine blue. A stereological analysis of vocal cord tissue was performed using a NIS-Elements D32 Imaging Software. Results: Lamina propria was observed to be edematous, and the lamina propria area was thickened starting from the second trimester. Glycosaminoglycans were observed to increase in the second trimester. Although none was encountered in the control, mast cells were observed in the lamina propria layer of the vocal cord starting in the muscular layer in the first trimester proceed to the subepithelial region as degranulated just before term. The covering epithelium remained unchanged throughout pregnancy. Conclusion: Lamina propria thickening may be attributed to both edema and increased glycosaminoglycans. The presence of mast cells in the cordal tissue may induce edema during pregnancy in rats.

  18. Effects of Manual Therapy on Bowel Function of Patients with Spinal Cord Injury

    PubMed Central

    Hu, Chunying; Ye, Miao; Huang, Qiuchen

    2013-01-01

    [Purpose] The purpose of this study was to observe the effects of manual therapy on bowel function of patients with spinal cord injury. [Subjects] The participants were 20 patients with spinal cord injury. [Methods] Manual therapy was applied to the intestine and along the colon ascendens, transverse colon, colon descendens and colon sigmoidem on the surface of abdomen. The results before and after 60 sessions (5 times/week, continued for 12 weeks) of manual therapy were compared. [Results] It was found that there were significant effects both on shortening of bowel time and decreasing dosage of glycerine enema every time patients needed to excrete. [Conclusion] Manual therapy had significant effects on bowel function of patients with spinal cord injury. PMID:24259830

  19. Neuroprotective Effect of Ulinastatin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits.

    PubMed

    Liu, Bingbing; Huang, Weihua; Xiao, Xiaoshan; Xu, Yao; Ma, Songmei; Xia, Zhengyuan

    2015-01-01

    Ulinastatin (UTI), a trypsin inhibitor, is isolated and purified from human urine and has been shown to exert protective effect on myocardial ischemia reperfusion injury in patients. The present study was aimed at investigating the effect of ulinastatin on neurologic functions after spinal cord ischemia reperfusion injury and the underlying mechanism. The spinal cord IR model was achieved by occluding the aorta just caudal to the left renal artery with a bulldog clamp. The drugs were administered immediately after the clamp was removed. The animals were terminated 48 hours after reperfusion. Neuronal function was evaluated with the Tarlov Scoring System. Spinal cord segments between L2 and L5 were harvested for pathological and biochemical analysis. Ulinastatin administration significantly improved postischemic neurologic function with concomitant reduction of apoptotic cell death. In addition, ulinastatin treatment increased SOD activity and decreased MDA content in the spinal cord tissue. Also, ulinastatin treatment suppressed the protein expressions of Bax and caspase-3 but enhanced Bcl-2 protein expression. These results suggest that ulinastatin significantly attenuates spinal cord ischemia-reperfusion injury and improves postischemic neuronal function and that this protection might be attributable to its antioxidant and antiapoptotic properties.

  20. Neuroprotective Effect of Ulinastatin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits

    PubMed Central

    Liu, Bingbing; Huang, Weihua; Xiao, Xiaoshan; Xu, Yao; Ma, Songmei; Xia, Zhengyuan

    2015-01-01

    Ulinastatin (UTI), a trypsin inhibitor, is isolated and purified from human urine and has been shown to exert protective effect on myocardial ischemia reperfusion injury in patients. The present study was aimed at investigating the effect of ulinastatin on neurologic functions after spinal cord ischemia reperfusion injury and the underlying mechanism. The spinal cord IR model was achieved by occluding the aorta just caudal to the left renal artery with a bulldog clamp. The drugs were administered immediately after the clamp was removed. The animals were terminated 48 hours after reperfusion. Neuronal function was evaluated with the Tarlov Scoring System. Spinal cord segments between L2 and L5 were harvested for pathological and biochemical analysis. Ulinastatin administration significantly improved postischemic neurologic function with concomitant reduction of apoptotic cell death. In addition, ulinastatin treatment increased SOD activity and decreased MDA content in the spinal cord tissue. Also, ulinastatin treatment suppressed the protein expressions of Bax and caspase-3 but enhanced Bcl-2 protein expression. These results suggest that ulinastatin significantly attenuates spinal cord ischemia-reperfusion injury and improves postischemic neuronal function and that this protection might be attributable to its antioxidant and antiapoptotic properties. PMID:26161241

  1. Time-related effects of general functional training in spinal cord-injured rats

    PubMed Central

    Miranda, Taisa Amoroso Bortolato; Vicente, Juliana Mendes Yule; Marcon, Raphael Martus; Cristante, Alexandre Fogaça; Morya, Edgard; do Valle, Angela Cristina

    2012-01-01

    OBJECTIVES: This prospective, randomized, experimental study with rats aimed to investigate the influence of general treatment strategies on the motor recovery of Wistar rats with moderate contusive spinal cord injury. METHODS: A total of 51 Wistar rats were randomized into five groups: control, maze, ramp, runway, and sham (laminectomy only). The rats underwent spinal cord injury at the T9-T10 levels using the NYU-Impactor. Each group was trained for 12 minutes twice a week for two weeks before and five weeks after the spinal cord injury, except for the control group. Functional motor recovery was assessed with the Basso, Beattie, and Bresnahan Scale on the first postoperative day and then once a week for five weeks. The animals were euthanized, and the spinal cords were collected for histological analysis. RESULTS: Ramp and maze groups showed an earlier and greater functional improvement effect than the control and runway groups. However, over time, unexpectedly, all of the groups showed similar effects as the control group, with spontaneous recovery. There were no histological differences in the injured area between the trained and control groups. CONCLUSION: Short-term benefits can be associated with a specific training regime; however, the same training was ineffective at maintaining superior long-term recovery. These results might support new considerations before hospital discharge of patients with spinal cord injuries. PMID:22892926

  2. Opposing effects of Toll-like receptors 2 and 4 on synaptic stability in the spinal cord after peripheral nerve injury

    PubMed Central

    2012-01-01

    Background Glial cells are involved in the synaptic elimination process that follows neuronal lesions, and are also responsible for mediating the interaction between the nervous and immune systems. Neurons and glial cells express Toll-like receptors (TLRs), which may affect the plasticity of the central nervous system (CNS). Because TLRs might also have non-immune functions in spinal-cord injury (SCI), we aimed to investigate the influence of TLR2 and TLR4 on synaptic plasticity and glial reactivity after peripheral nerve axotomy. Methods The lumbar spinal cords of C3H/HePas wild-type (WT) mice, C3H/HeJ TLR4-mutant mice, C57BL/6J WT mice, and C57BL/6J TLR2 knockout (KO) mice were studied after unilateral sciatic nerve transection. The mice were killed via intracardiac perfusion, and the spinal cord was processed for immunohistochemistry, transmission electron microscopy (TEM), western blotting, cell culture, and reverse transcriptase PCR. Primary cultures of astrocytes from newborn mice were established to study the astrocyte response in the absence of TLR2 and the deficiency of TLR4 expression. Results The results showed that TLR4 and TLR2 expression in the CNS may have opposite effects on the stability of presynaptic terminals in the spinal cord. First, TLR4 contributed to synaptic preservation of terminals in apposition to lesioned motor neurons after peripheral injury, regardless of major histocompatibility complex class I (MHC I) expression. In addition, in the presence of TLR4, there was upregulation of glial cell-derived neurotrophic factor and downregulation of interleukin-6, but no morphological differences in glial reactivity were seen. By contrast, TLR2 expression led to greater synaptic loss, correlating with increased astrogliosis and upregulation of pro-inflammatory interleukins. Moreover, the absence of TLR2 resulted in the upregulation of neurotrophic factors and MHC I expression. Conclusion TLR4 and TLR2 in the CNS may have opposite effects on the

  3. Iso-effect table for radiation tolerance of the human spinal cord

    SciTech Connect

    Cohen, L.; Creditor, M.

    1981-07-01

    Available literature on radiation injury to the human spinal cord was collected into a comprehensive data set relating the incidence of myelopathy to dosage, number of fractions and total treatment time. The data was analyzed using a search program (RAD3) to derive best-fitting cell kinetic parameters on the assumption that radiation myelopathy arises from cellular depletion in the irradiated tissues. From these parameters iso-effect tables were constructed for a wide range of treatment schedules, including daily treatment as well as fractionation at longer intervals. The tables provide a set of limiting doses, above which the risk of radiation injury to the spinal cord becomes substantial. General application of NSD tolerance limits could lead to systematic overdosage of the spinal cord, especially with large individual fractions or short treatment times. We conclude that the computed iso-effect tables provide a more reliable clinical guide than conventional time-dose equations.

  4. Effect of Docosahexaenoic Acid (DHA) on Spinal Cord Injury.

    PubMed

    Samaddar, Sreyashi

    2016-01-01

    Spinal cord injury (SCI) has become one of the most leading concerns in the past decade. Preclinical and research studies are now ongoing trying to understand the molecular mechanisms and develop treatment strategies for this neurodegenerative condition. In the last decade, researchers have deciphered few of the leading players that play a major role in worsening the condition. But till date none of these have been applied to the clinical treatment of patients with SCI. Here in this chapter I discuss about one of the dietary requirements that could ameliorate the condition of these patients. PMID:27651246

  5. In vivo magnetic resonance imaging at 11.7 Tesla visualized the effects of neonatal transection of infraorbital nerve upon primary and secondary trigeminal pathways in rats.

    PubMed

    Ooi, Yasuhiro; Inui-Yamamoto, Chizuko; Suzuki, Takashi; Nakadate, Hiromichi; Nagase, Yoshitaka; Seiyama, Akitoshi; Yoshioka, Yoshichika; Seki, Junji

    2014-09-01

    Using 11.7T ultra high-field T2-weighted MRI, the present study aimed to investigate pathological changes of primary and secondary trigeminal pathways following neonatal transection of infraorbital nerve in rats. The trigeminal pathways consist of spinal trigeminal tract, trigeminal sensory nuclear complex, medial lemniscus, ventromedial portion of external medullary lamina and ventral posterior nucleus of thalamus. By selecting optimum parameters of MRI such as repetition time, echo time, and slice orientation, this study visualized the trigeminal pathways in rats without any contrast agents. Pathological changes due to the nerve transection were found at 8 weeks of age as a marked reduction of the areas of the trigeminal pathways connecting from the injured nerve. In addition, T2-weighted MR images of the trigeminal nerve trunk and the spinal trigeminal tract suggest a communication of CSF through the trigeminal nerve between the inside and outside of the brain stem. These results support the utility of ultra high-field MRI system for noninvasive assessment of effects of trigeminal nerve injury upon the trigeminal pathways.

  6. In vivo magnetic resonance imaging at 11.7 Tesla visualized the effects of neonatal transection of infraorbital nerve upon primary and secondary trigeminal pathways in rats.

    PubMed

    Ooi, Yasuhiro; Inui-Yamamoto, Chizuko; Suzuki, Takashi; Nakadate, Hiromichi; Nagase, Yoshitaka; Seiyama, Akitoshi; Yoshioka, Yoshichika; Seki, Junji

    2014-09-01

    Using 11.7T ultra high-field T2-weighted MRI, the present study aimed to investigate pathological changes of primary and secondary trigeminal pathways following neonatal transection of infraorbital nerve in rats. The trigeminal pathways consist of spinal trigeminal tract, trigeminal sensory nuclear complex, medial lemniscus, ventromedial portion of external medullary lamina and ventral posterior nucleus of thalamus. By selecting optimum parameters of MRI such as repetition time, echo time, and slice orientation, this study visualized the trigeminal pathways in rats without any contrast agents. Pathological changes due to the nerve transection were found at 8 weeks of age as a marked reduction of the areas of the trigeminal pathways connecting from the injured nerve. In addition, T2-weighted MR images of the trigeminal nerve trunk and the spinal trigeminal tract suggest a communication of CSF through the trigeminal nerve between the inside and outside of the brain stem. These results support the utility of ultra high-field MRI system for noninvasive assessment of effects of trigeminal nerve injury upon the trigeminal pathways. PMID:25038563

  7. The effects of the mineral phase on C stabilization mechanisms and the microbial community along an eroding slope transect

    NASA Astrophysics Data System (ADS)

    Doetterl, S.; Opfergelt, S.; Cornelis, J.; Boeckx, P. F.; van oost, K.; Six, J.

    2013-12-01

    An increasing number of studies show the importance of including soil redistribution processes in understanding carbon (C) dynamics in eroding landscapes. The quality and quantity of soil organic carbon in sloping cropland differs with topographic position. These differences are commonly more visible in the subsoil, while the size and composition of topsoil C pools are similar along the hillslope. The type (plant- or microbial-derived) and quality (level of degradation) of C found in a specific soil fraction depends on the interplay between the temporal dynamic of the specific mechanism and it's strength to protect C from decomposition. Here, we present an analysis that aims to clarify the bio/geo-chemical and mineralogical components involved in stabilizing C at various depths and slope positions and how they affect the microbial community and the degradation of C. For this we analyzed soil samples from different soil depths along a slope transect applying (i) a sequential extraction of the reactive soil phase using pyrophosphate, oxalate and dithionite-citrate-bicarbonate, (ii) a semi-quantitative and qualitative analysis of the clay mineralogy, (iii) an analysis of the microbial community using amino sugars and (iv) an analysis of the level of degradation of C in different soil fractions focusing on the soil Lignin signature. The results show that the pattern of minerals and their relative importance in stabilizing C varies greatly along the transect. In the investigated soils, pyrophosphate extractable Manganese, and not Iron or Aluminum as often observed, is strongly correlated to C in the bulk soil and in the non-aggregated silt and clay fractions. This suggests a certain role of Manganese for C stabilization where physical protection is absent. In contrast, pyrophosphate extractable Iron and Aluminum components are largely abundant in water-stable soil aggregates but not correlated to C, suggesting importance of these extracts to stabilize aggregates and

  8. An experimental spinal cord injury rat model using customized impact device: A cost-effective approach

    PubMed Central

    Vijayaprakash, K.M.; Sridharan, N.

    2013-01-01

    Till date, NYU MASCIS (New York University, Multicenter Animal Spinal Cord Injury Study) impactor and Ohio State University electromagnetic spinal cord injury device impactor were under use for simulating an experimental spinal cord injury in rodents; functional recovery being assessed through Basso, Beattie and Bresnahan (BBB) scoring method which is an open field behavior based scoring system. Although, the cited impactors are state-of-art devices, affordability to scientists in developing and under developed countries is questionable. Since the acquisition of these impact devices are expensive, we designed a customized impact device based on the requirement, satisfying all the parameters to withstand a standard animal model for contusion type of spinal cord injury at the thoracic level without compromising the lesion reproducibility. Here, a spinal cord contusion is created using a blunt-force impactor in male Wistar rats. Our method gave consistent lesion effects as evaluated by behavior scoring methods. All the animals showed equal degree of performance in tests like narrow beam, inclined plane and horizontal ladder and in BBB scores (open field locomotor test). The aim of presenting our experience is to reinstate the fact that lack of affordability to get sophisticated instrumentation need not be a hurdle in the pursuit of science. PMID:23960429

  9. An experimental spinal cord injury rat model using customized impact device: A cost-effective approach.

    PubMed

    Vijayaprakash, K M; Sridharan, N

    2013-07-01

    Till date, NYU MASCIS (New York University, Multicenter Animal Spinal Cord Injury Study) impactor and Ohio State University electromagnetic spinal cord injury device impactor were under use for simulating an experimental spinal cord injury in rodents; functional recovery being assessed through Basso, Beattie and Bresnahan (BBB) scoring method which is an open field behavior based scoring system. Although, the cited impactors are state-of-art devices, affordability to scientists in developing and under developed countries is questionable. Since the acquisition of these impact devices are expensive, we designed a customized impact device based on the requirement, satisfying all the parameters to withstand a standard animal model for contusion type of spinal cord injury at the thoracic level without compromising the lesion reproducibility. Here, a spinal cord contusion is created using a blunt-force impactor in male Wistar rats. Our method gave consistent lesion effects as evaluated by behavior scoring methods. All the animals showed equal degree of performance in tests like narrow beam, inclined plane and horizontal ladder and in BBB scores (open field locomotor test). The aim of presenting our experience is to reinstate the fact that lack of affordability to get sophisticated instrumentation need not be a hurdle in the pursuit of science. PMID:23960429

  10. Shifts in methanogen community structure and function across a coastal marsh transect: effects of exotic Spartina alterniflora invasion

    PubMed Central

    Yuan, Junji; Ding, Weixin; Liu, Deyan; Kang, Hojeong; Xiang, Jian; Lin, Yongxin

    2016-01-01

    Invasion of Spartina alterniflora in coastal areas of China increased methane (CH4) emissions. To elucidate the underlying mechanisms, we measured CH4 production potential, methanogen community structure and biogeochemical factors along a coastal wetland transect comprised of five habitat regions: open water, bare tidal flat, invasive S. alterniflora marsh and native Suaeda salsa and Phragmites australis marshes. CH4 production potential in S. alterniflora marsh was 10 times higher than that in other regions, and it was significantly correlated with soil organic carbon, dissolved organic carbon and trimethylamine concentrations, but was not correlated with acetate or formate concentrations. Although the diversity of methanogens was lowest in S. alterniflora marsh, invasion increased methanogen abundance by 3.48-fold, compared with native S. salsa and P. australis marshes due to increase of facultative Methanosarcinaceae rather than acetotrophic and hydrogenotrophic methanogens. Ordination analyses suggested that trimethylamine was the primary factor regulating shift in methanogen community structure. Addition of trimethylamine increased CH4 production rates by 1255-fold but only by 5.61- and 11.4-fold for acetate and H2/CO2, respectively. S. alterniflora invasion elevated concentration of non-competitive trimethylamine, and shifted methanogen community from acetotrophic to facultative methanogens, which together facilitated increased CH4 production potential. PMID:26728134

  11. Shifts in methanogen community structure and function across a coastal marsh transect: effects of exotic Spartina alterniflora invasion

    NASA Astrophysics Data System (ADS)

    Yuan, Junji; Ding, Weixin; Liu, Deyan; Kang, Hojeong; Xiang, Jian; Lin, Yongxin

    2016-01-01

    Invasion of Spartina alterniflora in coastal areas of China increased methane (CH4) emissions. To elucidate the underlying mechanisms, we measured CH4 production potential, methanogen community structure and biogeochemical factors along a coastal wetland transect comprised of five habitat regions: open water, bare tidal flat, invasive S. alterniflora marsh and native Suaeda salsa and Phragmites australis marshes. CH4 production potential in S. alterniflora marsh was 10 times higher than that in other regions, and it was significantly correlated with soil organic carbon, dissolved organic carbon and trimethylamine concentrations, but was not correlated with acetate or formate concentrations. Although the diversity of methanogens was lowest in S. alterniflora marsh, invasion increased methanogen abundance by 3.48-fold, compared with native S. salsa and P. australis marshes due to increase of facultative Methanosarcinaceae rather than acetotrophic and hydrogenotrophic methanogens. Ordination analyses suggested that trimethylamine was the primary factor regulating shift in methanogen community structure. Addition of trimethylamine increased CH4 production rates by 1255-fold but only by 5.61- and 11.4-fold for acetate and H2/CO2, respectively. S. alterniflora invasion elevated concentration of non-competitive trimethylamine, and shifted methanogen community from acetotrophic to facultative methanogens, which together facilitated increased CH4 production potential.

  12. Effects of estrogen and fimbria/fornix transection on p75NGFR and ChAT expression in the medial septum and diagonal band of Broca.

    PubMed

    Gibbs, R B; Pfaff, D W

    1992-04-01

    NGF receptor-expressing cells located in the basal forebrain have recently been shown to contain estrogen (E) receptors (Toran-Allerand and MacLusky. 1989. Soc. Neurosci. Abstr. 15: 954). In the present study, we have examined the effects of E-treatment on p75NGFR and choline acetyltransferase (ChAT) expression by neurons in the medial septum (MS) and the vertical (VDB) and horizontal (HDB) limbs of the diagonal band of Broca using immunocytochemical and in situ hybridization techniques. First, since E-treatment has been shown to affect neuronal survival and to stimulate synaptic reorganization and growth within various regions of the brain, we hypothesized that E-treatment might attenuate the loss of p75NGFR immunoreactivity (IR) which occurs in the MS and VDB following transection of the fimbria/fornix. Contrary to our hypothesis, E-treatment did not attenuate the effects of fimbria/fornix transection. In fact, E-treatment alone produced a significant decrease in the number of p75NGFR-IR cells detected in the MS. Subsequent experiments confirmed that chronic E-treatment produces a down-regulation of both p75NGFR-IR and p75NGFR mRNA in the MS and VDB. In the MS, estrogen appeared to affect a subpopulation of p75NGFR-expressing neurons which were also affected by fimbria/fornix transection since the effects of these two treatments were not additive. In addition, effects of E-treatment on p75NGFR-IR were sex-specific (observed in females but not in males) and were reversible in the MS after 2 weeks, but not after 4 weeks (allowing 2 weeks recovery), of E-treatment. A time-course analysis revealed that effects of E-treatment on p75NGFR-IR were not observed until after 16 days (MS) or 30 days (VDB) of E-treatment and were preceded by a significant and transient increase in ChAT expression in both the MS and VDB. The data are consistent with the possibility that continuous, long-term exposure to gonadal steroids may contribute to a loss of p75NGFR-expressing neurons

  13. Effect of voice training in the voice rehabilitation of patients with vocal cord polyps after surgery

    PubMed Central

    LIN, LI; SUN, NA; YANG, QIUHUA; ZHANG, YA; SHEN, JI; SHI, LIXIN; FANG, QIN; SUN, GUANGBIN

    2014-01-01

    The objective of the present study was to determine the effect of voice training on the vocal rehabilitation of patients with vocal cords polyps following phonomicrosurgery. A total of 60 cases of vocal cord polyps treated by laser phonomicrosurgery were randomly divided into training and control groups with 30 cases in each group. The patients were treated with laser phonomicrosurgery, routine postoperative treatment and nursing. The training group were additionally treated with vocal training, including relaxation training, breathing training, basic pronunciation training, chewing voice training and tone sandhi pronunciation training, and attention was paid to the training steps. Subjective and objective voice evaluations of the two groups were compared three months after the surgery and the differences between groups were statistically significant (P<0.05). Voice training may significantly improve the postoperative voice quality of patients with vocal cord polyps and support rehabilitation. PMID:24669244

  14. Effect of voice training in the voice rehabilitation of patients with vocal cord polyps after surgery.

    PubMed

    Lin, Li; Sun, Na; Yang, Qiuhua; Zhang, Ya; Shen, Ji; Shi, Lixin; Fang, Qin; Sun, Guangbin

    2014-04-01

    The objective of the present study was to determine the effect of voice training on the vocal rehabilitation of patients with vocal cords polyps following phonomicrosurgery. A total of 60 cases of vocal cord polyps treated by laser phonomicrosurgery were randomly divided into training and control groups with 30 cases in each group. The patients were treated with laser phonomicrosurgery, routine postoperative treatment and nursing. The training group were additionally treated with vocal training, including relaxation training, breathing training, basic pronunciation training, chewing voice training and tone sandhi pronunciation training, and attention was paid to the training steps. Subjective and objective voice evaluations of the two groups were compared three months after the surgery and the differences between groups were statistically significant (P<0.05). Voice training may significantly improve the postoperative voice quality of patients with vocal cord polyps and support rehabilitation.

  15. Delayed cord clamping in red blood cell alloimmunization: safe, effective, and free?

    PubMed

    McAdams, Ryan M

    2016-04-01

    Hemolytic disease of the newborn (HDN), an alloimmune disorder due to maternal and fetal blood type incompatibility, is associated with fetal and neonatal complications related to red blood cell (RBC) hemolysis. After delivery, without placental clearance, neonatal hyperbilirubinemia may develop from ongoing maternal antibody-mediated RBC hemolysis. In cases refractory to intensive phototherapy treatment, exchange transfusions (ET) may be performed to prevent central nervous system damage by reducing circulating bilirubin levels and to replace antibody-coated red blood cells with antigen-negative RBCs. The risks and costs of treating HDN are significant, but appear to be decreased by delayed umbilical cord clamping at birth, a strategy that promotes placental transfusion to the newborn. Compared to immediate cord clamping (ICC), safe and beneficial short-term outcomes have been demonstrated in preterm and term neonates receiving delayed cord clamping (DCC), a practice that may potentially be effective in cases RBC alloimmunization.

  16. Effects of gamma and electron beam irradiation on the properties of calendered cord fabrics

    NASA Astrophysics Data System (ADS)

    Aytaç, Ayşe; Deniz, Veli; Şen, Murat; Hegazy, El-Sayed; Güven, Olgun

    2010-03-01

    The effects of gamma and e-beam irradiation on mechanical and structural properties of nylon 66 (Ny 66), nylon 6 (Ny 6) and poly(ethylene terephthalate) (PET) fabrics used in tyres were investigated. The untreated (greige), treated cords and calendered fabrics were irradiated at different doses. It is found that the effects of high energy irradiation on greige, treated cords and calendered fabrics are similar. No protective effect of compounds used in calendering was observed against radiation-induced oxidative degradation. The deterioration effect of gamma irradiation on mechanical properties is much higher than that of e-beam irradiation for all types of samples. Limiting viscosity numbers of both gamma and e-beam irradiated nylon 6 and nylon 66 cords were found to decrease with increasing dose. It is concluded that PET calendered fabric has higher resistance to ionizing radiation. Ny 6 and Ny 66 calendered fabrics are more sensitive even at low doses. Therefore, the effects of high energy irradiation on tyre cords have to be taken into consideration during tyre design reinforced with particularly Ny fabrics if pre-vulcanization with high energy radiation is to be applied.

  17. The isolation of the temperature effect on branched GDGT distribution in an elevation transect of the Eastern Cordillera, Colombia

    NASA Astrophysics Data System (ADS)

    Anderson, V. J.; Shanahan, T. M.; Saylor, J.; Horton, B. K.

    2012-12-01

    Recently, the distribution of branched GDGT's (glycerol dialkyl glycerol tetraethers) has been proposed as a proxy for temperature and pH in soils via the MBT/CBT index, and has been used to reconstruct past temperature variations in a number of settings ranging from marine sediments to loess deposits and paleosols. However, empirical calibrations of the MBT/CBT index against temperature show significant scatter, leading to uncertainties as large as ±2 degrees C . In this study we seek to add to and improve upon the existing soil calibration using a new set of samples spanning a large elevation (and temperature) gradient in the Eastern Cordillera of Colombia. At each site we buried temperature loggers to constrain the diurnal and seasonal temperature experienced by each soil sample. Located only 5 degrees north of the equator, our sites experience a very small seasonal temperature variation - most sites display an annual range of less than 4 degrees C. In addition, the pH of all of the soils is almost invariant across the transect, with the vast majority of samples having pH's between 4 and 5. This dataset represents a "best-case" scenario - small variations in seasonal temperature, pH, and well-constrained instrumental data - which allow us to examine the brGDGT-temperature relationship in the absence of major confounding factors such as seasonality and soil chemistry. Interestingly, the relationship between temperature and the MBT/CBT index is not improved using this dataset, suggesting that these factors are not the cause of the anomalous scatter in the calibration dataset. However, we find that using other parameterizations for the regression equation instead of the MBT and CBT indices, the errors in our temperature estimates are significantly reduced.

  18. The early effects of delayed cord clamping in term infants born to Libyan mothers.

    PubMed

    Emhamed, Musbah Omar; van Rheenen, Patrick; Brabin, Bernard J

    2004-10-01

    This study was conducted to evaluate the haematological effects of the timing of umbilical cord clamping in term infants 24 h after birth in Libya. Mother-infant pairs were randomly assigned to early cord clamping (within 10s after delivery) or delayed clamping (after the cord stopped pulsating). Maternal haematological status was assessed on admission in the delivery room. Infant haematological status was evaluated in cord blood and 24 h after birth. Bilirubin concentration was assessed at 24 h. 104 mother-infant pairs were randomized to delayed (n=58) or early cord clamping (n=46). At baseline the groups had similar demographic and biomedical characteristics, except for a difference in maternal haemoglobin, which was significantly higher in the early clamping group (11.7 g/dL, SD 1.3 g/dL versus 10.9 g/dL, SD 1.6 g/dL; P=0.0035). Twenty-four hours after delivery the mean infant haemoglobin level was significantly higher in the delayed clamping group (18.5 g/dL versus 17.1 g/dL; P=0.0005). No significant differences were found in clinical jaundice or plethora. Surprisingly, blood analysis showed that two babies in the early clamping group had total serum bilirubin levels (> 15 mg/dL) that necessitated phototherapy. There were no babies in the late clamping group who required phototherapy. Three infants in the delayed clamping group had polycythaemia without symptoms, for which no partial exchange transfusion was necessary. Delaying cord clamping until the pulsations stop increases the red cell mass in term infants. It is a safe, simple and low cost delivery procedure that should be incorporated in integrated programmes aimed at reducing iron deficiency anaemia in infants in developing countries.

  19. Effects of tetramethylpyrazine on microglia activation in spinal cord compression injury of mice.

    PubMed

    Shin, Jung-Won; Moon, Ja-Young; Seong, Ju-Won; Song, Sang-Hoon; Cheong, Young-Jin; Kang, Chulhun; Sohn, Nak-Won

    2013-01-01

    Secondary mechanisms, including inflammation and microglia activation, serve as targets for the development and application of pharmacological strategies in the management of spinal cord injury (SCI). Tetramethylpyrazine (TMP), an active ingredient of Ligusticum wallichii (chuanxiong), has shown anti-inflammatory and neuroprotective effects against SCI. However, it remains uncertain whether the inflammation-suppressive effects of TMP play a modulatory role over microglia activation in SCI. The present study investigated the effects of TMP on microglia activation and pro-inflammatory cytokines in spinal cord compression injury in mice. For a real-time PCR measurement of pro-inflammatory cytokines, SCI was induced in mice by the clip compression method (30 g force, 1 min) and TMP (15 or 30 mg/kg, i.p.) was administered once, 30 minutes before the SCI induction. For immunohistochemistry, TMP (30 mg/kg, i.p.) treatment was given three times during the first 48 hours after the SCI. 30 mg/kg of TMP treatment reduced the up-regulation of TNF-α, IL-1β and COX-2 mRNA in the spinal tissue at four hours after the SCI induction. TMP also significantly attenuated microglia activation and neutrophil infiltration at 48 hours after the SCI induction. In addition, iNOS expression in the spinal tissue was attenuated with TMP treatment. These results suggest that TMP plays a modulatory role in microglia activation and may protect the spinal cord from or potentially delay secondary spinal cord injury. PMID:24228606

  20. Effect of amiloride on endoplasmic reticulum stress response in the injured spinal cord of rats.

    PubMed

    Kuroiwa, Masahiro; Watanabe, Masahiko; Katoh, Hiroyuki; Suyama, Kaori; Matsuyama, Daisuke; Imai, Takeshi; Mochida, Joji

    2014-10-01

    After traumatic spinal cord injury (SCI), endoplasmic reticulum (ER) stress exacerbates secondary injury, leading to expansion of demyelination and reduced remyelination due to oligodendrocyte precursor cell (OPC) apoptosis. Although recent studies have revealed that amiloride controls ER stress and leads to improvement in several neurological disorders including SCI, its mechanism is not completely understood. Here, we used a rat SCI model to assess the effects of amiloride on functional recovery, secondary damage expansion, ER stress-induced cell death and OPC survival. Hindlimb function in rats with spinal cord contusion significantly improved after amiloride administration. Amiloride significantly decreased the expression of the pro-apoptotic transcription factor CHOP in the injured spinal cord and significantly increased the expression of the ER chaperone GRP78, which protects cells against ER stress. In addition, amiloride treatment led to a significant decrease in ER stress-induced apoptosis and a significant increase of NG2-positive OPCs in the injured spinal cord. Furthermore, in vitro experiments performed to investigate the direct effect of amiloride on OPCs revealed that amiloride reduced CHOP expression in OPCs cultured under ER stress. These results suggest that amiloride controls ER stress in SCI and inhibits cellular apoptosis, contributing to OPC survival. The present study suggests that amiloride may be an effective treatment to reduce ER stress-induced cell death in the acute phase of SCI.

  1. Effect of hyperbaric oxygen on MMP9/2 expression and motor function in rats with spinal cord injury

    PubMed Central

    Hou, Ying-Nuo; Ding, Wen-Yuan; Shen, Yong; Yang, Da-Long; Wang, Lin-Feng; Zhang, Peng

    2015-01-01

    To study the effect of hyperbaric oxygen intervention on the microenvironment of nerve regeneration after spinal cord injury modeling and to explore the possible mechanism of nerve regeneration and functional recovery in rats with spinal cord injury. In 98 adult female SD rats, 90 successful models were obtained, which were divided into sham group, spinal cord injury group and hyperbaric oxygen group using randomized block method, 30/group. Spinal cord injury rat model was established in accordance with the modified Allen method. Motor function was assessed at the time points of before modeling, one day, three days, one week, two weeks, three weeks and four weeks after modeling respectively by BBB rating, inclined plane test and improved Tarlov score. At 3 days after modeling, apoptosis of neuronal cells in spinal cord injury region in experimental group was detected by TUNEL method; gene and protein expression of MMP9/2 in spinal cord injury and surrounding tissues was detected by RT-PCR and Western blot assay. At 4 weeks after modeling, histopathological morphological changes in spinal cord injury were observed by HE staining; fluorogold retrograde tracing was used to observe the regeneration and distribution of spinal cord nerve fibers and axon regeneration was observed by TEM. The three motor function scores in hyperbaric oxygen group at each time point after two weeks of treatment were significantly increased compared with spinal cord injury group (P < 0.05). At 3 d after modeling, apoptosis index in hyperbaric oxygen group were significantly lower than those in spinal cord injury group (P < 0.05). At 72 h after modeling, compared with spinal cord injury group, MMP9/2 gene and protein expression in hyperbaric oxygen group was significantly lower (P < 0.05). At four weeks after modeling, fluorogold positive nerve fibers were the most sham group, followed by hyperbaric oxygen group and spinal cord injury group in order; the differences among the groups were

  2. Effect of hyperbaric oxygen on MMP9/2 expression and motor function in rats with spinal cord injury.

    PubMed

    Hou, Ying-Nuo; Ding, Wen-Yuan; Shen, Yong; Yang, Da-Long; Wang, Lin-Feng; Zhang, Peng

    2015-01-01

    To study the effect of hyperbaric oxygen intervention on the microenvironment of nerve regeneration after spinal cord injury modeling and to explore the possible mechanism of nerve regeneration and functional recovery in rats with spinal cord injury. In 98 adult female SD rats, 90 successful models were obtained, which were divided into sham group, spinal cord injury group and hyperbaric oxygen group using randomized block method, 30/group. Spinal cord injury rat model was established in accordance with the modified Allen method. Motor function was assessed at the time points of before modeling, one day, three days, one week, two weeks, three weeks and four weeks after modeling respectively by BBB rating, inclined plane test and improved Tarlov score. At 3 days after modeling, apoptosis of neuronal cells in spinal cord injury region in experimental group was detected by TUNEL method; gene and protein expression of MMP9/2 in spinal cord injury and surrounding tissues was detected by RT-PCR and Western blot assay. At 4 weeks after modeling, histopathological morphological changes in spinal cord injury were observed by HE staining; fluorogold retrograde tracing was used to observe the regeneration and distribution of spinal cord nerve fibers and axon regeneration was observed by TEM. The three motor function scores in hyperbaric oxygen group at each time point after two weeks of treatment were significantly increased compared with spinal cord injury group (P < 0.05). At 3 d after modeling, apoptosis index in hyperbaric oxygen group were significantly lower than those in spinal cord injury group (P < 0.05). At 72 h after modeling, compared with spinal cord injury group, MMP9/2 gene and protein expression in hyperbaric oxygen group was significantly lower (P < 0.05). At four weeks after modeling, fluorogold positive nerve fibers were the most sham group, followed by hyperbaric oxygen group and spinal cord injury group in order; the differences among the groups were

  3. Effect of hyperbaric oxygen on MMP9/2 expression and motor function in rats with spinal cord injury.

    PubMed

    Hou, Ying-Nuo; Ding, Wen-Yuan; Shen, Yong; Yang, Da-Long; Wang, Lin-Feng; Zhang, Peng

    2015-01-01

    To study the effect of hyperbaric oxygen intervention on the microenvironment of nerve regeneration after spinal cord injury modeling and to explore the possible mechanism of nerve regeneration and functional recovery in rats with spinal cord injury. In 98 adult female SD rats, 90 successful models were obtained, which were divided into sham group, spinal cord injury group and hyperbaric oxygen group using randomized block method, 30/group. Spinal cord injury rat model was established in accordance with the modified Allen method. Motor function was assessed at the time points of before modeling, one day, three days, one week, two weeks, three weeks and four weeks after modeling respectively by BBB rating, inclined plane test and improved Tarlov score. At 3 days after modeling, apoptosis of neuronal cells in spinal cord injury region in experimental group was detected by TUNEL method; gene and protein expression of MMP9/2 in spinal cord injury and surrounding tissues was detected by RT-PCR and Western blot assay. At 4 weeks after modeling, histopathological morphological changes in spinal cord injury were observed by HE staining; fluorogold retrograde tracing was used to observe the regeneration and distribution of spinal cord nerve fibers and axon regeneration was observed by TEM. The three motor function scores in hyperbaric oxygen group at each time point after two weeks of treatment were significantly increased compared with spinal cord injury group (P < 0.05). At 3 d after modeling, apoptosis index in hyperbaric oxygen group were significantly lower than those in spinal cord injury group (P < 0.05). At 72 h after modeling, compared with spinal cord injury group, MMP9/2 gene and protein expression in hyperbaric oxygen group was significantly lower (P < 0.05). At four weeks after modeling, fluorogold positive nerve fibers were the most sham group, followed by hyperbaric oxygen group and spinal cord injury group in order; the differences among the groups were

  4. Neuroprotective effect of epidural hypothermia after spinal cord lesion in rats

    PubMed Central

    Barbosa, Marcello Oliveira; Cristante, Alexandre Fogaça; dos Santos, Gustavo Bispo; Ferreira, Ricardo; Marcon, Raphael Martus; de Barros Filho, Tarcisio Eloy Pessoa

    2014-01-01

    OBJECTIVES : To evaluate the neuroprotective effect of epidural hypothermia in rats subjected to experimental spinal cord lesion. METHODS: Wistar rats (n = 30) weighing 320-360 g were randomized to two groups (hypothermia and control) of 15 rats per group. A spinal cord lesion was induced by the standardized drop of a 10-g weight from a height of 2.5 cm, using the New York University Impactor, after laminectomy at the T9-10 level. Rats in the hypothermia group underwent epidural hypothermia for 20 minutes immediately after spinal cord injury. Motor function was assessed for six weeks using the Basso, Beattie and Bresnahan motor scores and the inclined plane test. At the end of the final week, the rats' neurological status was monitored by the motor evoked potential test and the results for the two groups were compared. RESULTS: Analysis of the Basso, Beattie and Bresnahan scores obtained during the six-week period indicated that there were no significant differences between the two groups. There was no significant difference between the groups in the inclined plane test scores during the six-week period. Furthermore, at the end of the study, the latency and amplitude values of the motor evoked potential test were not significantly different between the two groups. CONCLUSION: Hypothermia did not produce a neuroprotective effect when applied at the injury level and in the epidural space immediately after induction of a spinal cord contusion in Wistar rats. PMID:25141116

  5. Effect of bone fragment impact velocity on biomechanical parameters related to spinal cord injury: a finite element study.

    PubMed

    Khuyagbaatar, Batbayar; Kim, Kyungsoo; Hyuk Kim, Yoon

    2014-08-22

    Several experimental and computational studies have investigated the effect of bone fragment impact on the spinal cord during trauma. However, the effect of the impact velocity of a fragment generated by a burst fracture on the stress and strain inside the spinal cord has not been computationally investigated, even though spinal canal occlusion and peak pressure at various impact velocities were provided in experimental studies. These stresses and strains are known factors related to clinical symptoms or injuries. In this study, a fluid-structure interaction model of the spinal cord, dura mater, and cerebrospinal fluid was developed and validated. The von-Mises stress distribution in the cord, the longitudinal strain, the cord compression and cross-sectional area at the impact center, and the obliteration of the cerebrospinal fluid layer were analyzed for three pellet sizes at impact velocities ranging from 1.5m/s to 7.5m/s. The results indicate that stress in the cord was substantially elevated when the initial impact velocity of the pellet exceeded a threshold of 4.5m/s. Cord compression, reduction in cross-sectional area, and obliteration of the cerebrospinal fluid increased gradually as the velocity of the pellet increased, regardless of the size of the pellet. The present study provides insight into the mechanisms underlying spinal cord injury.

  6. Amnesia in man following transection of the fornix. A review.

    PubMed

    Gaffan, D; Gaffan, E A

    1991-12-01

    Published accounts of the effects of fornix damage on memory in man are critically evaluated. Most weight is given to cases of surgical transection of the fornix, though other causes of fornix damage are briefly discussed. It is concluded that fornix transection causes amnesia.

  7. Effects of hemorrhagic hypotension on tyrosine concentrations in rat spinal cord and plasma

    NASA Technical Reports Server (NTRS)

    Conlay, L. A.; Maher, T. J.; Roberts, C. H.; Wurtman, R. J.

    1988-01-01

    Tyrosine is the precursor for catecholamine neurotransmitters. When catecholamine-containing neurons are physiologically active (as sympathoadrenal cells are in hypotension), tyrosine administration increases catecholamine synthesis and release. Since hypotension can alter plasma amino acid composition, the effects of an acute hypotensive insult on tyrosine concentrations in plasma and spinal cord were examined. Rats were cannulated and bled until the systolic blood pressure was 50 mmHg, or were kept normotensive for 1 h. Tyrosine and other large neutral amino acids (LNAA) known to compete with tyrosine for brain uptake were assayed in plasma and spinal cord. The rate at which intra-arterial (H-3)tyrosine disappeared from the plasma was also estimated in hemorrhaged and control rats. In plasma of hemorrhaged animals, both the tyrosine concentration and the tyrosine/LNAA ratio was elevated; moreover, the disappearance of (H-3)tyrosine was slowed. Tyrosine concentrations also increased in spinal cords of hemorrhaged-hypotensive rats when compared to normotensive controls. Changes in plasma amino acid patterns may thus influence spinal cord concentrations of amino acid precursors for neurotransmitters during the stress of hemorrhagic shock.

  8. THE EFFECT OF MONOSIALOGANGLYOSIDE (GM-1) ADMINISTRATION IN SPINAL CORD INJURY

    PubMed Central

    BARROS, TARCÍSIO ELOY PESSOA; ARAUJO, FERNANDO FLORES DE; HIGINO, LUCAS DA PAZ; MARCON, RAPHAEL MARTUS; CRISTANTE, ALEXANDRE FOGAÇA

    2016-01-01

    ABSTRACT Objective: To evaluate the effect of monosialoganglioside (GM-1) in spinal cord trauma patients seen in our service who have not been treated with methylprednisolone. Methods: Thirty patients with acute spinal cord trauma were randomly divided into two groups. In Group 1, patients received 200 mg GM-1 in the initial assessment and thereafter received 100 mg intravenous per day for 30 days and Group 2 (control) received saline. Patients were evaluated periodically (at 6 weeks, 6 months, one year and two years), using a standardized neurological assessment of the American Spinal Injury Association / International Spinal Cord Society. Results: The comparative statistical analysis of motor indices, sensitive indices for pain and touch according to the standardization of ASIA / ISCOS showed that the assessments at 6 weeks, 6 months and 2 years, GM-Group 1 patients had higher rates than the control group regarding sensitivity to pain and touch, with no statistically significant difference from the motor index. Conclusion: The functional assessment showed improvement in the sensitive indices of patients treated with GM1 after post-traumatic spinal cord injury compared to patients who received placebo. Level of Evidence IV, Prospective Case Studies Series. PMID:27217811

  9. Effect of cord blood serum on ex vivo human limbal epithelial cell culture.

    PubMed

    Chakraborty, Anindita; Dutta, Jayanta; Das, Sumantra; Datta, Himadri

    2012-12-01

    Limbal cell transplantation is an efficacious procedure for rehabilitation of visual acuity in patients with severe ocular surface disorders. Cultivation of limbal epithelial stem cell with fetal bovine serum for transplantation has been a promising treatment for reconstructing the ocular surface in severe limbal stem cell deficiency caused by Steven Johnson syndrome, chemical or thermal injury. This technique of "cell therapy" has been accepted worldwide but the cost of cultivating the cells for transplantation is high. The objective of this study was to investigate the effect of cord blood serum in place of fetal bovine serum on the growth of human limbal epithelial cell culture. Our group has experimented with human cord blood serum which was obtained free of cost from willing donors. The use of human cord blood serum in place of fetal bovine serum for ex vivo culture of limbal stem cell has helped us in reducing the cost of culture. Fresh human limbal tissues from donor cadavers were cultured on intact and denuded amniotic membrane. Cells were proliferated in vitro with cell culture media containing human cord blood serum. Reverse transcription-polymerase chain reaction and immunofluorescence cytochemistry of cultured human limbal epithelial stem cell was done for characterization of the cells.

  10. Effects of deep barbiturate coma on acute spinal cord injury in the cat.

    PubMed

    Ducati, A; Schieppati, M; Giovanelli, M A

    1984-04-01

    The effects of barbiturate administration on experimental balloon-induced spinal cord injury were tested in cats. Somatosensory evoked potentials from sciatic nerve stimulation were obtained before trauma and every 60 minutes after it up to the sixth hour, when the animals were killed. Eight cats received no barbiturate treatment. On histologic examination the traumatic lesion was found to be extensive (mean, 72.8% of total cross section of the cord area), sparing dorsal columns only in six cats. Somatosensory evoked potentials were absent in two cats and profoundly modified (that is, the late waves were absent) in six cats at the sixth hour. Eight cats were given a continuous infusion for 1 hour of intravenous thiopental sodium (total dose, 65-90 mg/kg) starting 30 minutes after trauma. In these eight cats, the extent of the traumatic lesion was significantly reduced (8.8% of the cord area). Among them, three animals presented with unaltered somatosensory evoked potentials (that is, with the presence of both primary components and late waves) at the sixth hour. It was concluded that thiopental sodium improves the response of the spinal cord to trauma, both at an anatomic and at a functional level.

  11. Non-transecting bulbar urethroplasty.

    PubMed

    Bugeja, Simon; Andrich, Daniela E; Mundy, Anthony R

    2015-02-01

    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.

  12. Arrested development of the dorsal column following neonatal spinal cord injury in the opossum, Monodelphis domestica.

    PubMed

    Wheaton, Benjamin J; Noor, Natassya M; Dziegielewska, Katarzyna M; Whish, Sophie; Saunders, Norman R

    2015-03-01

    Developmental studies of spinal cord injury in which regrowth of axons occurs across the site of transection rarely distinguish between the recovery of motor-controlling pathways and that of ascending axons carrying sensory information. We describe the morphological changes that occur in the dorsal column (DC) of the grey short-tailed opossum, Monodelphis domestica, following spinal cord injury at two early developmental ages. The spinal cords of opossums that had had their mid-thoracic spinal cords completely transected at postnatal day 7 (P7) or P28 were analysed. Profiles of neurofilament immunoreactivity in transected cords showing DC development were differentially affected by the injury compared with the rest of the cord and cytoarchitecture was modified in an age- and site-dependent manner. The ability of DC neurites to grow across the site of transection was confirmed by injection of fluorescent tracer below the injury. P7 transected cords showed labelling in the DC above the site of original transection indicating that neurites of this sensory tract were able to span the injury. No growth of any neuronal processes was seen after P28 transection. Thus, DC is affected by spinal injury in a differential manner depending on the age at which the transection occurs. This age-differential response, together with other facets of remodelling that occur after neonatal spinal injury, might explain the locomotor adaptations and recovery observed in these animals.

  13. [Effects of catalase on human umbilical cord mesenchymal stem cells].

    PubMed

    Hu, Lin-Ping; Gao, Ying-Dai; Zheng, Guo-Guang; Shi, Ying-Xu; Xie, Yin-Liang; Liu, Yong-Jun; Yuan, Wei-Ping; Cheng, Tao

    2010-04-01

    This study was aimed to investigate the growth and multiple differentiation potential of human umbilical cord tissue derived mesenchymal stem cells (UC-MSCs) transfected by a retroviral vector with catalase (CAT) gene. The UC-MSCs cultured in vitro were transfected by using pMSCV carrying GFP (pMSCV-GFP) and pMSCV carrying CAT (pMSCV-GFP-CAT) respectively, then the MSC-GFP cell line and MSC-GFP-CAT cell line were obtained by sorting of flow cytometry. The GFP expression was observed by a fluorescent microscopy at 48 hours after CAT gene transfection. The GFP+ cells were sorted by flow cytometry. The activity of CAT in GFP+ cells was detected by catalase assay kit. The proliferative capacity of transfected UC-MSCs was determined by cell counting kit-8. The differentiation ability of gene-transfected GFP+ cells into osteogenesis and adipogenesis was observed by von Kossa and oil red O staining. The results indicated that green fluorescence in UC-MSCs was observed at 48 hours after transfection, and the fluorescence gradually enhanced to a steady level on day 3. The percentage of MSCs-GFP was (25.54+/-8.65)%, while the percentage of MSCs-GFP-CAT was (35.4+/-18.57)%. The activity of catalase in UC-MSCs, MSCs-GFP, MSCs-GFP-CAT cells were 19.5, 20.3, 67.2 U, respectively. The transfected MSCs-GFP-CAT could be induced into osteoblasts and adipocytes. After 21 days, von Kossa staining showed induced osteoblasts. Many lipid droplets with high refractivity occurred in cytoplasm of the transfected UC-MSCs, and showed red fat granules in oil red O staining cells. There were no significant differences between transfected and non-transfected UC-MSCs cells (p>0.05). It is concluded that UC-MSCs are successfully transfected by retrovirus carrying GFP or CAT gene, the activity of catalase increased by 3.4-fold. The transfected UC-MSCs maintain proliferation potential and ability of differentiation into osteoblasts and adipocytes.

  14. Intraspinal stimulation for bladder voiding in cats before and after chronic spinal cord injury

    NASA Astrophysics Data System (ADS)

    Pikov, Victor; Bullara, Leo; McCreery, Douglas B.

    2007-12-01

    The long-term objective of this study is to develop neural prostheses for people with spinal cord injuries who are unable to voluntarily control their bladder. This feasibility study was performed in 22 adult cats. We implanted an array of microelectrodes into locations in the sacral spinal cord that are involved in the control of micturition reflexes. The effect of microelectrode stimulation was studied under light Propofol anesthesia at monthly intervals for up to 14 months. We found that electrical stimulation in the sacral parasympathetic nucleus at S2 level or in adjacent ventrolateral white matter produced bladder contractions insufficient for inducing voiding, while stimulation at or immediately dorsal to the dorsal gray commissure at S1 level produced strong (at least 20 mmHg) bladder contractions as well as strong (at least 40 mm Hg) external urethral sphincter relaxation, resulting in bladder voiding in 14 animals. In a subset of three animals, spinal cord transection was performed. For several months after the transection, intraspinal stimulation continued to be similarly or even more effective in inducing the bladder voiding as before the transection. We speculate that in the absence of the supraspinal connections, the plasticity in the local spinal circuitry played a role in the improved responsiveness to intraspinal stimulation.

  15. Changes in functional properties and 5-HT modulation above and below a spinal transection in lamprey

    PubMed Central

    Becker, Matthew I.; Parker, David

    2015-01-01

    In addition to the disruption of neural function below spinal cord injuries (SCI), there also can be changes in neuronal properties above and below the lesion site. The relevance of these changes is generally unclear, but they must be understood if we are to provide rational interventions. Pharmacological approaches to improving locomotor function have been studied extensively, but it is still unclear what constitutes an optimal approach. Here, we have used the lamprey to compare the modulatory effects of 5-HT and lesion-induced changes in cellular and synaptic properties in unlesioned and lesioned animals. While analyses typically focus on the sub-lesion spinal cord, we have also examined effects above the lesion to see if there are changes here that could potentially contribute to the functional recovery. Cellular and synaptic properties differed in unlesioned and lesioned spinal cords and above and below the lesion site. The cellular and synaptic modulatory effects of 5-HT also differed in lesioned and unlesioned animals, again in region-specific ways above and below the lesion site. A role for 5-HT in promoting recovery was suggested by the potential for improvement in locomotor activity when 5-HT was applied to poorly recovered animals, and by the consistent failure of animals to recover when they were incubated in PCPA to deplete 5-HT. However, PCPA did not affect swimming in animals that had already recovered, suggesting a difference in 5-HT effects after lesioning. These results show changes in 5-HT modulation and cellular and synaptic properties after recovery from a spinal cord transection. Importantly, effects are not confined to the sub-lesion spinal cord but also occur above the lesion site. This suggests that the changes may not simply reflect compensatory responses to the loss of descending inputs, but reflect the need for co-ordinated changes above and below the lesion site. The changes in modulatory effects should be considered in pharmacological

  16. Prolonged Local Hypothermia Has No Long-Term Adverse Effect on the Spinal Cord

    PubMed Central

    Vipin, Ashwati; Kortelainen, Jukka; Al-Nashash, Hasan; Chua, Soo Min; Thow, Xinyuan; Manivannan, Janani; Astrid; Thakor, Nitish V.; Kerr, Candace L.

    2015-01-01

    Hypothermia is known to be neuroprotective and is one of the most effective and promising first-line treatments for central nervous system (CNS) trauma. At present, induction of local hypothermia, as opposed to general hypothermia, is more desired because of its ease of application and safety; fewer side effects and an absence of severe complications have been noted. Local hypothermia involves temperature reduction of a small and specific segment of the spinal cord. Our group has previously shown the neuroprotective effect of short-term, acute moderate general hypothermia through improvements in electrophysiological and motor behavioral assessments, as well as histological examination following contusive spinal cord injury (SCI) in rats. We have also shown the benefit of using short-term local hypothermia versus short-term general hypothermia post-acute SCI. The overall neuroprotective benefit of hypothermia can be categorized into three main components: (1) induction modality, general versus local, (2) invasive, semi-invasive or noninvasive, and (3) duration of hypothermia induction. In this study, a series of experiments were designed to investigate the feasibility, long-term safety, as well as eventual complications and side effects of prolonged, semi-invasive, moderate local hypothermia (30°C±0.5°C for 5 and 8 hours) in rats with uninjured spinal cord while maintaining their core temperature at 37°C±0.5°C. The weekly somatosensory evoked potential and motor behavioral (Basso, Beattie and Bresnahan) assessments of rats that underwent 5 and 8 hours of semi-invasive local hypothermia, which revealed no statistically significant changes in electrical conductivity and behavioral outcomes. In addition, 4 weeks after local hypothermia induction, histological examination showed no anatomical damages or morphological changes in their spinal cord structure and parenchyma. We concluded that this method of prolonged local hypothermia is feasible, safe, and has the

  17. Spinal cord deformation due to nozzle gas flow effects using optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Wong, Ronnie J.; Jivraj, Jamil; Vuong, Barry; Ramjist, Joel; Sun, Cuiru; Huang, Yize; Yang, Victor X. D.

    2015-03-01

    The use of gas assistance in laser machining hard materials is well established in manufacturing but not in the context of surgery. Laser cutting of osseous tissue in the context of neurosurgery can benefit from gas-assist but requires an understanding of flow and pressure effects to minimize neural tissue damage. In this study we acquire volumetric flow rates through a gas nozzle on the spinal cord, with dura and without dura.

  18. Analysis of thermal damage in vocal cords for the prevention of collateral laser treatment effects

    NASA Astrophysics Data System (ADS)

    Fanjul Vélez, Félix; Luis Arce-Diego, José; del Barrio Fernández, Ángela; Borragán Torre, Alfonso

    2007-05-01

    The importance of vocal cords for the interaction with the world around is obviously known. Vocal cords disorders can be divided mainly into three categories: difficulty of movement of one or both vocal folds, lesion formation on them, and difficulty or lack of mucosal wave movement. In this last case, a laser heating treatment can be useful in order to improve tissue vibration. However, thermal damage should be considered to adjust laser parameters and so to prevent irreversible harmful effects to the patient. in this work, an analysis of thermal damage in vocal folds is proposed. Firstly thermo-optical laser-tissue interaction is studied, by means of a RTT (Radiation Transfer Theory) model solved with a Monte Carlo approach for the optical propagation of radiation, and a bio-heat equation, with a finite difference numerical method based solution, taking into account blood perfusion and boundary effects, for the thermal distribution. The spatial-temporal temperature distributions are obtained for two widely used lasers, Nd:YAG (1064 nm) and KTP (532 nm). From these data, an Arrhenius thermal damage analysis allows a prediction of possible laser treatment harmful effects on vocal cords that could cause scar formation or tissue burn. Different source powers and exposition times are considered, in such a way that an approximation of adequate wavelength, power and duration is achieved, in order to implement an efficient and safe laser treatment.

  19. Effects of robot training on bowel function in patients with spinal cord injury.

    PubMed

    Huang, Qiuchen; Yu, Lili; Gu, Rui; Zhou, Yue; Hu, Chunying

    2015-05-01

    [Purpose] The purpose of this study was to compare the effects of body weight-supported treadmill training (BWSTT) and robot-assisted rehabilitation (RAT) on bowel function in patients with spinal cord injury with respect to defecation time and defecation drug dose (enema). [Subjects] Twenty-four patients with spinal cord injury participated in the study. All subjects had an incomplete injury ranging from level T8 to L2. [Methods] The subjects were randomly divided into BWSTT and RAT groups. Walking training was provided to both groups for 20 minutes, four times a week, for one month. The defecation time and enema dose were measured before and after the experiment. [Results] The RAT group showed significant shortening of defecation time and decrease of enema dose. [Conclusion] The results demonstrated that significantly better improvement in bowel function can be achieved with RAT. PMID:26157223

  20. Effects of Therapy in Patients Suffering from Chronic Back Pain Treated with Spinal Cord Stimulation.

    PubMed

    Mosiewicz, Anna; Rutkowska, Elżbieta; Matacz, Monika; Mosiewicz, Barbara; Kaczmarczyk, Robert; Trojanowski, Tomasz

    2015-10-01

    Pain in the lumbosacral part of the spine in the course of degenerative disease is the most common cause of physical activity limitation in adults. Treatment includes pharmacotherapy, physiotherapy, psychotherapy, health promotion, and sometimes surgery. Surgical treatment is not always successful, and the various clinical and psychosomatic symptoms that result from surgical treatment failure are known as failed back surgery syndrome. For some patients with this condition, spinal cord stimulation can provide relief. The aim of the work was to define subjective and objective spinal cord stimulation effects by assessing chosen disability and physical activity limitation ratios. Pain intensity, level of disability, and presence of neurological symptoms were assessed. The examination was performed twice: before the stimulator implantation and at least 6 months postimplantation. The study was conducted at the Department of Neurosurgery and Paediatric Neurosurgery in Lublin. Thirty-six patients suffering from failed back surgery syndrome were recruited for this study. The Visual Analog Scale, modified Laitinen's pain questionnaire, and Oswestry Disability Index were used in this work. The study showed that spinal cord stimulation was effective in treating spinal and lower limb pain in 64% of patients, similar to results obtained in other departments. Although back pain and neuropathic pain radiating to the lower limbs decreased, moderate physical activity impairment was still observed according to the Oswestry Disability Index scale. The decrease in neuropathic pain radiating to the lower limbs had the most significant influence on reducing physical activity impairment. PMID:26187548

  1. Cost-effectiveness and clinical outcomes of double versus single cord blood transplantation in adults with acute leukemia in France

    PubMed Central

    Labopin, Myriam; Ruggeri, Annalisa; Gorin, Norbert Claude; Gluckman, Eliane; Blaise, Didier; Mannone, Lionel; Milpied, Noel; Yakoub-Agha, Ibrahim; Deconinck, Eric; Michallet, Mauricette; Fegueux, Nathalie; Socié, Gerard; Nguyen, Stephanie; Cahn, Jean Yves; de Revel, Thierry; Garnier, Federico; Faucher, Catherine; Taright, Namik; Kenzey, Chantal; Volt, Fernanda; Bertrand, Dominique; Mohty, Mohamad; Rocha, Vanderson

    2014-01-01

    Double cord blood transplantation extends the use of cord blood to adults for whom a single unit is not available, but the procedure is limited by its cost. To evaluate outcomes and cost-effectiveness of double compared to single cord blood transplantation, we analyzed 134 transplants in adults with acute leukemia in first remission. Transplants were performed in France with reduced intensity or myeloablative conditioning regimens. Costs were estimated from donor search to 1 year after transplantation. A Markov decision analysis model was used to calculate quality-adjusted life-years and cost-effectiveness ratio within 4 years. The overall survival at 2 years after single and double cord blood transplants was 42% versus 62%, respectively (P=0.03), while the leukemia-free-survival was 33% versus 53%, respectively (P=0.03). The relapse rate was 21% after double transplants and 42% after a single transplant (P=0.006). No difference was observed for non-relapse mortality or chronic graft-versus-host-disease. The estimated costs up to 1 year after reduced intensity conditioning for single and double cord blood transplantation were € 165,253 and €191,827, respectively. The corresponding costs after myeloablative conditioning were € 192,566 and € 213,050, respectively. Compared to single transplants, double cord blood transplantation was associated with supplementary costs of € 21,302 and € 32,420 up to 4 years, but with increases in quality-adjusted life-years of 0.616 and 0.484, respectively, and incremental cost-effectiveness ratios of € 34,581 and €66,983 in the myeloablative and reduced intensity conditioning settings, respectively. Our results showed that for adults with acute leukemia in first complete remission in France, double cord transplantation is more cost-effective than single cord blood transplantation, with better outcomes, including quality-adjusted life-years. PMID:24143000

  2. Treadmill step training promotes spinal cord neural plasticity after incomplete spinal cord injury

    PubMed Central

    Sun, Tiansheng; Ye, Chaoqun; Wu, Jun; Zhang, Zhicheng; Cai, Yanhua; Yue, Feng

    2013-01-01

    A large body of evidence shows that spinal circuits are significantly affected by training, and that intrinsic circuits that drive locomotor tasks are located in lumbosacral spinal segments in rats with complete spinal cord transection. However, after incomplete lesions, the effect of treadmill training has been debated, which is likely because of the difficulty of separating spontaneous stepping from specific training-induced effects. In this study, rats with moderate spinal cord contusion were jected to either step training on a treadmill or used in the model (control) group. The treadmill training began at day 7 post-injury and lasted 20 ± 10 minutes per day, 5 days per week for 10 weeks. The speed of the treadmill was set to 3 m/min and was increased on a daily basis according to the tolerance of each rat. After 3 weeks of step training, the step training group exhibited a sig-nificantly greater improvement in the Basso, Beattie and Bresnahan score than the model group. The expression of growth-associated protein-43 in the spinal cord lesion site and the number of tyrosine hydroxylase-positive ventral neurons in the second lumbar spinal segment were greater in the step training group than in the model group at 11 weeks post-injury, while the levels of brain-derived neurotrophic factor protein in the spinal cord lesion site showed no difference between the two groups. These results suggest that treadmill training significantly improves functional re-covery and neural plasticity after incomplete spinal cord injury. PMID:25206564

  3. Spinal cord fusion with PEG-GNRs (TexasPEG): Neurophysiological recovery in 24 hours in rats

    PubMed Central

    Kim, C-Yoon; Sikkema, William K. A.; Hwang, In-Kyu; Oh, Hanseul; Kim, Un Jeng; Lee, Bae Hwan; Tour, James M.

    2016-01-01

    Background: The GEMINI spinal cord fusion protocol has been developed to achieve a successful cephalosomatic anastomosis. Here, for the first time, we report the effects of locally applied water-soluble, conductive PEG(polyethylene glycol)ylated graphene nanoribbons (PEG-GNRs) on neurophysiologic conduction after sharp cervical cord transection in rats. PEG-GNRs were produced by the polymerization of ethylene oxide from anion-edged graphene nanoribbons. These combine the fusogenic potential of PEG with the electrical conducting properties of the graphene nanoribbons. Methods: Laminectomy and transection of cervical spinal cord (C5) was performed on Female Sprague-Dawley (SD) rats. After applying PEG-GNR on the severed part, electrophysiological recovery of the reconstructed cervical spinal cord was confirmed by somatosensory evoked potentials (SSEPs) at 24 h after surgery. Results: While no SSEPs were detected in the control group, PEG-GNR treated group showed fast recovery of SSEPs at 24 h after the surgery. Conclusion: In this preliminary dataset, for the first time, we report the effect of a novel form of PEG with the goal of rapid reconstruction of a sharply severed spinal cord. PMID:27656326

  4. Spinal cord fusion with PEG-GNRs (TexasPEG): Neurophysiological recovery in 24 hours in rats

    PubMed Central

    Kim, C-Yoon; Sikkema, William K. A.; Hwang, In-Kyu; Oh, Hanseul; Kim, Un Jeng; Lee, Bae Hwan; Tour, James M.

    2016-01-01

    Background: The GEMINI spinal cord fusion protocol has been developed to achieve a successful cephalosomatic anastomosis. Here, for the first time, we report the effects of locally applied water-soluble, conductive PEG(polyethylene glycol)ylated graphene nanoribbons (PEG-GNRs) on neurophysiologic conduction after sharp cervical cord transection in rats. PEG-GNRs were produced by the polymerization of ethylene oxide from anion-edged graphene nanoribbons. These combine the fusogenic potential of PEG with the electrical conducting properties of the graphene nanoribbons. Methods: Laminectomy and transection of cervical spinal cord (C5) was performed on Female Sprague-Dawley (SD) rats. After applying PEG-GNR on the severed part, electrophysiological recovery of the reconstructed cervical spinal cord was confirmed by somatosensory evoked potentials (SSEPs) at 24 h after surgery. Results: While no SSEPs were detected in the control group, PEG-GNR treated group showed fast recovery of SSEPs at 24 h after the surgery. Conclusion: In this preliminary dataset, for the first time, we report the effect of a novel form of PEG with the goal of rapid reconstruction of a sharply severed spinal cord.

  5. A mechanical microconnector system for restoration of tissue continuity and long-term drug application into the injured spinal cord.

    PubMed

    Brazda, Nicole; Voss, Christian; Estrada, Veronica; Lodin, Homaira; Weinrich, Nils; Seide, Klaus; Müller, Jörg; Müller, Hans W

    2013-12-01

    Complete transection of the spinal cord leaves a gap of several mm which fills with fibrous scar tissue. Several approaches in rodent models have used tubes, foams, matrices or tissue implants to bridge this gap. Here, we describe a mechanical microconnector system (mMS) to re-adjust the retracted spinal cord stumps. The mMS is a multi-channel system of polymethylmethacrylate (PMMA), designed to fit into the spinal cord tissue gap after transection, with an outlet tubing system to apply negative pressure to the mMS thus sucking the spinal cord stumps into the honeycomb-structured holes. The stumps adhere to the microstructure of the mMS walls and remain in the mMS after removal of the vacuum. We show that the mMS preserves tissue integrity and allows axonal regrowth at 2, 5 and 19 weeks post lesion with no adverse tissue effects like in-bleeding or cyst formation. Preliminary assessment of locomotor function in the open field suggested beneficial effects of the mMS. Additional inner micro-channels enable local substance delivery into the lesion center via an attached osmotic minipump. We suggest that the mMS is a suitable device to adapt and stabilize the injured spinal cord after surgical resection of scar tissue (e.g., for chronic patients) or traumatic injuries with large tissue and bone damages.

  6. 21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted spinal cord stimulator for bladder....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal... paraplegic patient who has a complete transection of the spinal cord and who is unable to empty his or...

  7. 21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Implanted spinal cord stimulator for bladder....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal... paraplegic patient who has a complete transection of the spinal cord and who is unable to empty his or...

  8. 21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted spinal cord stimulator for bladder....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal... paraplegic patient who has a complete transection of the spinal cord and who is unable to empty his or...

  9. 21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Implanted spinal cord stimulator for bladder....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal... paraplegic patient who has a complete transection of the spinal cord and who is unable to empty his or...

  10. 21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Implanted spinal cord stimulator for bladder....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal... paraplegic patient who has a complete transection of the spinal cord and who is unable to empty his or...

  11. The effect of chronic toxicity of pethidine on the spinal cord: an experimental model in rabbits.

    PubMed

    Peştean, C; Taulescu, M; Ober, C; Cătoi, C; Miclăuş, V; Oana, L; Bodolea, C

    2013-01-01

    The aim of this study was to evaluate the toxicity of chronic spinal analgesia with pethidine in a rabbit model. We introduced epidural catheters in twenty New Zealand white rabbits, divided into two groups, and we administered 0.5 mg/kg pethidine or the same volume of normal saline through the catheters, for three consecutive days. Throughout the experiment, the animals were evaluated in terms of neurological status using the Tarlov score. After the rabbit's euthanasia, 4 μm sections of spinal cord stained with Hematoxylin-Eosin were analyzed by a pathologist blinded to the study for neurohistopathological changes. The results were statistically analyzed with Prism 5 software for Windows. No significant differences were noticed between the two groups in as far as body temperature (p=0.295) and weight (p=0.139) were concerned. In the group of animals, which received epidural pethidine, nine rabbits showed histological changes suggestive for neurotoxicity at the lumbar level of the spinal cord. These findings were significantly different compared with the control group which received only saline (no microscopic lesions revealed; p=0.0006). When combining the data from both groups or using the pethidine group alone, there was a significant correlation between the presence of neurological injury (Tarlov score) and the presence of the histopathological lesions in the spinal cord (r=-0.709, p=0.0002 and r=-0.635, p=0.013, respectively). Based on our findings, the chronic epidural administration of pethidine in rabbits induces moderate to severe histological changes on the spinal cord, but further investigations are needed to make a definitive statement about the histological effect of pethidine on the neurological tissue. PMID:24068413

  12. The effect of whole-body resonance vibration in a porcine model of spinal cord injury.

    PubMed

    Streijger, Femke; Lee, Jae H T; Chak, Jason; Dressler, Dan; Manouchehri, Neda; Okon, Elena B; Anderson, Lisa M; Melnyk, Angela D; Cripton, Peter A; Kwon, Brian K

    2015-06-15

    Whole-body vibration has been identified as a potential stressor to spinal cord injury (SCI) patients during pre-hospital transportation. However, the effect that such vibration has on the acutely injured spinal cord is largely unknown, particularly in the frequency domain of 5 Hz in which resonance of the spine occurs. The objective of the study was to investigate the consequences of resonance vibration on the injured spinal cord. Using our previously characterized porcine model of SCI, we subjected animals to resonance vibration (5.7±0.46 Hz) or no vibration for a period of 1.5 or 3.0 h. Locomotor function was assessed weekly and cerebrospinal fluid (CSF) samples were collected to assess different inflammatory and injury severity markers. Spinal cords were evaluated histologically to quantify preserved white and gray matter. No significant differences were found between groups for CSF levels of monocyte chemotactic protein-1, interleukin 6 (IL-6) and lL-8. Glial fibrillary acidic protein levels were lower in the resonance vibration group, compared with the non-vibrated control group. Spared white matter tissue was increased within the vibrated group at 7 d post-injury but this difference was not apparent at the 12-week time-point. No significant difference was observed in locomotor recovery following resonance vibration of the spine. Here, we demonstrate that exposure to resonance vibration for 1.5 or 3 h following SCI in our porcine model is not detrimental to the functional or histological outcomes. Our observation that a 3.0-h period of vibration at resonance frequency induces modest histological improvement at one week post-injury warrants further study.

  13. Effect of Robotic-Assisted Gait Training in Patients With Incomplete Spinal Cord Injury

    PubMed Central

    Shin, Ji Cheol; Kim, Ji Yong; Park, Han Kyul

    2014-01-01

    Objective To determine the effect of robotic-assisted gait training (RAGT) compared to conventional overground training. Methods Sixty patients with motor incomplete spinal cord injury (SCI) were included in a prospective, randomized clinical trial by comparing RAGT to conventional overground training. The RAGT group received RAGT three sessions per week at duration of 40 minutes with regular physiotherapy in 4 weeks. The conventional group underwent regular physiotherapy twice a day, 5 times a week. Main outcomes were lower extremity motor score of American Spinal Injury Association impairment scale (LEMS), ambulatory motor index (AMI), Spinal Cord Independence Measure III mobility section (SCIM3-M), and walking index for spinal cord injury version II (WISCI-II) scale. Results At the end of rehabilitation, both groups showed significant improvement in LEMS, AMI, SCIM3-M, and WISCI-II. Based on WISCI-II, statistically significant improvement was observed in the RAGT group. For the remaining variables, no difference was found. Conclusion RAGT combined with conventional physiotherapy could yield more improvement in ambulatory function than conventional therapy alone. RAGT should be considered as one additional tool to provide neuromuscular reeducation in patient with incomplete SCI. PMID:25566469

  14. 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 Central

    2013-01-01

    Background 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. Methods 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. Results 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

  15. Effect of Combustion Temperature on Soil and Soil Organic Matter Properties: A Study of Soils from the Western Elevation Transect in Central Sierra Nevada, California

    NASA Astrophysics Data System (ADS)

    Araya, S. N.; Berhe, A. A.

    2014-12-01

    Fire is a common ecosystem perturbation that affects many soil physical and chemical properties and soil organic matter (SOM). We investigated the effect of combustion temperatures on the physical and chemical properties of five soils from an elevation transect that spans from 210 to 2865 m.a.s.l. along the Western slope of the Sierra Nevada. All soils formed on a granitic parent material under either oak woodland, oak/mixed-conifer forest, mixed-conifer forest or subalpine mixed-conifer forest ecosystem. Soils show significant differences in SOM content and mineralogy owing to the effects of climate on soil development. Soils from 0 to 5 cm depth were combusted in a muffle furnace at six different temperatures within major fire intensity classes (150, 250, 350, 450, 550 and 650ºC). We determined the effects of combustion temperature on aggregation; specific surface area; pH; mineralogy; cation exchange capacity; carbon (C) and nitrogen (N) content; 13C and 15N isotopic composition, and distribution within aggregate sizes; and quality of SOM through infrared spectroscopy. Among other things, we found significant reduction total C and N, accumulation of aromatic carbon functional groups, and loss of aggregation with implication to loss of protection of C as the combustion temperature increases. The findings demonstrate that most significant changes in the soils physical and chemical properties occur around 350ºC. Findings from this study are critical for estimating the amount and rate of change in C and N loss, and other essential soil properties that can be expected from topsoils exposed to different intensity fires.

  16. Transect Studies, An Environmental Investigation.

    ERIC Educational Resources Information Center

    National Wildlife Federation, Washington, DC.

    This environmental unit is one of a series designed for integration within an existing curriculum. The unit is self-contained and requires minimal teacher preparation. The philosophy of the units is based on an experience-oriented process that encourages self-paced independent student work. In this unit, students make a line transect and then…

  17. Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury.

    PubMed

    Kushchayev, Sergiy V; Giers, Morgan B; Hom Eng, Doris; Martirosyan, Nikolay L; Eschbacher, Jennifer M; Mortazavi, Martin M; Theodore, Nicholas; Panitch, Alyssa; Preul, Mark C

    2016-07-01

    neuroprotective effect on the spinal cord by decreasing the magnitude of secondary injury after a lacerating spinal cord injury. Although regeneration and behavioral improvement were not observed, the reduction in disorganized scar tissue and the retention of neurons near and above the lesion are important for future regenerative efforts. In addition, this gel would be useful as the base substrate in the development of a more complex scaffold. PMID:26943251

  18. Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury.

    PubMed

    Kushchayev, Sergiy V; Giers, Morgan B; Hom Eng, Doris; Martirosyan, Nikolay L; Eschbacher, Jennifer M; Mortazavi, Martin M; Theodore, Nicholas; Panitch, Alyssa; Preul, Mark C

    2016-07-01

    neuroprotective effect on the spinal cord by decreasing the magnitude of secondary injury after a lacerating spinal cord injury. Although regeneration and behavioral improvement were not observed, the reduction in disorganized scar tissue and the retention of neurons near and above the lesion are important for future regenerative efforts. In addition, this gel would be useful as the base substrate in the development of a more complex scaffold.

  19. Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury

    PubMed Central

    Duan, Hongmei; Ge, Weihong; Zhang, Aifeng; Xi, Yue; Chen, Zhihua; Luo, Dandan; Cheng, Yin; Fan, Kevin S.; Horvath, Steve; Sofroniew, Michael V.; Cheng, Liming; Yang, Zhaoyang; Sun, Yi E.; Li, Xiaoguang

    2015-01-01

    Spinal cord injury (SCI) is considered incurable because axonal regeneration in the central nervous system (CNS) is extremely challenging, due to harsh CNS injury environment and weak intrinsic regeneration capability of CNS neurons. We discovered that neurotrophin-3 (NT3)-loaded chitosan provided an excellent microenvironment to facilitate nerve growth, new neurogenesis, and functional recovery of completely transected spinal cord in rats. To acquire mechanistic insight, we conducted a series of comprehensive transcriptome analyses of spinal cord segments at the lesion site, as well as regions immediately rostral and caudal to the lesion, over a period of 90 days after SCI. Using weighted gene coexpression network analysis (WGCNA), we established gene modules/programs corresponding to various pathological events at different times after SCI. These objective measures of gene module expression also revealed that enhanced new neurogenesis and angiogenesis, and reduced inflammatory responses were keys to conferring the effect of NT3-chitosan on regeneration. PMID:26460053

  20. Proprioceptive neuropathy affects normalization of the H-reflex by exercise after spinal cord injury

    PubMed Central

    Ollivier-Lanvin, Karen; Keeler, Benjamin E.; Siegfried, Rachel; Houlé, John D.; Lemay, Michel A.

    2009-01-01

    The H-reflex habituates at relatively low frequency (10 Hz) stimulation in the intact spinal cord, but loss of descending inhibition resulting from spinal cord transection reduces this habituation. There is a return towards a normal pattern of low-frequency habituation in the reflex activity with cycling exercise of the affected hind limbs. This implies that repetitive passive stretching of the muscles in spinalized animals and the accompanying stimulation of large (Group I and II) proprioceptive fibers has modulatory effects on spinal cord reflexes after injury. To test this hypothesis, we induced pyridoxine neurotoxicity that preferentially affects large dorsal root ganglia neurons in intact and spinalized rats. Pyridoxine or saline injections were given twice daily (IP) for 6 weeks and half of the spinalized animals were subjected to cycling exercise during that period. After 6 weeks, the tibial nerve was stimulated electrically and recordings of M and H waves were made from interosseous muscles of the hind paw. Results show that pyridoxine treatment completely eliminated the H-reflex in spinal intact animals. In contrast, transection paired with pyridoxine treatment resulted in a reduction of the frequency-dependent habituation of the H-reflex that was not affected by exercise. These results indicate that normal Group I and II afferent input is critical to achieve exercise-based reversal of hyper-reflexia of the H-reflex after spinal cord injury. PMID:19913536

  1. Effects of Gestational Magnetic Resonance Imaging on Methylation Status of Leptin Promoter in the Placenta and Cord Blood.

    PubMed

    Wang, Ying; Yan, Feng-Shan; Lian, Jian-Min; Dou, She-Wei

    2016-01-01

    Over the past two decades, magnetic resonance imaging (MRI) has been widely used for diagnosis in gestational women. Though it has several advantages, animal and human studies on the safety of MRI for the fetus remain inconclusive. Epigenetic modifications, which are crucial for cellular functioning, are prone to being affected by environmental changes. Therefore, we hypothesized that MRI during gestation may cause epigenetic modification alterations. Here, we investigated DNA methylation patterns of leptin promoter in the placenta and cord blood of women exposed to MRI during gestation. Results showed that average methylation levels of leptin in the placenta and cord blood were not affected by MRI. We also found that the methylation levels in the placenta and cord blood were not affected by different magnetic fields (1.5T and 3.0T MRI). However, if pregnant women were exposed to MRI at 15 to 20 weeks of gestation, the methylation level of leptin in cord blood was visibly lower than that of pregnant women exposed to MRI after 20-weeks of gestation (P = 0.037). mRNA expression level of leptin in cord blood was also altered, though mRNA expression of leptin in the placenta was not significantly affected. Therefore, we concluded that gestational MRI may not have major effects on the methylation level of leptin in cord blood and the placenta except for MRI applied before 20 weeks of gestation.

  2. Effects of Gestational Magnetic Resonance Imaging on Methylation Status of Leptin Promoter in the Placenta and Cord Blood.

    PubMed

    Wang, Ying; Yan, Feng-Shan; Lian, Jian-Min; Dou, She-Wei

    2016-01-01

    Over the past two decades, magnetic resonance imaging (MRI) has been widely used for diagnosis in gestational women. Though it has several advantages, animal and human studies on the safety of MRI for the fetus remain inconclusive. Epigenetic modifications, which are crucial for cellular functioning, are prone to being affected by environmental changes. Therefore, we hypothesized that MRI during gestation may cause epigenetic modification alterations. Here, we investigated DNA methylation patterns of leptin promoter in the placenta and cord blood of women exposed to MRI during gestation. Results showed that average methylation levels of leptin in the placenta and cord blood were not affected by MRI. We also found that the methylation levels in the placenta and cord blood were not affected by different magnetic fields (1.5T and 3.0T MRI). However, if pregnant women were exposed to MRI at 15 to 20 weeks of gestation, the methylation level of leptin in cord blood was visibly lower than that of pregnant women exposed to MRI after 20-weeks of gestation (P = 0.037). mRNA expression level of leptin in cord blood was also altered, though mRNA expression of leptin in the placenta was not significantly affected. Therefore, we concluded that gestational MRI may not have major effects on the methylation level of leptin in cord blood and the placenta except for MRI applied before 20 weeks of gestation. PMID:26789724

  3. Sustaining intrinsic growth capacity of adult neurons promotes spinal cord regeneration

    NASA Astrophysics Data System (ADS)

    Neumann, Simona; Skinner, Kate; Basbaum, Allan I.

    2005-11-01

    The peripheral axonal branch of primary sensory neurons readily regenerates after peripheral nerve injury, but the central branch, which courses in the dorsal columns of the spinal cord, does not. However, if a peripheral nerve is transected before a spinal cord injury, sensory neurons that course in the dorsal columns will regenerate, presumably because their intrinsic growth capacity is enhanced by the priming peripheral nerve lesion. As the effective priming lesion is made before the spinal cord injury it would clearly have no clinical utility, and unfortunately, a priming lesion made after a spinal cord injury results in an abortive regenerative response. Here, we show that two priming lesions, one made at the time of a spinal cord injury and a second 1 week after a spinal cord injury, in fact, promote dramatic regeneration, within and beyond the lesion. The first lesion, we hypothesize, enhances intrinsic growth capacity, and the second one sustains it, providing a paradigm for promoting CNS regeneration after injury. primary afferents | dorsal columns | neurite outgrowth | sprouting | priming

  4. Schwann cell coculture improves the therapeutic effect of bone marrow stromal cells on recovery in spinal cord-injured mice.

    PubMed

    Xu, Xiaoyun; Geremia, Nicole; Bao, Feng; Pniak, Anna; Rossoni, Melissa; Brown, Arthur

    2011-01-01

    Studies of bone marrow stromal cells (MSCs) transplanted into the spinal cord-injured rat give mixed results: some groups report improved locomotor recovery while others only demonstrate improved histological appearance of the lesion. These studies show no clear correlation between neurological improvements and MSC survival. We examined whether MSC survival in the injured spinal cord could be enhanced by closely matching donor and recipient mice for genetic background and marker gene expression and whether exposure of MSCs to a neural environment (Schwann cells) prior to transplantation would improve their survival or therapeutic effects. Mice underwent a clip compression spinal cord injury at the fourth thoracic level and cell transplantation 7 days later. Despite genetic matching of donors and recipients, MSC survival in the injured spinal cord was very poor (∼1%). However, we noted improved locomotor recovery accompanied by improved histopathological appearance of the lesion in mice receiving MSC grafts. These mice had more white and gray matter sparing, laminin expression, Schwann cell infiltration, and preservation of neurofilament and 5-HT-positive fibers at and below the lesion. There was also decreased collagen and chondroitin sulphate proteoglycan deposition in the scar and macrophage activation in mice that received the MSC grafts. The Schwann cell cocultured MSCs had greater effects than untreated MSCs on all these indices of recovery. Analyses of chemokine and cytokine expression revealed that MSC/Schwann cell cocultures produced far less MCP-1 and IL-6 than MSCs or Schwann cells cultured alone. Thus, transplanted MSCs may improve recovery in spinal cord-injured mice through immunosuppressive effects that can be enhanced by a Schwann cell coculturing step. These results indicate that the temporary presence of MSCs in the injured cord is sufficient to alter the cascade of pathological events that normally occurs after spinal cord injury, generating a

  5. Involvement of spinal cord opioid mechanisms in the acute antinociceptive effect of hyperbaric oxygen in mice.

    PubMed

    Heeman, Jacqueline H; Zhang, Yangmiao; Shirachi, Donald Y; Quock, Raymond M

    2013-12-01

    Earlier research has demonstrated that treatment with hyperbaric oxygen (HBO2) can elicit an antinociceptive response in models of acute pain. We have demonstrated that this antinociceptive effect is centrally-mediated and is dependent on opioid receptors. The purpose of the present study was to examine the role of endogenous opioid peptides and opioid receptors specifically in the spinal cord in the acute antinociceptive effect of HBO2 in mice. Male NIH Swiss mice were exposed to HBO2 (100% oxygen at 3.5atm absolute) for 11min and their antinociceptive responsiveness was determined using the glacial acetic acid-induced abdominal constriction test. HBO2-induced antinociception was sensitive to antagonism by intrathecal (i.t.) pretreatment with the κ- and μ-selective opioid antagonists norbinaltorphimine and β-funaltrexamine, respectively, but not the δ-selective antagonist naltrindole. The antinociceptive effect of HBO2 was also significantly attenuated by i.t. pretreatment with a rabbit antiserum against rat dynorphin1-13 but not antisera against β-endorphin or methionine-enkephalin. Based on these experimental findings, the acute antinociceptive effect of HBO2 appears to involve neuronal release of dynorphin and activation of κ- and μ-opioid receptors in the spinal cord. PMID:24113418

  6. Antinociceptive effect of ambroxol in rats with neuropathic spinal cord injury pain

    PubMed Central

    Hama, Aldric T.; Plum, Ann Woodhouse; Sagen, Jacqueline

    2010-01-01

    Symptoms of neuropathic spinal cord injury (SCI) pain include evoked cutaneous hypersensitivity and spontaneous pain, which can be present below the level of the injury. Adverse side-effects obtained with currently available analgesics complicate effective pain management in SCI patients. Voltage-gated Na+ channels expressed in primary afferent nociceptors have been identified to mediate persistent hyperexcitability in dorsal root ganglia (DRG) neurons, which in part underlies the symptoms of nerve injury-induced pain. Ambroxol has previously demonstrated antinociceptive effects in rat chronic pain models and has also shown to potently block Na+ channel current in DRG neurons. Ambroxol was tested in rats that underwent a mid-thoracic spinal cord compression injury. Injured rats demonstrated robust hind paw (below-level) heat and mechanical hypersensitivity. Orally administered ambroxol significantly attenuated below-level hypersensitivity at doses that did not affect performance on the rotarod test. Intrathecal injection of ambroxol did not ameliorate below-level hypersensitivity. The current data suggest that ambroxol could be effective for clinical neuropathic SCI pain. Furthermore, the data suggests that peripherally expressed Na+ channels could lend themselves as targets for the development of pharmacotherapies for SCI pain. PMID:20732348

  7. Antinociceptive effect of ambroxol in rats with neuropathic spinal cord injury pain.

    PubMed

    Hama, Aldric T; Plum, Ann Woodhouse; Sagen, Jacqueline

    2010-12-01

    Symptoms of neuropathic spinal cord injury (SCI) pain include evoked cutaneous hypersensitivity and spontaneous pain, which can be present below the level of the injury. Adverse side-effects obtained with currently available analgesics complicate effective pain management in SCI patients. Voltage-gated Na(+) channels expressed in primary afferent nociceptors have been identified to mediate persistent hyperexcitability in dorsal root ganglia (DRG) neurons, which in part underlies the symptoms of nerve injury-induced pain. Ambroxol has previously demonstrated antinociceptive effects in rat chronic pain models and has also shown to potently block Na(+) channel current in DRG neurons. Ambroxol was tested in rats that underwent a mid-thoracic spinal cord compression injury. Injured rats demonstrated robust hind paw (below-level) heat and mechanical hypersensitivity. Orally administered ambroxol significantly attenuated below-level hypersensitivity at doses that did not affect performance on the rotarod test. Intrathecal injection of ambroxol did not ameliorate below-level hypersensitivity. The current data suggest that ambroxol could be effective for clinical neuropathic SCI pain. Furthermore, the data suggest that peripherally expressed Na(+) channels could lend themselves as targets for the development of pharmacotherapies for SCI pain.

  8. Comparative neuroprotective effect of sodium channel blockers after experimental spinal cord injury.

    PubMed

    Ates, Ozkan; Cayli, Suleyman R; Gurses, Ilal; Turkoz, Yusuf; Tarim, Ozcan; Cakir, Celal O; Kocak, Ayhan

    2007-07-01

    Spinal cord injury (SCI) results in loss of function below the lesion. Secondary injury following the primary impact includes a number of biochemical and cellular alterations leading to tissue necrosis and cell death. Influx of Na(+) ions into cells has been postulated to be a key early event in the pathogenesis of secondary traumatic and ischemic central nervous system injury. Previous studies have shown that some voltage-sensitive sodium channel blockers provide powerful neuroprotection. The purpose of the present study was to compare the neuroprotective effect of three sodium channel blockers-mexiletine, phenytoin and riluzole--after SCI. Ninety rats were randomly and blindly divided into five groups of 18 rats each: sham-operated group, trauma group (bolus injection of 1 mL physiological saline intraperiteonally [i.p.]), mexiletine treatment group (80 mg/kg, i.p.), phenytoin treatment group (200 mg/kg, i.p.) and riluzole treatment group (8 mg/kg, i.p.). Twenty-four hours after injury, the rats were killed for determination of spinal cord water content and malondialdehyde (MDA) levels. Motor function scores of six rats from each group were evaluated weekly for six weeks. Then the rats were killed for histopathological assessment. Although all the treatment groups revealed significantly lower MDA levels and spinal cord edema than the trauma group (p<0.05), the riluzole and mexiletine treatment groups were better than the phenytoin treatment group. In the chronic stage, riluzole and mexiletine treatment achieved better results for neurobehavioral and histopathological recovery than phenytoin treatment. In conclusion, all the tested Na(+) blockers had a neuroprotective effect after SCI; riluzole and mexiletine were superior to phenytoin. PMID:17532502

  9. 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.

  10. Raman-based imaging uncovers the effects of alginate hydrogel implants in spinal cord injury

    NASA Astrophysics Data System (ADS)

    Galli, Roberta; Tamosaityte, Sandra; Koch, Maria; Sitoci-Ficici, Kerim H.; Later, Robert; Uckermann, Ortrud; Beiermeister, Rudolf; Gelinsky, Michael; Schackert, Gabriele; Kirsch, Matthias; Koch, Edmund; Steiner, Gerald

    2015-07-01

    The treatment of spinal cord injury by using implants that provide a permissive environment for axonal growth is in the focus of the research for regenerative therapies. Here, Raman-based label-free techniques were applied for the characterization of morphochemical properties of surgically induced spinal cord injury in the rat that received an implant of soft unfunctionalized alginate hydrogel. Raman microspectroscopy followed by chemometrics allowed mapping the different degenerative areas, while multimodal multiphoton microscopy (e.g. the combination of coherent anti-Stokes Raman scattering (CARS), endogenous two-photon fluorescence and second harmonic generation on the same platform) enabled to address the morphochemistry of the tissue at cellular level. The regions of injury, characterized by demyelination and scarring, were retrieved and the distribution of key tissue components was evaluated by Raman mapping. The alginate hydrogel was detected in the lesion up to six months after implantation and had positive effects on the nervous tissue. For instance, multimodal multiphoton microscopy complemented the results of Raman mapping, providing the micromorphology of lipid-rich tissue structures by CARS and enabling to discern lipid-rich regions that contained myelinated axons from degenerative regions characterized by myelin fragmentation and presence of foam cells. These findings demonstrate that Raman-based imaging methods provide useful information for the evaluation of alginate implant effects and have therefore the potential to contribute to new strategies for monitoring degenerative and regenerative processes induced in SCI, thereby improving the effectiveness of therapies.

  11. Spinal cord pathways involved in initiation of swimming in the stingray, Dasyatis sabina: spinal cord stimulation and lesions.

    PubMed

    Williams, B J; Livingston, C A; Leonard, R B

    1984-03-01

    In spinally transected stingrays, electrical stimulation of a site just ventral to the dorsal root entry zone or a site in the intermediate portions of the lateral funiculus produced rhythmic swimming like movements of the contralateral pectoral fin. Electromyographic (EMG) records collected during cord-stimulated rhythms had the same pattern of activity and sometimes the same intersegmental coordination as those collected during spontaneous swimming of the same animal. In paralyzed, high-spinal stingrays, the only stimulation sites that produced rhythmic activity (fictive swimming) in the pectoral fin motor nerves were in the intermediate portion of the lateral funiculus. The evoked rhythm occurred in the motor nerves that were contralateral to the stimulated side of the spinal cord. The effects of subtotal lesions of the rostral spinal cord on spontaneous swimming behavior were assessed by analysis of EMG records taken before and after the lesions were made. Severe deficits in swimming occurred after bilateral ablation of intermediate portions of the lateral funiculi. In agreement with previous results, the stimulation experiments indicate that the stingray spinal cord contains an inherent capacity to generate properly coordinated rhythmic swimming. The current experiments also suggest that the descending pathways(s) that normally functions to initiate swimming projects through the intermediate aspects of the lateral funiculi. PMID:6699678

  12. The Effects of Difumarate Salt S-15176 after Spinal Cord Injury in Rats

    PubMed Central

    Tunçdemir, Matem; Kelten, Bilal; Akdemir, Osman; Karaoğlan, Alper; Taşdemiroğlu, Erol

    2015-01-01

    Objective In the present study we analyzed neuroprotective and antiapoptotic effect of the difumarate salt S-15176, as an anti-ischemic, an antioxidant and a stabilizer of mitochondrial membrane in secondary damage following spinal cord injury (SCI) in a rat model. Methods Three groups were performed with 30 Wistar rats; control (1), trauma (2), and a trauma+S-15176 (10 mg/kg i.p., dimethyl sulfoxide) treatment (3). SCI was performed at the thoracic level using the weight-drop technique. Spinal cord tissues were collected following intracardiac perfusion in 3rd and 7th days of posttrauma. Hematoxylin and eosin staining for histopatology, terminal deoxynucleotidyl transferase dUTP nick end labeling assay for apoptotic cells and immunohistochemistry for proapoptotic cytochrome-c, Bax and caspase 9 were performed to all groups. Functional recovery test were applied to each group in 3rd and 7th days following SCI. Results In trauma group, edematous regions, diffuse hemorrhage, necrosis, leukocyte infiltration and severe degeneration in motor neurons were observed prominently in gray matter. The number of apoptotic cells was significantly higher (p<0.05) than control group. In the S-15176-treated groups, apoptotic cell number in 3rd and 7th days (p<0.001), also cytochrome-c (p<0.001), Bax (p<0.001) and caspase 9 immunoreactive cells (p<0.001) were significantly decreased in number compared to trauma groups. Hemorrhage and edema in the focal areas were also noticed in gray matter of treatment groups. Results of the locomotor test were significantly increased in treatment group (p<0.05) when compared to trauma groups. Conclusion We suggest that difumarate salt S-15176 prevents mitochondrial pathways of apoptosis and protects spinal cord from secondary injury and helps to preserve motor function following SCI in rats. PMID:26180614

  13. Transition from fetal to neonatal circulation: Modeling the effect of umbilical cord clamping.

    PubMed

    Yigit, Mehmet B; Kowalski, William J; Hutchon, David J R; Pekkan, Kerem

    2015-06-25

    Hemodynamics of the fetal to neonatal transition are orchestrated through complex physiological changes and results in cardiovascular adaptation to the adult biventricular circulation. Clinical practice during this critical period can influence vital organ physiology for normal newborns, premature babies and congenital heart defect patients. Particularly, the timing of the cord clamping procedure, immediate (ICC) vs. delayed cord clamping (DCC), is hypothesized to be an important factor for the transitory fetal hemodynamics. The clinical need for a quantitative understanding of this physiology motivated the development of a lumped parameter model (LPM) of the fetal cardio-respiratory system covering the late-gestation to neonatal period. The LPM was validated with in vivo clinical data and then used to predict the effects of cord clamping procedures on hemodynamics and vital gases. Clinical time-dependent resistance functions to simulate the vascular changes were introduced. For DCC, placental transfusion (31.3 ml) increased neonatal blood volume by 11.7%. This increased blood volume is reflected in an increase in preload pressures by ~20% compared to ICC, which in turn increased the cardiac output (CO) by 20% (COICC=993 ml/min; CODCC=1197 ml/min). Our model accurately predicted dynamic flow patterns in vivo. DCC was shown to maintain oxygenation if the onset of pulmonary respiration was delayed or impaired. On the other hand, a significant 25% decrease in oxygen saturations was observed when applying ICC under the same physiological conditions. We conclude that DCC has a significant impact on newborn hemodynamics, mainly because of the improved blood volume and the sustained placental respiration.

  14. Protective effect of rosemary on acrylamide motor neurotoxicity in spinal cord of rat offspring: postnatal follow-up study

    PubMed Central

    Al-Gholam, Marwa A.; El-Mehi, Abeer E.; El-Barbary, Abd El-Moneum; Fokar, Ahmed Zo El

    2016-01-01

    The direct interactive effects of rosemary and acrylamide on the development of motor neurons in the spinal cord remains unknown. Our goal is to confirm the protective effects of rosemary against motor neuronal degeneration induced by acrylamide in the developing postnatal rat spinal cord using a postnatal rat model. We assigned the offspring of treated female rats into control, rosemary; acrylamide group; and recovery groups. This work depended on clinical, histopathological, morphometrically, immunohistochemical and genetic methods. In the acrylamide group, we observed oxidation, motor neuron degeneration, apoptosis, myelin degeneration, neurofilament reduction, reactive gliosis. Whoever, concomitant rosemary intake and withdrawal of acrylamide modulate these effects. These findings proof that dietary rosemary can directly protect motor neuron against acrylamide toxicity in the mammalian developing spinal cord. PMID:27051566

  15. Protective effect of rosemary on acrylamide motor neurotoxicity in spinal cord of rat offspring: postnatal follow-up study.

    PubMed

    Al-Gholam, Marwa A; Nooh, Hanaa Zakaria; El-Mehi, Abeer E; El-Barbary, Abd El-Moneum; Fokar, Ahmed Zo El

    2016-03-01

    The direct interactive effects of rosemary and acrylamide on the development of motor neurons in the spinal cord remains unknown. Our goal is to confirm the protective effects of rosemary against motor neuronal degeneration induced by acrylamide in the developing postnatal rat spinal cord using a postnatal rat model. We assigned the offspring of treated female rats into control, rosemary; acrylamide group; and recovery groups. This work depended on clinical, histopathological, morphometrically, immunohistochemical and genetic methods. In the acrylamide group, we observed oxidation, motor neuron degeneration, apoptosis, myelin degeneration, neurofilament reduction, reactive gliosis. Whoever, concomitant rosemary intake and withdrawal of acrylamide modulate these effects. These findings proof that dietary rosemary can directly protect motor neuron against acrylamide toxicity in the mammalian developing spinal cord. PMID:27051566

  16. Protective effect of rosemary on acrylamide motor neurotoxicity in spinal cord of rat offspring: postnatal follow-up study.

    PubMed

    Al-Gholam, Marwa A; Nooh, Hanaa Zakaria; El-Mehi, Abeer E; El-Barbary, Abd El-Moneum; Fokar, Ahmed Zo El

    2016-03-01

    The direct interactive effects of rosemary and acrylamide on the development of motor neurons in the spinal cord remains unknown. Our goal is to confirm the protective effects of rosemary against motor neuronal degeneration induced by acrylamide in the developing postnatal rat spinal cord using a postnatal rat model. We assigned the offspring of treated female rats into control, rosemary; acrylamide group; and recovery groups. This work depended on clinical, histopathological, morphometrically, immunohistochemical and genetic methods. In the acrylamide group, we observed oxidation, motor neuron degeneration, apoptosis, myelin degeneration, neurofilament reduction, reactive gliosis. Whoever, concomitant rosemary intake and withdrawal of acrylamide modulate these effects. These findings proof that dietary rosemary can directly protect motor neuron against acrylamide toxicity in the mammalian developing spinal cord.

  17. The effect of increased T2 signal intensity in the spinal cord on the injury severity and early neurological recovery in patients with central cord syndrome.

    PubMed

    Schroeder, Gregory D; Hjelm, Nik; Vaccaro, Alexander R; Weinstein, Michael S; Kepler, Christopher K

    2016-05-01

    OBJECTIVE The aim of this paper was to compare the severity of the initial neurological injury as well as the early changes in the American Spinal Injury Association (ASIA) motor score (AMS) between central cord syndrome (CCS) patients with and without an increased T2 signal intensity in their spinal cord. METHODS Patients with CCS were identified and stratified based on the presence of increased T2 signal intensity in their spinal cord. The severity of the initial neurological injury and the progression of the neurological injury over the 1st week were measured according to the patient's AMS. The effect of age, sex, congenital stenosis, surgery within 24 hours, and surgery in the initial hospitalization on the change in AMS was determined using an analysis of variance. RESULTS Patients with increased signal intensity had a more severe initial neurological injury (AMS 57.6 vs 75.3, respectively, p = 0.01). However, the change in AMS over the 1st week was less severe in patients with an increase in T2 signal intensity (-0.85 vs -4.3, p = 0.07). Analysis of variance did not find that age, sex, Injury Severity Score, congenital stenosis, surgery within 24 hours, or surgery during the initial hospitalization affected the change in AMS. CONCLUSIONS The neurological injury is different between patients with and without an increased T2 signal intensity. Patients with an increased T2 signal intensity are likely to have a more severe initial neurological deficit but will have relatively minimal early neurological deterioration. Comparatively, patients without an increase in the T2 signal intensity will likely have a less severe initial injury but can expect to have a slight decline in neurological function in the 1st week.

  18. Tamoxifen: an FDA approved drug with neuroprotective effects for spinal cord injury recovery.

    PubMed

    Colón, Jennifer M; Miranda, Jorge D

    2016-08-01

    Spinal cord injury (SCI) is a condition without a cure, affecting sensory and/or motor functions. The physical trauma to the spinal cord initiates a cascade of molecular and cellular events that generates a non-permissive environment for cell survival and axonal regeneration. Among these complex set of events are damage of the blood-brain barrier, edema formation, inflammation, oxidative stress, demyelination, reactive gliosis and apoptosis. The multiple events activated after SCI require a multi-active drug that could target most of these events and produce a permissive environment for cell survival, regeneration, vascular reorganization and synaptic formation. Tamoxifen, a selective estrogen receptor modulator, is an FDA approved drug with several neuroprotective properties that should be considered for the treatment of this devastating condition. Various investigators using different animal models and injury parameters have demonstrated the beneficial effects of this drug to improve functional locomotor recovery after SCI. Results suggest that the mechanism of action of Tamoxifen administration is to modulate anti-oxidant, anti-inflammatory and anti-gliotic responses. A gap of knowledge exists regarding the sex differences in response to Tamoxifen and the therapeutic window available to administer this treatment. In addition, the effects of Tamoxifen in axonal outgrowth or synapse formation needs to be investigated. This review will address some of the mechanisms activated by Tamoxifen after SCI and the results recently published by investigators in the field. PMID:27651756

  19. Tamoxifen: an FDA approved drug with neuroprotective effects for spinal cord injury recovery

    PubMed Central

    Colón, Jennifer M.; Miranda, Jorge D.

    2016-01-01

    Spinal cord injury (SCI) is a condition without a cure, affecting sensory and/or motor functions. The physical trauma to the spinal cord initiates a cascade of molecular and cellular events that generates a non-permissive environment for cell survival and axonal regeneration. Among these complex set of events are damage of the blood-brain barrier, edema formation, inflammation, oxidative stress, demyelination, reactive gliosis and apoptosis. The multiple events activated after SCI require a multi-active drug that could target most of these events and produce a permissive environment for cell survival, regeneration, vascular reorganization and synaptic formation. Tamoxifen, a selective estrogen receptor modulator, is an FDA approved drug with several neuroprotective properties that should be considered for the treatment of this devastating condition. Various investigators using different animal models and injury parameters have demonstrated the beneficial effects of this drug to improve functional locomotor recovery after SCI. Results suggest that the mechanism of action of Tamoxifen administration is to modulate anti-oxidant, anti-inflammatory and anti-gliotic responses. A gap of knowledge exists regarding the sex differences in response to Tamoxifen and the therapeutic window available to administer this treatment. In addition, the effects of Tamoxifen in axonal outgrowth or synapse formation needs to be investigated. This review will address some of the mechanisms activated by Tamoxifen after SCI and the results recently published by investigators in the field. PMID:27651756

  20. Tamoxifen: an FDA approved drug with neuroprotective effects for spinal cord injury recovery

    PubMed Central

    Colón, Jennifer M.; Miranda, Jorge D.

    2016-01-01

    Spinal cord injury (SCI) is a condition without a cure, affecting sensory and/or motor functions. The physical trauma to the spinal cord initiates a cascade of molecular and cellular events that generates a non-permissive environment for cell survival and axonal regeneration. Among these complex set of events are damage of the blood-brain barrier, edema formation, inflammation, oxidative stress, demyelination, reactive gliosis and apoptosis. The multiple events activated after SCI require a multi-active drug that could target most of these events and produce a permissive environment for cell survival, regeneration, vascular reorganization and synaptic formation. Tamoxifen, a selective estrogen receptor modulator, is an FDA approved drug with several neuroprotective properties that should be considered for the treatment of this devastating condition. Various investigators using different animal models and injury parameters have demonstrated the beneficial effects of this drug to improve functional locomotor recovery after SCI. Results suggest that the mechanism of action of Tamoxifen administration is to modulate anti-oxidant, anti-inflammatory and anti-gliotic responses. A gap of knowledge exists regarding the sex differences in response to Tamoxifen and the therapeutic window available to administer this treatment. In addition, the effects of Tamoxifen in axonal outgrowth or synapse formation needs to be investigated. This review will address some of the mechanisms activated by Tamoxifen after SCI and the results recently published by investigators in the field.

  1. Central neuromechanisms underlying control of intragastric pressure through acupuncture at Zusanli (ST36) in rats: the upper cervical cord is the key link between the ascending and descending pathways

    PubMed Central

    Yong, Chun-yan; Chen, Shu; Chen, Heng; Chu, Xiao; Zhang, Chao; Tan, Cheng; Ye, Lan; Li, Jiang-shan

    2016-01-01

    Sensory inputs stimulated by Zusanli (ST36) acupuncture in the abdomen are known to converge in the upper cervical cord. However, it is unclear whether these inputs are subsequently conveyed to the hypothalamic paraventricular nucleus and what kind of afferent fibers are involved. We focused on the upper cervical cord, where afferent inputs converge, and detected c-fos expression in oxytocinergic neurons. We found that Zusanli acupuncture therapy effectively elevated intragastric pressure, but inhibited expression of c-fos in oxytocinergic neurons of the paraventricular nucleus in upper cervical cord injured rats. These Zusanli acupuncture effects remained even after complete dorsal cord transection. However, after complete transection of the spinal cord or dorsolateral funiculus, the effects were significantly attenuated and even disappeared. These findings suggest that the paraventricular nucleus is responsible for pooling and integrating signals from the Zusanli acupuncture and sensory information from the intragastric pressure variation, thereby contributing to the regulation of intragastric pressure. The upper cervical cord serves as the key link between ascending and descending pathways, which conveys afferent inputs to the paraventricular nucleus through the dorsolateral funiculus. PMID:27482227

  2. Estimation of fractal dimensions from transect data

    SciTech Connect

    Loehle, C.

    1994-04-01

    Fractals are a useful tool for analyzing the topology of objects such as coral reefs, forest canopies, and landscapes. Transects are often studied in these contexts, and fractal dimensions computed from them. An open question is how representative a single transect is. Transects may also be used to estimate the dimensionality of a surface. Again the question of representativeness of the transect arises. These two issues are related. This note qualifies the conditions under which transect data may be considered to be representative or may be extrapolated, based on both theoretical and empirical results.

  3. Cost-effectiveness of surgery plus radiotherapy versus radiotherapy alone for metastatic epidural spinal cord compression

    SciTech Connect

    Thomas, Kenneth C.; Nosyk, Bohdan; Fisher, Charles G.; Dvorak, Marcel; Patchell, Roy A.; Regine, William F.; Loblaw, Andrew; Bansback, Nick; Guh, Daphne; Sun, Huiying; Anis, Aslam . E-mail: aslam.anis@ubc.ca

    2006-11-15

    Purpose: A recent randomized clinical trial has demonstrated that direct decompressive surgery plus radiotherapy was superior to radiotherapy alone for the treatment of metastatic epidural spinal cord compression. The current study compared the cost-effectiveness of the two approaches. Methods and Materials: In the original clinical trial, clinical effectiveness was measured by ambulation and survival time until death. In this study, an incremental cost-effectiveness analysis was performed from a societal perspective. Costs related to treatment and posttreatment care were estimated and extended to the lifetime of the cohort. Weibull regression was applied to extrapolate outcomes in the presence of censored clinical effectiveness data. Results: From a societal perspective, the baseline incremental cost-effectiveness ratio (ICER) was found to be $60 per additional day of ambulation (all costs in 2003 Canadian dollars). Using probabilistic sensitivity analysis, 50% of all generated ICERs were lower than $57, and 95% were lower than $242 per additional day of ambulation. This analysis had a 95% CI of -$72.74 to 309.44, meaning that this intervention ranged from a financial savings of $72.74 to a cost of $309.44 per additional day of ambulation. Using survival as the measure of effectiveness resulted in an ICER of $30,940 per life-year gained. Conclusions: We found strong evidence that treatment of metastatic epidural spinal cord compression with surgery in addition to radiotherapy is cost-effective both in terms of cost per additional day of ambulation, and cost per life-year gained.

  4. Gastrodin ameliorates spinal cord injury via antioxidant and anti-inflammatory effects.

    PubMed

    Du, Fangtao; Wang, Xiaoning; Shang, Bo; Fang, Jifeng; Xi, Yuting; Li, Aijuan; Diao, Yenze

    2016-01-01

    Spinal cord injury (SCI) is one of the most severe traumatic injuries that results in dysfunction of limbs and trunk below the damaged section. Recent studies have shown that gastrodin (GAS) could improve the recovery of SCI. In the current study, we aimed to examine the possible mechanism underlying the effect of GAS on recovery of SCI in rats. In rats with SCI, GAS improved locomotor functions and decreased permeability of blood-spinal cord barrier, as illustrated by increase of Basso-Beattie-Bresnahan scores and decrease of Evans blue leakage. In addition, GAS inhibited inflammation, as evidenced by decrease of proinflammatory cytokines, including tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β) in rats following SCI. Moreover, increase of TBARS content and decrease of glutathione (GSH) content and superoxide dismutase (SOD) activities in SCI rats were inhibited by GAS. Furthermore, GAS enhanced mRNA expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), catalytic subunit of γ-glutamylcysteine ligase (GCLc) and modified subunit of γ-glutamylcysteine ligase (GCLm). The data suggested that GAS may promote the recovery of SCI through the enhancement of Nrf2-GCLc/GCLm signaling pathway, and subsequent improvement of oxidative stress and inflammation, resulting in decrease of permeability of BSCB and improved recovery of locomotor function in rats with SCI. The results have provided novel insights into GAS-related therapy of SCI and associated neurodegenerative diseases. PMID:27474401

  5. Effects of cord compression on fetal blood flow distribution and O/sub 2/ delivery

    SciTech Connect

    Itskovitz, J.; LaGamma, E.F.; Rudolph, A.M.

    1987-01-01

    The authors used the radionuclide microsphere technique in nine fetal lambs to examine the effect of partial cord compression on distribution of cardiac output and O/sub 2/ delivery to fetal organs and venous flow patterns. With a 50% reduction in umbilical blood flow the fraction of fetal cardiac output distributed to the brain, heart, carcass, kidneys, and gastrointestinal tract increased. Pulmonary blood flow fell. O/sub 2/ delivery to the brain and myocardium was maintained but was reduced to peripheral, renal, and gastrointestinal circulations. Hepatic blood flow decreased and O/sub 2/ delivery fell by 75%. The proportion of umbilical venous blood passing through the ductus venosus increased from 43.9 to 71.8%. The preferential distribution of ductus venosus blood flow through the foramen ovale was enhanced and the proportion of O/sub 2/ delivery to upper body organs derived from the ductus venosus increased. Abdominal inferior vena caval blood flow increased, and it was also preferentially distributed through the foramen ovale and constituted the major fraction of the arterial blood supply to the upper body organs. Thus cord compression modified the distribution of cardiac output and the patterns of venous returns in the fetus. This pattern of circulatory response differs from that observed with other causes of reduced O/sub 2/ delivery.

  6. Effect of exercise on neurogenic inflammation in spinal cord of Type 1 diabetic rats.

    PubMed

    Thakur, Vikram; Gonzalez, Mayra; Pennington, Kristen; Nargis, Syeda; Chattopadhyay, Munmun

    2016-07-01

    Neuropathy is a long-standing and hard to treat complication of diabetes that interferes almost 25-30% of diabetic patients and impacts the quality of life of the patients. Unforeseen side effects, dependency and addiction made the existing medical treatments comparatively ineffective. A number of studies indicate that moderate physical activity provides health-related advantages. However, existing data do not confirm whether regular physical activity would reduce the amount of inflammation in the nervous system of the subjects with Type 1 diabetes. This study reveals the significance of exercise to alleviate inflammation in the spinal cord of the nervous system and preserve sensory nerve function in animals with Type 1 diabetes after 6 weeks of exercise paradigm. Streptozotocin-diabetic animals were placed in motorized running wheels for sixty minutes per day, for five days a week for 6 weeks starting at one week after diabetes. Emerging evidence suggests that the increases in inflammatory mediators play an important role in the development of sensory neuropathy. This study shows that moderate exercise can reduce the release of a number of proinflammatory cytokines in the dorsal horn (DH) of spinal cord, subsequently delaying the development of neuropathy along with an increase in the anti-inflammatory mediator IL10 in the DH. In general, this study indicates that exercise may provide an alternative to the treatment for sensory neuropathy in Type 1 diabetic subjects via reducing the use of medication and providing an easier way to manage neuropathy. PMID:27018295

  7. Therapeutic Effects of Traditional Chinese Medicine on Spinal Cord Injury: A Promising Supplementary Treatment in Future.

    PubMed

    Zhang, Qian; Yang, Hao; An, Jing; Zhang, Rui; Chen, Bo; Hao, Ding-Jun

    2016-01-01

    Objective. Spinal cord injury (SCI) is a devastating neurological disorder caused by trauma. Pathophysiological events occurring after SCI include acute, subacute, and chronic phases, while complex mechanisms are comprised. As an abundant source of natural drugs, Traditional Chinese Medicine (TCM) attracts much attention in SCI treatment recently. Hence, this review provides an overview of pathophysiology of SCI and TCM application in its therapy. Methods. Information was collected from articles published in peer-reviewed journals via electronic search (PubMed, SciFinder, Google Scholar, Web of Science, and CNKI), as well as from master's dissertations, doctoral dissertations, and Chinese Pharmacopoeia. Results. Both active ingredients and herbs could exert prevention and treatment against SCI, which is linked to antioxidant, anti-inflammatory, neuroprotective, or antiapoptosis effects. The detailed information of six active natural ingredients (i.e., curcumin, resveratrol, epigallocatechin gallate, ligustrazine, quercitrin, and puerarin) and five commonly used herbs (i.e., Danshen, Ginkgo, Ginseng, Notoginseng, and Astragali Radix) was elucidated and summarized. Conclusions. As an important supplementary treatment, TCM may provide benefits in repair of injured spinal cord. With a general consensus that future clinical approaches will be diversified and a combination of multiple strategies, TCM is likely to attract greater attention in SCI treatment. PMID:27118982

  8. Effects of electrode geometry and combination on nerve fibre selectivity in spinal cord stimulation.

    PubMed

    Holsheimer, J; Struijk, J J; Tas, N R

    1995-09-01

    The differential effects of the geometry of a rostrocaudal array of electrode contacts on dorsal column fibre and dorsal root fibre activation in spinal cord stimulation are analysed theoretically. 3-D models of the mid-cervical and mid-thoracic vertebral areas are used for the computation of stimulation induced field potentials, whereas a cable model of myelinated nerve fibre is used for the calculation of the excitation thresholds of large dorsal column and dorsal root fibres. The size and spacing of 2-D rectangular electrode contacts are varied while mono-, bi- and tripolar stimulation are applied. The model predicts that the highest preferential stimulation of dorsal root fibres is obtained in monopolar stimulation with a large cathode, whereas dorsal column fibre preference is highest in tripolar stimulation with small contacts and small contact spacings. Fibre type preference is most sensitive to variations of rostrocaudal contact size and least sensitive to variations of lateral contact size. Dorsal root fibre preference is increased and sensitivity to lead geometry is reduced as the distance from contacts to spinal cord is increased.

  9. Therapeutic Effects of Traditional Chinese Medicine on Spinal Cord Injury: A Promising Supplementary Treatment in Future

    PubMed Central

    Zhang, Qian; Yang, Hao; An, Jing; Zhang, Rui; Chen, Bo; Hao, Ding-Jun

    2016-01-01

    Objective. Spinal cord injury (SCI) is a devastating neurological disorder caused by trauma. Pathophysiological events occurring after SCI include acute, subacute, and chronic phases, while complex mechanisms are comprised. As an abundant source of natural drugs, Traditional Chinese Medicine (TCM) attracts much attention in SCI treatment recently. Hence, this review provides an overview of pathophysiology of SCI and TCM application in its therapy. Methods. Information was collected from articles published in peer-reviewed journals via electronic search (PubMed, SciFinder, Google Scholar, Web of Science, and CNKI), as well as from master's dissertations, doctoral dissertations, and Chinese Pharmacopoeia. Results. Both active ingredients and herbs could exert prevention and treatment against SCI, which is linked to antioxidant, anti-inflammatory, neuroprotective, or antiapoptosis effects. The detailed information of six active natural ingredients (i.e., curcumin, resveratrol, epigallocatechin gallate, ligustrazine, quercitrin, and puerarin) and five commonly used herbs (i.e., Danshen, Ginkgo, Ginseng, Notoginseng, and Astragali Radix) was elucidated and summarized. Conclusions. As an important supplementary treatment, TCM may provide benefits in repair of injured spinal cord. With a general consensus that future clinical approaches will be diversified and a combination of multiple strategies, TCM is likely to attract greater attention in SCI treatment. PMID:27118982

  10. Serine-threonine protein kinase activation may be an effective target for reducing neuronal apoptosis after spinal cord injury

    PubMed Central

    Jin, Mu; Yang, Yan-wei; Cheng, Wei-ping; Lu, Jia-kai; Hou, Si-yu; Dong, Xiu-hua; Liu, Shi-yao

    2015-01-01

    The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, including extracellular signal-regulated kinase (ERK), serine-threonine protein kinase (Akt) and c-Jun N-terminal kinase (JNK) signaling pathways. We established a rat model of acute spinal cord injury by inserting a catheter balloon in the left subclavian artery for 25 minutes. Rat models exhibited notable hindlimb dysfunction. Apoptotic cells were abundant in the anterior horn and central canal of the spinal cord. The number of apoptotic neurons was highest 48 hours post injury. The expression of phosphorylated Akt (p-Akt) and phosphorylated ERK (p-ERK) increased immediately after reperfusion, peaked at 4 hours (p-Akt) or 2 hours (p-ERK), decreased at 12 hours, and then increased at 24 hours. Phosphorylated JNK expression reduced after reperfusion, increased at 12 hours to near normal levels, and then showed a downward trend at 24 hours. Pearson linear correlation analysis also demonstrated that the number of apoptotic cells negatively correlated with p-Akt expression. These findings suggest that activation of Akt may be a key contributing factor in the delay of neuronal apoptosis after spinal cord ischemia, particularly at the stage of reperfusion, and thus may be a target for neuronal protection and reduction of neuronal apoptosis after spinal cord injury. PMID:26807120

  11. 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

  12. Autologous umbilical cord blood transfusion.

    PubMed Central

    Ballin, A.; Arbel, E.; Kenet, G.; Berar, M.; Kohelet, D.; Tanay, A.; Zakut, H.; Meytes, D.

    1995-01-01

    The purpose of this study was to examine some aspects of umbilical cord blood collection for autologous transfusion in premature infants. All 120 microbacterial cultures (aerobic and anaerobic) of cord blood samples as well as 30 cultures of mycoplasma were treated. Cord prothrombin fragment (F 1 + 2) concentrations were quantified at one and 10 minutes after clamping of the cord. F 1 + 2 concentrations assessed on 25 newborn infants were similar and no linear association with time of clamping could be drawn. This means that cord blood thrombosis is not activated for at least 10 minutes following clamping of the cord. As far as is known, the first newborn infant to benefit from this method of transfusion is reported here. The premature infant received two portions of autologous blood (on days 5 and 7). No untoward effects were noted. Blood, collected from the umbilical cord, is a safe source for autotransfusion, provided that bacteriological testing has been carried out. PMID:8535878

  13. Neuroprotective effects of atomoxetine against traumatic spinal cord injury in rats

    PubMed Central

    Hou, Qing-Xian; Yu, Li; Tian, Shao-Qi; Jiang, Cui-Jun; Yang, Wen-Jiu; Wang, Zhi-Jie

    2016-01-01

    Objective(s): Spinal cord injury (SCI) often causes serious and irreversible neurological deficit leading to disability or impairment of normal physical activity. Atomoxetine, a selective norepinephrine transporter (NET) inhibitor has gained much attention in the field of the neurodevelopmental disorder, but its effect on SCI has not been evaluated. The present study has been undertaken to investigate the neuroprotective effects of atomoxetine. Materials and Methods: Administration of atomoxetine 20 mg/kg IP was compared with methylprednisolone (MP) 30 mg/kg IP in traumatic spinal cord injured Wistar rats. Tissue samples were evaluated for apoptosis, inflammation, and oxidative stress, along with histopathological examination and neurological evaluation. Results: There was no significant difference in the caspase-3 activity between the control and the sham groups or between the MP and the atomoxetine groups (P=0.811). The administration of atomoxetine significantly reduced tissue tumour necrosis factor alpha (TNF-α), and nitric oxide (NO) levels compared to the trauma group (P<0.001). Treatment with atomoxetine also decreased the tissue myeloperoxidase (MPO) activity (P=0.026) and increased the tissue superoxide dismutase (SOD) activity compared to the trauma group (P=0.001 and P=0.004, respectively). Histopathological examination showed less degenerated neurons in the atomoxetine group compared to trauma group. Conclusion: This is the first experimental evidence showing meaningful neuroprotective effects of atomoxetine over SCI through anti-apoptotic, anti-inflammatory, and antioxidant effects by reducing lipid peroxidation, which was confirmed by biochemical, histopathological and the functional evaluation. PMID:27114797

  14. Effects of Lumbosacral Spinal Cord Epidural Stimulation for Standing after Chronic Complete Paralysis in Humans

    PubMed Central

    Rejc, Enrico; Angeli, Claudia; Harkema, Susan

    2015-01-01

    Sensory and motor complete spinal cord injury (SCI) has been considered functionally complete resulting in permanent paralysis with no recovery of voluntary movement, standing or walking. Previous findings demonstrated that lumbosacral spinal cord epidural stimulation can activate the spinal neural networks in one individual with motor complete, but sensory incomplete SCI, who achieved full body weight-bearing standing with independent knee extension, minimal self-assistance for balance and minimal external assistance for facilitating hip extension. In this study, we showed that two clinically sensory and motor complete participants were able to stand over-ground bearing full body-weight without any external assistance, using their hands to assist balance. The two clinically motor complete, but sensory incomplete participants also used minimal external assistance for hip extension. Standing with the least amount of assistance was achieved with individual-specific stimulation parameters, which promoted overall continuous EMG patterns in the lower limbs’ muscles. Stimulation parameters optimized for one individual resulted in poor standing and additional need of external assistance for hip and knee extension in the other participants. During sitting, little or negligible EMG activity of lower limb muscles was induced by epidural stimulation, showing that the weight-bearing related sensory information was needed to generate sufficient EMG patterns to effectively support full weight-bearing standing. In general, electrode configurations with cathodes selected in the caudal region of the array at relatively higher frequencies (25–60 Hz) resulted in the more effective EMG patterns for standing. These results show that human spinal circuitry can generate motor patterns effective for standing in the absence of functional supraspinal connections; however the appropriate selection of stimulation parameters is critical. PMID:26207623

  15. Neuromuscular interaction is required for neurotrophins-mediated locomotor recovery following treadmill training in rat spinal cord injury.

    PubMed

    Wu, Qinfeng; Cao, Yana; Dong, Chuanming; Wang, Hongxing; Wang, Qinghua; Tong, Weifeng; Li, Xiangzhe; Shan, Chunlei; Wang, Tong

    2016-01-01

    Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training allowed the retention of hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX-A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery. PMID:27190721

  16. Neuromuscular interaction is required for neurotrophins-mediated locomotor recovery following treadmill training in rat spinal cord injury.

    PubMed

    Wu, Qinfeng; Cao, Yana; Dong, Chuanming; Wang, Hongxing; Wang, Qinghua; Tong, Weifeng; Li, Xiangzhe; Shan, Chunlei; Wang, Tong

    2016-01-01

    Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training allowed the retention of hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX-A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery.

  17. Neuromuscular interaction is required for neurotrophins-mediated locomotor recovery following treadmill training in rat spinal cord injury

    PubMed Central

    Wu, Qinfeng; Cao, Yana; Dong, Chuanming; Wang, Hongxing; Wang, Qinghua; Tong, Weifeng; Li, Xiangzhe

    2016-01-01

    Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training allowed the retention of hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX-A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery. PMID:27190721

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

    PubMed

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

    2015-01-01

    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. PMID:26782566

  19. Pharmacological activation of locomotor patterns in larval and adult frog spinal cords.

    PubMed

    McClellan, A D; Farel, P B

    1985-04-15

    The effects of amino acids, catecholamines, and their agonists shown to elicit locomotor activity in several vertebrate species were examined in spinal animals and isolated nervous systems of developing tadpoles (Rana catesbiana) and adult frogs (R. catesbiana and pipiens). Elicited activity was correlated in spinal animals by video and electromyographic analysis, and in in vitro spinal cords by recordings of tail and hindlimb motor activity. Of the agents tested, only N-methyl-DL-aspartate (NMA), an amino acid agonist, was effective in eliciting motor activity in spinal animals. In isolated nervous systems, both NMA and D-glutamate added to the bath activated locomotor activity. NMA injected i.p. into tadpoles with high spinal cord transections elicited coordinated swimming motor activity in axial and hindlimb muscles that was roughly typical for the stage of development of the animal. In late stage tadpoles (st. XX), NMA also elicited wiping and alternating or synchronous (i.e. kicking or jumping) hindlimb movements. Addition of NMA or glutamate to a bath containing an in vitro tadpole spinal cord preparation elicited ventral root motor activity characteristic of swimming, but without a rostrocaudal phase lag. Rhythmic activity thought to underlie stepping and kicking was seen in lateral ventral rootlets innervating the hindlimbs. In adult frogs with high spinal cord transections, injection of NMA elicited a general sequence of spontaneous hindlimb motor functions: reflex wiping, stepping, and kicking or jumping. Isolated frog spinal cords were not responsive to bath applied NMA, under the present conditions. The activation by amino acids or their agonists of different motor functions in both larval and adult frogs, as well as in higher and lower vertebrates, suggests a general significance of amino acid-activated receptors in the neural networks controlling locomotor function. PMID:3888346

  20. Recovery of bimodal locomotion in the spinal-transected salamander, Pleurodeles waltlii.

    PubMed

    Chevallier, Stéphanie; Landry, Marc; Nagy, Frédéric; Cabelguen, Jean-Marie

    2004-10-01

    Electromyographic (EMG) analysis was used to provide an assessment of the recovery of locomotion in spinal-transected adult salamanders (Pleurodeles waltlii). EMG recordings were performed during swimming and overground stepping in the same animal before and at various times (up to 500 days) after a mid-trunk spinalization. Two-three weeks after spinalization, locomotor EMG activity was limited to the forelimbs and the body rostral to the transection. Thereafter, there was a return of the locomotor EMG activity at progressively more caudal levels below the transection. The animals reached stable locomotor patterns 3-4 months post-transection. Several locomotor parameters (cycle duration, burst duration, burst proportion, intersegmental phase lag, interlimb coupling) measured at various recovery times after spinalization were compared with those in intact animals. These comparisons revealed transient and long-term alterations in the locomotor parameters both above and below the transection site. These alterations were much more pronounced for swimming than for stepping and revealed differences in adaptive plasticity between the two locomotor networks. Recovered locomotor activity was immediately abolished by retransection at the site of the original spinalization, suggesting that the spinal cord caudal to the transection was reinnervated by descending brain and/or propriospinal axons, and that this regeneration contributed to the restoration of locomotor activity. Anatomical studies conducted in parallel further demonstrated that some of the regenerated axons came from glutamatergic and serotoninergic immunoreactive cells within the reticular formation.

  1. Effect of local application of an antibody against brain-derived neurotrophic factor on neuroma formation after transection of the inferior alveolar nerve in the rat.

    PubMed

    Valverde Guevara, Yessenia M; Yoshikawa, Hiroyuki; Saito, Isao; Maeda, Takeyasu; Seo, Kenji

    2014-09-10

    This study aimed to examine the contributions of brain-derived neurotrophic factor (BDNF) at the injury site toward neuroma formation and nerve regeneration after inferior alveolar nerve transection. Histological analysis confirmed neuroma formation at 2 weeks after complete transection of the inferior alveolar nerve. A local administration of an antibody to BDNF inhibited connective tissue proliferation at the injury site and promoted nerve fiber integrity. Fluorogold labeling showed a significantly higher number of labeled cells in the trigeminal ganglion in the anti-BDNF-treated group compared with the vehicle control group. In-situ hybridization histochemistry showed intense signals for tropomyosin receptor kinase B mRNA in the area of the injury site containing fibrous or granular tissue in the anti-BDNF-treated group. In contrast, these signals were close to the detection limit in the area of the perineurium in intact nerve trunks, indicating that the signals were expressed by fibroblasts within the connective tissue. These findings suggest that antagonization of endogenous BDNF induced by nerve injury reduces neuroma formation, without inhibiting damaged axon regeneration.

  2. Effect of local application of an antibody against brain-derived neurotrophic factor on neuroma formation after transection of the inferior alveolar nerve in the rat

    PubMed Central

    Valverde Guevara, Yessenia M.; Yoshikawa, Hiroyuki; Saito, Isao; Maeda, Takeyasu

    2014-01-01

    This study aimed to examine the contributions of brain-derived neurotrophic factor (BDNF) at the injury site toward neuroma formation and nerve regeneration after inferior alveolar nerve transection. Histological analysis confirmed neuroma formation at 2 weeks after complete transection of the inferior alveolar nerve. A local administration of an antibody to BDNF inhibited connective tissue proliferation at the injury site and promoted nerve fiber integrity. Fluorogold labeling showed a significantly higher number of labeled cells in the trigeminal ganglion in the anti-BDNF-treated group compared with the vehicle control group. In-situ hybridization histochemistry showed intense signals for tropomyosin receptor kinase B mRNA in the area of the injury site containing fibrous or granular tissue in the anti-BDNF-treated group. In contrast, these signals were close to the detection limit in the area of the perineurium in intact nerve trunks, indicating that the signals were expressed by fibroblasts within the connective tissue. These findings suggest that antagonization of endogenous BDNF induced by nerve injury reduces neuroma formation, without inhibiting damaged axon regeneration. PMID:25055143

  3. Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization

    PubMed Central

    Corleto, Jose A.; Bravo-Hernández, Mariana; Kamizato, Kota; Kakinohana, Osamu; Santucci, Camila; Navarro, Michael R.; Platoshyn, Oleksandr; Cizkova, Dasa; Lukacova, Nadezda; Taylor, Julian; Marsala, Martin

    2015-01-01

    The development of spinal hyper-reflexia as part of the spasticity syndrome represents one of the major complications associated with chronic spinal traumatic injury (SCI). The primary mechanism leading to progressive appearance of muscle spasticity is multimodal and may include loss of descending inhibitory tone, alteration of segmental interneuron-mediated inhibition and/or increased reflex activity to sensory input. Here, we characterized a chronic thoracic (Th 9) complete transection model of muscle spasticity in Sprague-Dawley (SD) rats. Isoflurane-anesthetized rats received a Th9 laminectomy and the spinal cord was transected using a scalpel blade. After the transection the presence of muscle spasticity quantified as stretch and cutaneous hyper-reflexia was identified and quantified as time-dependent changes in: i) ankle-rotation-evoked peripheral muscle resistance (PMR) and corresponding electromyography (EMG) activity, ii) Hoffmann reflex, and iii) EMG responses in gastrocnemius muscle after paw tactile stimulation for up to 8 months after injury. To validate the clinical relevance of this model, the treatment potency after systemic treatment with the clinically established anti-spastic agents baclofen (GABAB receptor agonist), tizanidine (α2-adrenergic agonist) and NGX424 (AMPA receptor antagonist) was also tested. During the first 3 months post spinal transection, a progressive increase in ankle rotation-evoked muscle resistance, Hoffmann reflex amplitude and increased EMG responses to peripherally applied tactile stimuli were consistently measured. These changes, indicative of the spasticity syndrome, then remained relatively stable for up to 8 months post injury. Systemic treatment with baclofen, tizanidine and NGX424 led to a significant but transient suppression of spinal hyper-reflexia. These data demonstrate that a chronic Th9 spinal transection model in adult SD rat represents a reliable experimental platform to be used in studying the

  4. Cell elimination as a strategy for repair in acute spinal cord injury.

    PubMed

    Kalderon, Nurit

    2005-01-01

    Following injury, as part of the wound-healing process, cell proliferation occurs mostly to replace damaged cells and to reconstitute the tissue back to normal condition/function. In the spinal cord some of the dividing cells following injury interfere with the repair processes. This interference occurs at the later stages of wound healing (the third week after injury) triggering chronic inflammation and progressive tissue decay that is the characteristic pathology of spinal cord injury. Specific cell elimination within a critical time window after injury can lead to repair in the acutely injured spinal cord. Cell proliferation events can be manipulated/modified by x-irradiation. Clinically, numerous radiation protocols (i.e., radiation therapy) have been developed that specifically eliminate the rapidly dividing cells without causing any noticeable/significant damage to the tissue as a whole. Radiation therapy when applied within the critical time window after injury prevents the onset of chronic inflammation thus leading to repair of structure and function. Various aspects of the development of this cell-elimination strategy for repair in acute spinal cord injury by utilizing radiation therapy are being reviewed. Topics reviewed here: identifying the window of opportunity; and the beneficial repair effects of radiation therapy in a transection injury model and in a model relevant to human injury, the contusion injury model. The possible involvement of cellular components of the blood-spinal cord barrier as the trigger of chronic inflammation and/or target of the radiation therapy is discussed. PMID:15853680

  5. Lizard tail spinal cord: a new experimental model of spinal cord injury without limb paralysis.

    PubMed

    Szarek, Dariusz; Marycz, Krzysztof; Lis, Anna; Zawada, Zbigniew; Tabakow, Paweł; Laska, Jadwiga; Jarmundowicz, Włodzimierz

    2016-04-01

    Spinal cord injury (SCI) is a well-known devastating lesion that sadly is very resistant to all treatment attempts. This fact has stimulated the exploration of multiple regenerative strategies that are examined at both the basic and clinical level. For laboratory research, differentin vivomodels are used, but each has many important limitations. The main limitation of these models is the high level of animal suffering related to the inflicted neurologic injury. It has caused a growing tendency to limit the injury, but this, in turn, produces incomplete SCI models and uncertainties in the neuroregeneration interpretation. To overcome such limitations, a new experimental SCI model is proposed. Geckos have been extensively examined as a potential animal model of SCI. Their spinal cord extends into the tail and can be transected without causing the typical neurologic consequences observed in rat models. In this study, we compared the gecko tail SCI model with the rat model of thoracic SCI. Anatomic and histologic analyses showed comparability between the gecko and rat in diameter of spinal canal and spinal cord, as well as applicability of multiple staining techniques (hematoxylin and eosin, immunostaining, and scanning and transmission electron microscopy). We tested the suitability ofin vivostudy with 3 prototype implants for the reconstruction of SCI: a multichannel sponge, a multilaminar tube, and a gel cylinder. These were compared with a spinal cord excision (control). A 20-wk observation revealed no adverse effects of SCI on the animals' well-being. The animals were easily housed and observed. Histologic analysis showed growth of nervous tissue elements on implant surface and implant cellular colonization. The study showed that the gecko SCI model can be used as a primary model for the assessment of SCI treatment methods. It provides a platform for testing multiple solutions with limited animal suffering before performing tests on mammals. Detailed results of

  6. Lizard tail spinal cord: a new experimental model of spinal cord injury without limb paralysis.

    PubMed

    Szarek, Dariusz; Marycz, Krzysztof; Lis, Anna; Zawada, Zbigniew; Tabakow, Paweł; Laska, Jadwiga; Jarmundowicz, Włodzimierz

    2016-04-01

    Spinal cord injury (SCI) is a well-known devastating lesion that sadly is very resistant to all treatment attempts. This fact has stimulated the exploration of multiple regenerative strategies that are examined at both the basic and clinical level. For laboratory research, differentin vivomodels are used, but each has many important limitations. The main limitation of these models is the high level of animal suffering related to the inflicted neurologic injury. It has caused a growing tendency to limit the injury, but this, in turn, produces incomplete SCI models and uncertainties in the neuroregeneration interpretation. To overcome such limitations, a new experimental SCI model is proposed. Geckos have been extensively examined as a potential animal model of SCI. Their spinal cord extends into the tail and can be transected without causing the typical neurologic consequences observed in rat models. In this study, we compared the gecko tail SCI model with the rat model of thoracic SCI. Anatomic and histologic analyses showed comparability between the gecko and rat in diameter of spinal canal and spinal cord, as well as applicability of multiple staining techniques (hematoxylin and eosin, immunostaining, and scanning and transmission electron microscopy). We tested the suitability ofin vivostudy with 3 prototype implants for the reconstruction of SCI: a multichannel sponge, a multilaminar tube, and a gel cylinder. These were compared with a spinal cord excision (control). A 20-wk observation revealed no adverse effects of SCI on the animals' well-being. The animals were easily housed and observed. Histologic analysis showed growth of nervous tissue elements on implant surface and implant cellular colonization. The study showed that the gecko SCI model can be used as a primary model for the assessment of SCI treatment methods. It provides a platform for testing multiple solutions with limited animal suffering before performing tests on mammals. Detailed results of

  7. Image-guided ureteral reconstruction using rendezvous technique for complex ureteric transection after gunshot injuries

    PubMed Central

    Arabi, Mohammad; Mat’hami, Abdulaziz; Said, Mohammad T.; Bulbul, Muhammad; Haddad, Maurice; Al-Kutoubi, Aghiad

    2016-01-01

    Management of complex ureteric transection poses a significant clinical challenge, particularly after gunshot injuries due to marked distortion of anatomy and associated tissue loss. We report two cases of total ureteric transection due to gunshot injury successfully repaired using fluoroscopy-guided rendezvous procedure and double J stent placement. This minimally invasive approach may offer a safe and effective technique to repair complete ureteral transection and obviate the need for complex surgical procedures. PMID:26955601

  8. Effects of sciatic nerve transection on ultrastructure, NADPH-diaphorase reaction and serotonin-, tyrosine hydroxylase-, c-Fos-, glucose transporter 1- and 3-like immunoreactivities in frog dorsal root ganglion.

    PubMed

    Rigon, F; Rossato, D; Auler, V B; Dal Bosco, L; Faccioni-Heuser, M C; Partata, W A

    2013-06-01

    Frogs have been used as an alternative model to study pain mechanisms. Since we did not find any reports on the effects of sciatic nerve transection (SNT) on the ultrastructure and pattern of metabolic substances in frog dorsal root ganglion (DRG) cells, in the present study, 18 adult male frogs (Rana catesbeiana) were divided into three experimental groups: naive (frogs not subjected to surgical manipulation), sham (frogs in which all surgical procedures to expose the sciatic nerve were used except transection of the nerve), and SNT (frogs in which the sciatic nerve was exposed and transected). After 3 days, the bilateral DRG of the sciatic nerve was collected and used for transmission electron microscopy. Immunohistochemistry was used to detect reactivity for glucose transporter (Glut) types 1 and 3, tyrosine hydroxylase, serotonin and c-Fos, as well as nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase). SNT induced more mitochondria with vacuolation in neurons, satellite glial cells (SGCs) with more cytoplasmic extensions emerging from cell bodies, as well as more ribosomes, rough endoplasmic reticulum, intermediate filaments and mitochondria. c-Fos immunoreactivity was found in neuronal nuclei. More neurons and SGCs surrounded by tyrosine hydroxylase-like immunoreactivity were found. No change occurred in serotonin- and Glut1- and Glut3-like immunoreactivity. NADPH-diaphorase occurred in more neurons and SGCs. No sign of SGC proliferation was observed. Since the changes of frog DRG in response to nerve injury are similar to those of mammals, frogs should be a valid experimental model for the study of the effects of SNT, a condition that still has many unanswered questions. PMID:23739744

  9. Rapid corticosterone-induced impairment of amplectic clasping occurs in the spinal cord of roughskin newts (taricha granulosa).

    PubMed

    Lewis, Christine M; Rose, James D

    2003-01-01

    Courtship clasping, a reproductive behavior in male roughskin newts (Taricha granulosa), is rapidly blocked by an action of corticosterone (CORT) at a specific neuronal membrane receptor. The CORT-induced impairment of clasping in behaving newts appears to be mediated partly by an elimination of clasping-related activity in medullary reticulospinal neurons. Previous studies of rapid CORT actions in Taricha have focused on the brain, so existence of CORT action in the spinal cord or peripheral nervous system has not been assessed. The present study used newts with a high cervical spinal transection to examine potential spinal or peripheral CORT effects on clasping by the hindlimbs in response to pressure on the cloaca. Spinal transection causes clasps elicited by cloacal stimulation to be very sustained beyond the termination of the eliciting stimulus. In spinally transected newts, CORT caused a dose-dependent depression in the duration as well as quality of the clasp that appeared within 10 min of injection. CORT selectively impaired the usual sustained maintenance of a clasp after termination of cloacal stimulation, but not clasp elicitation during stimulation. These effects were not produced by dexamethasone, a synthetic glucocorticoid that binds poorly to the CORT membrane receptor. The CORT effect on clasp maintenance but not clasp elicitation implies selective action on an intraspinal generator for clasping but not on sensory or efferent neuromuscular aspects of the response. These results indicate the presence in the newt spinal cord of the CORT membrane receptor that exerts functional effects distinctly different from those on the brainstem.

  10. Effects of ganglioside G(M1) and erythropoietin on spinal cord lesions in rats: functional and histological evaluations

    PubMed Central

    Marcon, Raphael Martus; Cristante, Alexandre Fogaça; de Barros Filho, Tarcísio Eloy Pessoa; Ferreira, Ricardo; dos Santos, Gustavo Bispo

    2016-01-01

    OBJECTIVE: To evaluate the functional and histological effects of ganglioside G(M1) and erythropoietin after experimental spinal cord contusion injury. METHODS: Fifty male Wistar rats underwent experimental spinal cord lesioning using an NYU-Impactor device and were randomly divided into the following groups, which received treatment intraperitoneally. The G(M1) group received ganglioside G(M1) (30 mg/kg); the erythropoietin group received erythropoietin (1000 IU/kg); the combined group received both drugs; and the saline group received saline (0.9%) as a control. A fifth group was the laminectomy group, in which the animals were subjected to laminectomy alone, without spinal lesioning or treatment. The animals were evaluated according to the Basso, Beattie and Bresnahan (BBB) scale, motor evoked potential recordings and, after euthanasia, histological analysis of spinal cord tissue. RESULTS: The erythropoietin group had higher BBB scores than the G(M1) group. The combined group had the highest BBB scores, and the saline group had the lowest BBB scores. No significant difference in latency was observed between the three groups that underwent spinal cord lesioning and intervention. However, the combined group showed a significantly higher signal amplitude than the other treatment groups or the saline group (p<0.01). Histological tissue analysis showed no significant difference between the groups. Axonal index was significantly enhanced in the combined group than any other intervention (p<0.01). CONCLUSION: G(M1) and erythropoietin exert therapeutic effects on axonal regeneration and electrophysiological and motor functions in rats subjected to experimental spinal cord lesioning and administering these two substances in combination potentiates their effects. PMID:27438570

  11. Neuroprotective effects of adipose-derived stem cells against ischemic neuronal damage in the rabbit spinal cord.

    PubMed

    Chung, Jin Young; Kim, Woosuk; Im, Wooseok; Yoo, Dae Young; Choi, Jung Hoon; Hwang, In Koo; Won, Moo-Ho; Chang, In Bok; Cho, Byung Moon; Hwang, Hyung Sik; Moon, Seung Myung

    2012-06-15

    Transplantation of adipose-derived stem cells (ASCs) is one of the possible therapeutic tools for ischemic damage. In this study, we observed the effects of ASCs against ischemic damage in the ventral horn of L(5-6) levels in the rabbit spinal cord. ASCs were isolated from rabbits, and cell type was confirmed by flow cytometry analysis, labeling with CM-DiI dye and differentiation into adipocytes in adipogenesis differentiation medium. ASCs were administered intrathecally into recipient rabbits (2 × 10⁵) immediately after reperfusion following a 15-min aortic artery occlusion in the subrenal region. Transplantation of ASCs significantly improved functions of the hindlimb and morphology of the ventral horn of spinal cord although CM-DiI-labeled ASCs were not observed in the spinal cord parenchyma. In addition, transplantation of ASCs significantly increased brain-derived neurotrophic factor (BDNF) levels at 72h after ischemia/reperfusion. These results suggest that transplantation of ASCs prevents motor neurons from spinal ischemic damage and reactive gliosis by increasing neurotrophic factors such as BDNF in the spinal cord.

  12. Neuroprotective effects of thymoquinone against spinal cord ischemia-reperfusion injury by attenuation of inflammation, oxidative stress, and apoptosis.

    PubMed

    Gökce, Emre Cemal; Kahveci, Ramazan; Gökce, Aysun; Cemil, Berker; Aksoy, Nurkan; Sargon, Mustafa Fevzi; Kısa, Üçler; Erdoğan, Bülent; Güvenç, Yahya; Alagöz, Fatih; Kahveci, Ozan

    2016-06-01

    OBJECTIVE Ischemia-reperfusion (I/R) injury of the spinal cord following thoracoabdominal aortic surgery remains the most devastating complication, with a life-changing impact on the patient. Thymoquinone (TQ), the main constituent of the volatile oil from Nigella sativa seeds, is reported to possess strong antioxidant, antiinflammatory, and antiapoptotic properties. This study investigated the effects of TQ administration following I/R injury to the spinal cord. METHODS Thirty-two rats were randomly allocated into 4 groups. Group 1 underwent only laparotomy. For Group 2, aortic clip occlusion was introduced to produce I/R injury. Group 3 was given 30 mg/kg of methylprednisolone intraperitoneally immediately after the I/R injury. Group 4 was given 10 mg/kg of TQ intraperitoneally for 7 days before induction of spinal cord I/R injury, and administration was continued until the animal was euthanized. Locomotor function (Basso, Beattie, and Bresnahan scale and inclined plane test) was assessed at 24 hours postischemia. Spinal cord tissue samples were harvested to analyze tissue concentrations of malondialdehyde, nitric oxide, tumor necrosis factor-α, interleukin-1, superoxide dismutase, glutathione-peroxidase, catalase, and caspase-3. In addition, histological and ultrastructural evaluations were performed. RESULTS Thymoquinone treatment improved neurological outcome, which was supported by decreased levels of oxidative products (malondialdehyde and nitric oxide) and proinflammatory cytokines (tumor necrosis factor-α and interleukin-1), increased activities of antioxidant enzymes (superoxide dismutase, glutathione-peroxidase, and catalase), as well as reduction of motor neuron apoptosis. Light microscopy and electron microscopy results also showed preservation of tissue structure in the treatment group. CONCLUSIONS As shown by functional, biochemical, histological, and ultrastructural analysis, TQ exhibits an important protective effect against I/R injury of the

  13. Neuroprotective effects of thymoquinone against spinal cord ischemia-reperfusion injury by attenuation of inflammation, oxidative stress, and apoptosis.

    PubMed

    Gökce, Emre Cemal; Kahveci, Ramazan; Gökce, Aysun; Cemil, Berker; Aksoy, Nurkan; Sargon, Mustafa Fevzi; Kısa, Üçler; Erdoğan, Bülent; Güvenç, Yahya; Alagöz, Fatih; Kahveci, Ozan

    2016-06-01

    OBJECTIVE Ischemia-reperfusion (I/R) injury of the spinal cord following thoracoabdominal aortic surgery remains the most devastating complication, with a life-changing impact on the patient. Thymoquinone (TQ), the main constituent of the volatile oil from Nigella sativa seeds, is reported to possess strong antioxidant, antiinflammatory, and antiapoptotic properties. This study investigated the effects of TQ administration following I/R injury to the spinal cord. METHODS Thirty-two rats were randomly allocated into 4 groups. Group 1 underwent only laparotomy. For Group 2, aortic clip occlusion was introduced to produce I/R injury. Group 3 was given 30 mg/kg of methylprednisolone intraperitoneally immediately after the I/R injury. Group 4 was given 10 mg/kg of TQ intraperitoneally for 7 days before induction of spinal cord I/R injury, and administration was continued until the animal was euthanized. Locomotor function (Basso, Beattie, and Bresnahan scale and inclined plane test) was assessed at 24 hours postischemia. Spinal cord tissue samples were harvested to analyze tissue concentrations of malondialdehyde, nitric oxide, tumor necrosis factor-α, interleukin-1, superoxide dismutase, glutathione-peroxidase, catalase, and caspase-3. In addition, histological and ultrastructural evaluations were performed. RESULTS Thymoquinone treatment improved neurological outcome, which was supported by decreased levels of oxidative products (malondialdehyde and nitric oxide) and proinflammatory cytokines (tumor necrosis factor-α and interleukin-1), increased activities of antioxidant enzymes (superoxide dismutase, glutathione-peroxidase, and catalase), as well as reduction of motor neuron apoptosis. Light microscopy and electron microscopy results also showed preservation of tissue structure in the treatment group. CONCLUSIONS As shown by functional, biochemical, histological, and ultrastructural analysis, TQ exhibits an important protective effect against I/R injury of the

  14. Hypoxic preconditioning increases the protective effect of bone marrow mesenchymal stem cells on spinal cord ischemia/reperfusion injury.

    PubMed

    Wang, Zhilin; Fang, Bo; Tan, Zhibin; Zhang, Dong; Ma, Hong

    2016-03-01

    Transplantation of bone marrow mesenchymal stem cells (BMSCs) protect against spinal cord ischemia/reperfusion injury (SCIRI). However, a large number of transplanted BMSCs often undergo apoptosis, which severely affects the treatment outcome. Previous studies have demonstrated that hypoxic preconditioning effectively increases the survival rate of BMSCs following transplantation, and increases their protective effect on injured tissues. However, there have been few reports regarding roles of hypoxic preconditioning in SCIRI. The present study isolated rat BMSCs and separately transplanted hypoxia‑ and non‑hypoxia‑preconditioned BMSCs into the spinal cord tissues of rats with SCIRI. The role of hypoxic preconditioning in the promotion of the protective effect of BMSCs on SCIRI was investigated using neurological function scores, Evans blue staining, hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling. In addition, reverse transcription‑quantitative polymerase chain reaction and western blotting were used to detect the expression levels of hypoxia‑inducible factor 1α (HIF‑1α), and to investigate its possible underlying mechanism of action. The results indicated that hypoxic preconditioning effectively increased the protective effects of BMSCs on neurological function, blood spinal cord barrier and tissue damage following SCIRI, and inhibited apoptosis. Furthermore, hypoxic preconditioned BMSCs upregulated the expression of HIF‑1α in spinal cord tissues. Therefore, hypoxic preconditioning effectively increased the protective effect of BMSCs on SCIRI and may be associated with upregulation of the expression of HIF‑1α. Hypoxic preconditioning may serve as an effective means of increasing the protective effect of BMSCs on SCIRI.

  15. 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. PMID:26826448

  16. 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.

  17. [Effect of local hypothermia on H- and M-responses after spinal cord contusion in dogs].

    PubMed

    Iafarova, G G; Tumakaev, R F; Khazieva, A R; Baltina, T V

    2014-01-01

    In this study we investigated a motor-neuronal functional state based on H- and M-responses from m. quadratus plantae in dogs before and after experimental spinal cord contusion with and without following local intraoperative hypothermia. H- and M-responses from m. quadratus plantae were recorded during stimulation of the tibial nerve and results were compared between the groups. Our results demonstrate that local hypothermia applied after spinal cord contusion reduces amplitude of both M- and H-responses and also H(max)/M(max) ratio that may indicate depression of motorneurons excitability. After spinal cord contusion without following hypothermia the excitability of the spinal motorneurons during post-traumatic period, in opposite, was significantly increased. These results support a conclusion that intraoperative hypothermia after spinal cord contusion can delay development of functional excitability of the motoneurons and protect from further changes in H- and M-responses.

  18. Effects and Safety of Aqueous Extract of Poncirus fructus in Spinal Cord Injury with Neurogenic Bowel

    PubMed Central

    Kim, Ji Hee; Lee, Su Kyung

    2016-01-01

    Objective. To investigate the effects and safety of the aqueous extract of the dried, immature fruit of Poncirus trifoliata (L.) Raf., known as Poncirus fructus (PF), in spinal cord injury (SCI) patients with neurogenic bowel. Methods. Thirty-one SCI patients with neurogenic bowel were recruited. Patients were evaluated based on clinical information, constipation score, Bristol Stool Form Scale, stool retention score using plain abdominal radiograph, and colon transit time. PF was administered in dosages of 800 mg each prior to breakfast and lunch for 14 days. Results. The morphological feature of the stool before and after administration indicated a statistically significant difference from 3.52 ± 1.33 to 4.32 ± 1.44 points (p < 0.05). Stool retention score before and after administration of PF was represented with low significance (7.25 ± 1.60 to 6.46 ± 1.53 points) in the whole colon (p < 0.05), and the colon transit time was significantly shortened (57.41 ± 20.7 to 41.2 ± 25.5 hours) in terms of the whole transit time (p < 0.05). Side effects were observed in 7 people (28.0%) consisting of 2 people with soft stools and 5 people with diarrhea. Conclusion. For SCI patients, PF administration significantly improved defecation patterns, defecation retention, and colon transit time. PF could be an effective aid to improve colonic motility and constipation. PMID:27738444

  19. Effect of Spinal Cord Stimulation on Gait in a Patient with Thalamic Pain.

    PubMed

    Yozu, Arito; Sumitani, Masahiko; Shin, Masahiro; Ishi, Kazuhiko; Osumi, Michihiro; Katsuhira, Junji; Chiba, Ryosuke; Haga, Nobuhiko

    2016-01-01

    Thalamic pain is a central neuropathic pain disorder which occurs after stroke. Its severe chronic pain is often intractable to pharmacotherapies and affects the patients' activities of daily living (ADL) and quality of life (QOL). Recently, spinal cord stimulation (SCS) has been reported to be effective in relieving the pain of thalamic pain; however, the effect of SCS on gait performance in patients is unknown. Therefore, we evaluated the gait performance before and after SCS in a case with thalamic pain. A 73-year-old male with thalamic pain participated in this study. We evaluated the gait of the patient two times: before SCS insertion and after 6 days of SCS. At the second evaluation, we measured the gait in three conditions: stimulation off, comfortable stimulation, and strong stimulation. SCS succeeded in improving the pain from 7 to 2 on an 11-point numerical rating scale. Step frequency and the velocity of gait tended to increase between pre- and poststimulation periods. There were no apparent differences in gait among the three stimulation conditions (off, comfortable, and strong) at the poststimulation period. SCS may be effective on gait in patients with thalamic pain. PMID:27579198

  20. Effect of Spinal Cord Stimulation on Gait in a Patient with Thalamic Pain

    PubMed Central

    Shin, Masahiro; Ishi, Kazuhiko; Osumi, Michihiro; Katsuhira, Junji; Chiba, Ryosuke; Haga, Nobuhiko

    2016-01-01

    Thalamic pain is a central neuropathic pain disorder which occurs after stroke. Its severe chronic pain is often intractable to pharmacotherapies and affects the patients' activities of daily living (ADL) and quality of life (QOL). Recently, spinal cord stimulation (SCS) has been reported to be effective in relieving the pain of thalamic pain; however, the effect of SCS on gait performance in patients is unknown. Therefore, we evaluated the gait performance before and after SCS in a case with thalamic pain. A 73-year-old male with thalamic pain participated in this study. We evaluated the gait of the patient two times: before SCS insertion and after 6 days of SCS. At the second evaluation, we measured the gait in three conditions: stimulation off, comfortable stimulation, and strong stimulation. SCS succeeded in improving the pain from 7 to 2 on an 11-point numerical rating scale. Step frequency and the velocity of gait tended to increase between pre- and poststimulation periods. There were no apparent differences in gait among the three stimulation conditions (off, comfortable, and strong) at the poststimulation period. SCS may be effective on gait in patients with thalamic pain. PMID:27579198

  1. [Effect of aspirin on function of human umbilical cord blood-derived late endothelial progenitor cells].

    PubMed

    Liu, Zhen-Zhen; Li, Guo-Qiang; Liu, Meng; Sun, Sheng-Xuan; An, Guan-Yu; Dong, Ning-Zheng

    2013-08-01

    This study was aimed to investigate whether aspirin has effect on function of late endothelial progenitor cells (EPC). Cord blood CD34(+) cells were purified using the ficoll density gradient centrifugation and human CD34 positive selection kit, then the cells were inoculated on fibronectin-coated culture plate. After culture for 2 weeks, adherent cells were identified as EPC by flow cytometry, immunofluorescence, RT-PCR, uptake of Dil-Ac-LDL and matrigel tube formation assay. EPC were treated with different concentrations of aspirin (0.1, 1, 10, 100, 1 000, 10 000 µmol/L) for 24 h, then the proliferation, adhesion and migration ability of these cells were analyzed by CCK-8 assay and transwell methods. The results indicated that the low concentrations of aspirin (0.1 and 1 000 µmol/L) promoted late EPC adhesive and migratory capacity, but no obvious effect on proliferation of late EPC were observed. On the other hand, the high concentrations of aspirin (10 000 µmol/L) inhibited proliferation and migratory capacity of EPC, but had no obvious effect on adhesive ability of EPC. It is concluded that low concentration of aspirin promotes migration and adhesion of late EPC, while the high concentration of aspirin decreases EPC proliferation and migratory capacity of EPC.

  2. Therapeutic effects of human umbilical cord mesenchymal stem cells transplantation on hypoxic ischemic encephalopathy

    PubMed Central

    Xie, Bingchuan; Gu, Ping; Wang, Wenting; Dong, Ci; Zhang, Lina; Zhang, Jun; Liu, Huimiao; Qiu, Fucheng; Han, Rui; Zhang, Zhenqing; Yan, Baoyong

    2016-01-01

    Objective: Human umbilical cord mesenchymal stem cells (hUC-MSCs) hold substantial promise for the treatment of ischemic neurological disease, but few clinical data are currently available about its therapeutic effects in hypoxic ischemic encephalopathy (HIE). This study is to evaluate the effects of hUC-MSCs transplantation on patients with HIE. Methods A total 22 patients with HIEwere randomly divided into hUC-MSCs transplantation group (n = 12) and control group (n = 10). After isolation, hUC-MSCs were cultured for 3 to 5 passages in vitro and then intravenously administered to HIE patients in the transplantation group, while the control group received routine treatment only. The outcomes of HIE patients were evaluated at designated time points by clinical assessment scales, including NIHSS, Barthel Index, MMSE, HAMA24, HAMD14 and UPDRS. Results: hUC-MSCs were identified by morphological analysis and flow cytometry assays before clinic transplantation. No significant differences of demographic characteristics were observed between the two groups of subjects. Compared to the control group, hUC-MSCs transplantation markedly improved the outcomes of HIE patients leading to better recovery of neurological function, cognition ability, emotional reaction and extrapyramidal function. No significant adverse effects were found in subjects with hUC-MSCs transplantation during a 180-day follow-up period. Conclusion: These data suggest that hUC-MSCs therapy markedly improves the outcomes of patients with HIE, which is potential for the routine treatment of ischemic neurological disease. PMID:27508046

  3. The effects of aging and electrical stimulation exercise on bone after spinal cord injury.

    PubMed

    Dolbow, James D; Dolbow, David R; Gorgey, Ashraf S; Adler, Robert A; Gater, David R

    2013-06-01

    Age related bone loss predisposes adults to osteoporosis. This is especially true for individuals with spinal cord injury (SCI). The effects of decreased bone loading with older age and paralysis significantly contribute to decreased bone mass and increased risk for fragility fractures. Loading bone via volitional muscle contractions or by using electrical stimulation are common methods for helping to prevent and/or decrease bone loss. However the effectiveness and safety of electrical stimulation activities remain unclear. The purpose of this review is to investigate the factors associated with aging and osteoporosis after SCI, the accuracy of bone measurement, the effects of various forms of bone loading activities with a focus on electrical stimulation activities and the safety of physical exercise with a focus on electrical stimulation cycling. Osteoporosis remains a disabling and costly condition for older adults and for those with paralysis. Both dual energy x-ray absorptiometry and peripheral quantitative computed tomography are valuable techniques for measuring bone mineral density (BMD) with the latter having the ability to differentiate trabecular and cortical bone. Physical activities have shown to be beneficial for increasing BMD however, the extent of the benefits related to aging and paralysis remain undetermined. Electrical stimulation activities administered appropriately are assumed safe due to thousands of documented safe FES cycling sessions. However, specific documentation is needed to verify safety and to development formal guidelines for optimal use.

  4. Effects of passive pedaling exercise on the intracortical inhibition in subjects with spinal cord injury.

    PubMed

    Nardone, Raffaele; Langthaler, Patrick B; Bathke, Arne C; Höller, Yvonne; Brigo, Francesco; Lochner, Piergiorgio; Christova, Monica; Trinka, Eugen

    2016-06-01

    Cortical reorganization can be induced by exercise below the level of the lesion after spinal cord injury (SCI). The aim of the present study was to investigate the effect of passive and active pedaling exercise on leg motor cortical area excitability of subjects with traumatic SCI. Ten subjects with chronic cervical or thoracic SCI were enrolled in the study. We found a significant effect of pedaling on short-interval intracortical inhibition (SICI), which did not interact with the experimental condition (active vs. passive). This corresponded to a significant reduction of SICI in the subjects with SCI, together with no evidence that this pattern differed for passive vs. active pedaling. We found no significant effect of pedaling on intracortical facilitation. Our results showed that also passive cycling may be beneficial in activating motor cortical regions and possibly also facilitating motor recovery after SCI. The present study confirms and extends the findings of previous studies that have observed task-specific cortical activation during passive pedaling. Therefore passive exercise therapies when applied below the level of the lesion in subjects with SCI could promote cortical neuroplastic reorganization.

  5. EFFECTS OF THALLIUM SALTS ON NEURONAL MITOCHONDRIA IN ORGANOTYPIC CORD-GANGLIA-MUSCLE COMBINATION CULTURES

    PubMed Central

    Spencer, Peter S.; Peterson, Edith R.; Madrid A., Ricardo; Raine, Cedric S.

    1973-01-01

    A functionally coupled organotypic complex of cultured dorsal root ganglia, spinal cord peripheral nerve, and muscle has been employed in an experimental approach to the investigation of the neurotoxic effects of thallium. Selected cultures, grown for up to 12 wk in vitro, were exposed to thallous salts for periods ranging up to 4 days. Cytopathic effects were first detected after 2 h of exposure with the appearance of considerably enlarged mitochondria in axons of peripheral nerve fibers. With time, the matrix space of these mitochondria became progressively swollen, transforming the organelle into an axonal vacuole bounded by the original outer mitochondrial membrane. Coalescence of adjacent axonal vacuoles produced massive internal axon compartments, the membranes of which were shown by electron microprobe mass spectrometry to have an affinity for thallium. Other axoplasmic components were displaced within a distended but intact axolemma. The resultant fiber swelling caused myelin retraction from nodes of Ranvier but no degeneration. Impulses could still propagate along the nerve fibers throughout the time course of the experiment. Comparable, but less severe changes were seen in dorsal root ganglion neurons and in central nerve fibers. Other cell types showed no mitochondrial change. It is uncertain how these findings relate to the neurotoxic effects of thallium in vivo, but a sensitivity of the nerve cell and especially its axon to thallous salts is indicated. PMID:4125375

  6. The Effects of Aging and Electrical Stimulation Exercise on Bone after Spinal Cord Injury

    PubMed Central

    Dolbow, James D.; Dolbow, David R.; Gorgey, Ashraf S.; Adler, Robert A.; Gater, David R.

    2013-01-01

    Age related bone loss predisposes adults to osteoporosis. This is especially true for individuals with spinal cord injury (SCI). The effects of decreased bone loading with older age and paralysis significantly contribute to decreased bone mass and increased risk for fragility fractures. Loading bone via volitional muscle contractions or by using electrical stimulation are common methods for helping to prevent and/or decrease bone loss. However the effectiveness and safety of electrical stimulation activities remain unclear. The purpose of this review is to investigate the factors associated with aging and osteoporosis after SCI, the accuracy of bone measurement, the effects of various forms of bone loading activities with a focus on electrical stimulation activities and the safety of physical exercise with a focus on electrical stimulation cycling. Osteoporosis remains a disabling and costly condition for older adults and for those with paralysis. Both dual energy x-ray absorptiometry and peripheral quantitative computed tomography are valuable techniques for measuring bone mineral density (BMD) with the latter having the ability to differentiate trabecular and cortical bone. Physical activities have shown to be beneficial for increasing BMD however, the extent of the benefits related to aging and paralysis remain undetermined. Electrical stimulation activities administered appropriately are assumed safe due to thousands of documented safe FES cycling sessions. However, specific documentation is needed to verify safety and to development formal guidelines for optimal use. PMID:23730530

  7. Neurotherapeutic and neuroprosthetic effects of implanted functional electrical stimulation for ambulation after incomplete spinal cord injury.

    PubMed

    Bailey, Stephanie Nogan; Hardin, Elizabeth C; Kobetic, Rudi; Boggs, Lisa M; Pinault, Gilles; Triolo, Ronald J

    2010-01-01

    The purpose of this single-subject study was to determine the neurotherapeutic and neuroprosthetic effects of an implanted functional electrical stimulation (FES) system designed to facilitate walking in an individual with a longstanding motor and sensory incomplete spinal cord injury. An implanted pulse generator and eight intramuscular stimulating electrodes were installed unilaterally, activating weak or paralyzed hip flexors, hip and knee extensors, and ankle dorsiflexors during 36 sessions of gait training with FES. The neurotherapeutic effects were assessed by a comparison of pre- and posttraining volitional walking. The neuroprosthetic effects were assessed by a comparison of posttraining volitional and FES-assisted walking. Treatment resulted in significant (p < 0.005) volitional improvements in 6-minute walking distance and speed, speed during maximum walk, double support time, and 10 m walking speed. Posttraining FES-assisted walking resulted in significant additional improvements in all these measures, except 10 m walking speed. When the subject was using FES-assisted gait, maximum walking distance, peak knee flexion in swing, peak ankle dorsiflexion in swing, and knee extension moment also significantly increased. Neuroprosthetic gains were sufficient to enable the subject to advance from household ambulation to limited community ambulation. Additionally, the subject could perform multiple walks per day when using FES-assisted gait, which was impossible with volitional effort alone.

  8. Effects of passive pedaling exercise on the intracortical inhibition in subjects with spinal cord injury.

    PubMed

    Nardone, Raffaele; Langthaler, Patrick B; Bathke, Arne C; Höller, Yvonne; Brigo, Francesco; Lochner, Piergiorgio; Christova, Monica; Trinka, Eugen

    2016-06-01

    Cortical reorganization can be induced by exercise below the level of the lesion after spinal cord injury (SCI). The aim of the present study was to investigate the effect of passive and active pedaling exercise on leg motor cortical area excitability of subjects with traumatic SCI. Ten subjects with chronic cervical or thoracic SCI were enrolled in the study. We found a significant effect of pedaling on short-interval intracortical inhibition (SICI), which did not interact with the experimental condition (active vs. passive). This corresponded to a significant reduction of SICI in the subjects with SCI, together with no evidence that this pattern differed for passive vs. active pedaling. We found no significant effect of pedaling on intracortical facilitation. Our results showed that also passive cycling may be beneficial in activating motor cortical regions and possibly also facilitating motor recovery after SCI. The present study confirms and extends the findings of previous studies that have observed task-specific cortical activation during passive pedaling. Therefore passive exercise therapies when applied below the level of the lesion in subjects with SCI could promote cortical neuroplastic reorganization. PMID:27108543

  9. Effectiveness of repeated transplantations of hematopoietic stem cells in spinal cord injury

    PubMed Central

    Bryukhovetskiy, Andrey S; Bryukhovetskiy, Igor S

    2015-01-01

    AIM: To evaluate the short and long-term effects of the complex cell therapy of 202 cases of spinal cord injury (SCI). METHODS: The main arm included 202 cases of SCI and the control arm included 20 SCI cases. For the therapy the hematopoietic stem cells (HSCs) and progenitor cells (PCs) were mobilized to peripheral blood by 8 subcutaneous injections of granulocyte colony-stimulating factor (G-CSF) for 4 d and are harvested at day 5. The cells were administered to the main arm intrathecally every 3 mo for a long term (3-5 years) according to the internal research protocol international medical institute of tissue engineering. Magnetic resonance imaging of the site of injury and urodynamic tests were performed every 6 mo. Motor evoked potentials (MEP), somatosensory evoked potentials (SSEP) were evaluated every 3 mo. The patients were evaluated with american spianl injury association (ASIA) index, functional independence measure index, the Medical Research Council Scale, the International Standards for Neurological Classification of Spinal Cord Injury (ISCSCI-92) and specifically developed scales. The function of bladder was evaluated by a specifically developed clinical scale. The long-term clinical outcomes were assessed for the SCI patients who received no less than 20 intrathecal transplantations of HSCs and hematopoietic precursors (HPs). RESULTS: The restoration of neurologic deficit after HSCs and HPs transplantations was proved stable and evident in 57.4% of the cases. In 42.6% cases no neurologic improvement has been observed. In 50% of the cases the motor restoration began after the first transplantation, which is confirmed in average by 9.9 points improvement in neurologic impairment as compared to the baseline (P < 0.05). Repair of the urinary system was observed in 47.7% of the cases. The sensitivity improved from baseline 124.3 points to 138.4 after the first and to 153.5 points after the second transplantations of HSCs and HPs (P < 0.05, between the

  10. Combination of fasudil and celecoxib promotes the recovery of injured spinal cord in rats better than celecoxib or fasudil alone

    PubMed Central

    Hou, Xiao-lin; Chen, Yan; Yin, Hua; Duan, Wei-gang

    2015-01-01

    Resistance mechanisms of rho-associated kinase (ROCK) inhibitors are associated with the enhanced expression of cyclooxygenase-2 (COX-2). The therapeutic effects of ROCK on nervous system diseases might be enhanced by COX-2 inhibitors. This study investigated the synergistic effect of the combined use of the ROCK inhibitor fasudil and a COX-2 inhibitor celecoxib on spinal cord injury in a rat model established by transecting the right half of the spinal cord at T11. Rat models were orally administrated with celecoxib (20 mg/kg) and/or intramuscularly with fasudil (10 mg/kg) for 2 weeks. Results demonstrated that the combined use of celecoxib and fasudil significantly decreased COX-2 and Rho kinase II expression surrounding the lesion site in rats with spinal cord injury, improved the pathomorphology of the injured spinal cord, and promoted the recovery of motor function. Moreover, the effects of the drug combination were better than celecoxib or fasudil alone. This study demonstrated that the combined use of fasudil and celecoxib synergistically enhanced the functional recovery of injured spinal cord in rats. PMID:26807121

  11. Combination of fasudil and celecoxib promotes the recovery of injured spinal cord in rats better than celecoxib or fasudil alone.

    PubMed

    Hou, Xiao-Lin; Chen, Yan; Yin, Hua; Duan, Wei-Gang

    2015-11-01

    Resistance mechanisms of rho-associated kinase (ROCK) inhibitors are associated with the enhanced expression of cyclooxygenase-2 (COX-2). The therapeutic effects of ROCK on nervous system diseases might be enhanced by COX-2 inhibitors. This study investigated the synergistic effect of the combined use of the ROCK inhibitor fasudil and a COX-2 inhibitor celecoxib on spinal cord injury in a rat model established by transecting the right half of the spinal cord at T11. Rat models were orally administrated with celecoxib (20 mg/kg) and/or intramuscularly with fasudil (10 mg/kg) for 2 weeks. Results demonstrated that the combined use of celecoxib and fasudil significantly decreased COX-2 and Rho kinase II expression surrounding the lesion site in rats with spinal cord injury, improved the pathomorphology of the injured spinal cord, and promoted the recovery of motor function. Moreover, the effects of the drug combination were better than celecoxib or fasudil alone. This study demonstrated that the combined use of fasudil and celecoxib synergistically enhanced the functional recovery of injured spinal cord in rats.

  12. Effect of service dogs on manual wheelchair users with spinal cord injury: a pilot study.

    PubMed

    Hubert, Geoffroy; Tousignant, Michel; Routhier, François; Corriveau, Hélène; Champagne, Noël

    2013-01-01

    Service dogs help people with mobility impairments. They are trained to perform a variety of tasks, such as opening doors, retrieving the telephone, picking up objects, and pulling manual wheelchairs (MWCs). More specifically, using the traction provided by the service dog has physical benefits because MWC users can operate their MWCs with less effort. The objective of this study was to document the effect of a service dog on MWC mobility and user shoulder pain, social participation, and quality of life. Eleven MWC users with spinal cord injury were assessed before and after training with a service dog and 7 mo later. Based on a standardized protocol, all study participants learned how to use the service dog safely and how to move around efficiently in different environments and under different conditions. Results showed that using a service dog increased the distance covered by the MWC users and also significantly decreased shoulder pain and intensity of effort. Using the service dog also produced slight but significant improvements in MWC user skills and social participation and may indicate a trend for improvement in quality of life. More extensive research is needed to precisely identify the effect of service dogs on the long-term management of MWC use.

  13. The Effects of Testosterone on Oxidative Stress Markers in Mice with Spinal Cord Injuries

    PubMed Central

    Choobineh, Hamid; Sadighi Gilani, Mohammad Ali; Pasalar, Parvin; Jahanzad, Issa; Ghorbani, Rostam; Hassanzadeh, Gholamreza

    2016-01-01

    Background Spinal cord injury (SCI) causes infertility in male patients through erectile dysfunction, ejaculatory dysfunction, semen and hormone abnormalities. Oxidative stress (OS) is involved in poor semen quality and subsequent infertility in males with SCI. The aim of this study is to examine the effects of SCI on the level of testosterone hormone. Materials and Methods In this experimental study, we evaluated the effects of exogenous testosterone on the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) as well as the levels of malondialdehyde (MDA) and protein carbonylation (PCO), as markers of OS, in 10 groups of SCI mice. Total antioxidant capacity (TAC) was determined using the 2,29-azinobis-(3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS) radical cation assay. Results Exogenous testosterone administration in mice with SCI significantly reduced SOD and GPx enzyme activities and MDA level. There was no significant decrease in PCO content. In addition, TAC remarkably increased in the sham and SCI groups not treated with testosterone but remained unchanged in all other experimental groups. Exogenous testosterone also reduced serum testosterone levels in all groups except the positive control group. Conclusion Our cumulative data indicated that SCI could cause sterility by disturbing the plasmatic testosterone balance. The normal level of endogenous testosterone was not completely restored by exogenous testosterone administration. PMID:27123205

  14. The effects of human umbilical cord perivascular cells on rat hepatocyte structure and functional polarity.

    PubMed

    Gómez-Aristizábal, Alejandro; Davies, John Edward

    2013-06-01

    Hepatocyte culture is a useful tool for the study of their biology and the development of bioartificial livers. However, many challenges have to be overcome since hepatocytes rapidly lose their normal phenotype in vitro. We have recently demonstrated that human umbilical cord perivascular cells (HUCPVCs) are able to provide support to hepatocytes. In the present study we go further into exploring the effects that HUCPVCs have in the functional polarization, and both the internal and external organization, of hepatocytes. Also, we investigate HUCPVC-hepatocyte crosstalk by tracking both the effects of HUCPVCs on hepatocyte transcription factors and those of hepatocytes on the expression of hepatotrophic factors in HUCPVCs. Our results show that HUCPVCs maintain the functional polarity of hepatocytes ex vivo, as judged by the secretion of fluorescein into bile canaliculi, for at least 40 days. Transmission electron microscopy revealed that hepatocytes in coculture organize in an organoid-like structure embedded in extracellular matrix surrounded by HUCPVCs. In coculture, hepatocytes displayed a higher expression of C/EBPα, implicated in maintenance of the mature hepatocyte phenotype, and HUCPVCs upregulated hepatocyte growth factor and Jagged1 indicating that these genes may play important roles in HUCPVC-hepatocyte interactions.

  15. Biological effects of low-level laser irradiation on umbilical cord mesenchymal stem cells

    NASA Astrophysics Data System (ADS)

    Chen, Hongli; Wang, Hong; Li, Yingxin; Liu, Weichao; Wang, Chao; Chen, Zhuying

    2016-04-01

    Low-level laser irradiation (LLLI) can enhance stem cell (SC) activity by increasing migration and proliferation. This study investigated the effects of LLLI on proliferation, enzymatic activity, and growth factor production in human umbilical cord mesenchymal SCs (hUC-MSCs) as well as the underlying mechanisms. hUC-MSCs were assigned to a control group (non-irradiation group) and three LLLI treatment groups (635 nm group, 808 nm group, and 635/808 nm group). Laser power density and energy density of 20 mW/cm2 and 12 J/cm2, respectively, were used for each experiment. The proliferation rate was higher in the 635 nm as compared to the other groups. LLLI at 808 nm did not induce cell proliferation. ROS levels in cells exposed to 635, 808, and 635/808 nm radiation were increased by 52.81%, 26.89%, and 21.15%, respectively, relative to the control group. CAT, tGPx, and SOD activity was increased. LLLI at 808 nm increased the levels of IL-1, IL-6, and NFκB but not VEGF. LLLI improved hUC-MSCs function and increased antioxidant activity. Dual-wavelength LLLI had more potent effects on hUC-MSCs than single-wavelength treatment. LLLI has potential applications in the preconditioning of hUC-MSCs in vitro prior to transplantation, which could improve the regenerative capacity of cells.

  16. Effects of conventional and alternating cushion weight-shifting in persons with spinal cord injury

    PubMed Central

    Wu, Gary A.; Bogie, Kath M.

    2015-01-01

    A repeated-measures study of 13 adult full-time wheelchair users with spinal cord injury (SCI) was carried out to determine whether alternating-pressure air cushion (APAC) use compared with independent pressure relief (IPR) provides reliable, effective pressure relief for individuals with SCI. Bilateral mean ischial interface pressure (IP), transcutaneous oxygen tension (TcPO2), and unilateral laser Doppler blood flow were evaluated. Blood flow component contributions were determined using short-time Fourier transform (STFT)-based spectral analysis. IPR assessment was carried out at recruitment. Study participants then used an APAC for 2 wk every 3 mo for 18 mo. IPR weight-shifting decreased mean ischial IP (p < 0.05) and increased mean TcPO2 (p < 0.05). All variables rapidly returned to preintervention levels following weight-shifting except for the cardiac component of blood flow. APAC-induced weight-shifting decreased mean ischial IP (p < 0.05). Mean TcPO2 increased and was higher than for IPR. STFT analysis indicated that quiet sitting following APAC-induced weight-shifting produced a higher neurogenic component of blood flow than following IPR (p = 0.02). Thus, IPR positively affects multiple aspects of tissue health but produces transient improvements and must be repeated regularly. APAC activation dynamically and continuously alters IP distribution with more sustained positive tissue health effects. PMID:25629607

  17. Predicted effects of pulse width programming in spinal cord stimulation: a mathematical modeling study.

    PubMed

    Lee, Dongchul; Hershey, Brad; Bradley, Kerry; Yearwood, Thomas

    2011-07-01

    To understand the theoretical effects of pulse width (PW) programming in spinal cord stimulation (SCS), we implemented a mathematical model of electrical fields and neural activation in SCS to gain insight into the effects of PW programming. The computational model was composed of a finite element model for structure and electrical properties, coupled with a nonlinear double-cable axon model to predict nerve excitation for different myelinated fiber sizes. Mathematical modeling suggested that mediolateral lead position may affect chronaxie and rheobase values, as well as predict greater activation of medial dorsal column fibers with increased PW. These modeling results were validated by a companion clinical study. Thus, variable PW programming in SCS appears to have theoretical value, demonstrated by the ability to increase and even 'steer' spatial selectivity of dorsal column fiber recruitment. It is concluded that the computational SCS model is a valuable tool to understand basic mechanisms of nerve fiber excitation modulated by stimulation parameters such as PW and electric fields.

  18. Effects of conventional and alternating cushion weight-shifting in persons with spinal cord injury.

    PubMed

    Wu, Gary A; Bogie, Kath M

    2014-01-01

    A repeated-measures study of 13 adult full-time wheelchair users with spinal cord injury (SCI) was carried out to determine whether alternating-pressure air cushion (APAC) use compared with independent pressure relief (IPR) provides reliable, effective pressure relief for individuals with SCI. Bilateral mean ischial interface pressure (IP), transcutaneous oxygen tension (TcPO2), and unilateral laser Doppler blood flow were evaluated. Blood flow component contributions were determined using short-time Fourier transform (STFT)-based spectral analysis. IPR assessment was carried out at recruitment. Study participants then used an APAC for 2 wk every 3 mo for 18 mo. IPR weight-shifting decreased mean ischial IP (p < 0.05) and increased mean TcPO2 (p < 0.05). All variables rapidly returned to preintervention levels following weight-shifting except for the cardiac component of blood flow. APAC-induced weight-shifting decreased mean ischial IP (p < 0.05). Mean TcPO2 increased and was higher than for IPR. STFT analysis indicated that quiet sitting following APAC-induced weight-shifting produced a higher neurogenic component of blood flow than following IPR (p = 0.02). Thus, IPR positively affects multiple aspects of tissue health but produces transient improvements and must be repeated regularly. APAC activation dynamically and continuously alters IP distribution with more sustained positive tissue health effects. PMID:25629607

  19. Effects of non-toxic cryoprotective agents on the viability of cord blood derived MNCs.

    PubMed

    Bissoyi, Akalabya; Pramanik, K

    2013-01-01

    The present work investigates the effects of a variety of natural cryoprotectants in combination on post-thaw viability and apoptosis of cryopreserved mononuclear cells (MNCs) derived from umbilical cord blood. The extracellular cryoprotectants (10 mM) namely trehalose, hydroxyl ethyl starch, polyvinyl pyrrolidine and intracellular CPAs (5 mM) like erythritol, taurine and ectoine were used to prepare different combinations of freezing medium following L9 (3(4)) Taguchi orthogonal array. Catalase, coenzyme Q10 and n-acetyl cystine (100 microg/m) were added as antioxidants. Among various combinations, freezing medium consisting of hydroxyl ethyl starch, ectoin and co-enzyme Q10 with 10% FBS is found to be most effective combination achieving maximum cell viability of 93%, 5.6% early apoptotic, 0.7% late apoptotic and 0.1% necrotic cells. SEM and phase contrast microscopy confirmed the normal cell morphology of the post-thaw cultured cells with retaining their membrane integrity. The survival rate of MNCs is higher than the rate achieved using conventional Me2SO. PMID:24448765

  20. Computed Tomography Perfusion Assessment of Radiation Therapy Effects on Spinal Cord Hemodynamics

    SciTech Connect

    Spampinato, Maria Vittoria; Bisdas, Sotirios; Sharma, Anand K.; McDonald, Daniel; Strojan, Primoz; Rumboldt, Zoran

    2010-07-01

    Purpose: We used computed tomography (CT) perfusion to evaluate the acute and late effect of radiation therapy (RT) on spinal cord (SC) hemodynamics in patients without symptoms of myelopathy. We hypothesized that SC perfusion could be acutely altered during RT. Methods and Materials: We analyzed neck CT perfusion studies of 36 head-and-neck cancer patients (N1), 16 of whom had previously undergone RT. In a separate group of 6 patients (N2), CT perfusion studies were obtained before RT, after 40 Gy, and after treatment completion. Results: In the N1 group, SC blood flow (BF), blood volume (BV), mean transit time (MTT), and capillary permeability (CP) maps were not significantly different between RT-treated and RT-naive patients. In the N2 group, BF and CP were significantly increased during treatment compared with the baseline and post-RT studies. Conclusions: Radiation therapy of the head and neck may cause transient perturbations of SC perfusion that seem to reverse after treatment. There are no definite chronic effects of RT on SC perfusion observeable at the typical doses administered during treatment of head and neck malignancies.

  1. The effect of obesity on outcome of unrelated cord blood transplant in children with malignant diseases.

    PubMed

    Pine, M; Wang, L; Harrell, F E; Calder, C; Manes, B; Evans, M; Domm, J; Frangoul, H

    2011-10-01

    Obesity has become a pandemic, affecting both children and adults. We sought to determine the effect of obesity among 200 children who were prospectively enrolled on a multicenter cord blood transplant (CBT) trial. All patients received myeloablative preparative regimens. Children were classified into groups according to body mass index percentile. Normal weight was defined as body mass index between the 5th and 85th percentile (n=117), overweight between the 85th and 95th percentile (n=35) and obesity above 95th percentile (n=39) for age and gender. A total of 55 patients (27%) had AML, 113 patients (57%) had ALL and 32 patients (16%) had other malignant diseases. There was no evidence for a difference in all major characteristics among the groups. Time to neutrophil and platelet engraftment, TRM, risk of acute GVHD, disease-free survival and OS were not significantly different in overweight or obese patients compared with normal weight patients. There was a trend towards increased risk of chronic GVHD in obese patients (P=0.05) compared with normal weight patients. In conclusion, there is insufficient evidence from this sample that obesity has an effect on multiple outcomes after unrelated CBT in children with malignant diseases.

  2. Mild hypothermia combined with a scaffold of NgR-silenced neural stem cells/Schwann cells to treat spinal cord injury.

    PubMed

    Wang, Dong; Liang, Jinhua; Zhang, Jianjun; Liu, Shuhong; Sun, Wenwen

    2014-12-15

    Because the inhibition of Nogo proteins can promote neurite growth and nerve cell differentiation, a cell-scaffold complex seeded with Nogo receptor (NgR)-silenced neural stem cells and Schwann cells may be able to improve the microenvironment for spinal cord injury repair. Previous studies have found that mild hypothermia helps to attenuate secondary damage in the spinal cord and exerts a neuroprotective effect. Here, we constructed a cell-scaffold complex consisting of a poly(D,L-lactide-co-glycolic acid) (PLGA) scaffold seeded with NgR-silenced neural stem cells and Schwann cells, and determined the effects of mild hypothermia combined with the cell-scaffold complexes on the spinal cord hemi-transection injury in the T9 segment in rats. Compared with the PLGA group and the NgR-silencing cells + PLGA group, hindlimb motor function and nerve electrophysiological function were clearly improved, pathological changes in the injured spinal cord were attenuated, and the number of surviving cells and nerve fibers were increased in the group treated with the NgR-silenced cell scaffold + mild hypothermia at 34°C for 6 hours. Furthermore, fewer pathological changes to the injured spinal cord and more surviving cells and nerve fibers were found after mild hypothermia therapy than in injuries not treated with mild hypothermia. These experimental results indicate that mild hypothermia combined with NgR gene-silenced cells in a PLGA scaffold may be an effective therapy for treating spinal cord injury.

  3. Diffusion tensor imaging of ex vivo cervical spinal cord specimens: the immediate and long term effects of fixation on diffusivity

    PubMed Central

    Kim, T. H.; Zollinger, L.; Shi, X. F.; Rose, J.; Jeong, E-K.

    2010-01-01

    Diffusion Tensor imaging (DTI) is an emerging noninvasive method for evaluating tissue microstructure, but is highly susceptible to in vivo motion artifact. Ex vivo experiments on fixed tissues are needed to improve DTI techniques, which require fixed tissue specimens. Several efforts have been made to study the effect of fixation on both human and mouse tissue, with varying results. Four human cervical cords and three segments of pig vivo cervical spinal cord specimens were imaged both before and after tissue fixation using 3D multi-shot diffusion weighted imaging (ms-DWEPI). Fixation caused a significant decrease in the longitudinal diffusivity while the relative anisotropy (RA), and radial diffusivity remained unaffected. Additionally, once adequately preserved the diffusivity parameters of fixed tissue remain constant over time. Fixation has important effects on the diffusivity of tissue specimens. These findings have important implications for the determination of tissue microstructure and function using DTI technologies. PMID:19051255

  4. Antiepileptic and neuroprotective effects of human umbilical cord blood mononuclear cells in a pilocarpine-induced epilepsy model.

    PubMed

    Costa-Ferro, Zaquer Suzana Munhoz; de Borba Cunha, Fernanda; de Freitas Souza, Bruno Solano; Leal, Marcos Maurício Tosta; da Silva, Adelson Alves; de Bellis Kühn, Telma Ingrid Borges; Forte, Andresa; Sekiya, Eliseo Joji; Soares, Milena Botelho Pereira; Dos Santos, Ricardo Ribeiro

    2014-03-01

    Status epilepticus (SE) is a condition of persistent seizure that leads to brain damage and, frequently, to the establishment of chronic epilepsy. Cord blood is an important source of adult stem cells for the treatment of neurological disorders. The present study aimed to evaluate the effects of human umbilical cord blood mononuclear cells (HUCBC) transplanted into rats after induction of SE by the administration of lithium and pilocarpine chloride. Transplantation of HUCBC into epileptic rats protected against neuronal loss in the hippocampal subfields CA1, CA3 and in the hilus of the dentate gyrus, up to 300 days after SE induction. Moreover, transplanted rats had reduced frequency and duration of spontaneous recurrent seizures (SRS) 15, 120 and 300 days after the SE. Our study shows that HUCBC provide prominent antiepileptic and neuroprotective effects in the experimental model of epilepsy and reinforces that early interventions can protect the brain against the establishment of epilepsy.

  5. CD14{sup +} monocytes promote the immunosuppressive effect of human umbilical cord matrix stem cells

    SciTech Connect

    Wang, Ding; Chen, Ke; Du, Wei Ting; Han, Zhi-Bo; Ren, He; Chi, Ying; and others

    2010-09-10

    Here, the effect of CD14{sup +} monocytes on human umbilical cord matrix stem cell (hUC-MSC)-mediated immunosuppression was studied in vitro. hUC-MSCs exerted a potent inhibitory effect on the proliferation and interferon-{gamma} (IFN-{gamma}) secretion capacities of CD4{sup +} and CD8{sup +} T cells in response to anti-CD3/CD28 stimulation. Transwell co-culture system revealed that the suppressive effect was primarily mediated by soluble factors. Addition of prostaglandin synthesis inhibitors (indomethacin or NS-398) almost completely abrogated the immunosuppression activity of hUC-MSCs, identifying prostaglandin E{sub 2} (PGE{sub 2}) as an important soluble mediator. CD14{sup +} monocytes were found to be able to enhance significantly the immunosuppressive effect of hUC-MSCs in a dose-dependent fashion. Moreover, the inflammatory cytokine IL-1{beta}, either exogenously added or produced by CD14{sup +} monocytes in culture, could trigger expression of high levels of PGE{sub 2} by hUC-MSCs, whereas inclusion of the IL-1 receptor antagonist (IL-1RA) in the culture down-regulated not only PGE{sub 2} expression, but also reversed the promotional effect of CD14{sup +} monocytes and partially restored CD4{sup +} and CD8{sup +} T cell proliferation and IFN-{gamma} secretion. Our data demonstrate an important role of monocytes in the hUC-MSC-induced immunomodulation, which may have important implications in future efforts to explore the clinical potentials of hUC-MSCs.

  6. GEMINI: Initial behavioral results after full severance of the cervical spinal cord in mice

    PubMed Central

    Kim, C-Yoon; Oh, Hanseul; Hwang, In-Kyu; Hong, Ki-Sung

    2016-01-01

    Background: The GEMINI spinal cord fusion protocol has been developed to achieve a successful cephalosomatic anastomosis. Here, we report the preliminary data on the use of a fusogen [polyethylene glycol (PEG)] after full cervical cord transection in mice to facilitate the fusion of both ends of a sharply transected spinal cord. Methods: Cervical laminectomy and a complete, visually confirmed cervical cord (C 5) transection was performed on female albino mice (n = 16). In Group 1 (n = 8), a fusogen, (PEG) was used to bridge the gap between the cut ends of the spinal cord. Group 2 received the same spinal cord transection but was treated with saline. Outcome was assessed daily using a standard scale (modified 22-point Basso-Beattie-Bresnahan scale) and filmed on camera. Results: The PEG group (group 1) showed partial restoration of motor function after 4 weeks of observation; group 2 (placebo) did not recover any useful motor activity. Conclusion: In this preliminary experiment, PEG, but not saline, promoted partial motor recovery in mice submitted to full cervical transection. PMID:27656325

  7. GEMINI: Initial behavioral results after full severance of the cervical spinal cord in mice

    PubMed Central

    Kim, C-Yoon; Oh, Hanseul; Hwang, In-Kyu; Hong, Ki-Sung

    2016-01-01

    Background: The GEMINI spinal cord fusion protocol has been developed to achieve a successful cephalosomatic anastomosis. Here, we report the preliminary data on the use of a fusogen [polyethylene glycol (PEG)] after full cervical cord transection in mice to facilitate the fusion of both ends of a sharply transected spinal cord. Methods: Cervical laminectomy and a complete, visually confirmed cervical cord (C 5) transection was performed on female albino mice (n = 16). In Group 1 (n = 8), a fusogen, (PEG) was used to bridge the gap between the cut ends of the spinal cord. Group 2 received the same spinal cord transection but was treated with saline. Outcome was assessed daily using a standard scale (modified 22-point Basso-Beattie-Bresnahan scale) and filmed on camera. Results: The PEG group (group 1) showed partial restoration of motor function after 4 weeks of observation; group 2 (placebo) did not recover any useful motor activity. Conclusion: In this preliminary experiment, PEG, but not saline, promoted partial motor recovery in mice submitted to full cervical transection.

  8. Neuroprotective Effect of Simvastatin via Inducing the Autophagy on Spinal Cord Injury in the Rat Model.

    PubMed

    Gao, Kai; Wang, Guannan; Wang, Yansong; Han, Donghe; Bi, Jing; Yuan, Yajiang; Yao, Tianchen; Wan, Zhanghui; Li, Haihong; Mei, Xifan

    2015-01-01

    Simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, is invariably used to treat cardiovascular diseases. Simvastatin has been recently demonstrated to have a neuroprotective effect in nervous system diseases. The present study aimed to further verify the neuroprotection and molecular mechanism of simvastatin on rats after spinal cord injury (SCI). The expression of Beclin-1 and LC3-B was evidently enhanced at postoperation days 3 and 5, respectively. However, the reduction of the mTOR protein and ribosomal protein S6 kinase p70 subtype (p70S6K) phosphorylation level occurred at the same time after SCI. Simvastatin significantly increased the expression of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Meanwhile, immunofluorescence results indicated that the expression of chondroitin sulfate proteoglycan (CSPG) and caspase-3 protein was obviously reduced by simvastatin. Furthermore, Nissl staining and Basso, Beattie, and Bresnahan (BBB) scores showed that the quantity and function of motor neurons were visibly preserved by simvastatin after SCI. The findings of this study showed that simvastatin induced autophagy by inhibiting the mTOR signaling pathway and contributed to neuroprotection after SCI. PMID:26539474

  9. Effect of human umbilical cord mesenchymal stem cells on endometriotic cell proliferation and apoptosis.

    PubMed

    Xu, L N; Lin, N; Xu, B N; Li, J B; Chen, S Q

    2015-12-11

    The objective of this study was to observe the effects of human umbilical cord mesenchymal stem cells (UCMSCs) on the proliferation and apoptosis of endometriotic cells. Endometriotic cells and UCMSCs were primarily cultured in vitro. In the experimental group, a UCMSC and endometriotic cell non-contact co-culture system was established. The control group consisted of 1 x 10(5) endometriotic cells cultured alone. The proliferation and apoptosis of endometriotic cells were respectively detected using the MTT method and flow cytometry. The mRNA expression level of the tensin homologue gene (PTEN) in endometriotic cells was detected by reverse transcription-polymerase chain reaction amplification. Compared with the control group, the proliferation of endometriotic cells in the experimental group was clearly inhibited (P < 0.05) and time-dependent (P < 0.05). In addition, the number of apoptotic cells were significantly increased (P < 0.05), and the amount of cells, which entered S phase from G1 phase, decreased significantly. Furthermore, the mRNA expression level of the PTEN gene in the experimental group was significantly higher than in the control group (P < 0.05). These results suggest that UCMSCs might inhibit the proliferation of human endometriotic cells in vitro and promote their apoptosis by upregulating the expression of PTEN.

  10. Effects of spinal cord stimulation on peripheral blood circulation in rats with streptozotocin-induced diabetes.

    PubMed

    Wu, Mingyuan; Thorkilsen, Marielouise Muus; Qin, Chao; Farber, Jay P; Linderoth, Bengt; Foreman, Robert D

    2007-07-01

    Objective.  The aim of this study was to investigate the effects of spinal cord stimulation (SCS) on peripheral circulation in rats with streptozotocin (STZ)-induced diabetes. Materials and Methods.  Four weeks after streptozotocin or vehicle was injected (i.p.) in male Sprague-Dawley rats, SCS-induced vasodilation was examined. Results.  Plasma glucose concentration was significantly higher in diabetic rats than in the control animals. Motor threshold (MT) was significantly higher in diabetic rats than in control rats. SCS-induced vasodilation was attenuated at 90% of the MT, but not at 30% and 60% of MT in diabetic rats when compared to control rats (p < 0.001, N = 13). Furthermore, increasing SCS from 30% to 90% of MT typically produced a progressive increase in blood flow in control rats but not in diabetic rats (p < 0.01, N = 13). Conclusion.  This study suggested that SCS-induced vasodilation improves peripheral blood flow, although the pathways were partially impaired in the diabetic condition.

  11. Effects of inspiratory muscle training on exercise responses in Paralympic athletes with cervical spinal cord injury.

    PubMed

    West, C R; Taylor, B J; Campbell, I G; Romer, L M

    2014-10-01

    We asked whether specific inspiratory muscle training (IMT) improves respiratory structure and function and peak exercise responses in highly trained athletes with cervical spinal cord injury (SCI). Ten Paralympic wheelchair rugby players with motor-complete SCI (C5-C7) were paired by functional classification then randomly assigned to an IMT or placebo group. Diaphragm thickness (B-mode ultrasonography), respiratory function [spirometry and maximum static inspiratory (PI ,max ) and expiratory (PE ,max ) pressures], chronic activity-related dyspnea (Baseline and Transition Dyspnea Indices), and physiological responses to incremental arm-crank exercise were assessed before and after 6 weeks of pressure threshold IMT or sham bronchodilator treatment. Compared to placebo, the IMT group showed significant increases in diaphragm thickness (P = 0.001) and PI ,max (P = 0.016). There was a significant increase in tidal volume at peak exercise in IMT vs placebo (P = 0.048) and a strong trend toward an increase in peak work rate (P = 0.081, partial eta-squared = 0.33) and peak oxygen uptake (P = 0.077, partial eta-squared = 0.34). No other indices changed post-intervention. In conclusion, IMT resulted in significant diaphragmatic hypertrophy and increased inspiratory muscle strength in highly trained athletes with cervical SCI. The strong trend, with large observed effect, toward an increase in peak aerobic performance suggests IMT may provide a useful adjunct to training in this population.

  12. Neuroprotective Effect of Simvastatin via Inducing the Autophagy on Spinal Cord Injury in the Rat Model

    PubMed Central

    Gao, Kai; Wang, Guannan; Wang, Yansong; Han, Donghe; Bi, Jing; Yuan, Yajiang; Yao, Tianchen; Wan, Zhanghui; Li, Haihong; Mei, Xifan

    2015-01-01

    Simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, is invariably used to treat cardiovascular diseases. Simvastatin has been recently demonstrated to have a neuroprotective effect in nervous system diseases. The present study aimed to further verify the neuroprotection and molecular mechanism of simvastatin on rats after spinal cord injury (SCI). The expression of Beclin-1 and LC3-B was evidently enhanced at postoperation days 3 and 5, respectively. However, the reduction of the mTOR protein and ribosomal protein S6 kinase p70 subtype (p70S6K) phosphorylation level occurred at the same time after SCI. Simvastatin significantly increased the expression of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Meanwhile, immunofluorescence results indicated that the expression of chondroitin sulfate proteoglycan (CSPG) and caspase-3 protein was obviously reduced by simvastatin. Furthermore, Nissl staining and Basso, Beattie, and Bresnahan (BBB) scores showed that the quantity and function of motor neurons were visibly preserved by simvastatin after SCI. The findings of this study showed that simvastatin induced autophagy by inhibiting the mTOR signaling pathway and contributed to neuroprotection after SCI. PMID:26539474

  13. Effect of Spinal Cord Injury on the Respiratory System: Basic Research and Current Clinical Treatment Options

    PubMed Central

    Zimmer, M. Beth; Nantwi, Kwaku; Goshgarian, Harry G

    2007-01-01

    Summary: Spinal cord injury (SCI) often leads to an impairment of the respiratory system. The more rostral the level of injury, the more likely the injury will affect ventilation. In fact, respiratory insufficiency is the number one cause of mortality and morbidity after SCI. This review highlights the progress that has been made in basic and clinical research, while noting the gaps in our knowledge. Basic research has focused on a hemisection injury model to examine methods aimed at improving respiratory function after SCI, but contusion injury models have also been used. Increasing synaptic plasticity, strengthening spared axonal pathways, and the disinhibition of phrenic motor neurons all result in the activation of a latent respiratory motor pathway that restores function to a previously paralyzed hemidiaphragm in animal models. Human clinical studies have revealed that respiratory function is negatively impacted by SCI. Respiratory muscle training regimens may improve inspiratory function after SCI, but more thorough and carefully designed studies are needed to adequately address this issue. Phrenic nerve and diaphragm pacing are options available to wean patients from standard mechanical ventilation. The techniques aimed at improving respiratory function in humans with SCI have both pros and cons, but having more options available to the clinician allows for more individualized treatment, resulting in better patient care. Despite significant progress in both basic and clinical research, there is still a significant gap in our understanding of the effect of SCI on the respiratory system. PMID:17853653

  14. Soft tissue effects of the THC:YAG laser on canine vocal cords.

    PubMed

    Kay, S L; Oz, M C; Haber, M; Blitzer, A; Treat, M R; Trokel, S L

    1992-09-01

    Recently, a laser based on a thulium-holmium-chromium (THC) doped Yttrium-aluminum-garnet (YAG) rod has been developed that produces light of 2.15 microns wavelength and can be transmitted through a low OH- silica fiberoptic cable. This wavelength falls on one of the peaks of the energy absorption spectrum of water. Thus, the THC:YAG laser eliminates the disadvantage of a cumbersome delivery system found in the CO2 laser while still providing precise cutting and minimal tissue injury inherent in lasers emitting light absorbed by water. We evaluated the soft tissue effects of this laser on canine vocal cords. Ablative lesions were produced by the THC:YAG laser and histologically examined on postoperative days 1, 7, and 28. Results indicate that the depth of tissue penetration is easily controlled and the healing response to tissue injury is comparable to that of the CO2 laser. The THC:YAG laser should prove to be a superior laser for use in otorhinolaryngology, especially when adapted to a flexible endoscope.

  15. Repair of spinal cord injury by implantation of bFGF-incorporated HEMA-MOETACL hydrogel in rats

    NASA Astrophysics Data System (ADS)

    Chen, Bo; He, Jianyu; Yang, Hao; Zhang, Qian; Zhang, Lingling; Zhang, Xian; Xie, En; Liu, Cuicui; Zhang, Rui; Wang, Yi; Huang, Linhong; Hao, Dingjun

    2015-03-01

    There is no effective strategy for the treatment of spinal cord injury (SCI). An appropriate combination of hydrogel materials and neurotrophic factor therapy is currently thought to be a promising approach. In this study, we performed experiments to evaluate the synergic effect of implanting hydroxyl ethyl methacrylate [2-(methacryloyloxy)ethyl] trimethylammonium chloride (HEMA-MOETACL) hydrogel incorporated with basic fibroblast growth factor (bFGF) into the site of surgically induced SCI. Prior to implantation, the combined hydrogel was surrounded by an acellular vascular matrix. Sprague-Dawley rats underwent complete spinal cord transection at the T-9 level, followed by implantation of bFGF/HEMA-MOETACL 5 days after transection surgery. Our results showed that the bFGF/HEMA-MOETACL transplant provided a scaffold for the ingrowth of regenerating tissue eight weeks after implantation. Furthermore, this newly designed implant promoted both nerve tissue regeneration and functional recovery following SCI. These results indicate that HEMA-MOETACL hydrogel is a promising scaffold for intrathecal, localized and sustained delivery of bFGF to the injured spinal cord and provide evidence for the possibility that this approach may have clinical applications in the treatment of SCI.

  16. Cord blood T cells mediate enhanced antitumor effects compared with adult peripheral blood T cells.

    PubMed

    Hiwarkar, Prashant; Qasim, Waseem; Ricciardelli, Ida; Gilmour, Kimberly; Quezada, Sergio; Saudemont, Aurore; Amrolia, Persis; Veys, Paul

    2015-12-24

    Unrelated cord blood transplantation (CBT) without in vivo T-cell depletion is increasingly used to treat high-risk hematologic malignancies. Following T-replete CBT, naïve CB T cells undergo rapid peripheral expansion with memory-effector differentiation. Emerging data suggest that unrelated CBT, particularly in the context of HLA mismatch and a T-replete graft, may reduce leukemic relapse. To study the role of CB T cells in mediating graft-versus-tumor responses and dissect the underlying immune mechanisms for this, we compared the ability of HLA-mismatched CB and adult peripheral blood (PB) T cells to eliminate Epstein-Barr virus (EBV)-driven human B-cell lymphoma in a xenogeneic NOD/SCID/IL2rg(null) mouse model. CB T cells mediated enhanced tumor rejection compared with equal numbers of PB T cells, leading to improved survival in the CB group (P < .0003). Comparison of CB T cells that were autologous vs allogeneic to the lymphoma demonstrated that this antitumor effect was mediated by alloreactive rather than EBV-specific T cells. Analysis of tumor-infiltrating lymphocytes demonstrated that CB T cells mediated this enhanced antitumor effect by rapid infiltration of the tumor with CCR7(+)CD8(+) T cells and prompt induction of cytotoxic CD8(+) and CD4(+) T-helper (Th1) T cells in the tumor microenvironment. In contrast, in the PB group, this antilymphoma effect is impaired because of delayed tumoral infiltration of PB T cells and a relative bias toward suppressive Th2 and T-regulatory cells. Our data suggest that, despite being naturally programmed toward tolerance, reconstituting T cells after unrelated T-replete CBT may provide superior Tc1-Th1 antitumor effects against high-risk hematologic malignancies.

  17. Effects of Serotonergic Medications on Locomotor Performance in Humans with Incomplete Spinal Cord Injury

    PubMed Central

    Leech, Kristan A.; Kinnaird, Catherine R.

    2014-01-01

    Abstract Incomplete spinal cord injury (iSCI) often results in significant motor impairments that lead to decreased functional mobility. Loss of descending serotonergic (5HT) input to spinal circuits is thought to contribute to motor impairments, with enhanced motor function demonstrated through augmentation of 5HT signaling. However, the presence of spastic motor behaviors in SCI is attributed, in part, to changes in spinal 5HT receptors that augment their activity in the absence of 5HT, although data demonstrating motor effects of 5HT agents that deactivate these receptors are conflicting. The effects of enhancement or depression of 5HT signaling on locomotor function have not been thoroughly evaluated in human iSCI. Therefore, the aim of the current study was to investigate acute effects of 5HT medications on locomotion in 10 subjects with chronic (>1 year) iSCI. Peak overground and treadmill locomotor performance, including measures of gait kinematics, electromyographic (EMG) activity, and oxygen consumption, were assessed before and after single-dose administration of either a selective serotonin reuptake inhibitor (SSRI) or a 5HT antagonist using a double-blinded, randomized, cross-over design. Results indicate that neither medication led to improvements in locomotion, with a significant decrease in peak overground gait speed observed after 5HT antagonists (from 0.8±0.1 to 0.7±0.1 m/s; p=0.01). Additionally, 5-HT medications had differential effects on EMG activity, with 5HT antagonists decreasing extensor activity and SSRIs increasing flexor activity. Our data therefore suggest that acute manipulation of 5HT signaling, despite changes in muscle activity, does not improve locomotor performance after iSCI. PMID:24742292

  18. Effects of Rolipram on Adult Rat Oligodendrocytes and Functional Recovery after Contusive Cervical Spinal Cord Injury

    PubMed Central

    Beaumont, Eric; Whitaker, Christopher M.; Burke, Darlene A.; Hetman, Michal; Onifer, Stephen M.

    2009-01-01

    Traumatic human spinal cord injury causes devastating and long-term hardships. These are due to the irreparable primary mechanical injury and secondary injury cascade. In particular, oligodendrocyte cell death, white matter axon damage, spared axon demyelination, and the ensuing dysfunction in action potential conduction lead to the initial deficits and impair functional recovery. For these reasons, and that oligodendrocyte and axon survival may be related, various neuroprotective strategies after SCI are being investigated. We previously demonstrated that oligodendrocytes in the adult rat epicenter ventrolateral funiculus express 3′-5′-cyclic adenosine monophosphate-dependent phosphodiesterase 4 subtypes and that their death was attenuated up to 3 days after contusive cervical spinal cord injury when rolipram, a specific inhibitor of phosphodiesterase 4, was administered. Here, we report that 1) there are more oligodendrocyte somata in the adult rat epicenter ventrolateral funiculus, 2) descending and ascending axonal conductivity in the ventrolateral funiculus improves, and that 3) there are fewer hindlimb footfall errors during grid-walking at 5 weeks after contusive cervical spinal cord injury when rolipram is delivered for 2 weeks. This is the first demonstration of improved descending and ascending long-tract axonal conductivity across a spinal cord injury with this pharmacological approach. Since descending long-tract axonal conductivity did not return to normal, further evaluations of the pharmacokinetics and therapeutic window of rolipram as well as optimal combinations are necessary before consideration for neuroprotection in humans with spinal cord injury. PMID:19635528

  19. Effects of air stacking on pulmonary function and peak cough flow in patients with cervical spinal cord injury.

    PubMed

    Jeong, Jong-Hwa; Yoo, Won-Gyu

    2015-06-01

    [Purpose] This study evaluated the effects of air stacking on pulmonary function and peak cough flow in patients with cervical spinal cord injury. [Subjects] Twenty-six patients were included in the study and were randomized into experimental (n = 14) and control (n = 12) groups. [Methods] Both groups performed therapeutic exercises: the control group performed incentive spirometry, while the experimental group performed 20 repetitions of air stacking exercise twice a day. The training for both groups continued for 5 days a week for 6 weeks. [Results] Forced vital capacity and peak cough flow increased significantly in the experimental group compared to the controls. All within-group variables in the experimental group differed significantly at 6 weeks compared to baseline, while in the control group only Forced vital capacity differed significantly at 6 weeks compared to baseline. [Conclusion] Air stacking exercise significantly improved pulmonary function and peak cough flow in patients with a cervical spinal cord injury. PMID:26180355

  20. Effects of air stacking on pulmonary function and peak cough flow in patients with cervical spinal cord injury

    PubMed Central

    Jeong, Jong-hwa; Yoo, Won-gyu

    2015-01-01

    [Purpose] This study evaluated the effects of air stacking on pulmonary function and peak cough flow in patients with cervical spinal cord injury. [Subjects] Twenty-six patients were included in the study and were randomized into experimental (n = 14) and control (n = 12) groups. [Methods] Both groups performed therapeutic exercises: the control group performed incentive spirometry, while the experimental group performed 20 repetitions of air stacking exercise twice a day. The training for both groups continued for 5 days a week for 6 weeks. [Results] Forced vital capacity and peak cough flow increased significantly in the experimental group compared to the controls. All within-group variables in the experimental group differed significantly at 6 weeks compared to baseline, while in the control group only Forced vital capacity differed significantly at 6 weeks compared to baseline. [Conclusion] Air stacking exercise significantly improved pulmonary function and peak cough flow in patients with a cervical spinal cord injury. PMID:26180355

  1. An audit of the effect of two cord-care regimens on bacterial colonization in newborn infants.

    PubMed

    Paes, B; Jones, C C

    1987-03-01

    Proper care of the umbilical cord of newborn infants may prevent later infections. When St Joseph's Hospital in Hamilton, Ontario, started using alcohol instead of triple dye for umbilical cord care, there was a dramatic increase in the incidence of bacterial colonization in newborns in the nursery and, later, in the number of cases of staphylococcus-related skin infections in infants born at the hospital. Follow-up on 1,545 infants revealed that triple dye was significantly more effective than alcohol in reducing the growth of gram-positive organisms, especially Staphylococcus aureus and group B streptococcus, and several gram-negative organisms. Because hospital medical staff had carefully collected data on bacterial colonization, they were quickly aware of the problem and could justify resuming the use of triple dye.

  2. Effect of late vs early clamping of the umbilical cord (on haemoglobin level) in full-term neonates.

    PubMed

    Nesheli, Hassan Mahmoodi; Esmailzadeh, Seddigheh; Haghshenas, Mohsen; Bijani, Ali; Moghaddams, Tahereh Galini

    2014-11-01

    Sixty term infants delivered vaginally were assigned randomly to one of the two management groups; early cord clamping (ECC) or delayed cord clamping (DCC). Six months after delivery, the children in both groups were called back for follow-up. Blood samples were obtained for measuring haemoglobin (Hb), haematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), serum iron (SI), transferrin saturation (TS) and serum ferritin (SF) levels. The mean Hb, HCT, SI and TS at 6 months were significantly higher in the DCC group (95% confidence interval (CI); p<0.001, p<0.001, p<0.024 and p<0.009). The mean SF at 6 months was also higher in the DCC group but it was not significant (p<0.071). Polycythaemia, jaundice and other undesirable side-effects of DCC were not seen.

  3. [Effect of embryonic anlage allografts of the rat spinal cord on growth of regenerating fibers of the recipient nerve].

    PubMed

    Petrova, E S; Isaeva, E N

    2014-01-01

    A comparative study of the effect of tissue and suspension allografts of an embryonic spinal cord on regeneration of nerve fibers of impaired (by application of a ligature) sciatic nerve in rats was conducted. It was demonstrated that unlike tissue grafts that reach a large volume 21 and 60 days after transplantation, suspension grafts do not inhibit the growth of axons of the recipient to the periphery. It was established that introduction of a suspension of dissociated cells of the spinal cord embryonic anlages (but not fragments of these anlages) into the impaired sciatic nerve in rats results in an increase in the amount of myelinated regenerating nerve fibers of the recipient 60 days after the operation.

  4. [Effects of delayed cord clamping on hemoglobin and ferritin levels in infants at three months of age].

    PubMed

    Venâncio, Sonia Isoyama; Levy, Renata Bertazzi; Saldiva, Sílvia Regina Dias Médici; Mondini, Lenise; Alves, Maria Cecília Goi Porto; Leung, Siu Lum

    2008-01-01

    This study assessed the effect of delayed (1 minute after delivery) clamping of the umbilical cord on hemoglobin and ferritin levels in infants at three months of age. Mothers and their infants born through vaginal delivery, at term, and without congenital anomalies (325 pairs) were recruited at a hospital in São Paulo, Brazil, in 2006 (164 in the delayed clamping subgroup and 161 in the early clamping subgroup). Maternal hemoglobin at delivery, umbilical cord hemoglobin, and ferritin were recorded. At three months follow-up, venous blood samples were drawn from 224 (69%) infants for hemoglobin and ferritin measurement. Socioeconomic, maternal reproductive, anthropometric, and infant feeding variables were studied. Multiple linear regression models were used to analyze the data. The effect of delayed clamping at birth, measured at three months, was only significant for ferritin (p = 0.040), and the concentration was higher (23.29ng/mL) in this subgroup as compared to the early clamping subgroup. Delayed umbilical cord clamping can serve as a strategy to improve infant iron status and prevent iron deficiency.

  5. Fat Grafting in Burn Scar Alleviates Neuropathic Pain via Anti-Inflammation Effect in Scar and Spinal Cord.

    PubMed

    Huang, Shu-Hung; Wu, Sheng-Hua; Lee, Su-Shin; Chang, Kao-Ping; Chai, Chee-Yin; Yeh, Jwu-Lai; Lin, Sin-Daw; Kwan, Aij-Lie; David Wang, Hui-Min; Lai, Chung-Sheng

    2015-01-01

    Burn-induced neuropathic pain is complex, and fat grafting has reportedly improved neuropathic pain. However, the mechanism of fat grafting in improving neuropathic pain is unclear. Previous investigations have found that neuroinflammation causes neuropathic pain, and anti-inflammatory targeting may provide potential therapeutic opportunities in neuropathic pain. We hypothesized that fat grafting in burn scars improves the neuropathic pain through anti-inflammation. Burn-induced scar pain was confirmed using a mechanical response test 4 weeks after burn injuries, and autologous fat grafting in the scar area was performed simultaneously. After 4 weeks, the animals were sacrificed, and specimens were collected for the inflammation test, including COX-2, iNOS, and nNOS in the injured skin and spinal cord dorsal horns through immunohistochemistry and Western assays. Furthermore, pro-inflammatory cytokines (IL-1 β and TNF-α) in the spinal cord were collected. Double immunofluorescent staining images for measuring p-IκB, p-NFκB, p-JNK, and TUNEL as well as Western blots of AKT, Bax/Bcl-2 for the inflammatory process, and apoptosis were analyzed. Fat grafting significantly reduced COX2, nNOS, and iNOS in the skin and spinal cord dorsal horns, as well as IL-1β and TNF-α, compared with the burn group. Moreover, regarding the anti-inflammatory effect, the apoptosis cells in the spinal cord significantly decreased after the fat grafting in the burn injury group. Fat grafting was effective in treating burn-induced neuropathic pain through the alleviation of neuroinflammation and ameliorated spinal neuronal apoptosis. PMID:26368011

  6. Effect of cannabinoids on CGRP release in the isolated rat lumbar spinal cord.

    PubMed

    Milne, Michael; Ashton, John C

    2016-02-12

    Cannabinoids produce analgesia through a variety of mechanisms. It has been proposed that one mechanism is by modulating the release of CGRP in the spinal cord pain pathways. Previous studies have reported that cannabinoids, particularly CB2 receptor agonists, can modulate CGRP release in the isolated rat spinal cord. In our experiments, the TRPV1 agonist capsaicin evoked CGRP release and this was supressed by the TRPV1 antagonist capsazepine and by the opioid receptor agonist DAMGO. However, none of the cannabinoid receptor agonists that we tested were able to modulate evoked CGRP release; including WIN 55,212-2, methanandamide, and GW405833. These results question the role of spinal cord cannabinoid receptors in the regulation of CGRP signaling.

  7. Selected suitable seed cell, scaffold and growth factor could maximize the repair effect using tissue engineering method in spinal cord injury.

    PubMed

    Ji, Wen-Chen; Zhang, Xiao-Wei; Qiu, Yu-Sheng

    2016-08-20

    Spinal cord injury usually leads to permanent disability, which could cause a huge financial problem to the patient. Up to now there is no effective method to treat this disease. The key of the treatment is to enable the damage zone axonal regeneration and luckily it could go through the damage zone; last a connection can be established with the target neurons. This study attempts to combine stem cell, material science and genetic modification technology together, by preparing two genes modified adipose-derived stem cells and inducing them into neuron direction; then by compositing them on the silk fibroin/chitosan scaffold and implanting them into the spinal cord injury model, seed cells can have features of neuron cells. At the same time, it could stably express the brain-derived neurotrophic factor and neurotrophin-3, both of which could produce synergistic effects, which have a positive effect on the recovery of spinal cord. The spinal cord scaffold bridges the broken end of the spinal cord and isolates with the surrounding environment, which could avoid a scar effect on the nerve regeneration and provide three-dimensional space for the seed cell growth, and at last we hope to provide a new treatment for spinal cord injury with the tissue engineering technique. PMID:27622154

  8. Selected suitable seed cell, scaffold and growth factor could maximize the repair effect using tissue engineering method in spinal cord injury.

    PubMed

    Ji, Wen-Chen; Zhang, Xiao-Wei; Qiu, Yu-Sheng

    2016-08-20

    Spinal cord injury usually leads to permanent disability, which could cause a huge financial problem to the patient. Up to now there is no effective method to treat this disease. The key of the treatment is to enable the damage zone axonal regeneration and luckily it could go through the damage zone; last a connection can be established with the target neurons. This study attempts to combine stem cell, material science and genetic modification technology together, by preparing two genes modified adipose-derived stem cells and inducing them into neuron direction; then by compositing them on the silk fibroin/chitosan scaffold and implanting them into the spinal cord injury model, seed cells can have features of neuron cells. At the same time, it could stably express the brain-derived neurotrophic factor and neurotrophin-3, both of which could produce synergistic effects, which have a positive effect on the recovery of spinal cord. The spinal cord scaffold bridges the broken end of the spinal cord and isolates with the surrounding environment, which could avoid a scar effect on the nerve regeneration and provide three-dimensional space for the seed cell growth, and at last we hope to provide a new treatment for spinal cord injury with the tissue engineering technique.

  9. Selected suitable seed cell, scaffold and growth factor could maximize the repair effect using tissue engineering method in spinal cord injury

    PubMed Central

    Ji, Wen-Chen; Zhang, Xiao-Wei; Qiu, Yu-Sheng

    2016-01-01

    Spinal cord injury usually leads to permanent disability, which could cause a huge financial problem to the patient. Up to now there is no effective method to treat this disease. The key of the treatment is to enable the damage zone axonal regeneration and luckily it could go through the damage zone; last a connection can be established with the target neurons. This study attempts to combine stem cell, material science and genetic modification technology together, by preparing two genes modified adipose-derived stem cells and inducing them into neuron direction; then by compositing them on the silk fibroin/chitosan scaffold and implanting them into the spinal cord injury model, seed cells can have features of neuron cells. At the same time, it could stably express the brain-derived neurotrophic factor and neurotrophin-3, both of which could produce synergistic effects, which have a positive effect on the recovery of spinal cord. The spinal cord scaffold bridges the broken end of the spinal cord and isolates with the surrounding environment, which could avoid a scar effect on the nerve regeneration and provide three-dimensional space for the seed cell growth, and at last we hope to provide a new treatment for spinal cord injury with the tissue engineering technique.

  10. Selected suitable seed cell, scaffold and growth factor could maximize the repair effect using tissue engineering method in spinal cord injury

    PubMed Central

    Ji, Wen-Chen; Zhang, Xiao-Wei; Qiu, Yu-Sheng

    2016-01-01

    Spinal cord injury usually leads to permanent disability, which could cause a huge financial problem to the patient. Up to now there is no effective method to treat this disease. The key of the treatment is to enable the damage zone axonal regeneration and luckily it could go through the damage zone; last a connection can be established with the target neurons. This study attempts to combine stem cell, material science and genetic modification technology together, by preparing two genes modified adipose-derived stem cells and inducing them into neuron direction; then by compositing them on the silk fibroin/chitosan scaffold and implanting them into the spinal cord injury model, seed cells can have features of neuron cells. At the same time, it could stably express the brain-derived neurotrophic factor and neurotrophin-3, both of which could produce synergistic effects, which have a positive effect on the recovery of spinal cord. The spinal cord scaffold bridges the broken end of the spinal cord and isolates with the surrounding environment, which could avoid a scar effect on the nerve regeneration and provide three-dimensional space for the seed cell growth, and at last we hope to provide a new treatment for spinal cord injury with the tissue engineering technique. PMID:27622154

  11. Neurotherapeutic Effect of Cord Blood Derived CD45+ Hematopoietic Cells in Mice after Traumatic Brain Injury

    PubMed Central

    Arien-Zakay, Hadar; Gincberg, Galit; Nagler, Arnon; Cohen, Gadi; Liraz-Zaltsman, Sigal; Trembovler, Victoria; Alexandrovich, Alexander G.; Matok, Ilan; Galski, Hanan; Elchalal, Uriel; Lelkes, Peter I.; Shohami, Esther

    2014-01-01

    Abstract Treatment of traumatic brain injury (TBI) is still an unmet need. Cell therapy by human umbilical cord blood (HUCB) has shown promising results in animal models of TBI and is under evaluation in clinical trials. HUCB contains different cell populations but to date, only mesenchymal stem cells have been evaluated for therapy of TBI. Here we present the neurotherapeutic effect, as evaluated by neurological score, using a single dose of HUCB-derived mononuclear cells (MNCs) upon intravenous (IV) administration one day post-trauma in a mouse model of closed head injury (CHI). Delayed (eight days post-trauma) intracerebroventricular administration of MNCs showed improved neurobehavioral deficits thereby extending the therapeutic window for treating TBI. Further, we demonstrated for the first time that HUCB-derived pan-hematopoietic CD45 positive (CD45+) cells, isolated by magnetic sorting and characterized by expression of CD45 and CD11b markers (96–99%), improved the neurobehavioral deficits upon IV administration, which persisted for 35 days. The therapeutic effect was in a direct correlation to a reduction in the lesion volume and decreased by pre-treatment of the cells with anti-human-CD45 antibody. At the site of brain injury, 1.5-2 h after transplantation, HUCB-derived cells were identified by near infrared scanning and immunohistochemistry using anti-human-CD45 and anti-human-nuclei antibodies. Nerve growth factor and vascular endothelial growth factor levels were differentially expressed in both ipsilateral and contralateral brain hemispheres, thirty-five days after CHI, measured by enzyme-linked immunosorbent assay. These findings indicate the neurotherapeutic potential of HUCB-derived CD45+ cell population in a mouse model of TBI and propose their use in the clinical setting of human TBI. PMID:24640955

  12. Effect of HSA coated iron oxide labeling on human umbilical cord derived mesenchymal stem cells

    NASA Astrophysics Data System (ADS)

    Sanganeria, Purva; Chandra, Sudeshna; Bahadur, Dhirendra; Khanna, Aparna

    2015-03-01

    Human umbilical cord derived mesenchymal stem cells (hUC-MSCs) are known for self-renewal and differentiation into cells of various lineages like bone, cartilage and fat. They have been used in biomedical applications to treat degenerative disorders. However, to exploit the therapeutic potential of stem cells, there is a requirement of sensitive non-invasive imaging techniques which will offer the ability to track transplanted cells, bio-distribution, proliferation and differentiation. In this study, we have analyzed the efficacy of human serum albumin coated iron oxide nanoparticles (HSA-IONPs) on the differentiation of hUC-MSCs. The colloidal stability of the HSA-IONPs was tested over a long period of time (≥20 months) and the optimized concentration of HSA-IONPs for labeling the stem cells was 60 μg ml-1. Detailed in vitro assays have been performed to ascertain the effect of the nanoparticles (NPs) on stem cells. Lactate dehydrogenase (LDH) assay showed minimum release of LDH depicting the least disruptions in cellular membrane. At the same time, mitochondrial impairment of the cells was also not observed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry analysis revealed lesser generation of reactive oxygen species in HSA-IONPs labeled hUC-MSCs in comparison to bare and commercial IONPs. Transmission electron microscopy showed endocytic engulfment of the NPs by the hUC-MSCs. During the process, the gross morphologies of the actin cytoskeleton were found to be intact as shown by immunofluorescence microscopy. Also, the engulfment of the HSA-IONPs did not show any detrimental effect on the differentiation potential of the stem cells into adipocytes, osteocytes and chondrocytes, thereby confirming that the inherent properties of stem cells were maintained.

  13. Regeneration of adult rat spinal cord is promoted by the soluble KDI domain of gamma1 laminin.

    PubMed

    Wiksten, Markus; Väänänen, Antti J; Liebkind, Ron; Liesi, Päivi

    2004-11-01

    Regeneration in the central nervous system (CNS) of adult mammals is hampered by formation of a glial scar and by proteins released from the myelin sheaths of injured neuronal pathways. Our recent data indicate that the KDI (Lys-Asp-Ile) domain of gamma1 laminin neutralizes both glial- and myelin-derived inhibitory signals and promotes survival and neurite outgrowth of cultured human spinal cord neurons. We show that after complete transection of the adult rat spinal cord, animals receiving onsite infusion of the KDI domain via osmotic mini-pumps recover and are able to sustain their body weights and walk with their hindlimbs. Animals treated with placebo suffer from irreversible hindlimb paralysis. Microscopic and molecular analyses of the spinal cords indicate that the KDI domain reduces tissue damage at the lesion site and enables neurite outgrowth through the injured area to effect functional recovery of the initially paralyzed animals. That the KDI domain enhances regeneration of acute spinal cord injuries in the adult rat suggests that it may be used to promote regeneration of spinal cord injuries in humans.

  14. Effects of 50 MeV/sub d. -->. Be/ neutron irradiation on Rhesus monkey cervical spinal cord

    SciTech Connect

    Jardine, J.H.; Hussey, D.H.; Raulston, G.L.; Chester, D.V.M.; Gleiser, C.A.; Gray, K.N.; Huchton, J.I.; Almond, P.R.

    1980-03-01

    The cervical spinal cords of ten Rhesus monkeys were irradiated with 50 MeV/sub d ..-->.. Be/ neutrons according to one of two dosage schedules: (1) 1300 rad/ sub n..gamma../ in nine fractions over 29 days, and (2) 1550 rad/sub n..gamma../ in nine fractions over 29 days. These doses are equivalent to 4000 rad/sub eq/ and 4800 rad/sub eq/, respectively, with /sup 60/Co using an RBE of 3.1 for late effects (conventional 200 rad per day fractionation). Whereas none of five monkeys that received a spinal cord dose of 1300 rad/sub n..gamma../ developed signs of neurologic dysfunction, all five animals that were irradiated to a dose of 1550 rad/sub n..gamma../ developed significant radiation myelitis. The histopathologic changes correlated well with the clinical observations. All of the animals that received 1550 rad/sub n..gamma../ exhibited severe malacia and moderate to severe demyelination of the white matter of the cervical spinal cord. The histopathologic changes in the monkeys irradiated with 1300 rad/sub n..gamma../ were minimal by comparison.

  15. The dose response relation for rat spinal cord paralysis analyzed in terms of the effective size of the functional subunit

    NASA Astrophysics Data System (ADS)

    Adamus-Górka, Magdalena; Mavroidis, Panayiotis; Brahme, Anders; Lind, Bengt K.

    2008-11-01

    Radiobiological models for estimating normal tissue complication probability (NTCP) are increasingly used in order to quantify or optimize the clinical outcome of radiation therapy. A good NTCP model should fulfill at least the following two requirements: (a) it should predict the sigmoid shape of the corresponding dose-response curve and (b) it should accurately describe the probability of a specified response for arbitrary non-uniform dose delivery for a given endpoint as accurately as possible, i.e. predict the volume dependence. In recent studies of the volume effect of a rat spinal cord after irradiation with narrow and broad proton beams the authors claim that none of the existing NTCP models is able to describe their results. Published experimental data have been used here to try to quantify the change in the effective dose (D50) causing 50% response for different field sizes. The present study was initiated to describe the induction of white matter necrosis in a rat spinal cord after irradiation with narrow proton beams in terms of the mean dose to the effective volume of the functional subunit (FSU). The physically delivered dose distribution was convolved with a function describing the effective size or, more accurately, the sensitivity distribution of the FSU to obtain the effective mean dose deposited in it. This procedure allows the determination of the mean D50 value of the FSUs of a certain size which is of interest for example if the cell nucleus of the oligodendrocyte is the sensitive target. Using the least-squares method to compare the effective doses for different sizes of the functional subunits with the experimental data the best fit was obtained with a length of about 9 mm. For the non-uniform dose distributions an effective FSU length of 8 mm gave the optimal fit with the probit dose-response model. The method could also be used to interpret the so-called bath and shower experiments where the heterogeneous dose delivery was used in the

  16. Proximal and distal changes in collagen content of peripheral nerve that follow transection and crush lesions.

    PubMed

    Eather, T F; Pollock, M; Myers, D B

    1986-05-01

    Collagen content of rat sciatic nerve was measured 10 weeks after either nerve transection or nerve crush. Nerve transection led to a significant increase in fascicular collagen in nerve segments 2.5 mm proximal and distal to the injury site. Remote from the transection, fascicular collagen was also significantly increased, this effect being most marked distally. Nerve crush by comparison resulted in only a small increase in fascicular collagen, significantly less than after transection. The greater amount of fascicular collagen far distal to the nerve injury could relate to a predominantly caudal endoneurial flow of inflammatory or growth factors. Differences in the amount of fascicular collagen formed after nerve transection compared with nerve crush are clearly due to factors other than axonal degeneration, and may relate to collagen synthesis by denervated Schwann cells or to the severity of the nerve injury.

  17. Effects of gabapentin on thermal sensitivity following spinal nerve ligation or spinal cord compression.

    PubMed

    Yezierski, Robert P; Green, Megan; Murphy, Karen; Vierck, Charles J

    2013-10-01

    Neuropathic pain challenges healthcare professionals and researchers to develop new strategies of treatment and experimental models to better understand the pathophysiology of this condition. In the present study, the efficacy of gabapentin on thermal sensitivity following spinal nerve ligation and spinal cord compression was evaluated. The method of behavioral assessment was a well-validated cortically dependent operant escape task. Spinal nerve ligation produced peripheral neuropathic pain whereas spinal cord compression, achieved with an expanding polymer placed extradurally, produced a condition of central neuropathic pain. Changes in thermal sensitivity were also observed in animals undergoing nerve ligation surgery without nerve injury. Gabapentin (50 and 100 mg/kg) significantly reduced thermal sensitivity to 10 and 44.5 °C in surgically naive animals as well as those undergoing spinal nerve ligation and spinal cord compression. In conclusion, an operant method of behavioral assessment was used to show that spinal nerve ligation and spinal cord compression produced increases in sensitivity to noxious cold and heat stimuli. A decrease in thermal sensitivity was observed following administration of gabapentin. The results achieved with these methods are consistent with the clinical profile of gabapentin in treating conditions of neuropathic pain.

  18. Sciatic nerve transection modulates oxidative parameters in spinal and supraspinal regions.

    PubMed

    Scheid, Taína; Bosco, Lidiane Dal; Guedes, Renata P; Pavanato, Maria Amália; Belló-Klein, Adriane; Partata, Wania A

    2013-05-01

    Neuropathic pain is a very common dysfunction caused by several types of nerve injury. This condition leads to a variety of pathological changes in central nervous system regions related to pain transmission. It has been demonstrated that nociception is modulated by reactive oxidative species and treatments with antioxidant compounds produce antinociceptive effects. Thus, the aim of the present study was to investigate oxidative parameters in spinal and supraspinal regions following sciatic nerve transection (SNT). In behavioral assessments, animals showed mechanical allodynia and a significant functional impairment following SNT, measured by von Frey hairs test and sciatic functional index, respectively. Superoxide dismutase activity was increased 3 and 7 days following SNT in cerebral cortex and brainstem. Catalase activity was also increased in cerebral cortex 3 days after SNT. Ascorbic acid levels were decreased 7 days in the spinal cord only in SNT group. We also showed an increase in lipid peroxidation in cerebral cortex and brainstem 3 days after surgery in SNT and sham groups. These results showed that supraspinal regions also exhibit changes in antioxidant activity after SNT and demonstrate an intricate relationship among antioxidant defenses in different regions of the neuro axis related to pain transmission. PMID:23423532

  19. Effects of exercise training on urinary tract function after spinal cord injury.

    PubMed

    Hubscher, Charles H; Montgomery, Lynnette R; Fell, Jason D; Armstrong, James E; Poudyal, Pradeepa; Herrity, April N; Harkema, Susan J

    2016-06-01

    Spinal cord injury (SCI) causes dramatic changes in the quality of life, including coping with bladder dysfunction which requires repeated daily and nightly catheterizations. Our laboratory has recently demonstrated in a rat SCI model that repetitive sensory information generated through task-specific stepping and/or loading can improve nonlocomotor functions, including bladder function (Ward PJ, Herrity AN, Smith RR, Willhite A, Harrison BJ, Petruska JC, Harkema SJ, Hubscher CH. J Neurotrauma 31: 819-833, 2014). To target potential underlying mechanisms, the current study included a forelimb-only exercise group to ascertain whether improvements may be attributed to general activity effects that impact target organ-neural interactions or to plasticity of the lumbosacral circuitry that receives convergent somatovisceral inputs. Male Wistar rats received a T9 contusion injury and were randomly assigned to three groups 2 wk postinjury: quadrupedal locomotion, forelimb exercise, or a nontrained group. Throughout the study (including preinjury), all animals were placed in metabolic cages once a week for 24 h to monitor water intake and urine output. Following the 10-wk period of daily 1-h treadmill training, awake cystometry data were collected and bladder and kidney tissue harvested for analysis. Metabolic cage frequency-volume measurements of voiding and cystometry reveal an impact of exercise training on multiple SCI-induced impairments related to various aspects of urinary tract function. Improvements in both the quadrupedal and forelimb-trained groups implicate underlying mechanisms beyond repetitive sensory information from the hindlimbs driving spinal network excitability of the lumbosacral urogenital neural circuitry. Furthermore, the impact of exercise training on the upper urinary tract (kidney) underscores the health benefit of activity-based training on the entire urinary system within the SCI population. PMID:26984956

  20. Effects of exercise training on urinary tract function after spinal cord injury.

    PubMed

    Hubscher, Charles H; Montgomery, Lynnette R; Fell, Jason D; Armstrong, James E; Poudyal, Pradeepa; Herrity, April N; Harkema, Susan J

    2016-06-01

    Spinal cord injury (SCI) causes dramatic changes in the quality of life, including coping with bladder dysfunction which requires repeated daily and nightly catheterizations. Our laboratory has recently demonstrated in a rat SCI model that repetitive sensory information generated through task-specific stepping and/or loading can improve nonlocomotor functions, including bladder function (Ward PJ, Herrity AN, Smith RR, Willhite A, Harrison BJ, Petruska JC, Harkema SJ, Hubscher CH. J Neurotrauma 31: 819-833, 2014). To target potential underlying mechanisms, the current study included a forelimb-only exercise group to ascertain whether improvements may be attributed to general activity effects that impact target organ-neural interactions or to plasticity of the lumbosacral circuitry that receives convergent somatovisceral inputs. Male Wistar rats received a T9 contusion injury and were randomly assigned to three groups 2 wk postinjury: quadrupedal locomotion, forelimb exercise, or a nontrained group. Throughout the study (including preinjury), all animals were placed in metabolic cages once a week for 24 h to monitor water intake and urine output. Following the 10-wk period of daily 1-h treadmill training, awake cystometry data were collected and bladder and kidney tissue harvested for analysis. Metabolic cage frequency-volume measurements of voiding and cystometry reveal an impact of exercise training on multiple SCI-induced impairments related to various aspects of urinary tract function. Improvements in both the quadrupedal and forelimb-trained groups implicate underlying mechanisms beyond repetitive sensory information from the hindlimbs driving spinal network excitability of the lumbosacral urogenital neural circuitry. Furthermore, the impact of exercise training on the upper urinary tract (kidney) underscores the health benefit of activity-based training on the entire urinary system within the SCI population.

  1. Comparative effects of glibenclamide and riluzole in a rat model of severe cervical spinal cord injury.

    PubMed

    Simard, J Marc; Tsymbalyuk, Orest; Keledjian, Kaspar; Ivanov, Alexander; Ivanova, Svetlana; Gerzanich, Volodymyr

    2012-01-01

    Both glibenclamide and riluzole reduce necrosis and improve outcome in rat models of spinal cord injury (SCI). In SCI, gene suppression experiments show that newly upregulated sulfonylurea receptor 1 (Sur1)-regulated NC(Ca-ATP) channels in microvascular endothelial cells are responsible for "persistent sodium currents" that cause capillary fragmentation and "progressive hemorrhagic necrosis". Glibenclamide is a potent blocker of Sur1-regulated NC(Ca-ATP) channels (IC(50), 6-48 nM). Riluzole is a pleotropic drug that blocks "persistent sodium currents" in neurons, but in SCI, its molecular mechanism of action is uncertain. We hypothesized that riluzole might block the putative pore-forming subunits of Sur1-regulated NC(Ca-ATP) channels, Trpm4. In patch clamp experiments, riluzole blocked Sur1-regulated NC(Ca-ATP) channels in endothelial cells and heterologously expressed Trpm4 (IC(50), 31 μM). Using a rat model of cervical SCI associated with high mortality, we compared the effects of glibenclamide and riluzole administered beginning at 3h and continuing for 7 days after impact. During the acute phase, both drugs reduced capillary fragmentation and progressive hemorrhagic necrosis, and both prevented death. At 6 weeks, modified (unilateral) Basso, Beattie, Bresnahan locomotor scores were similar, but measures of complex function (grip strength, rearing, accelerating rotarod) and tissue sparing were significantly better with glibenclamide than with riluzole. We conclude that both drugs act similarly, glibenclamide on the regulatory subunit, and riluzole on the putative pore-forming subunit of the Sur1-regulated NC(Ca-ATP) channel. Differences in specificity, dose-limiting potency, or in spectrum of action may account for the apparent superiority of glibenclamide over riluzole in this model of severe SCI. PMID:22177998

  2. Effects of Reducing Suppressors of Cytokine Signaling-3 (SOCS3) Expression on Dendritic Outgrowth and Demyelination after Spinal Cord Injury.

    PubMed

    Park, Keun Woo; Lin, Ching-Yi; Li, Kevin; Lee, Yu-Shang

    2015-01-01

    Suppressors of cytokine signaling-3 (SOCS3) is associated with limitations of nerve growth capacity after injury to the central nervous system. Although genetic manipulations of SOCS3 can enhance axonal regeneration after optic injury, the role of SOCS3 in dendritic outgrowth after spinal cord injury (SCI) is still unclear. The present study investigated the endogenous expression of SOCS3 and its role in regulating neurite outgrowth in vitro. Interleukin-6 (IL-6) induces SOCS3 expression at the mRNA and protein levels in neuroscreen-1 (NS-1) cells. In parallel to SOCS3 expression, IL-6 induced tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3) in NS-1 cells. Lentiviral delivery of short hairpin RNA (shSOCS3) (Lenti-shSOCS3) to decrease SOCS3 expression into NS-1 cells enhanced IL-6-induced tyrosine phosphorylation of STAT3 (P-STAT3 Tyr705) and promoted neurite outgrowth. In addition, we determined if reduction of SOCS3 expression by microinjection of Lenti-shSOCS3 into spinal cord enhances dendrite outgrowth in spinal cord neurons after SCI. Knocking down of SOCS3 in spinal cord neurons with Lenti-shSOCS3 increased complete SCI-induced P-STAT3 Tyr705. Immunohistochemical analysis showed that complete SCI induced a significant reduction of microtubule association protein 2-positive (MAP-2+) dendrites in the gray and white matter at 1 and 4 weeks after injury. The SCI-induced reduction of MAP-2+ dendrites was inhibited by infection with Lenti-shSOCS3 in areas both rostral and caudal to the lesion at 1 and 4 weeks after complete SCI. Furthermore, shSOCS3 treatment enhanced up-regulation of growth associated protein-43 (GAP-43) expression, which co-localized with MAP-2+ dendrites in white matter and with MAP-2+ cell bodies in gray matter, indicating Lenti-shSOCS3 may induce dendritic regeneration after SCI. Moreover, we demonstrated that Lenti-shSOCS3 decreased SCI-induced demyelination in white matter of spinal cord both rostral and

  3. Effects of Reducing Suppressors of Cytokine Signaling-3 (SOCS3) Expression on Dendritic Outgrowth and Demyelination after Spinal Cord Injury

    PubMed Central

    Park, Keun Woo; Lin, Ching-Yi; Li, Kevin; Lee, Yu-Shang

    2015-01-01

    Suppressors of cytokine signaling-3 (SOCS3) is associated with limitations of nerve growth capacity after injury to the central nervous system. Although genetic manipulations of SOCS3 can enhance axonal regeneration after optic injury, the role of SOCS3 in dendritic outgrowth after spinal cord injury (SCI) is still unclear. The present study investigated the endogenous expression of SOCS3 and its role in regulating neurite outgrowth in vitro. Interleukin-6 (IL-6) induces SOCS3 expression at the mRNA and protein levels in neuroscreen-1 (NS-1) cells. In parallel to SOCS3 expression, IL-6 induced tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3) in NS-1 cells. Lentiviral delivery of short hairpin RNA (shSOCS3) (Lenti-shSOCS3) to decrease SOCS3 expression into NS-1 cells enhanced IL-6-induced tyrosine phosphorylation of STAT3 (P-STAT3 Tyr705) and promoted neurite outgrowth. In addition, we determined if reduction of SOCS3 expression by microinjection of Lenti-shSOCS3 into spinal cord enhances dendrite outgrowth in spinal cord neurons after SCI. Knocking down of SOCS3 in spinal cord neurons with Lenti-shSOCS3 increased complete SCI-induced P-STAT3 Tyr705. Immunohistochemical analysis showed that complete SCI induced a significant reduction of microtubule association protein 2-positive (MAP-2+) dendrites in the gray and white matter at 1 and 4 weeks after injury. The SCI-induced reduction of MAP-2+ dendrites was inhibited by infection with Lenti-shSOCS3 in areas both rostral and caudal to the lesion at 1 and 4 weeks after complete SCI. Furthermore, shSOCS3 treatment enhanced up-regulation of growth associated protein-43 (GAP-43) expression, which co-localized with MAP-2+ dendrites in white matter and with MAP-2+ cell bodies in gray matter, indicating Lenti-shSOCS3 may induce dendritic regeneration after SCI. Moreover, we demonstrated that Lenti-shSOCS3 decreased SCI-induced demyelination in white matter of spinal cord both rostral and

  4. Neuroprotective effects of electroacupuncture on early- and late-stage spinal cord injury.

    PubMed

    Wu, Min-Fei; Zhang, Shu-Quan; Liu, Jia-Bei; Li, Ye; Zhu, Qing-San; Gu, Rui

    2015-10-01

    Previous studies have shown that the neurite growth inhibitor Nogo-A can cause secondary neural damage by activating RhoA. In the present study, we hypothesized that electroacupuncture promotes neurological functional recovery after spinal cord injury by inhibiting RhoA expression. We established a rat model of acute spinal cord injury using a modification of Allen's method. The rats were given electroacupuncture treatment at Dazhui (Du14), Mingmen (Du4), Sanyinjiao (SP6), Huantiao (GB30), Zusanli (ST36) and Kunlun (BL60) acupoints with a sparse-dense wave at a frequency of 4 Hz for 30 minutes, once a day, for a total of 7 days. Seven days after injury, the Basso, Beattie and Bresnahan (BBB) locomotor scale and inclined plane test scores were significantly increased, the number of apoptotic cells in the spinal cord tissue was significantly reduced, and RhoA and Nogo-A mRNA and protein expression levels were decreased in rats given electroacupuncture compared with rats not given electroacupuncture. Four weeks after injury, pathological tissue damage in the spinal cord at the site of injury was alleviated, the numbers of glial fibrillary acidic protein- and neurofilament 200-positive fibers were increased, the latencies of somatosensory-evoked and motor-evoked potentials were shortened, and their amplitudes were increased in rats given electroacupuncture. These findings suggest that electroacupuncture treatment reduces neuronal apoptosis and decreases RhoA and Nogo-A mRNA and protein expression at the site of spinal cord injury, thereby promoting tissue repair and neurological functional recovery. PMID:26692861

  5. Neuroprotective effects of electroacupuncture on early- and late-stage spinal cord injury

    PubMed Central

    Wu, Min-fei; Zhang, Shu-quan; Liu, Jia-bei; Li, Ye; Zhu, Qing-san; Gu, Rui

    2015-01-01

    Previous studies have shown that the neurite growth inhibitor Nogo-A can cause secondary neural damage by activating RhoA. In the present study, we hypothesized that electroacupuncture promotes neurological functional recovery after spinal cord injury by inhibiting RhoA expression. We established a rat model of acute spinal cord injury using a modification of Allen's method. The rats were given electroacupuncture treatment at Dazhui (Du14), Mingmen (Du4), Sanyinjiao (SP6), Huantiao (GB30), Zusanli (ST36) and Kunlun (BL60) acupoints with a sparse-dense wave at a frequency of 4 Hz for 30 minutes, once a day, for a total of 7 days. Seven days after injury, the Basso, Beattie and Bresnahan (BBB) locomotor scale and inclined plane test scores were significantly increased, the number of apoptotic cells in the spinal cord tissue was significantly reduced, and RhoA and Nogo-A mRNA and protein expression levels were decreased in rats given electroacupuncture compared with rats not given electroacupuncture. Four weeks after injury, pathological tissue damage in the spinal cord at the site of injury was alleviated, the numbers of glial fibrillary acidic protein- and neurofilament 200-positive fibers were increased, the latencies of somatosensory-evoked and motor-evoked potentials were shortened, and their amplitudes were increased in rats given electroacupuncture. These findings suggest that electroacupuncture treatment reduces neuronal apoptosis and decreases RhoA and Nogo-A mRNA and protein expression at the site of spinal cord injury, thereby promoting tissue repair and neurological functional recovery. PMID:26692861

  6. A Coral-Derived Compound Improves Functional Recovery after Spinal Cord Injury through Its Antiapoptotic and Anti-Inflammatory Effects

    PubMed Central

    Chen, Chun-Hong; Chen, Nan-Fu; Feng, Chien-Wei; Cheng, Shu-Yu; Hung, Han-Chun; Tsui, Kuan-Hao; Hsu, Chi-Hsin; Sung, Ping-Jyun; Chen, Wu-Fu; Wen, Zhi-Hong

    2016-01-01

    Background: Our previous in vitro results demonstrated that 11-dehydrosinulariolide significantly reduced 6-hydroxydopamine-induced cytotoxicity and apoptosis in a human neuroblastoma cell line, SH-SY5Y, and suppressed the expression of inducible NO synthase (iNOS) and cyclooxygenase 2 in lipopolysaccharide-stimulated macrophage cells. The neuroprotective and anti-inflammatory effects of 11-dehydrosinulariolide may be suitable for treating spinal cord injury (SCI). Methods: In the present study, Wistar rats were pretreated with 11-dehydrosinulariolide or saline through intrathecal injection after a thoracic spinal cord contusion injury induced using a New York University (NYU) impactor. The apoptotic cells were assessed using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expression and localization of proinflammatory, apoptosis-associated and cell survival-related pathway proteins were examined through immunoblotting and immunohistochemistry. Results: 11-Dehydrosinulariolide attenuated SCI-induced cell apoptosis by upregulating the antiapoptotic protein Bcl-2 and cell survival-related pathway proteins p-Akt and p-ERK, 8 h after SCI. Furthermore, the transcription factor p-CREB, which regulates Bcl-2 expression, was upregulated after 11-dehydrosinulariolide treatment. On day 7 after SCI, 11-dehydrosinulariolide exhibited an anti-inflammatory effect, attenuating SCI-induced upregulation of the inflammatory proteins iNOS and tumor necrosis factor-α. 11-Dehydrosinulariolide also induced an increase in the expression of arginase-1 and CD206, markers of M2 microglia, in the injured spinal cord on day 7 after SCI. Thus, the anti-inflammatory effect of 11-dehydrosinulariolide may be related to the promotion of an alternative pathway of microglia activation. Conclusion: The results show that 11-dehydrosinulariolide exerts antiapoptotic effects at 8 h after SCI and anti-inflammatory effects at 7 days after SCI. We consider that this

  7. Intensity dependent effects of tDCS on corticospinal excitability in chronic Spinal Cord Injury

    PubMed Central

    Murray, Lynda M; Edwards, Dylan J; Ruffini, Giulio; Labar, Douglas; Stampas, Argyrios; Pascual-Leone, Alvaro; Cortes, Mar

    2014-01-01

    Objective To investigate the effects of anodal transcranial direct current stimulation (a-tDCS) intensity on corticospinal excitability and affected muscle activation in individuals with chronic spinal cord injury (SCI). Design Single blind, randomized, sham-controlled, crossover study. Setting Medical Research Institute and Rehabilitation Hospital. Participants Nine volunteers with chronic SCI and motor dysfunction in wrist extensor muscles. Intervention Three single session exposures to 20 minutes of a-tDCS (anode over the extensor carpi radialis (ECR) muscle representation on the left primary motor cortex, cathode over the right supraorbital area), using 1 mA, 2 mA or sham stimulation, delivered at rest, with at least one week between sessions. Outcome Measures Corticospinal excitability was assessed with motor evoked potentials (MEPs) from the ECR muscle using surface electromyography (EMG) following transcranial magnetic stimulation. Changes in spinal excitability, sensory threshold and muscle strength were also investigated. Results Mean MEP amplitude significantly increased by ~40% immediately following 2 mA a-tDCS (Pre 0.36±0.1 mV; Post 0.47±0.11 mV; p=0.001), but not with 1 mA or sham. Maximal voluntary EMG measures remained unaltered across all conditions. Sensory threshold significantly decreased over time following 1 mA (p=0.002) and 2 mA (p=0.039) a-tDCS, and did not change with sham. F-wave persistence showed a non-significant trend for increase (Pre: 32±12%; Post: 41±10%; Follow-up: 46±12%) following 2 mA stimulation. No adverse effects were reported with any of the experimental conditions. Conclusion Anodal-tDCS can transiently raise corticospinal excitability to affected muscles in chronic SCI patients following 2 mA stimulation. Sensory perception can improve with both 1 and 2 mA stimulation. This study gives support to the safe and effective use of a-tDCS using small electrodes in SCI patients, and highlights the importance of stimulation

  8. White matter atlas of the human spinal cord with estimation of partial volume effect.

    PubMed

    Lévy, S; Benhamou, M; Naaman, C; Rainville, P; Callot, V; Cohen-Adad, J

    2015-10-01

    Template-based analysis has proven to be an efficient, objective and reproducible way of extracting relevant information from multi-parametric MRI data. Using common atlases, it is possible to quantify MRI metrics within specific regions without the need for manual segmentation. This method is therefore free from user-bias and amenable to group studies. While template-based analysis is common procedure for the brain, there is currently no atlas of the white matter (WM) spinal pathways. The goals of this study were: (i) to create an atlas of the white matter tracts compatible with the MNI-Poly-AMU template and (ii) to propose methods to quantify metrics within the atlas that account for partial volume effect. The WM atlas was generated by: (i) digitalizing an existing WM atlas from a well-known source (Gray's Anatomy), (ii) registering this atlas to the MNI-Poly-AMU template at the corresponding slice (C4 vertebral level), (iii) propagating the atlas throughout all slices of the template (C1 to T6) using regularized diffeomorphic transformations and (iv) computing partial volume values for each voxel and each tract. Several approaches were implemented and validated to quantify metrics within the atlas, including weighted-average and Gaussian mixture models. Proof-of-concept application was done in five subjects for quantifying magnetization transfer ratio (MTR) in each tract of the atlas. The resulting WM atlas showed consistent topological organization and smooth transitions along the rostro-caudal axis. The median MTR across tracts was 26.2. Significant differences were detected across tracts, vertebral levels and subjects, but not across laterality (right-left). Among the different tested approaches to extract metrics, the maximum a posteriori showed highest performance with respect to noise, inter-tract variability, tract size and partial volume effect. This new WM atlas of the human spinal cord overcomes the biases associated with manual delineation and partial

  9. Effects of combining methylprednisolone with magnesium sulfate on neuropathic pain and functional recovery following spinal cord injury in male rats.

    PubMed

    Farsi, Leila; Naghib Zadeh, Maryam; Afshari, Khashayar; Norouzi-Javidan, Abbas; Ghajarzadeh, Mahsa; Naghshband, Zeinab; Keshavarz, Mansoor

    2015-01-01

    Methylprednisolone (MP) has been widely used as a standard therapeutic agent for the treatment of spinal cord injury (SCI). Because of its controversial useful effects, the combination of MP and other pharmacological agents to enhance neuroprotective effects is desirable. Magnesium sulfate (MgSO4) has been shown to have neuroprotective and antihyperalgesic effects. In the present study, we sought to determine the effect of combining MP and MgSO4, on neuropathic pain and functional recovery following spinal cord injury (SCI) in male rats. A total of 48 adult male rats (weight 300-350 g) were used. After laminectomy, complete SCI was achieved by compression of the spinal cord for one minute with aneurysm clips. Single doses of Magnesium sulfate (MgSO4), (600 mg/kg), Methylprednisolone (MP), (30 mg/kg) or combining MgSO4 and MP were injected intraperitoneally. Prior to surgery and during four weeks of study Tail flick latency (TFL) and BBB (Basso-Beattie-Bresnahan) score and the acetone drop test were evaluated. In mean values of BBB score, a significant difference was observed in SCI+veh compared with other groups (P<0.05). Mean TFL also was significantly higher in SCI+veh compared with other groups (P<0.05). Mean acetone drop test score and weight were significantly different in MgSO4, MP and combining MgSO4 and MP  treated groups compared with SCI+veh group (P<0.05). These findings revealed that MP, MgSO4 and combining MgSO4 and MP treatment can attenuate neuropathic pains following SCI in rats include: thermal hyperalgesia and cold allodynia. They also can yield better improvement in motor function and decrease weight loss after SCI in rats compared with the control group. PMID:25796020

  10. 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

  11. 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

  12. MANAGEMENT OF CORD AND PLACENTAL BLOOD AND ITS EFFECT UPON THE NEWBORN, Part I

    PubMed Central

    McCausland, A. M.; Holmes, Frances; Schumann, William R.

    1949-01-01

    A comparative study was made of erythrocyte counts and weights of the newborn at term. Three groups were used: Cases in which the cord was clamped at once, those in which the cord was allowed to pulsate five minutes, and those in which the cord and placental blood was stripped into the baby. Standards and procedure were set up so that there would be a minimum of error. Evidence was elicited showing that babies in the “pulsating” and the “stripped” groups received a significant amount of blood which was beneficial. The amount varied, but when the stripping method was used, the term baby received about 100 cc. of blood. Babies receiving this blood had higher erythrocyte counts, higher hemoglobin values, higher initial weights, less weight loss, and less rapid loss of weight. It is believed the additional blood supplied is of benefit especially to prematures and to those infants who are in any degree of shock following long labors, difficult deliveries, abruptio placenta, placenta previa, or compression of the cord. The added blood benefits the baby by combating the initial shock, by aiding in filling the capillary bed of the expanding lungs, by increasing iron reserve, by lessening demand upon blood-forming organs (especially in prematures), by protecting the breakdown of body proteins and by aiding the transition from one source of oxygen to another. Five minutes, as a rule, is not long enough to wait for pulsation if the baby is to receive its quota of available blood. Stripping of cord and placental blood into the infant is not a harmful procedure when done gently and is particularly useful in cases where the condition of the mother or child is such that it is inadvisable to wait for the uterus to force the blood physiologically into the child. The additional blood does not cause icterus. The pulsating of the umbilical cord plays only a minor role in the process by which the baby receives blood after the second stage of labor. The pressure of the uterine

  13. Management of cord and placental blood and its effect upon the newborn.

    PubMed

    McCAUSLAND, A M; HOLMES, F; SCHUMANN, W R

    1949-09-01

    A comparative study was made of erythrocyte counts and weights of the newborn at term. Three groups were used: Cases in which the cord was clamped at once, those in which the cord was allowed to pulsate five minutes, and those in which the cord and placental blood was stripped into the baby. Standards and procedure were set up so that there would be a minimum of error. Evidence was elicited showing that babies in the "pulsating" and the "stripped" groups received a significant amount of blood which was beneficial. The amount varied, but when the stripping method was used, the term baby received about 100 cc. of blood.Babies receiving this blood had higher erythrocyte counts, higher hemoglobin values, higher initial weights, less weight loss, and less rapid loss of weight. It is believed the additional blood supplied is of benefit especially to prematures and to those infants who are in any degree of shock following long labors, difficult deliveries, abruptio placenta, placenta previa, or compression of the cord. The added blood benefits the baby by combating the initial shock, by aiding in filling the capillary bed of the expanding lungs, by increasing iron reserve, by lessening demand upon blood-forming organs (especially in prematures), by protecting the breakdown of body proteins and by aiding the transition from one source of oxygen to another. Five minutes, as a rule, is not long enough to wait for pulsation if the baby is to receive its quota of available blood. Stripping of cord and placental blood into the infant is not a harmful procedure when done gently and is particularly useful in cases where the condition of the mother or child is such that it is inadvisable to wait for the uterus to force the blood physiologically into the child. The additional blood does not cause icterus. The pulsating of the umbilical cord plays only a minor role in the process by which the baby receives blood after the second stage of labor. The pressure of the uterine

  14. [Examination of low temperature effect on cord blood serum by microwave dielectric method].

    PubMed

    Nardid, O A; Horobchenko, O A; Nikolov, O T; Lipina, O V; Moshko, Iu O

    2005-01-01

    The influence of the freezing velocities and final temperatures of storage on the complex dielectric permittivity of cord blood serum have been studied. On the temperature dependences of the dielectric permittivity the non-monotonous changes at the characteristic temperatures accompanying with the change of the activation energy of the water molecules dielectric relaxation were found out. The drastic deflection of the temperature dependence of ?' from the monotone curve at 15 degrees C region correlates with the fracture of Arrhenius plots of the dielectric relaxation time and viscosity at the same temperature. Slow freezing (1-2 degrees C/min) of cord blood serum results in ?' diminution in comparison with control, that testifies an increase of bound water amount because of loosening in this case the surface of biomacromolecule polypeptide chains. Rapid freezing (300-400 degrees C/min) results in ?' increase of serum, that is caused, apparently, by the cryoaggregation of biomacro-molecules, which can thus happen.

  15. Effects of ghrelin and des-acyl ghrelin on neurogenesis of the rat fetal spinal cord

    SciTech Connect

    Sato, Miho; Nakahara, Keiko; Goto, Shintaro; Kaiya, Hiroyuki; Miyazato, Mikiya . E-mail: a0d201u@cc.miyazaki-u.ac.jp; Date, Yukari; Nakazato, Masamitsu; Kangawa, Kenji; Murakami, Noboru

    2006-11-24

    Expressions of the growth hormone secretagogue receptor (GHS-R) mRNA and its protein were confirmed in rat fetal spinal cord tissues by RT-PCR and immunohistochemistry. In vitro, over 3 nM ghrelin and des-acyl ghrelin induced significant proliferation of primary cultured cells from the fetal spinal cord. The proliferating cells were then double-stained using antibodies against the neuronal precursor marker, nestin, and the cell proliferation marker, 5-bromo-2'-deoxyuridine (BrdU), and the nestin-positive cells were also found to be co-stained with antibody against GHS-R. Furthermore, binding studies using [{sup 125}I]des-acyl ghrelin indicated the presence of a specific binding site for des-acyl ghrelin, and confirmed that the binding was displaced with unlabeled des-acyl ghrelin or ghrelin. These results indicate that ghrelin and des-acyl ghrelin induce proliferation of neuronal precursor cells that is both dependent and independent of GHS-R, suggesting that both ghrelin and des-acyl ghrelin are involved in neurogenesis of the fetal spinal cord.

  16. Effects of enriched housing on functional recovery after spinal cord contusive injury in the adult rat.

    PubMed

    Lankhorst, A J; ter Laak, M P; van Laar, T J; van Meeteren, N L; de Groot, J C; Schrama, L H; Hamers, F P; Gispen, W H

    2001-02-01

    To date, most research performed in the area of spinal cord injury focuses on treatments designed to either prevent spreading lesion (secondary injury) or to enhance outgrowth of long descending and ascending fiber tracts around or through the lesion. In the last decade, however, several authors have shown that it is possible to enhance locomotor function after spinal cord injury in both animals and patients using specific training paradigms. As a first step towards combining such training paradigms with pharmacotherapy, we evaluated recovery of function in adult rats sustaining a spinal cord contusion injury (MASCIS device, 12.5 mm at T8), either housed in an enriched environment or in standard cages (n = 15 in both groups). The animals in the enriched environment were stimulated to increase their locomotor activity by placing water and food on opposite sides of the cage. As extra stimuli, a running wheel and several other objects were added to the cage. We show that exposure to the enriched environment improves gross and fine locomotor recovery as measured by the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale, the BBB subscale, the Gridwalk, and the Thoracolumbar height test. However, no group differences were found on our electrophysiological parameters nor on the amount of spared white matter. These data justify further studies on enriched housing and more controlled exercise training, with their use as potential additive to pharmacological intervention. PMID:11229712

  17. Late effects of radiation on the lumbar spinal cord of guinea pigs: Re-treatment tolerance

    SciTech Connect

    Mason, K.A. ); Withers, H.R.; Chiang, Chi-Shiun )

    1993-07-15

    Using a guinea pig model of lumbar myelopathy, various factors affecting the tolerance of spinal cord to irradiation were assessed: (a) extent of initial injury; (b) time interval between priming and test doses; and (c) animal age at the time of initial radiation treatment. A 3 cm section of lumbar spinal cord of guinea pigs was irradiated with fractionated doses of 4.5 Gy gamma rays given as 9 fractions per week. Guinea pigs were primed with 9 x 4.5 Gy in 7 days which is 60% of the ED[sub 50] for a continuous course of treatment. After 28 or 40 weeks, animal were retreated with 6-14 fractions of 4.5 Gy. Animals were observed for 2 years following the priming dose and both the incidence and latency of myelopathy recorded. Young adult guinea pigs (8 wk old) showed both a decreased radiation tolerance and latency compared to old individuals (40 wk old). At 28 or 40 wk after 9 x 4.5 Gy, only about 8% of the initial injury was remembered in young adult guinea pigs. The amount of residual injury was dependent on the initial damage as a proportion of the tolerance dose. The spinal cord shows a greater capacity for long-term recovery than generally appreciated and re-treatment doses clinically prescribed may be lower than necessary. 8 refs., 3 figs., 2 tabs.

  18. GDNF-Enhanced Axonal Regeneration and Myelination Following Spinal Cord Injury is Mediated by Primary Effects on Neurons

    PubMed Central

    Zhang, Liqun; Ma, Zhengwen; Smith, George M.; Wen, Xuejun; Pressman, Yelena; Wood, Patrick M.; Xu, Xiao-Ming

    2010-01-01

    We previously demonstrated that coadministration of glial cell line-derived neurotrophic factor (GDNF) with grafts of Schwann cells (SCs) enhanced axonal regeneration and remyelination following spinal cord injury (SCI). However, the cellular target through which GDNF mediates such actions was unclear. Here, we report that GDNF enhanced both the number and caliber of regenerated axons in vivo and increased neurite outgrowth of dorsal root ganglion neurons (DRGN) in vitro, suggesting that GDNF has a direct effect on neurons. In SC-DRGN coculture, GDNF significantly increased the number of myelin sheaths produced by SCs. GDNF treatment had no effect on the proliferation of isolated SCs but enhanced the proliferation of SCs already in contact with axons. GDNF increased the expression of the 140 kDa neural cell adhesion molecule (NCAM) in isolated SCs but not their expression of the adhesion molecule L1 or the secretion of the neurotrophins NGF, NT3, or BDNF. Overall, these results support the hypothesis that GDNF-enhanced axonal regeneration and SC myelination is mediated mainly through a direct effect of GDNF on neurons. They also suggest that the combination of GDNF administration and SC transplantation may represent an effective strategy to promote axonal regeneration and myelin formation after injury in the spinal cord. PMID:19170182

  19. Involvement of spinal cord opioid mechanisms in the acute antinociceptive effect of hyperbaric oxygen in mice1

    PubMed Central

    Heeman, Jacqueline H.; Zhang, Yangmiao; Shirachi, Donald Y.; Quock, Raymond M.

    2013-01-01

    Earlier research has demonstrated that treatment with hyperbaric oxygen (HBO2) can elicit an antinociceptive response in models of acute pain. We have demonstrated that this antinociceptive effect is centrally-mediated and is dependent on opioid receptors. The purpose of the present study was to examine the role of endogenous opioid peptides and opioid receptors specifically in the spinal cord in the acute antinociceptive effect of HBO2 in mice. Male NIH Swiss mice were exposed to HBO2 (100% oxygen @ 3.5 atmospheres absolute) for 11 min and their antinociceptive responsiveness was determined using the glacial acetic acid-induced abdominal constriction test. HBO2-induced antinociception was sensitive to antagonism by intrathecal (i.t.) pretreatment with the κ- and μ-selective opioid antagonists norbinaltorphimine and β-funalrexamine, respectively, but not the δ-selective antagonist naltrindole. The antinociceptive effect of HBO2 was also significantly attenuated by i.t. pretreatment with a rabbit antiserum against rat dynorphin1-13 but not antisera against β-endorphin or methionine-enkephalin. Based on these experimental findings, the acute antinociceptive effect of HBO2 appears to involve neuronal release of dynorphin and activation of κ and μ opioid receptors in the spinal cord. PMID:24113418

  20. The effect of mesenchymal stem cell transplantation on the recovery of bladder and hindlimb function after spinal cord contusion in rats

    PubMed Central

    2010-01-01

    Background Mesenchymal stem cells are widely used for transplantation into the injured spinal cord in vivo model and for safety, many human clinical trials are continuing to promote improvements of motor and sensory functions after spinal cord injury. Yet the exact mechanism for these improvements remains undefined. Neurogenic bladder following spinal cord injury is the main problem decreasing the quality of life for patients with spinal cord injury, but there are no clear data using stem cell transplantation for the improvement of neurogenic bladder for in vivo studies and the clinical setting. The purpose of this study was to delineate the effect of human mesenchymal stem cell (hMSCs) transplantation on the restoration of neurogenic bladder and impaired hindlimb function after spinal cord contusion of rats and the relationship between neurotrophic factors such as brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and bladder and hindlimb functions. Results Modified moderate contusion injury were performed on the thoracic spinal cord of Sprague-Dawley rats using MASCIS impactor and hMSCs, human fibroblasts or phosphate-buffered saline were transplanted into injured spinal cord 9 days after injury for hMSC and two control groups respectively. Ladder test showed more rapid restoration of hindlimb function in hMSC group than in control group, but Basso, Beattie, and Bresnahan score and coupling score were not different significantly among hMSC and two control groups. Neurogenic bladder was not improved in either group. ED1 positive macrophages were significantly reduced in hMSC group than in two control groups, but ELISA and RT-PCR studies revealed BDNF and NT-3 levels in spinal cord and bladder were not different among hMSC and two control groups regardless the experimental duration. Conclusion hMSC transplantation was effective in reducing inflammatory reaction after spinal cord contusion of rats but not sufficient to recover locomotor and bladder

  1. Tethered Spinal Cord Syndrome

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Tethered Spinal Cord Syndrome Information Page Table of Contents (click to ... being done? Clinical Trials Organizations What is Tethered Spinal Cord Syndrome? Tethered spinal cord syndrome is a neurological ...

  2. Spinal Cord Infarction

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Spinal Cord Infarction Information Page Table of Contents (click to ... Organizations Related NINDS Publications and Information What is Spinal Cord Infarction? Spinal cord infarction is a stroke either ...

  3. Fetal transplants rescue axial muscle representations in M1 cortex of neonatally transected rats that develop weight support.

    PubMed

    Giszter, S F; Kargo, W J; Davies, M; Shibayama, M

    1998-12-01

    Fetal transplants rescue axial muscle representations in M1 cortex of neonatally transected rats that develop weight support. J. Neurophysiol. 80: 3021-3030, 1998. Intraspinal transplants of fetal spinal tissue partly alleviate motor deficits caused by spinal cord injury. How transplants modify body representation and muscle recruitment by motor cortex is currently largely unknown. We compared electromyographic responses from motor cortex stimulation in normal adult rats, adult rats that received complete spinal cord transection at the T8-T10 segmental level as neonates (TX rats), and similarly transected rats receiving transplants of embryonic spinal cord (TP rats). Rats were also compared among treatments for level of weight support and motor performance. Sixty percent of TP rats showed unassisted weight-supported locomotion as adults, whereas approximately 30% of TX rats with no intervention showed unassisted weight-supported locomotion. In the weight-supporting animals we found that the transplants enabled motor responses to be evoked by microstimulation of areas of motor cortex that normally represent the lumbar axial muscles in rats. These same regions were silent in all TX rats with transections but no transplants, even those exhibiting locomotion with weight support. In weight-supporting TX rats low axial muscles could be recruited from the rostral cortical axial representation, which normally represents the neck and upper trunk. No operated animal, even those with well-integrated transplants and good weight-supported locomotion, had a hindlimb motor representation in cortex. The data demonstrate that spinal transplants allow the development of some functional interactions between areas of motor cortex and spinal cord that are not available to the rat lacking the intervention. The data also suggest that operated rats that achieve weight support may primarily use the axial muscles to steer the pelvis and hindlimbs indirectly rather than use explicit hindlimb

  4. Cording Following Treatment for Breast Cancer

    PubMed Central

    O’Toole, Jean; Miller, Cynthia L; Specht, Michelle C; Skolny, Melissa N; Jammallo, Lauren S; Horick, Nora; Elliott, Krista; Niemierko, Andrzej; Taghian, Alphonse G

    2013-01-01

    Background Treatment for breast cancer may result in the formation of palpable cords in the axillary region. Our aim was to evaluate cording incidence, risk factors, and association with upper extremity functional impairment and measured arm volume change. Methods We included 308 patients with unilateral breast cancer prospectively screened for upper extremity lymphedema, symptoms and function. Patients were assessed pre- and post-operatively and at 3 – 8 month intervals with perometer arm measurements and the LEFT-BC questionnaire. Cording was determined by patient self-report. The cumulative incidence of cording and its association with clinicopathologic factors, upper extremity functional impairment, and measured arm volume change were analyzed. Results 31.5% (97/308) of patients reported cording, with a cumulative incidence of 36.2% at 24 months post-operative. Clinicopathologic factors significantly associated with cording by multivariate analysis included axillary lymph node dissection (p<.0001) and younger age at diagnosis (p=0.0005). Cording was associated with increased functional impairment (p=0.0018) and an arm volume increase of ≥5% (p=0.028). Conclusions Cording following breast cancer treatment is common, and may occur beyond the post-operative period. Our findings emphasize the importance of identifying patients at high risk for cording, and developing strategies to minimize functional impairment and arm volume elevation associated with cording. Future studies should investigate the effectiveness of interventions for cording following breast cancer treatment. PMID:23813304

  5. Novel combination strategies to repair the injured mammalian spinal cord.

    PubMed

    Bunge, Mary Bartlett

    2008-01-01

    Due to the varied and numerous changes in spinal cord tissue following injury, successful treatment for repair may involve strategies combining neuroprotection (pharmacological prevention of some of the damaging intracellular cascades that lead to secondary tissue loss), axonal regeneration promotion (cell transplantation, genetic engineering to increase growth factors, neutralization of inhibitory factors, reduction in scar formation), and rehabilitation. Our goal has been to find effective combination strategies to improve outcome after injury to the adult rat thoracic spinal cord. Combination interventions tested have been implantation of Schwann cells (SCs) plus neuroprotective agents and growth factors administered in various ways, olfactory ensheathing cell (OEC) implantation, chondroitinase addition, or elevation of cyclic AMP. The most efficacious strategy in our hands for the acute complete transection/SC bridge model, including improvement in locomotion [Basso, Beattie, Bresnahan Scale (BBB)], is the combination of SCs, OECs, and chondroitinase administration (BBB 2.1 vs 6.6, 3 times more myelinated axons in the SC bridge, increased serotonergic axons in the bridge and beyond, and significant correlation between the number of bridge myelinated axons and functional improvement). We found the most successful combination strategy for a subacute spinal cord contusion injury (12.5-mm, 10-g weight, MASCIS impactor) to be SCs and elevation of cyclic AMP (BBB 10.4 vs 15, significant increases in white matter sparing, in myelinated axons in the implant, and in responding reticular formation and red and raphe nuclei, and a significant correlation between the number of serotonergic fibers and improvement in locomotion). Thus, in two injury paradigms, these combination strategies as well as others studied in our laboratory have been found to be more effective than SCs alone and suggest ways in which clinical application may be developed. PMID:18795474

  6. Effects of Electroacupuncture at Governor Vessel Acupoints on Neurotrophin-3 in Rats with Experimental Spinal Cord Injury.

    PubMed

    Mo, Yu-Ping; Yao, Hai-Jiang; Lv, Wei; Song, Liang-Yu; Song, Hong-Tao; Yuan, Xiao-Chen; Mao, Ying-Qiu; Jing, Quan-Kai; Shi, Su-Hua; Li, Zhi-Gang

    2016-01-01

    In an effort to explore new, noninvasive treatment options for spinal cord injuries (SCI), this study investigated the effects of electroacupuncture (EA) for SCI rat models. SCI was induced by a modified Allen's weight-drop method. We investigated the response of EA at Dazhui (GV 14) and Mingmen (GV 4) acupoints to understand the effects and mechanisms of EA in neuroprotection and neuronal function recovery after SCI. BBB testing was used to detect motor function of rats' hind limbs among groups, and EA was shown to promote the recovery of SCI rats' motor function. Nissl staining showed a restored neural morphology and an increase in the quantity of neurons after EA. Also, the antiapoptosis role was exposed by TUNEL staining. Western blotting analysis was used to determine the protein expression of neurotrophin-3 (NT-3) in spinal cord tissue. Compared to the sham group, the expression levels of NT-3 were significantly decreased and EA was shown to upregulate the expression of NT-3. The present study suggests that the role of EA in neuroprotection and dorsal neuronal function recovery after SCI in rats, especially EA stimulation at GV 14 and GV 4, can greatly promote neuronal function recovery, which may result from upregulating the expression of NT-3. PMID:27597902

  7. Effects of Electroacupuncture at Governor Vessel Acupoints on Neurotrophin-3 in Rats with Experimental Spinal Cord Injury

    PubMed Central

    Lv, Wei; Song, Liang-yu; Song, Hong-tao; Yuan, Xiao-chen; Mao, Ying-qiu; Jing, Quan-kai

    2016-01-01

    In an effort to explore new, noninvasive treatment options for spinal cord injuries (SCI), this study investigated the effects of electroacupuncture (EA) for SCI rat models. SCI was induced by a modified Allen's weight-drop method. We investigated the response of EA at Dazhui (GV 14) and Mingmen (GV 4) acupoints to understand the effects and mechanisms of EA in neuroprotection and neuronal function recovery after SCI. BBB testing was used to detect motor function of rats' hind limbs among groups, and EA was shown to promote the recovery of SCI rats' motor function. Nissl staining showed a restored neural morphology and an increase in the quantity of neurons after EA. Also, the antiapoptosis role was exposed by TUNEL staining. Western blotting analysis was used to determine the protein expression of neurotrophin-3 (NT-3) in spinal cord tissue. Compared to the sham group, the expression levels of NT-3 were significantly decreased and EA was shown to upregulate the expression of NT-3. The present study suggests that the role of EA in neuroprotection and dorsal neuronal function recovery after SCI in rats, especially EA stimulation at GV 14 and GV 4, can greatly promote neuronal function recovery, which may result from upregulating the expression of NT-3.

  8. Effect of noradrenalin and EGb 761 pretreatment on the ischemia-reperfusion injured spinal cord neurons in rabbits.

    PubMed

    Mechírová, Eva; Domoráková, Iveta; Danková, Marianna; Danielisová, Viera; Burda, Jozef

    2009-09-01

    Short term sublethal ischemia or ischemic preconditioning gives protection to the neurons against subsequent lethal ischemic attack. This so-called ischemic tolerance can also be provided by certain drugs. We examined the effect of noradrenalin and EGb 761 on the spinal cord neurons injured by 30 min occlusion of abdominal aorta in rabbits. The animals survived 48 and 72 h. Degenerated neurons were visualized by Fluoro Jade B method, viable neurons were demonstrated immunohistochemically with NeuN and ubiquitin antibodies. The rabbits with noradrenalin administration 48 h before 30 min of ischemia and 48/72 h of reperfusion, showed significant increase of degenerated Fluoro Jade B labeled neurons. Animals of both groups were paraplegic. Rabbits pretreated 7 days with EGb 761 prior to 30 min of ischemia and with 48/72 h of reperfusion revealed significant decrease of Fluoro Jade B-positive neurons when compared with the groups with 30 min of ischemia followed by 48/72 h of reperfusion. In the NeuN sections, the number of viable neurons was moderately decreased. These animals showed no paraplegia. Ubiquitin aggregates occurred in the cytoplasm of degenerated neurons in the sections of rabbits preconditioned with noradrenalin 48 h prior to 30 min of ischemia and followed by 48 h of reperfusion while after 72 h of reperfusion, shrunk light shadows without ubiquitin reaction were visible. Our results indicate that EGb 761 could be involved in protection of spinal cord neurons against ischemic injury while effect of noradrenalin is not unambiguous.

  9. Effect of technique and timing of tracheostomy in patients with acute traumatic spinal cord injury undergoing mechanical ventilation

    PubMed Central

    Ganuza, Javier Romero; Forcada, Angel Garcia; Gambarrutta, Claudia; De La Lastra Buigues, Elena Diez; Gonzalez, Victoria Eugenia Merlo; Fuentes, Fátima Paz; Luciani, Alejandro A.

    2011-01-01

    Objective To assess the effect of timing and techniques of tracheostomy on morbidity, mortality, and the burden of resources in patients with acute traumatic spinal cord injuries (SCIs) undergoing mechanical ventilation. Design Review of a prospectively collected database. Setting Intensive and intermediate care units of a monographic hospital for the treatment of SCI. Participants Consecutive patients admitted to the intensive care unit (ICU) during their first inpatient rehabilitation for cervical and thoracic traumatic SCI. A total of 323 patients were included: 297 required mechanical ventilation and 215 underwent tracheostomy. Outcome measures Demographic data, data relevant to the patients’ neurological injuries (level and grade of spinal cord damage), tracheostomy technique and timing, duration of mechanical ventilation, length of stay at ICU, incidence of pneumonia, incidence of perioperative and early postoperative complications, and mortality. Results Early tracheostomy (<7 days after orotracheal intubation) tracheostomy was performed in 101 patients (47%) and late (≥7 days) in 114 (53%). Surgical tracheostomy was employed in 119 cases (55%) and percutaneous tracheostomy in 96 (45%). There were 61 complications in 53 patients related to all tracheostomy procedures. Two were qualified as serious (tracheoesophageal fistula and mediastinal abscess). Other complications were mild. Bleeding was moderate in one case (late, percutaneous tracheostomy). Postoperative infection rate was low. Mortality of all causes was also low. Conclusion Early tracheostomy may have favorable effects in patients with acute traumatic SC. Both techniques, percutaneous and surgical tracheostomy, can be performed safely in the ICU. PMID:21528630

  10. Effects of Electroacupuncture at Governor Vessel Acupoints on Neurotrophin-3 in Rats with Experimental Spinal Cord Injury

    PubMed Central

    Lv, Wei; Song, Liang-yu; Song, Hong-tao; Yuan, Xiao-chen; Mao, Ying-qiu; Jing, Quan-kai

    2016-01-01

    In an effort to explore new, noninvasive treatment options for spinal cord injuries (SCI), this study investigated the effects of electroacupuncture (EA) for SCI rat models. SCI was induced by a modified Allen's weight-drop method. We investigated the response of EA at Dazhui (GV 14) and Mingmen (GV 4) acupoints to understand the effects and mechanisms of EA in neuroprotection and neuronal function recovery after SCI. BBB testing was used to detect motor function of rats' hind limbs among groups, and EA was shown to promote the recovery of SCI rats' motor function. Nissl staining showed a restored neural morphology and an increase in the quantity of neurons after EA. Also, the antiapoptosis role was exposed by TUNEL staining. Western blotting analysis was used to determine the protein expression of neurotrophin-3 (NT-3) in spinal cord tissue. Compared to the sham group, the expression levels of NT-3 were significantly decreased and EA was shown to upregulate the expression of NT-3. The present study suggests that the role of EA in neuroprotection and dorsal neuronal function recovery after SCI in rats, especially EA stimulation at GV 14 and GV 4, can greatly promote neuronal function recovery, which may result from upregulating the expression of NT-3. PMID:27597902

  11. The Effect of Injury-Related Characteristics on Changes in Marital Status after Spinal Cord Injury

    PubMed Central

    MERGHATI KHOI, Effat; LATIFI, Sahar; RAHDARI, Fereshteh; SHAKERI, Hania; ARMAN, Farid; KOUSHKI, Davood; NOROUZI JAVIDAN, Abbas; TAHERI OTAGHSARA, Seyede-Mohadeseh

    2015-01-01

    Background: Spinal cord injury (SCI) imposes a significant burden on the social and marital life. Here, we assessed the divorce rate and changes in marital status among a sample of Iranian individuals with SCI. Methods: Referred patients to Brain and Spinal Cord Injury Research Center were invited to participate in this cross-sectional investigation. The Main exclusion criteria were coincidental brain injury, history of chronic diseases before SCI and substance use. Demographic characteristics (including age, gender, educational level, marital status before and after injury and duration of marriage) and Injury characteristics (level of the injury, American spinal injury association (ASIA) scale and Spinal cord independence measure III (SCIM)) were collected. Results: Total of 241 subjects with SCI participated in this investigation (164 (68%) male and 77 (32%) female). Among men, 16.5% [95% CI: 10.81%–22.18%] and among women 18.2% [95% CI: 9.58%–26.81%] got divorced after injury. Duration of marriage before injury was significantly related to lower divorce rate (P< 0.001 and 0.016 in men and women, respectively). Injury characteristics had no relationship with marital longevity. Age was a protective factor against marital dissolution only in men (P< 0.004). Conclusion: Our study revealed the divorce rate of 17% [95% CI: 13%–20.9%] after SCI in a sample of Iranian population. The protective influence of age in maintenance of marriage was only detected in men, which proposes existence of a sexual polymorphism in the role of age. Divorce rate was similar between two genders and injury characteristics were not related to divorce rate as well. PMID:26576353

  12. Ameliorative Effects of p75NTR-ED-Fc on Axonal Regeneration and Functional Recovery in Spinal Cord-Injured Rats.

    PubMed

    Wang, Yong-Tang; Lu, Xiu-Min; Zhu, Feng; Huang, Peng; Yu, Ying; Long, Zai-Yun; Wu, Ya-Min

    2015-12-01

    As a co-receptor of Nogo-66 receptor (NgR) and a critical receptor for paired immunoglobulin-like receptor (PirB), p75 neurotrophin receptor (p75NTR) mediates the inhibitory effects of myelin-associated inhibitors on axonal regeneration after spinal cord injury. Therefore, the p75NTR antagonist, such as recombinant p75NTR protein or its homogenates may block the inhibitory effects of myelin and promote the axonal regeneration and functional recovery. The purposes of this study are to subclone and express the extracellular domain gene of human p75NTR with IgG-Fc (hp75NTR-ED-Fc) in prokaryotic expression system and investigate the effects of the recombinant protein on axonal regeneration and functional recovery in spinal cord-injured rats. The hp75NTR-ED-Fc coding sequence was amplified from pcDNA-hp75NTR-ED-Fc by polymerase chain reaction (PCR) and subcloned into vector pET32a (+), then the effects of the purified recombinant protein on neurite outgrowth of dorsal root ganglion (DRG) neurons cultured with myelin-associated glycoprotein (MAG) were determined, and the effects of the fusion protein on axonal regeneration, functional recovery, and its possible mechanisms in spinal cord-injured rats were further investigated. The results indicated that the purified infusion protein could promote neurite outgrowth of DRG neurons, promote axonal regeneration and functional recovery, and decrease RhoA activation in spinal cord-injured rats. Taken together, the findings revealed that p75NTR still may be a potential and novel target for therapeutic intervention for spinal cord injury and that the hp75NTR-ED-Fc fusion protein treatment enhances functional recovery by limiting tissue loss and stimulating axonal growth in spinal cord-injured rats, which may result from decreasing the activation of RhoA.

  13. Appendiceal transection associated with seat belt restraint

    PubMed Central

    Go, Seung Je; Ye, Jin Bong; Kim, Joong Suck

    2016-01-01

    The seat belt is designed for safety in a motor vehicle and should be worn to prevent severe injuries. But, the seat belt itself can be an injury factor in combination with deceleration forces applied to fixation points of mobile viscera. Here, we present a 23-year-man with traumatic transection of the appendix, highly mobile viscera, following seat belt injury. PMID:27478816

  14. Consequences of Neurite Transection In Vitro

    PubMed Central

    Cengiz, Nurettin; Erdoğan, Ender; Him, Aydın; Oğuz, Elif Kaval

    2012-01-01

    Abstract In order to quantify degenerative and regenerative changes and analyze the contribution of multiple factors to the outcome after neurite transection, we cultured adult mouse dorsal root ganglion neurons, and with a precise laser beam, we transected the nerve fibers they extended. Cell preparations were continuously visualized for 24 h with time-lapse microscopy. More distal cuts caused a more elongated field of degeneration, while thicker neurites degenerated faster than thinner ones. Transected neurites degenerated more if the uncut neurites of the same neuron simultaneously degenerated. If any of these uncut processes regenerated, the transected neurites underwent less degeneration. Regeneration of neurites was limited to distal cuts. Unipolar neurons had shorter regeneration than multipolar ones. Branching slowed the regenerative process, while simultaneous degeneration of uncut neurites increased it. Proximal lesions, small neuronal size, and extensive and rapid neurite degeneration were predictive of death of an injured neuron, which typically displayed necrotic rather than apoptotic form. In conclusion, this in vitro model proved useful in unmasking many new aspects and correlates of mechanically-induced neurite injury. PMID:20121423

  15. Regulatory effects of intermittent noxious stimulation on spinal cord injury-sensitive microRNAs and their presumptive targets following spinal cord contusion

    PubMed Central

    Strickland, Eric R.; Woller, Sarah A.; Garraway, Sandra M.; Hook, Michelle A.; Grau, James W.; Miranda, Rajesh C.

    2014-01-01

    Uncontrollable nociceptive stimulation adversely affects recovery in spinally contused rats. Spinal cord injury (SCI) results in altered microRNA (miRNA) expression both at, and distal to the lesion site. We hypothesized that uncontrollable nociception further influences SCI-sensitive miRNAs and associated gene targets, potentially explaining the progression of maladaptive plasticity. Our data validated previously described sensitivity of miRNAs to SCI alone. Moreover, following SCI, intermittent noxious stimulation decreased expression of miR124 in dorsal spinal cord 24 h after stimulation and increased expression of miR129-2 in dorsal, and miR1 in ventral spinal cord at 7 days. We also found that brain-derived neurotrophic factor (BDNF) mRNA expression was significantly down-regulated 1 day after SCI alone, and significantly more so, after SCI followed by tailshock. Insulin-like growth factor-1 (IGF-1) mRNA expression was significantly increased at both 1 and 7 days post-SCI, and significantly more so, 7 days post-SCI with shock. MiR1 expression was positively and significantly correlated with IGF-1, but not BDNF mRNA expression. Further, stepwise linear regression analysis indicated that a significant proportion of the changes in BDNF and IGF-1 mRNA expression were explained by variance in two groups of miRNAs, implying co-regulation. Collectively, these data show that uncontrollable nociception which activates sensorimotor circuits distal to the injury site, influences SCI-miRNAs and target mRNAs within the lesion site. SCI-sensitive miRNAs may well mediate adverse consequences of uncontrolled sensorimotor activation on functional recovery. However, their sensitivity to distal sensory input also implicates these miRNAs as candidate targets for the management of SCI and neuropathic pain. PMID:25278846

  16. Biocompatibility of reduced graphene oxide nanoscaffolds following acute spinal cord injury in rats

    PubMed Central

    Palejwala, Ali H.; Fridley, Jared S.; Mata, Javier A.; Samuel, Errol L. G.; Luerssen, Thomas G.; Perlaky, Laszlo; Kent, Thomas A.; Tour, James M.; Jea, Andrew

    2016-01-01

    Background: Graphene has unique electrical, physical, and chemical properties that may have great potential as a bioscaffold for neuronal regeneration after spinal cord injury. These nanoscaffolds have previously been shown to be biocompatible in vitro; in the present study, we wished to evaluate its biocompatibility in an in vivo spinal cord injury model. Methods: Graphene nanoscaffolds were prepared by the mild chemical reduction of graphene oxide. Twenty Wistar rats (19 male and 1 female) underwent hemispinal cord transection at approximately the T2 level. To bridge the lesion, graphene nanoscaffolds with a hydrogel were implanted immediately after spinal cord transection. Control animals were treated with hydrogel matrix alone. Histologic evaluation was performed 3 months after the spinal cord transection to assess in vivo biocompatibility of graphene and to measure the ingrowth of tissue elements adjacent to the graphene nanoscaffold. Results: The graphene nanoscaffolds adhered well to the spinal cord tissue. There was no area of pseudocyst around the scaffolds suggestive of cytotoxicity. Instead, histological evaluation showed an ingrowth of connective tissue elements, blood vessels, neurofilaments, and Schwann cells around the graphene nanoscaffolds. Conclusions: Graphene is a nanomaterial that is biocompatible with neurons and may have significant biomedical application. It may provide a scaffold for the ingrowth of regenerating axons after spinal cord injury. PMID:27625885

  17. Biocompatibility of reduced graphene oxide nanoscaffolds following acute spinal cord injury in rats

    PubMed Central

    Palejwala, Ali H.; Fridley, Jared S.; Mata, Javier A.; Samuel, Errol L. G.; Luerssen, Thomas G.; Perlaky, Laszlo; Kent, Thomas A.; Tour, James M.; Jea, Andrew

    2016-01-01

    Background: Graphene has unique electrical, physical, and chemical properties that may have great potential as a bioscaffold for neuronal regeneration after spinal cord injury. These nanoscaffolds have previously been shown to be biocompatible in vitro; in the present study, we wished to evaluate its biocompatibility in an in vivo spinal cord injury model. Methods: Graphene nanoscaffolds were prepared by the mild chemical reduction of graphene oxide. Twenty Wistar rats (19 male and 1 female) underwent hemispinal cord transection at approximately the T2 level. To bridge the lesion, graphene nanoscaffolds with a hydrogel were implanted immediately after spinal cord transection. Control animals were treated with hydrogel matrix alone. Histologic evaluation was performed 3 months after the spinal cord transection to assess in vivo biocompatibility of graphene and to measure the ingrowth of tissue elements adjacent to the graphene nanoscaffold. Results: The graphene nanoscaffolds adhered well to the spinal cord tissue. There was no area of pseudocyst around the scaffolds suggestive of cytotoxicity. Instead, histological evaluation showed an ingrowth of connective tissue elements, blood vessels, neurofilaments, and Schwann cells around the graphene nanoscaffolds. Conclusions: Graphene is a nanomaterial that is biocompatible with neurons and may have significant biomedical application. It may provide a scaffold for the ingrowth of regenerating axons after spinal cord injury.

  18. [Sutureless hepatic transection using a new radiofrequency assisted device. Theoretical model, experimental study and clinic trial].

    PubMed

    Martínez-Serrano, María Ángeles; Grande, Luis; Burdío, Fernando; Berjano, Enrique; Poves, Ignasi; Quesada, Rita

    2011-03-01

    The ideal instrument for performing hepatic transection should combine safe and rapid haemostasis in a single tool. We present a new multidisciplinary investigation designed to develop a hepatic transection device assisted by radiofrequency (RF); the investigation included: a computerised theoretical model, and experimental study and a clinical trial of this device. The theoretic modelling was performed by computer, based on the Finite Elements Method (FEM), with the objective of studying the distribution of electrical energy and temperature in the tissue, and to assess the effect of the characteristics of the instrument. The experimental study, based on an in vivo porcine model, suggested that the new instrument would allow the transection velocity of the hepatic parenchyma to be increased with lower bleeding per transection area compared with other techniques extensively used in liver surgery. These data should enable the first phase of clinical trial to be conducted, with preliminary results that suggest that the new device is safe and effective.

  19. 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

    2016-05-01

    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.

  20. Biochemical Monitoring of Spinal Cord Injury by FT-IR Spectroscopy—Effects of Therapeutic Alginate Implant in Rat Models

    PubMed Central

    Uckermann, Ortrud; Sitoci-Ficici, Kerim H.; Later, Robert; Beiermeister, Rudolf; Doberenz, Falko; Gelinsky, Michael; Leipnitz, Elke; Schackert, Gabriele; Koch, Edmund; Sablinskas, Valdas; Steiner, Gerald; Kirsch, Matthias

    2015-01-01

    Spinal cord injury (SCI) induces complex biochemical changes, which result in inhibition of nervous tissue regeneration abilities. In this study, Fourier-transform infrared (FT-IR) spectroscopy was applied to assess the outcomes of implants made of a novel type of non-functionalized soft calcium alginate hydrogel in a rat model of spinal cord hemisection (n = 28). Using FT-IR spectroscopic imaging, we evaluated the stability of the implants and the effects on morphology and biochemistry of the injured tissue one and six months after injury. A semi-quantitative evaluation of the distribution of lipids and collagen showed that alginate significantly reduced injury-induced demyelination of the contralateral white matter and fibrotic scarring in the chronic state after SCI. The spectral information enabled to detect and localize the alginate hydrogel at the lesion site and proved its long-term persistence in vivo. These findings demonstrate a positive impact of alginate hydrogel on recovery after SCI and prove FT-IR spectroscopic imaging as alternative method to evaluate and optimize future SCI repair strategies. PMID:26559822

  1. Effect of exercise on the expression of nerve growth factor in the spinal cord of rats with induced osteoarthritis.

    PubMed

    Park, Soo-Jin; Yong, Min-Sik; Na, Sang-Su

    2015-08-01

    [Purpose] We examined the impact of exercise on the expression pattern of nerve growth factor in the spinal cord of rats with induced osteoarthritis of the knee joint. [Subjects and Methods] To produce monosodium iodoacetate-induced arthritis, rats were administered 3 mg/50 µL monosodium iodoacetate through the interarticular space of the right knee. The animals were randomly divided into four groups: rats sacrificed 3 weeks after 0.9% saline solution injection (shame group, n = 10), rats sacrificed 3 weeks after monosodium iodoacetate injection (control group, n = 10), rats with 4 weeks rest from 3 weeks after monosodium iodoacetate injection (no exercise group, n = 10), and rats with 4 weeks treadmill training from 3 weeks after monosodium iodoacetate injection (exercise group, n = 10). Serial coronal sections of the lumbar spine were cut and processed for immunohistochemistry. [Results] The expression of nerve growth factor was significantly increased in the EG compared with the SG, CG, and NEG. [Conclusion] Increased nerve growth factor expression in the spinal cord due to exercise-induced stimulation can be effective in treating chronic pain. Such treatment will contribute not only to improving the joint function of patients with chronic pain but also their quality of life. PMID:26357438

  2. Changes in autophagy in rats after spinal cord injury and the effect of hyperbaric oxygen on autophagy.

    PubMed

    Sun, Yongming; Liu, Dong; Su, Peng; Lin, Fanguo; Tang, Qifeng

    2016-04-01

    The purpose of this study was to explore the effects of Hyperbaric oxygen (HBO) on the autophagic changes after induction of spinal cord injury (SCI) in rats. A total of 75 rats were randomly divided into the sham-operated group, the spinal cord injury group, and the SCI+HBO group. We found that at 7 d and 14 d after surgery, the BBB scores were higher in the SCI+HBO group in comparison to the SCI group. The expression of Beclin-1 and LC3II was upregulated in the SCI and SCI+HBO groups after SCI. Fluorescently stained Beclin-1 and LC3II proteins were barely detectable in the sham group. In contrast, Beclin-l and LC3II expression was observed in neurons and glial cells from the SCI and SCI+HBO groups. Beclin-1 and LC3II expression appeared at 6h after SCI. At each time point, Beclin-1 and LC3II expression was significantly higher in the SCI+HBO group compared to the SCI group. These results suggest that autophagy is activated in rats after SCI and sustained over a period of time. HBO treatment enhances autophagy expression in rats after SCI and accelerates cell repair rate, which may represent one of the mechanisms of action of HBO in the treatment of SCI.

  3. Effect of Locomotor Training on Motor Recovery and Walking Ability in Patients with Incomplete Spinal Cord Injury: A Case Series

    PubMed Central

    Anwer, Shahnawaz; Equebal, Ameed; Palekar, Tushar J; Nezamuddin, M; Neyaz, Osama; Alghadir, Ahmad

    2014-01-01

    [Purpose] The aim of this study was to describe the effect of locomotor training on a treadmill for three individuals who have an incomplete spinal cord injury (SCI). [Subjects and Methods] Three indivduals (2 males, 1 female) with incomplete paraplegia participated in this prospective case series. All subjects participated in locomotor training for a maximum of 20 minutes on a motorized treadmill without elevation at a comfortable walking speed three days a week for four weeks as an adjunct to a conventional physiotherapy program. The lower extremity strength and walking capabilities were used as the outcome measures of this study. Lower extremity strength was measured by lower extremity motor score (LEMS). Walking capability was assessed using the Walking Index for Spinal Cord Injury (WISCI II). [Results] An increase in lower extremity motor score and walking capabilities at the end of training program was found. [Conclusion] Gait training on a treadmill can enhance motor recovery and walking capabilities in subjects with incomplete SCI. Further research is needed to generalize these findings and to identify which patients might benefit from locomotor training. PMID:25013303

  4. Inhibition of intracranial self-stimulation in brain stem-transected cats--a proposed mechanism of aversive effects produced by brain stimulation.

    PubMed

    Ikegami, S; Kawamura, H

    1981-12-21

    Effects of intracranial self-stimulation of central 'punishment areas' were studied on an operant conditioning of vertical eye movements in the midpontine pretrigeminal cats as well as in the encéphale isolé cats. In 36 pretrigeminal cats, the ventromedial hypothalamus (VMH), basal amygdaloid nuclei (AMY), dorsal central gray (CG) of the midbrain and the thalamic nuclei such as the ventralis posteromedialis (VPM) and ventralis posterolateralis (VPL) were tested. No suppression of eye movements indicating a passive avoidance conditioning from stimulation of these 'punishment areas' was obtained in 92 electrode tip sites. In 49 encéphale isolé cats, stimulation of the VPM associated with contraction of the facial muscles, demonstrated a marked passive avoidance effect on the eye movements. After blocking both the trigeminal (5N) and facial nerves (7N), VPM stimulation no longer produced an increase of facial EMG activity and the suppressive effect on eye movements was abolished. Extracranial blockade of 7N alone, which induced facial muscle paralysis also showed similar effects. Bilateral blockade of cranial nerves from acoustic (8N) to hypoglossal (12N) nerves had no significant effect on the avoidance conditioning. The mass neural activity recorded from the 5N showed a marked increase of discharge by VPM stimulation which was reduced significantly after 7N blockade. These results may suggest a possibility that punishing effects of brain stimulation depend on feedback from the periphery (muscles, blood vessels and visceral organs), whereas reward effects essentially depend on neural circuitry confined within the forebrain above the rostral pons. PMID:7306820

  5. Exercise modulates chloride homeostasis after spinal cord injury.

    PubMed

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

    2014-07-01

    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.

  6. Low-intensity pulsed ultrasound accelerates nerve regeneration following inferior alveolar nerve transection in rats.

    PubMed

    Sato, Mai; Motoyoshi, Mitsuru; Shinoda, Masamichi; Iwata, Koichi; Shimizu, Noriyoshi

    2016-06-01

    Inferior alveolar nerve (IAN) injury, which is frequently caused by orofacial surgery or trauma, induces sensory loss in orofacial regions innervated by the IAN. However, no effective treatment for orofacial sensory loss currently exists. We determined whether sensory loss in facial skin above the mental foramen following IAN transection was recovered by exposure of the transected IAN to low-intensity pulsed ultrasound (LIPUS). Inferior alveolar nerve transection (IANX) was performed in 7-wk-old male Sprague-Dawley rats. On day 7 after IANX, the effect of daily LIPUS (from day 0) on the transected IAN, in terms of sensitivity to mechanical stimulation of the facial skin above the mental foramen, was examined. Moreover, the number of trigeminal ganglion (TG) neurons innervating the facial skin above the mental foramen of rats with IANX treated daily with LIPUS was counted using the retrograde neurotracing technique. Daily exposure of the transected IAN to LIPUS significantly promoted recovery of the head-withdrawal threshold in response to mechanical stimulation of the facial skin above the mental foramen, and the number of TG neurons innervating the facial skin above mental foramen was significantly increased in rats with IANX treated daily with LIPUS compared with sham or LIPUS-unexposed rats. Daily treatment of stumps of the transected IAN with LIPUS facilitated morphological and functional regeneration, suggesting that LIPUS is an effective and novel therapy for IAN injury. PMID:27058986

  7. Low doses of urethane effectively inhibit spinal seizures evoked by sudden cooling of toad isolated spinal cord

    SciTech Connect

    Pina-crespo, J.C.; Dalo, N.L. )

    1992-01-01

    The effect of low doses of urethane on three phases of spinal seizures evoked by sudden cooling (SSSC) of toad isolated spinal cord was studied. In control toads, SSSC began with a latency of 91[plus minus]3 sec exhibiting brief tremors, followed by clonic muscle contractions and finally reaching a tonic contraction. The latency of onset of seizures was significantly enhanced. The tonic phase was markedly abolished in toads pretreated intralymphaticaly with 0.15 g/kg of urethane. Tremors were the only phase observed in 55% of toads that received doses of 0.2 g/kg, and a total blockage of seizures was seen after doses of 0.25 g/kg of urethane in 50% of the preparations. A possible depressant effect of urethane on transmission mediated by excitatory amino acids is suggested.

  8. A systematic review of the effects of pharmacological agents on walking function in people with spinal cord injury.

    PubMed

    Domingo, Antoinette; Al-Yahya, Abdulaziz A; Asiri, Yousif; Eng, Janice J; Lam, Tania

    2012-03-20

    Studies of spinalized animals indicate that some pharmacological agents may act on receptors in the spinal cord, helping to produce coordinated locomotor movement. Other drugs may help to ameliorate the neuropathological changes resulting from spinal cord injury (SCI), such as spasticity or demyelination, to improve walking. The purpose of this study was to systematically review the effects of pharmacological agents on gait in people with SCI. A keyword literature search of articles that evaluated the effects of drugs on walking after SCI was performed using the databases MEDLINE/PubMed, CINAHL, EMBASE, PsycINFO, and hand searching. Two reviewers independently evaluated each study, using the Physiotherapy Evidence Database (PEDro) tool for randomized clinical trials (RCTs), and the modified Downs & Black scale for all other studies. Results were tabulated and levels of evidence were assigned. Eleven studies met the inclusion criteria. One RCT provided Level 1 evidence that GM-1 ganglioside in combination with physical therapy improved motor scores, walking velocity, and distance better than placebo and physical therapy in persons with incomplete SCI. Multiple studies (levels of evidence 1-5) showed that clonidine and cyproheptadine may improve locomotor function and walking speed in severely impaired individuals with incomplete SCI. Gains in walking speed associated with GM-1, cyproheptadine, and clonidine are low compared to those seen with locomotor training. There was also Level 1 evidence that 4-aminopyridine and L-dopa were no better than placebo in helping to improve gait. Two Level 5 studies showed that baclofen had little to no effect on improving walking in persons with incomplete SCI. There is limited evidence that pharmacological agents tested so far would facilitate the recovery of walking after SCI. More studies are needed to better understand the effects of drugs combined with gait training on walking outcomes in people with SCI.

  9. Neuroprotective effects and impact on caspase-12 expression of tauroursodeoxycholic acid after acute spinal cord injury in rats

    PubMed Central

    Dong, Yi; Miao, Lei; Hei, Long; Lin, Leilei; Ding, Huiqiang

    2015-01-01

    Objective: To observe the effects of tauroursodeoxycholic acid (TUDCA) on nerve function after acute spinal cord injury (SCI) in rats, observe its effect on neuronal apoptosis and caspase-12 expression levels, and investigate the underlying mechanism. Methods: We used a modified Allen’s weight-drop trauma method to establish a rat acute SCI model. The rats were randomly divided into three groups: group A (sham surgery group), group B (DMSO control group) and group C (TUDCA treatment group), with 36 rats in each group. At one minute and at 24 hours after successfully establishing the model, rats in group C received an intraperitoneal injection of TUDCA (200 mg/kg), while rats in group B received an equal amount of DMSO at the same time points. At 24 hours, three days, and five days after injury, a modified Tarlov scoring method and Rivlin’s oblique plate test were used to evaluate rat spinal cord nerve function recovery. Animals were sacrificed at 24 hours, three days, and five days after injury. Specimens were obtained from the center of the injury sites; the pathological changes in spinal cord tissue were observed after hematoxylin-eosin (HE) staining; apoptosis was detected using the TUNEL method, and the expression of caspase-12 was measured at the protein level using immunohistochemistry and Western blots. Results: Group C differed significantly from group B in Tarlov scores and the oblique table test as early as 24 hours after the injury (P < 0.05). The TUNEL assay test results showed that neurons underwent apoptosis after SCI, which peaked at 24 hours. The ratios of apoptotic cells in group C were significantly lower than those in group B at 24 hours, three days, and five days after injury (P < 0.01). The immunohistochemistry and Western blot results showed that the caspase-12 expression levels of group C were lower than those of group B at 24 hours, three days, and five days after injury (P < 0.05). Conclusion: TUDCA can inhibit the expression of caspase

  10. Effect of older age on treatment decisions and outcomes among patients with traumatic spinal cord injury

    PubMed Central

    Ahn, Henry; Bailey, Christopher S.; Rivers, Carly S.; Noonan, Vanessa K.; Tsai, Eve C.; Fourney, Daryl R.; Attabib, Najmedden; Kwon, Brian K.; Christie, Sean D.; Fehlings, Michael G.; Finkelstein, Joel; Hurlbert, R. John; Townson, Andrea; Parent, Stefan; Drew, Brian; Chen, Jason; Dvorak, Marcel F.

    2015-01-01

    Background: Older people are at increased risk of traumatic spinal cord injury from falls. We evaluated the impact of older age (≥ 70 yr) on treatment decisions and outcomes. Methods: We identified patients with traumatic spinal cord injury for whom consent and detailed data were available from among patients recruited (2004–2013) at any of the 31 acute care and rehabilitation hospitals participating in the Rick Hansen Spinal Cord Injury Registry. Patients were assessed by age group (< 70 v. ≥ 70 yr). The primary outcome was the rate of acute surgical treatment. We used bivariate and multivariate regression models to assess patient and injury-related factors associated with receiving surgical treatment and with the timing of surgery after arrival to a participating centre. Results: Of the 1440 patients included in our study cohort, 167 (11.6%) were 70 years or older at the time of injury. Older patients were more likely than younger patients to be injured by falling (83.1% v. 37.4%; p < 0.001), to have a cervical injury (78.0% v. 61.6%; p = 0.001), to have less severe injuries on admission (American Spinal Injury Association Impairment Scale grade C or D: 70.5% v. 46.9%; p < 0.001), to have a longer stay in an acute care hospital (median 35 v. 28 d; p < 0.005) and to have a higher in-hospital mortality (4.2% v. 0.6%; p < 0.001). Multivariate analysis did not show that age of 70 years or more at injury was associated with a decreased likelihood of surgical treatment (adjusted odds ratio [OR] 0.48, 95% confidence interval [CI] 0.22–1.07). An unplanned sensitivity analysis with different age thresholds showed that a threshold of 65 years was associated with a decreased chance of surgical treatment (OR 0.39, 95% CI 0.19–0.80). Older patients who underwent surgical treatment had a significantly longer wait time from admission to surgery than younger patients (37 v. 19 h; p < 0.001). Interpretation: We found chronological age to be a factor influencing

  11. The Effectiveness and Cost‐Effectiveness of Spinal Cord Stimulation for Refractory Angina (RASCAL Study): A Pilot Randomized Controlled Trial

    PubMed Central

    Thomson, Simon; Duarte, Rui; Brookes, Morag; deBelder, Mark; Raphael, Jon; Davies, Ed; Taylor, Rod

    2016-01-01

    Background Patients with “refractory angina” (RA) unsuitable for coronary revascularization experience high levels of hospitalization and poor health‐related quality of life. Randomized trials have shown spinal cord stimulation (SCS) to be a promising treatment for chronic stable angina and RA; however, none has compared SCS with usual care (UC). The aim of this pilot study was to address the key uncertainties of conducting a definitive multicenter trial to assess the clinical and cost‐effectiveness of SCS in RA patients, i.e., recruitment and retention of patients, burden of outcome measures, our ability to standardize UC in a UK NHS setting. Methods RA patients deemed suitable were randomized in a 1:1 ratio to SCS plus UC (SCS group) or UC alone (UC group). We sought to assess: recruitment, uptake, and retention of patients; feasibility and acceptability of SCS treatment; the feasibility and acceptability of standardizing UC; and the feasibility and acceptability of the proposed trial outcome measures. Patient outcomes were assessed at baseline (prerandomization) and three and six months postrandomization. Results We failed to meet our planned recruitment target (45 patients) and randomized 29 patients (15 SCS group, 14 UC group) over a 42‐month period across four sites. None of the study participants chose to withdraw following consent and randomization. With exception of two deaths, all completed evaluation at baseline and follow‐up. Although the study was not formally powered to compare outcomes between groups, we saw a trend toward larger improvements in both primary and secondary outcomes in the SCS group. Conclusions While patient recruitment was found to be challenging, levels of participant retention, outcome completion, and acceptability of SCS therapy were high. A number of lessons are presented in order to take forward a future definitive pragmatic randomized trial. PMID:26387883

  12. Nerve regeneration restores supraspinal control of bladder function after complete spinal cord injury.

    PubMed

    Lee, Yu-Shang; Lin, Ching-Yi; Jiang, Hai-Hong; Depaul, Marc; Lin, Vernon W; Silver, Jerry

    2013-06-26

    A life-threatening disability after complete spinal cord injury is urinary dysfunction, which is attributable to lack of regeneration of supraspinal pathways that control the bladder. Although numerous strategies have been proposed that can promote the regrowth of severed axons in the adult CNS, at present, the approaches by which this can be accomplished after complete cord transection are quite limited. In the present study, we modified a classic peripheral nerve grafting technique with the use of chondroitinase to facilitate the regeneration of axons across and beyond an extensive thoracic spinal cord transection lesion in adult rats. The novel combination treatment allows for remarkably lengthy regeneration of certain subtypes of brainstem and propriospinal axons across the injury site and is followed by markedly improved urinary function. Our studies provide evidence that an enhanced nerve grafting strategy represents a potential regenerative treatment after severe spinal cord injury.

  13. Nerve Regeneration Restores Supraspinal Control of Bladder Function after Complete Spinal Cord Injury

    PubMed Central

    Lin, Ching-Yi; Jiang, Hai-Hong; DePaul, Marc; Lin, Vernon W.

    2013-01-01

    A life-threatening disability after complete spinal cord injury is urinary dysfunction, which is attributable to lack of regeneration of supraspinal pathways that control the bladder. Although numerous strategies have been proposed that can promote the regrowth of severed axons in the adult CNS, at present, the approaches by which this can be accomplished after complete cord transection are quite limited. In the present study, we modified a classic peripheral nerve grafting technique with the use of chondroitinase to facilitate the regeneration of axons across and beyond an extensive thoracic spinal cord transection lesion in adult rats. The novel combination treatment allows for remarkably lengthy regeneration of certain subtypes of brainstem and propriospinal axons across the injury site and is followed by markedly improved urinary function. Our studies provide evidence that an enhanced nerve grafting strategy represents a potential regenerative treatment after severe spinal cord injury. PMID:23804083

  14. Effects of spinal cord injury on body composition and metabolic profile – Part I

    PubMed Central

    Gorgey, Ashraf S.; Dolbow, David R.; Dolbow, James D.; Khalil, Refka K.; Castillo, Camilo; Gater, David R.

    2014-01-01

    Several body composition and metabolic-associated disorders such as glucose intolerance, insulin resistance, and lipid abnormalities occur prematurely after spinal cord injury (SCI) and at a higher prevalence compared to able-bodied populations. Within a few weeks to months of the injury, there is a significant decrease in total lean mass, particularly lower extremity muscle mass and an accompanying increase in fat mass. The infiltration of fat in intramuscular and visceral sites is associated with abnormal metabolic profiles. The current review will summarize the major changes in body composition and metabolic profiles that can lead to comorbidities such as type 2 diabetes mellitus and cardiovascular diseases after SCI. It is crucial for healthcare specialists to be aware of the magnitude of these changes. Such awareness may lead to earlier recognition and treatment of metabolic abnormalities that may reduce the co-morbidities seen over the lifetime of persons living with SCI. PMID:25001559

  15. [Maximal exercise in spinal cord injured subjects: effects of an antigravity suit].

    PubMed

    Bazzi-Grossin, C; Bonnin, P; Bailliart, O; Bazzi, H; Kedra, A W; Martineaud, J P

    1996-01-01

    Paraplegics have low aerobic capacity because of the spinal cord injury. Their functional muscle mass is reduced and usually untrained. They have to use upperbody muscles for displacements and daily activities. Sympathic nervous system injury is responsible of vasomotricity disturbances in leg vessels and possible abdominal vessels, proportionally to level injury. If cord injury level is higher than T5, then sympathic cardiac efferences may be damaged. Underbody muscles atrophy and vasomotricity disturbances contribute to phlebostasis. This stasis may decrease venous return, preload and stroke volume (Starling). To maintain appropriate cardiac output, tachycardia is necessary, especially during exercise. Low stroke volume, all the more since it is associated with cardio-acceleration disturbances, may reduce cardiac output reserve, and so constitutes a limiting factor for adaptation to exercise. The aim of this study was to verify if use of an underlesional pressure suit may increase cardiac output reserve because of lower venous stasis, and increase performance. We studied 10 able-bodied and 14 traumatic paraplegic subjects. Able-bodied subjects were 37 +/- 6 years old, wellbeing, not especially trained with upperbody muscles: there were 2 women and 8 men. Paraplegics were 27 +/- 7 years old, wellbeing except paraplegia, five of them practiced sport regularly (athletism or basket for disabled), and the others just daily propelled their wheelchair; there were 5 women and 9 men. For 8 of them, cord injury levels were located below T7, between T1 and T6 for the others. The age disability varied from 6 months to 2 years for 9 of them, it was approximately five years for 4 of them, and 20 years for one. We used a maximal triangular arm crank exercise with an electro-magnetic ergocycle Gauthier frame. After five minutes warm up, it was proceeded in one minute successive stages until maximal oxygen consumption is raised. VO2, VCO2, RER were measured by direct method with

  16. Effects of discontinuing cover gowns on a postpartal ward upon cord colonization of the newborn.

    PubMed

    Renaud, M T

    1983-01-01

    To determine if the incidence of bacterial cord colonization in neonates increased when cover gowns were discontinued on a postpartal ward, a study was conducted. All infants who were admitted to and discharged from the well infant nursery at an Army medical center in Denver, Colorado, were cultured at the umbilicus at the time of admission and at discharge. The control group (N = 74) continued to gown as usual; the experimental group (N = 50) did not wear gowns. Visitors in both groups received the same instructions regarding handwashing. For all organisms, the control group demonstrated 80% colonization of infants who were negative on admission, and the experimental group demonstrated a colonization rate of 62%. When the chi square is applied, these data are statistically significant for P = 0.02 and P = 0.05. The experimental group had less colonization than the control group.

  17. The Effectiveness of FES-Evoked EMG Potentials to Assess Muscle Force and Fatigue in Individuals with Spinal Cord Injury

    PubMed Central

    Ibitoye, Morufu Olusola; Estigoni, Eduardo H.; Hamzaid, Nur Azah; Wahab, Ahmad Khairi Abdul; Davis, Glen M.

    2014-01-01

    The evoked electromyographic signal (eEMG) potential is the standard index used to monitor both electrical changes within the motor unit during muscular activity and the electrical patterns during evoked contraction. However, technical and physiological limitations often preclude the acquisition and analysis of the signal especially during functional electrical stimulation (FES)-evoked contractions. Hence, an accurate quantification of the relationship between the eEMG potential and FES-evoked muscle response remains elusive and continues to attract the attention of researchers due to its potential application in the fields of biomechanics, muscle physiology, and rehabilitation science. We conducted a systematic review to examine the effectiveness of eEMG potentials to assess muscle force and fatigue, particularly as a biofeedback descriptor of FES-evoked contractions in individuals with spinal cord injury. At the outset, 2867 citations were identified and, finally, fifty-nine trials met the inclusion criteria. Four hypotheses were proposed and evaluated to inform this review. The results showed that eEMG is effective at quantifying muscle force and fatigue during isometric contraction, but may not be effective during dynamic contractions including cycling and stepping. Positive correlation of up to r = 0.90 (p < 0.05) between the decline in the peak-to-peak amplitude of the eEMG and the decline in the force output during fatiguing isometric contractions has been reported. In the available prediction models, the performance index of the eEMG signal to estimate the generated muscle force ranged from 3.8% to 34% for 18 s to 70 s ahead of the actual muscle force generation. The strength and inherent limitations of the eEMG signal to assess muscle force and fatigue were evident from our findings with implications in clinical management of spinal cord injury (SCI) population. PMID:25025551

  18. Spasticity in spinal cord injured patients: 2. Initial measures and long-term effects of surface electrical stimulation.

    PubMed

    Robinson, C J; Kett, N A; Bolam, J M

    1988-10-01

    Electrical stimulation of paralyzed muscles has been shown to affect their spasticity, especially in patients with hemiplegia. But little has been reported on the long-term effects of such stimulation on individuals with spinal cord injury. This paper documents initial quadriceps spasticity in 31 spinal cord injured subjects, and the effect of four to eight weeks of reconditioning using electrical stimulation. Spasticity was quantified through the use of a normalized relaxation index (R2n) obtained from a pendulum drop test. The reconditioning protocol consisted of twice daily 20-minute exercise sessions at least four hours apart, six days per week. Spasticity and stimulated quadriceps torque were measured during one to three evaluations performed at least one day apart at the beginning of the program, and at four and eight weeks. There was no significant difference in average initial measures of spasticity between left and right legs and no effect of time since injury on average R2n values. Significant differences were seen for right leg average baseline R2n values when grouped by lesion level or completeness. Quadriplegic individuals were more spastic than paraplegic individuals, and subjects with incomplete lesions were more spastic than those with complete lesions. These findings are interrelated since most of the quadriplegic subjects (14 of 16) had incomplete lesions. Most participants had increased spasticity after four weeks of reconditioning but not after eight weeks. However, only eight subjects completed eight weeks of reconditioning. Subjects who had the greatest increases in spasticity also had the greatest gains in stimulated torque, both after four and eight weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3263102

  19. The effectiveness of FES-evoked EMG potentials to assess muscle force and fatigue in individuals with spinal cord injury.

    PubMed

    Ibitoye, Morufu Olusola; Estigoni, Eduardo H; Hamzaid, Nur Azah; Wahab, Ahmad Khairi Abdul; Davis, Glen M

    2014-07-14

    The evoked electromyographic signal (eEMG) potential is the standard index used to monitor both electrical changes within the motor unit during muscular activity and the electrical patterns during evoked contraction. However, technical and physiological limitations often preclude the acquisition and analysis of the signal especially during functional electrical stimulation (FES)-evoked contractions. Hence, an accurate quantification of the relationship between the eEMG potential and FES-evoked muscle response remains elusive and continues to attract the attention of researchers due to its potential application in the fields of biomechanics, muscle physiology, and rehabilitation science. We conducted a systematic review to examine the effectiveness of eEMG potentials to assess muscle force and fatigue, particularly as a biofeedback descriptor of FES-evoked contractions in individuals with spinal cord injury. At the outset, 2867 citations were identified and, finally, fifty-nine trials met the inclusion criteria. Four hypotheses were proposed and evaluated to inform this review. The results showed that eEMG is effective at quantifying muscle force and fatigue during isometric contraction, but may not be effective during dynamic contractions including cycling and stepping. Positive correlation of up to r = 0.90 (p < 0.05) between the decline in the peak-to-peak amplitude of the eEMG and the decline in the force output during fatiguing isometric contractions has been reported. In the available prediction models, the performance index of the eEMG signal to estimate the generated muscle force ranged from 3.8% to 34% for 18 s to 70 s ahead of the actual muscle force generation. The strength and inherent limitations of the eEMG signal to assess muscle force and fatigue were evident from our findings with implications in clinical management of spinal cord injury (SCI) population.

  20. Antiallodynic effect of tianeptine via modulation of the 5-HT7 receptor of GABAergic interneurons in the spinal cord of neuropathic rats.

    PubMed

    Lin, Hai; Heo, Bong Ha; Kim, Woong Mo; Kim, Yong Chul; Yoon, Myung Ha

    2015-06-26

    Although tianeptine, an atypical antidepressant has been reported to have antinociceptive effects, the mode of action is different from that of tricyclic antidepressants despite structural similarities. We examined the antiallodynic effect of intrathecal tianeptine in neuropathic pain rats and determined the involvement of 5-hydroxytryptamine type 7 (5-HT7) receptor of the GABAergic interneurons in the spinal cord. Neuropathic pain was induced by spinal nerve ligation (SNL). After observation of the effect from intrathecal tianeptine, a 5-HT7 receptor antagonist (SB-269970) was administered intrathecally 10 min before delivery of tianeptine, to determine the contribution of spinal 5-HT7 receptor on the activity of tianeptine. GAD expression and GABA concentrations were assessed. Intrathecal tianeptine dose-dependently attenuated mechanical allodynia in SNL rats. Pre-treatment with intrathecal SB-269970 reversed the antiallodynic effect of tianeptine. Both GAD65 expression and the GABA concentration in the spinal cord were decreased in neuropathic rats but were increased by tianeptine. Additionally, 5-HT7 receptor and GAD65 were co-localized in the spinal cord. Intrathecal tianeptine reduces neuropathic pain. 5-HT7 receptor of the GABAergic interneurons together with GAD65 plays a role in the activity of tianeptine at the spinal cord level.

  1. Antiallodynic effect of tianeptine via modulation of the 5-HT7 receptor of GABAergic interneurons in the spinal cord of neuropathic rats.

    PubMed

    Lin, Hai; Heo, Bong Ha; Kim, Woong Mo; Kim, Yong Chul; Yoon, Myung Ha

    2015-06-26

    Although tianeptine, an atypical antidepressant has been reported to have antinociceptive effects, the mode of action is different from that of tricyclic antidepressants despite structural similarities. We examined the antiallodynic effect of intrathecal tianeptine in neuropathic pain rats and determined the involvement of 5-hydroxytryptamine type 7 (5-HT7) receptor of the GABAergic interneurons in the spinal cord. Neuropathic pain was induced by spinal nerve ligation (SNL). After observation of the effect from intrathecal tianeptine, a 5-HT7 receptor antagonist (SB-269970) was administered intrathecally 10 min before delivery of tianeptine, to determine the contribution of spinal 5-HT7 receptor on the activity of tianeptine. GAD expression and GABA concentrations were assessed. Intrathecal tianeptine dose-dependently attenuated mechanical allodynia in SNL rats. Pre-treatment with intrathecal SB-269970 reversed the antiallodynic effect of tianeptine. Both GAD65 expression and the GABA concentration in the spinal cord were decreased in neuropathic rats but were increased by tianeptine. Additionally, 5-HT7 receptor and GAD65 were co-localized in the spinal cord. Intrathecal tianeptine reduces neuropathic pain. 5-HT7 receptor of the GABAergic interneurons together with GAD65 plays a role in the activity of tianeptine at the spinal cord level. PMID:25982324

  2. The Effect of Frequency and Type of Internet Use on Perceived Social Support and Sense of Well-Being in Individuals with Spinal Cord Injury

    ERIC Educational Resources Information Center

    Miller, Susan M.

    2008-01-01

    This article examines the effect of frequency and type of Internet use on perceived social support and sense of well-being in persons with spinal cord injury. The results show that Internet use is not significantly related to perceived social support. Bivariate analysis indicates that there is a significant negative association between total…

  3. Carbon Ion Irradiation of the Rat Spinal Cord: Dependence of the Relative Biological Effectiveness on Linear Energy Transfer

    SciTech Connect

    Saager, Maria; Glowa, Christin; Peschke, Peter; Brons, Stephan; Scholz, Michael; Huber, Peter E.; Debus, Jürgen; Karger, Christian P.

    2014-09-01

    Purpose: To measure the relative biological effectiveness (RBE) of carbon ions in the rat spinal cord as a function of linear energy transfer (LET). Methods and Materials: As an extension of a previous study, the cervical spinal cord of rats was irradiated with single doses of carbon ions at 6 positions of a 6-cm spread-out Bragg peak (16-99 keV/μm). The TD{sub 50} values (dose at 50% complication probability) were determined according to dose-response curves for the development of paresis grade 2 within an observation time of 300 days. The RBEs were calculated using TD{sub 50} for photons of our previous study. Results: Minimum latency time was found to be dose-dependent, but not significantly LET-dependent. The TD{sub 50} values for the onset of paresis grade 2 within 300 days were 19.5 ± 0.4 Gy (16 keV/μm), 18.4 ± 0.4 Gy (21 keV/μm), 17.7 ± 0.3 Gy (36 keV/μm), 16.1 ± 1.2 Gy (45 keV/μm), 14.6 ± 0.5 Gy (66 keV/μm), and 14.8 ± 0.5 Gy (99 keV/μm). The corresponding RBEs increased from 1.26 ± 0.05 (16 keV/μm) up to 1.68 ± 0.08 at 66 keV/μm. Unexpectedly, the RBE at 99 keV/μm was comparable to that at 66 keV/μm. Conclusions: The data suggest a linear relation between RBE and LET at high doses for late effects in the spinal cord. Together with additional data from ongoing fractionated irradiation experiments, these data will provide an extended database to systematically benchmark RBE models for further improvements of carbon ion treatment planning.

  4. Asiaticoside attenuates the effects of spinal cord injury through antioxidant and anti‑inflammatory effects, and inhibition of the p38‑MAPK mechanism.

    PubMed

    Luo, Yang; Fu, Changfeng; Wang, Zhenyu; Zhang, Zhuo; Wang, Hongxia; Liu, Yi

    2015-12-01

    Asiaticoside has potent pharmacological activity and broader pharmacological effects, including anti‑oxidant, antidepressant and hepatic protection effects, and the inhibition of tumor cell proliferation. However, the mechanism underlying the effects of asiaticoside on neurological pain in spinal cord injury (SCI) remain to be fully elucidated. Therefore, the present study investigated the specific mechanism underlying the beneficial action of asiaticoside in a SCI rat model. In the present study, Basso, Beattie and Bresnahan scores was determined to analyze the therapeutic effects of asiaticoside on the neurological function of the SCI rat model. The water content of the spinal cord was also determined to measure its effects on the SCI rats. Oxidative stress, levels of nitric oxide and inflammation were detected using commercial kits. Western blot analysis was used to measure the protein expression levels of p38‑mitogen‑activated protein kinase (MAPK) in the SCI rat. Asiaticoside effectively augmented the Basso, Beattie and Bresnahan scores of the SCI rats. Significant reductions in the water content of the spinal cord, the levels of inducible nitric oxide synthase (iNOS), and the activities of the nuclear factor‑κB p65 unit, tumor necrosis factor‑α, interleukin(IL)‑1β and IL‑6 were observed in the experimental animals. Furthermore, on examination of the oxidative stress‑associated parameters, increased production of malondialdehyde and decreased levels of superoxide dismutase, glutathione and glutathione peroxidase were detected in the SCI rat model. Asiaticoside also significantly suppressed the expression of p38‑MAPK, which indicated that the therapeutic effects of asiaticoside may be associated with the p38‑MAPK pathway. These data confirmed that asiaticoside attenuates SCI through antioxidant and anti‑inflammatory effects, and through inhibition of the p38‑MAPK mechanism. PMID:26458544

  5. Asiaticoside attenuates the effects of spinal cord injury through antioxidant and anti‑inflammatory effects, and inhibition of the p38‑MAPK mechanism.

    PubMed

    Luo, Yang; Fu, Changfeng; Wang, Zhenyu; Zhang, Zhuo; Wang, Hongxia; Liu, Yi

    2015-12-01

    Asiaticoside has potent pharmacological activity and broader pharmacological effects, including anti‑oxidant, antidepressant and hepatic protection effects, and the inhibition of tumor cell proliferation. However, the mechanism underlying the effects of asiaticoside on neurological pain in spinal cord injury (SCI) remain to be fully elucidated. Therefore, the present study investigated the specific mechanism underlying the beneficial action of asiaticoside in a SCI rat model. In the present study, Basso, Beattie and Bresnahan scores was determined to analyze the therapeutic effects of asiaticoside on the neurological function of the SCI rat model. The water content of the spinal cord was also determined to measure its effects on the SCI rats. Oxidative stress, levels of nitric oxide and inflammation were detected using commercial kits. Western blot analysis was used to measure the protein expression levels of p38‑mitogen‑activated protein kinase (MAPK) in the SCI rat. Asiaticoside effectively augmented the Basso, Beattie and Bresnahan scores of the SCI rats. Significant reductions in the water content of the spinal cord, the levels of inducible nitric oxide synthase (iNOS), and the activities of the nuclear factor‑κB p65 unit, tumor necrosis factor‑α, interleukin(IL)‑1β and IL‑6 were observed in the experimental animals. Furthermore, on examination of the oxidative stress‑associated parameters, increased production of malondialdehyde and decreased levels of superoxide dismutase, glutathione and glutathione peroxidase were detected in the SCI rat model. Asiaticoside also significantly suppressed the expression of p38‑MAPK, which indicated that the therapeutic effects of asiaticoside may be associated with the p38‑MAPK pathway. These data confirmed that asiaticoside attenuates SCI through antioxidant and anti‑inflammatory effects, and through inhibition of the p38‑MAPK mechanism.

  6. Transection of Radioactive Seeds in Breast Specimens.

    PubMed

    Gilcrease, Michael Z; Dogan, Basak E; Black, Dalliah M; Contreras, Alejandro; Dryden, Mark J; Jimenez, Sandra M

    2016-10-01

    Radioactive seed localization is a new procedure for localizing breast lesions that has several advantages over the standard wire-localization procedure. It is reported to be safe for both patients and medical personnel. Although it is theoretically possible to transect the titanium-encapsulated seed while processing the breast specimen in the pathology laboratory, the likelihood of such an event is thought to be exceedingly low. In fact, there are no previous reports of such an event in the literature to date. We recently encountered 2 cases in which a radioactive seed was inadvertently transected while slicing a breast specimen at the grossing bench. In this report, we describe each case and offer recommendations for minimizing radioactive exposure to personnel and for preventing radioactive contamination of laboratory equipment. PMID:27627744

  7. [Forest soil organic matter delta 13C along a altitudinal transect on northern slope of Changbai Mountains under effects of simulated warming].

    PubMed

    Fan, Jin-juan; Meng, Xian-jing; Zhang, Xin-yu; Sun, Xiao-min; Gao, Lu-peng

    2010-07-01

    The litters, bulk soils, and soil particle-size fractions were sampled from three typical natural forests, i.e., broadleaf Korean pine (Pinus koraiensis) mixed forest (PB, altitude 740 m), spruce-fir (Picea asperata-Abies nephrolepis) forest (SF, altitude 1350 m), and Erman's birch (Betula ermanii) forest (EB, altitude 1996 m), on the northern slope of Changbai Mountains to analyze their organic matter delta13C values, and the intact soil cores (20 cm depth) from EB (high altitude) were relocated to PB and SF (low altitudes) for a year to study the responses of the delta13C values to simulated warming. It was shown that the litters had a significantly lower delta13C value than the soils, and the delta13C values of the litters and soils increased downward through the litter- and soil layers in all the three typical forest types. Soil particle-size fractions had an increased delta13C value with decreasing particle size fractions. The delta13C value of the litters was in the order of SF (-28.3 per thousand) >PB (-29.0 per thousand) >EB (-29.6 per thousand), while that of the soils was in the order of EB (-25.5 per thousand) >PB (-25.8 per thousand) >SF (-26.2 per thousand). Over one-year soil warming (an increment of 0.7 degrees C - 2.9 degrees C) , the delta13C values of the bulk soils and soil particle-size fractions all presented a decreasing trend, and the decrement of the delta13C value was larger in <2 microm (0.48 per thousand) and 2-63 microm fractions (0.47 per thousand) than in >63 microm fraction (0.33 per thousand). The results suggested that climate warming could have great effects on the older organic carbon associated with fine soil particle-size fractions.

  8. Bombing Target Identification from Limited Transect Data

    SciTech Connect

    Roberts, Barry L.; Hathaway, John E.; Pulsipher, Brent A.; McKenna, Sean A.

    2006-08-07

    A series of sensor data combined with geostatistical techniques were used to determine likely target areas for a historic military aerial bombing range. Primary data consisted of magnetic anomaly information from limited magnetometer transects across the site. Secondary data included airborne LIDAR, orthophotography, and other general site characterization information. Identification of likely target areas relied primarily upon kriging estimates of magnetic anomaly densities across the site. Secondary information, such as impact crater locations, was used to refine the boundary delineations.

  9. Rodent Models and Behavioral Outcomes of Cervical Spinal Cord Injury

    PubMed Central

    Geissler, Sydney A.; Schmidt, Christine E.; Schallert, Timothy

    2014-01-01

    Rodent spinal cord injury (SCI) models have been developed to examine functional and physiological deficits after spinal cord injury with the hope that these models will elucidate information about human SCI. Models are needed to examine possible treatments and to understand histopathology after SCI; however, they should be considered carefully and chosen based on the goals of the study being performed. Contusion, compression, transection, and other models exist and have the potential to reveal important information about SCI that may be related to human SCI and the outcomes of treatment and timing of intervention. PMID:25309824

  10. Assisted ejaculation combined with in vitro fertilisation: an effective technique treating male infertility due to spinal cord injury.

    PubMed

    Hultling, C; Levi, R; Garoff, L; Nylund, L; Rosenborg, L; Sjöblom, P; Hillensjö, T

    1994-07-01

    Infertility due to spinal cord injury (SCI) in males has been identified for decades as an area of major concern and techniques for assisted ejaculation are available. There has not been an overall consensus regarding which type of assisted procreation is the most appropriate for these couples. We describe here our experience from a programme based on assisted ejaculation combined with in vitro fertilization (IVF). Twelve couples have been treated so far and altogether 22 cycles with ovum pick-up have been completed. Fertilisation of the oocytes was obtained in 18 of these cycles. The overall oocyte fertilisation rate was 49%. Embryo transfer took place in 17 cycles, leading to seven clinical pregnancies. Four of the pregnancies are delivered or are ongoing, whereas three ended in first trimester spontaneous abortion. Thus our initial experience suggests that assisted ejaculation in combination with IVF is an effective option for these couples.

  11. Independent evaluation of the anatomical and behavioral effects of Taxol in rat models of spinal cord injury.

    PubMed

    Popovich, Phillip G; Tovar, C Amy; Lemeshow, Stanley; Yin, Qin; Jakeman, Lyn B

    2014-11-01

    The goal of the current manuscript was to replicate published data that show intrathecal infusions of Taxol® (paclitaxel), an anti-neoplastic microtubule stabilizing agent, reduce fibrogliotic scarring caused by a dorsal spinal hemisection (DHx) injury and increase functional recovery and growth of serotonergic axons after moderate spinal contusion injury. These experiments were completed as part of an NIH-NINDS contract entitled "Facilities of Research Excellence in Spinal Cord Injury (FORE-SCI) - Replication". Here, data are presented that confirm the anti-scarring effects of Taxol after DHx injury; however, Taxol did not confer neuroprotection or promote serotonergic axon growth nor did it improve functional recovery in a model of moderate spinal contusion injury. Thus, only partial replication was achieved. Possible explanations for disparate results in our studies and published data are discussed. PMID:24999028

  12. The Adjustment Process for Individuals with Spinal Cord Injury: The Effect of Perceived Premorbid Sense of Coherence

    ERIC Educational Resources Information Center

    Lustig, Daniel C.

    2005-01-01

    This study investigated the relationship between perceived changes in sense of coherence from pre- to postinjury and adjustment for a group of individuals with spinal cord injury. It was hypothesized that after a spinal cord injury, an individual's belief that he or she had significantly reduced his or her sense of coherence would be associated…

  13. Evaluation of Early and Late Effects into the Acute Spinal Cord Injury of an Injectable Functionalized Self-Assembling Scaffold

    PubMed Central

    Cigognini, Daniela; Satta, Alessandro; Colleoni, Bianca; Silva, Diego; Donegà, Matteo; Antonini, Stefania; Gelain, Fabrizio

    2011-01-01

    The complex physiopathological events occurring after spinal cord injury (SCI) make this devastating trauma still incurable. Self-assembling peptides (SAPs) are nanomaterials displaying some appealing properties for application in regenerative medicine because they mimic the structure of the extra-cellular matrix (ECM), are reabsorbable, allow biofunctionalizations and can be injected directly into the lesion. In this study we evaluated the putative neurorigenerative properties of RADA16-4G-BMHP1 SAP, proved to enhance in vitro neural stem cells survival and differentiation. This SAP (RADA16-I) has been functionalized with a bone marrow homing motif (BMHP1) and optimized via the insertion of a 4-glycine-spacer that ameliorates scaffold stability and exposure of the biomotifs. We injected the scaffold immediately after contusion in the rat spinal cord, then we evaluated the early effects by semi-quantitative RT-PCR and the late effects by histological analysis. Locomotor recovery over 8 weeks was assessed using Basso, Beattie, Bresnahan (BBB) test. Gene expression analysis showed that at 7 days after lesion the functionalized SAP induced a general upregulation of GAP-43, trophic factors and ECM remodelling proteins, whereas 3 days after SCI no remarkable changes were observed. Hystological analysis revealed that 8 weeks after SCI our scaffold increased cellular infiltration, basement membrane deposition and axon regeneration/sprouting within the cyst. Moreover the functionalized SAP showed to be compatible with the surrounding nervous tissue and to at least partially fill the cavities. Finally SAP injection resulted in a statistically significant improvement of both hindlimbs' motor performance and forelimbs-hindlimbs coordination. Altogether, these results indicate that RADA16-4G-BMHP1 induced favourable reparative processes, such as matrix remodelling, and provided a physical and trophic support to nervous tissue ingrowth. Thus this biomaterial, eventually

  14. Assessment of the Neuroprotective Effects of Lavandula angustifolia Extract on the Contusive Model of Spinal Cord Injury in Wistar Rats

    PubMed Central

    Kaka, Gholamreza; Yaghoobi, Kayvan; Davoodi, Shaghayegh; Hosseini, Seyed R.; Sadraie, Seyed H.; Mansouri, Korosh

    2016-01-01

    Introduction: Spinal cord injury (SCI) involves a primary trauma and secondary cellular processes that can lead to severe damage to the nervous system, resulting in long-term spinal deficits. At the cellular level, SCI causes astrogliosis, of which glial fibrillary acidic protein (GFAP) is a major index. Objective: The aim of this study was to investigate the neuroprotective effects of Lavandula angustifolia (Lav) on the repair of spinal cord injuries in Wistar rats. Materials and Methods: Forty-five female rats were randomly divided into six groups of seven rats each: the intact, sham, control (SCI), Lav 100, Lav 200, and Lav 400 groups. Every week after SCI onset, all animals were evaluated for behavior outcomes by the Basso, Beattie, and Bresnahan (BBB) score. H&E staining was performed to examine the lesions post-injury. GFAP expression was assessed for astrogliosis. Somatosensory evoked potential (SEP) testing was performed to detect the recovery of neural conduction. Results: BBB scores were significantly increased and delayed responses on sensory tests were significantly decreased in the Lav 200 and Lav 400 groups compared to the control group. The greatest decrease of GFAP was evident in the Lav 200 and Lav 400 groups. EMG results showed significant improvement in the hindlimbs in the Lav 200 and Lav 400 groups compared to the control group. Cavity areas significantly decreased and the number of ventral motor neurons significantly increased in the Lav 200 and Lav 400 groups. Conclusion: Lav at doses of 200 and 400 mg/kg can promote structural and functional recovery after SCI. The neuroprotective effects of L. angustifolia can lead to improvement in the contusive model of SCI in Wistar rats. PMID:26903793

  15. Early applied electric field stimulation attenuates secondary apoptotic responses and exerts neuroprotective effects in acute spinal cord injury of rats.

    PubMed

    Zhang, C; Zhang, G; Rong, W; Wang, A; Wu, C; Huo, X

    2015-04-16

    Injury potential, which refers to a direct current voltage between intact and injured nerve ends, is mainly caused by injury-induced Ca2+ influx. Our previous studies revealed that injury potential increased with the onset and severity of spinal cord injury (SCI), and an application of applied electric field stimulation (EFS) with the cathode distal to the lesion could delay and attenuate injury potential formation. As Ca2+ influx is also considered as a major trigger for secondary injury after SCI, we hypothesize that EFS would protect an injured spinal cord from secondary injury and consequently improve functional and pathological outcomes. In this study, rats were divided into three groups: (1) sham group, laminectomy only; (2) control group, subjected to SCI only; and (3) EFS group, received EFS immediately post-injury with the injury potential modulated to 0±0.5 mV by EFS. Functional recovery of the hind limbs was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. Results revealed that EFS-treated rats exhibited significantly better locomotor function recovery. Luxol fast blue staining was performed to assess the spared myelin area. Immunofluorescence was used to observe the number of myelinated nerve fibers. Ultrastructural analysis was performed to evaluate the size of myelinated nerve fibers. Findings showed that the EFS group rats exhibited significantly less myelin loss and had larger and more myelinated nerve fibers than the control group rats in dorsal corticospinal tract (dCST) 8 weeks after SCI. Furthermore, we found that EFS inhibited the activation of calpain and caspase-3, as well as the expression of Bax, as detected by Western blot analysis. Moreover, EFS decreased cellular apoptosis, as measured by TUNEL, within 4 weeks post-injury. Results suggest that early EFS could significantly reduce spinal cord degeneration and improve functional and historical recovery. Furthermore, these neuroprotective effects may be related to

  16. MASCIS evaluation of open field locomotor scores: effects of experience and teamwork on reliability. Multicenter Animal Spinal Cord Injury Study.

    PubMed

    Basso, D M; Beattie, M S; Bresnahan, J C; Anderson, D K; Faden, A I; Gruner, J A; Holford, T R; Hsu, C Y; Noble, L J; Nockels, R; Perot, P L; Salzman, S K; Young, W

    1996-07-01

    The Multicenter Animal Spinal Cord Injury Study (MASCIS) adopted a modified 21-point open field locomotor scale developed by Basso, Beattie, and Bresnahan (BBB) at Ohio State University (OSU) to measure motor recovery in spinal-injured rats. BBB scores categorize combinations of rat hindlimb movements, trunk position and stability, stepping, coordination, paw placement, toe clearance, and tail position, representing sequential recovery stages that rats attain after spinal cord injury. A total of 22 observers from 8 participating centers assessed 18 hindlimbs of 9 rats at 2-6 weeks after graded spinal cord injury. The observers were segregated into 10 teams. The teams were grouped into 3 cohorts (A, B, and C), consisting of one experienced team from OSU and two non-OSU teams. The cohorts evaluated the rats in three concurrent and sequential sessions. After viewing a rat for 4 min, individual observers first assigned scores without discussion. Members of each team then discussed and assigned a team score. Experience (OSU vs. non-OSU) and teamwork (individual vs. team) had no significant effect on mean scores although the mean scores of one cohort differed significantly from the others (p = 0.0002, ANOVA). However, experience and teamwork significantly influenced reliability of scoring. OSU team scores had a mean standard deviation or discordance of 0.59 points, significantly less than 1.31 points for non-OSU team scores (p = 0.003, ANOVA) and 1.30 points for non-OSU individual scores (p = 0.001, ANOVA). Discordances were greater at the upper and lower ends of the scale, exceeding 2.0 in the lower (< 5) and upper (> 15) ends of the scale but were < 1.0 for scores between 4 and 16. Comparisons of non-OSU and OSU team scores indicated a high reliability coefficient of 0.892 and a correlation index (r2) of 0.894. These results indicate that inexperienced observers can learn quickly to assign consistent BBB scores that approach those given by experienced teams, that the

  17. The effect of fractionated doses of radiation on mouse spinal cord

    SciTech Connect

    Lo, Y.C. Memorial Sloan-Kettering Cancer Center, New York, NY ); Taylor, J.M.G.; McBridge, W.H.; Withers, H.R. )

    1993-09-20

    The purpose was to determine: (a) the dose-response relationship and latent time to paralysis following fractionated doses of radiation in mice, (b) the values of parameters for isoeffect curves, and (c) whether these parameters depend on the size of dose per fraction and the severity of injury. The spinal cords (T[sub 9]-L[sub 5]) of 608 C[sub 3]Hf/Sed/Kam mice were irradiated with fractionated doses of x-radiation. Three levels of neurological damage were used to grade the spinal cord response. Animals which did not develop paralysis were observed for at least 18 months after irradiation. The fractionated schedules consisted of either 2, 3, 4, 6, 10, or 20 fractions in addition to single doses. For the fractionated regimes the daily fraction size ranged from 2 Gy to 24 Gy, and for single doses the range was 12 Gy to 52 Gy. Both the latent time to paralysis and the incidence of paralysis were considered as endpoints. For analysis of the sparing associated with fractionation, the dose points were divided into two groups: a [open quotes]low damage[close quotes] group consisting of doses of near or less than the ED[sub 50] at 450 days and a [open quotes]high damage[close quotes] group consisting of doses much larger than the ED[sub 50] at 450 days in which there was 100% incidence of paralysis. The latent time depended on the radiation dose; for each fixed fraction number the latent period became progressively shorter with higher total doses. Differences in histology in fractionation sensitivity are observed between the two groups. The low damage data in each fractionation treatment are the important data in the analysis of long-term incidence of paralysis. On the other hand, the high damage data were emphasized for the analysis of latency. Three statistical methods (mixture model, Cox model, and Fe-plot) were used to fit the linear-quadratic dose response model and the [open quotes]Nominal Standard Dose[close quotes] (NSD) model. 29 refs., 4 figs., 5 tabs.

  18. An effective strategy of magnetic stem cell delivery for spinal cord injury therapy

    NASA Astrophysics Data System (ADS)

    Tukmachev, Dmitry; Lunov, Oleg; Zablotskii, Vitalii; Dejneka, Alexandr; Babic, Michal; Syková, Eva; Kubinová, Šárka

    2015-02-01

    Spinal cord injury (SCI) is a condition that results in significant mortality and morbidity. Treatment of SCI utilizing stem cell transplantation represents a promising therapy. However, current conventional treatments are limited by inefficient delivery strategies of cells into the injured tissue. In this study, we designed a magnetic system and used it to accumulate stem cells labelled with superparamagnetic iron oxide nanoparticles (SPION) at a specific site of a SCI lesion. The loading of stem cells with engineered SPIONs that guarantees sufficient attractive magnetic forces was achieved. Further, the magnetic system allowed rapid guidance of the SPION-labelled cells precisely to the lesion location. Histological analysis of cell distribution throughout the cerebrospinal channel showed a good correlation with the calculated distribution of magnetic forces exerted onto the transplanted cells. The results suggest that focused targeting and fast delivery of stem cells can be achieved using the proposed non-invasive magnetic system. With future implementation the proposed targeting and delivery strategy bears advantages for the treatment of disease requiring fast stem cell transplantation.Spinal cord injury (SCI) is a condition that results in significant mortality and morbidity. Treatment of SCI utilizing stem cell transplantation represents a promising therapy. However, current conventional treatments are limited by inefficient delivery strategies of cells into the injured tissue. In this study, we designed a magnetic system and used it to accumulate stem cells labelled with superparamagnetic iron oxide nanoparticles (SPION) at a specific site of a SCI lesion. The loading of stem cells with engineered SPIONs that guarantees sufficient attractive magnetic forces was achieved. Further, the magnetic system allowed rapid guidance of the SPION-labelled cells precisely to the lesion location. Histological analysis of cell distribution throughout the cerebrospinal

  19. Complete Spinal Cord Injury and Brain Dissection Protocol for Subsequent Wholemount In Situ Hybridization in Larval Sea Lamprey

    PubMed Central

    Barreiro-Iglesias, Antón; Zhang, Guixin; Selzer, Michael E.; Shifman, Michael I.

    2014-01-01

    After a complete spinal cord injury, sea lampreys at first are paralyzed below the level of transection. However, they recover locomotion after several weeks, and this is accompanied by short distance regeneration (a few mm) of propriospinal axons and spinal-projecting axons from the brainstem. Among the 36 large identifiable spinal-projecting neurons, some are good regenerators and others are bad regenerators. These neurons can most easily be identified in wholemount CNS preparations. In order to understand the neuron-intrinsic mechanisms that favor or inhibit axon regeneration after injury in the vertebrates CNS, we determine differences in gene expression between the good and bad regenerators, and how expression is influenced by spinal cord transection. This paper illustrates the techniques for housing larval and recently transformed adult sea lampreys in fresh water tanks, producing complete spinal cord transections under microscopic vision, and preparing brain and spinal cord wholemounts for in situ hybridization. Briefly, animals are kept at 16 °C and anesthetized in 1% Benzocaine in lamprey Ringer. The spinal cord is transected with iridectomy scissors via a dorsal approach and the animal is allowed to recover in fresh water tanks at 23 °C. For in situ hybridization, animals are reanesthetized and the brain and cord removed via a dorsal approach. PMID:25350040

  20. Effects of estrogen on functional and neurological recovery after spinal cord injury: An experimental study with rats

    PubMed Central

    Letaif, Olavo Biraghi; Cristante, Alexandre Fogaça; de Barros Filho, Tarcísio Eloy Pessoa; Ferreira, Ricardo; dos Santos, Gustavo Bispo; da Rocha, Ivan Dias; Marcon, Raphael Martus

    2015-01-01

    OBJECTIVES: To evaluate the functional and histological effects of estrogen as a neuroprotective agent after a standard experimentally induced spinal cord lesion. METHODS: In this experimental study, 20 male Wistar rats were divided into two groups: one group with rats undergoing spinal cord injury (SCI) at T10 and receiving estrogen therapy with 17-beta estradiol (4mg/kg) immediately following the injury and after the placement of skin sutures and a control group with rats only subjected to SCI. A moderate standard experimentally induced SCI was produced using a computerized device that dropped a weight on the rat's spine from a height of 12.5 mm. Functional recovery was verified with the Basso, Beattie and Bresnahan scale on the 2nd, 7th, 14th, 21st, 28th, 35th and 42nd days after injury and by quantifying the motor-evoked potential on the 42nd day after injury. Histopathological evaluation of the SCI area was performed after euthanasia on the 42nd day. RESULTS: The experimental group showed a significantly greater functional improvement from the 28th to the 42nd day of observation compared to the control group. The experimental group showed statistically significant improvements in the motor-evoked potential compared with the control group. The results of pathological histomorphometry evaluations showed a better neurological recovery in the experimental group, with respect to the proportion and diameter of the quantified nerve fibers. CONCLUSIONS: Estrogen administration provided benefits in neurological and functional motor recovery in rats with SCI beginning at the 28th day after injury. PMID:26598084

  1. Beneficial Effect of Human Induced Pluripotent Stem Cell-Derived Neural Precursors in Spinal Cord Injury Repair.

    PubMed

    Romanyuk, Nataliya; Amemori, Takashi; Turnovcova, Karolina; Prochazka, Pavel; Onteniente, Brigitte; Sykova, Eva; Jendelova, Pavla

    2015-01-01

    Despite advances in our understanding and research of induced pluripotent stem cells (iPSCs), their use in clinical practice is still limited due to lack of preclinical experiments. Neural precursors (NPs) derived from a clone of human iPSCs (IMR90) were used to treat a rat spinal cord lesion 1 week after induction. Functional recovery was evaluated using the BBB, beam walking, rotarod, and plantar tests. Lesion morphology, endogenous axonal sprouting, graft survival, and iPSC-NP differentiation were analyzed immunohistochemically. Quantitative polymerase chain reaction (qPCR) was used to evaluate the effect of transplanted iPSC-NPs on endogenous regenerative processes and also to monitor their behavior after transplantation. Human iPSC-NPs robustly survived in the lesion, migrated, and partially filled the lesion cavity during the entire period of observation. Transplanted animals displayed significant motor improvement already from the second week after the transplantation of iPSC-NPs. qPCR revealed the increased expression of human neurotrophins 8 weeks after transplantation. Simultaneously, the white and gray matter were spared in the host tissue. The grafted cells were immunohistochemically positive for doublecortin, MAP2, βIII-tubulin, GFAP, and CNPase 8 weeks after transplantation. Human iPSC-NPs further matured, and 17 weeks after transplantation differentiated toward interneurons, dopaminergic neurons, serotoninergic neurons, and ChAT-positive motoneurons. Human iPSC-NPs possess neurotrophic properties that are associated with significant early functional improvement and the sparing of spinal cord tissue. Their ability to differentiate into tissue-specific neurons leads to the long-term restoration of the lesioned tissue, making the cells a promising candidate for future cell-based therapy of SCI. PMID:25259685

  2. Presynaptic and postsynaptic effects of local cathodal DC polarization within the spinal cord in anaesthetized animal preparations

    PubMed Central

    Bolzoni, F; Jankowska, E

    2015-01-01

    The present study aimed to compare presynaptic and postsynaptic actions of direct current polarization in the spinal cord, focusing on DC effects on primary afferents and motoneurons. To reduce the directly affected spinal cord region, a weak polarizing direct current (0.1–0.3 μA) was applied locally in deeply anaesthetized cats and rats; within the hindlimb motor nuclei in the caudal lumbar segments, or in the dorsal horn within the terminal projection area of low threshold skin afferents. Changes in the excitability of primary afferents activated by intraspinal stimuli (20–50 μA) were estimated using increases or decreases in compound action potentials recorded from the dorsal roots or peripheral nerves as their measure. Changes in the postsynaptic actions of the afferents were assessed from intracellularly recorded monosynaptic EPSPs in hindlimb motoneurons and monosynaptic extracellular field potentials (evoked by group Ia afferents in motor nuclei, or by low threshold cutaneous afferents in the dorsal horn). The excitability of motoneurons activated by intraspinal stimuli was assessed using intracellular records or motoneuronal discharges recorded from a ventral root or a muscle nerve. Cathodal polarization was found to affect motoneurons and afferents providing input to them to a different extent. The excitability of both was markedly increased during DC application, although post-polarization facilitation was found to involve presynaptic afferents and some of their postsynaptic actions, but only negligibly motoneurons themselves. Taken together, these results indicate that long-lasting post-polarization facilitation of spinal activity induced by locally applied cathodal current primarily reflects the facilitation of synaptic transmission. PMID:25416625

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

    USGS Publications Warehouse

    Ostrand, W.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.

  4. Exercise therapy after spinal cord injury: the effects on heath and function.

    PubMed

    Ditor, David S; Hicks, Audrey L

    2009-01-01

    Individuals with spinal cord injury (SCI) are susceptible to an array of secondary health complications. Some of these health concerns are attributable to the SCI per se, but many are secondary to the resulting immobility. For example, the incidence of pressure ulcers, type 2 diabetes, and cardiovascular disease are greatly increased in this population. Despite the need for exercise training as a means to reverse these health risks, individuals with SCI have traditionally been one of the most inactive segments of society. Physical activity programs and information about how activity can promote health are two of the services most desired but least available to people with SCI. Recently, efforts have been made to increase exercise options for individuals with SCI and to study the health benefits of exercise in this population. Accessible resistance and aerobic exercise training, functional electrically stimulated exercise, and body weight-supported treadmill training have all shown promise as ways to reverse some of the physiological consequences of SCI. Future research will determine whether these physiological adaptations actually translate to a long-term reduction in disease and mortality.

  5. Protective effects of gallic acid against spinal cord injury-induced oxidative stress.

    PubMed

    Yang, Yong Hong; Wang, Zao; Zheng, Jie; Wang, Ran

    2015-08-01

    The present study aimed to investigate the role of gallic acid in oxidative stress induced during spinal cord injury (SCI). In order to measure oxidative stress, the levels of lipid peroxide, protein carbonyl, reactive oxygen species and nitrates/nitrites were determined. In addition, the antioxidant status during SCI injury and the protective role of gallic acid were investigated by determining glutathione levels as well as the activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase. Adenosine triphophatase (ATPase) enzyme activities were determined to evaluate the role of gallic acid in SCI-induced deregulation of the activity of enzymes involved in ion homeostasis. The levels of inflammatory markers such as nuclear factor (NF)-κB and cycloxygenase (COX)-2 were determined by western blot analysis. Treatment with gallic acid was observed to significantly mitigate SCI-induced oxidative stress and the inflammatory response by reducing the oxidative stress, decreasing the expression of NF-κB and COX-2 as well as increasing the antioxidant status of cells. In addition, gallic acid modulated the activity of ATPase enzymes. Thus the present study indicated that gallic acid may have a role as a potent antioxidant and anti-inflammatory agent against SCI.

  6. The effect of spinal cord injury on the neurochemical properties of vagal sensory neurons

    PubMed Central

    Herrity, April N.; Petruska, Jeffrey C.; Stirling, David P.; Rau, Kristofer K.

    2015-01-01

    The vagus nerve is composed primarily of nonmyelinated sensory neurons whose cell bodies are located in the nodose ganglion (NG). The vagus has widespread projections that supply most visceral organs, including the bladder. Because of its nonspinal route, the vagus nerve itself is not directly damaged from spinal cord injury (SCI). Because most viscera, including bladder, are dually innervated by spinal and vagal sensory neurons, an impact of SCI on the sensory component of vagal circuitry may contribute to post-SCI visceral pathologies. To determine whether SCI, in male Wistar rats, might impact neurochemical characteristics of NG neurons, immunohistochemical assessments were performed for P2X3 receptor expression, isolectin B4 (IB4) binding, and substance P expression, three known injury-responsive markers in sensory neuronal subpopulations. In addition to examining the overall population of NG neurons, those innervating the urinary bladder also were assessed separately. All three of the molecular markers were represented in the NG from noninjured animals, with the majority of the neurons binding IB4. In the chronically injured rats, there was a significant increase in the number of NG neurons expressing P2X3 and a significant decrease in the number binding IB4 compared with noninjured animals, a finding that held true also for the bladder-innervating population. Overall, these results indicate that vagal afferents, including those innervating the bladder, display neurochemical plasticity post-SCI that may have implications for visceral homeostatic mechanisms and nociceptive signaling. PMID:25855310

  7. The effect of spinal cord injury on the neurochemical properties of vagal sensory neurons.

    PubMed

    Herrity, April N; Petruska, Jeffrey C; Stirling, David P; Rau, Kristofer K; Hubscher, Charles H

    2015-06-15

    The vagus nerve is composed primarily of nonmyelinated sensory neurons whose cell bodies are located in the nodose ganglion (NG). The vagus has widespread projections that supply most visceral organs, including the bladder. Because of its nonspinal route, the vagus nerve itself is not directly damaged from spinal cord injury (SCI). Because most viscera, including bladder, are dually innervated by spinal and vagal sensory neurons, an impact of SCI on the sensory component of vagal circuitry may contribute to post-SCI visceral pathologies. To determine whether SCI, in male Wistar rats, might impact neurochemical characteristics of NG neurons, immunohistochemical assessments were performed for P2X3 receptor expression, isolectin B4 (IB4) binding, and substance P expression, three known injury-responsive markers in sensory neuronal subpopulations. In addition to examining the overall population of NG neurons, those innervating the urinary bladder also were assessed separately. All three of the molecular markers were represented in the NG from noninjured animals, with the majority of the neurons binding IB4. In the chronically injured rats, there was a significant increase in the number of NG neurons expressing P2X3 and a significant decrease in the number binding IB4 compared with noninjured animals, a finding that held true also for the bladder-innervating population. Overall, these results indicate that vagal afferents, including those innervating the bladder, display neurochemical plasticity post-SCI that may have implications for visceral homeostatic mechanisms and nociceptive signaling. PMID:25855310

  8. Effects of Hypoxia and Chitosan on Equine Umbilical Cord-Derived Mesenchymal Stem Cells

    PubMed Central

    Cho, J.; Wagoner Johnson, A.

    2016-01-01

    Chitosan opens new perspectives in regenerative medicine as it enhances the properties of mesenchymal stem cells (MSCs) through formation of spheroids. Hypoxia has also been proposed to enhance stemness and survival of MSCs after in vivo implantation. These characteristics are relevant to the development of an off-the-shelf source of allogenic cells for regenerative therapy of tendinopathies. Umbilical cord-derived MSCs (UCM-MSCs) offer an abundant source of immature and immunoprivileged stem cells. In this study, equine UCM-MSCs (eqUCM-MSCs) conditioned for 3 and 7 days on chitosan films at 5% oxygen were compared to eqUCM-MSCs under standard conditions. Equine UCM-MSCs formed spheroids on chitosan but yielded 72% less DNA than standard eqUCM-MSCs. Expression of Sox2, Oct4, and Nanog was 4 to 10 times greater in conditioned cells at day 7. Fluorescence-labeled cells cultured for 7 days under standard conditions or on chitosan films under hypoxia were compared in a bilateral patellar tendon defect model in rats. Fluorescence was present in all treated tendons, but the modulus of elasticity under tension was greater in tendons treated with conditioned cells. Chitosan and hypoxia affected cell yield but improved the stemness of eqUCM-MSCs and their contribution to the healing of tissues. Given the abundance of allogenic cells, these properties are highly relevant to clinical applications and outweigh the negative impact on cell proliferation. PMID:27379167

  9. [Modulating effect of dopamine on amplitude of GABA-produced chemocontrolled currents in multipolar spinal cord neurons of ammocaete].

    PubMed

    Bukinich, A A

    2010-01-01

    By using the patch-clamp method in the whole cell configuration, modulating effect of dopamine on GABA-activated currents has been studied on isolated multipolar spinal cord neurons of the ammocaete (larva of the lamprey Lampetra planeri). At application of dopamine (5 microM), there was observed in some cases a decrease of the GABA-activated current, on average, by 33.3 +/- 8.7 (n = 8, p < 0.01), in other cases--an increase of the amplitude, on average, by 37.3 +/- 11.8% (n = 5, p < 0.01). Concentration of GABA amounted to 2 mM. Study of action of agonists of D1- and D2-receptors on amplitude of che-mocontrolled currents has shown that agonist of D1-receptors (+)-SKF-38393 (5 microM) decreases the GABA-activated current amplitude, on average, by 63.1 +/- 11.7% (n = 8, p < 0.01); the agonist of D2-receptors (-)-quinpirole (5 microM) produces in various cells the dopamine-like effects: an increase of the GABA-activated current amplitude, on average, by 61.0 +/- 13.8% (n = 8, p < 0.01) and a decrease of amplitude, on average, by 55.7 +/- 2.0 % (n = 6, p < 0.01). It has been shown that antagonist of D2-receptors sulpiride (5 microM) does not block effects produced by dopamine. The dopamine effects were partially blocked by antagonist of D1-receptors (+)-SCH-23390 (5 microM): a decrease of the GABA-activated amplitude current amounted, on average, to 11.7 +/- 1.8 % (n = 7, p < 0.01), while an increase of amplitude--8.3 +/- 2.0 % (n = 5,p < 0.01). At the same time, effects of agonist of D1-receptors quinpirole (5 microM) were partially blocked by antagonist of D1-receptors (+)-SCH-23390: a decrease of the GABA-activated current amplitude amounted, on average, to 9.2 +/- 3.4 % (n = 6, p < 0.01) and an increase of amplitude--6.3 +/- 1.8 % (n = 10, p < 0.01). The obtained data indicate differences of mechanisms of the receptor-mediated effect of agonists of dopamine receptors on GABA-activated and potential-activated currents of multipolar neurons of the ammocaete spinal

  10. Therapeutic approaches for spinal cord injury

    PubMed Central

    Cristante, Alexandre Fogaça; de Barros Filho, Tarcísio Eloy Pessoa; Marcon, Raphael Martus; Letaif, Olavo Biraghi; da Rocha, Ivan Dias

    2012-01-01

    This study reviews the literature concerning possible therapeutic approaches for spinal cord injury. Spinal cord injury is a disabling and irreversible condition that has high economic and social costs. There are both primary and secondary mechanisms of damage to the spinal cord. The primary lesion is the mechanical injury itself. The secondary lesion results from one or more biochemical and cellular processes that are triggered by the primary lesion. The frustration of health professionals in treating a severe spinal cord injury was described in 1700 BC in an Egyptian surgical papyrus that was translated by Edwin Smith; the papyrus reported spinal fractures as a “disease that should not be treated.” Over the last two decades, several studies have been performed to obtain more effective treatments for spinal cord injury. Most of these studies approach a patient with acute spinal cord injury in one of four manners: corrective surgery or a physical, biological or pharmacological treatment method. Science is unraveling the mechanisms of cell protection and neuroregeneration, but clinically, we only provide supportive care for patients with spinal cord injuries. By combining these treatments, researchers attempt to enhance the functional recovery of patients with spinal cord injuries. Advances in the last decade have allowed us to encourage the development of experimental studies in the field of spinal cord regeneration. The combination of several therapeutic strategies should, at minimum, allow for partial functional recoveries for these patients, which could improve their quality of life. PMID:23070351

  11. Effect of prenatal and early life paracetamol exposure on the level of neurotransmitters in rats--Focus on the spinal cord.

    PubMed

    Blecharz-Klin, Kamilla; Joniec-Maciejak, Ilona; Jawna, Katarzyna; Pyrzanowska, Justyna; Piechal, Agnieszka; Wawer, Adriana; Widy-Tyszkiewicz, Ewa

    2015-12-01

    The present study has examined the influence of the prenatal and early life administration of paracetamol on the level of neurotransmitters in the spinal cord of rat pups. The effect of the drug was evaluated in 2-month old Wistar male rats exposed to paracetamol in doses of 5 (P5, n=9) or 15 mg/kg (P15, n=9) p.o. during the prenatal period and after birth until the completion of the second month of life. A parallel control group received tap water (Con, n=9). In this study we have determined the level of monoamines, their metabolites and amino acids in the spinal cord of rats using high performance liquid chromatography (HPLC) in the second month of life. The present experiment demonstrates the action of paracetamol at the molecular level associated with significant modulation of neurotransmission in the spinal cord related to dopaminergic and noradrenergic systems. Simultaneously, paracetamol administration increases the content of an aspartic and glutamic acids in the spinal cord at a critical time during development. PMID:26390956

  12. Transplanted astrocytes derived from BMP- or CNTF-treated glial-restricted precursors have opposite effects on recovery and allodynia after spinal cord injury

    PubMed Central

    Davies, Jeannette E; Pröschel, Christoph; Zhang, Ningzhe; Noble, Mark; Mayer-Pröschel, Margot; Davies, Stephen JA

    2008-01-01

    Background Two critical challenges in developing cell-transplantation therapies for injured or diseased tissues are to identify optimal cells and harmful side effects. This is of particular concern in the case of spinal cord injury, where recent studies have shown that transplanted neuroepithelial stem cells can generate pain syndromes. Results We have previously shown that astrocytes derived from glial-restricted precursor cells (GRPs) treated with bone morphogenetic protein-4 (BMP-4) can promote robust axon regeneration and functional recovery when transplanted into rat spinal cord injuries. In contrast, we now show that transplantation of GRP-derived astrocytes (GDAs) generated by exposure to the gp130 agonist ciliary neurotrophic factor (GDAsCNTF), the other major signaling pathway involved in astrogenesis, results in failure of axon regeneration and functional recovery. Moreover, transplantation of GDACNTF cells promoted the onset of mechanical allodynia and thermal hyperalgesia at 2 weeks after injury, an effect that persisted through 5 weeks post-injury. Delayed onset of similar neuropathic pain was also caused by transplantation of undifferentiated GRPs. In contrast, rats transplanted with GDAsBMP did not exhibit pain syndromes. Conclusion Our results show that not all astrocytes derived from embryonic precursors are equally beneficial for spinal cord repair and they provide the first identification of a differentiated neural cell type that can cause pain syndromes on transplantation into the damaged spinal cord, emphasizing the importance of evaluating the capacity of candidate cells to cause allodynia before initiating clinical trials. They also confirm the particular promise of GDAs treated with bone morphogenetic protein for spinal cord injury repair. PMID:18803859

  13. The penile erection efficacy of a new phosphodiesterase type 5 inhibitor, mirodenafil (SK3530), in rabbits with acute spinal cord injury.

    PubMed

    Jung, Ji-Youn; Kim, Sang-Ki; Kim, Byeong-Soo; Lee, Seung-Ho; Park, Young-Seok; Kim, So-Jung; Choi, Changsun; Yoon, Seong-Il; Kim, Jong-Suk; Cho, Sung-Dae; Im, Gwang-Jin; Lee, Soo-Min; Jung, Ji-Won; Lee, Yong-Soon

    2008-11-01

    Mirodenafil (SK3530) is a new potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5). Recent clinical trials have demonstrated that mirodenafil is an effective treatment for erectile dysfunction. Its mechanism of action is enhancement of nitric oxide (NO) induced cGMP formation resulting in significant relaxation of the corpus cavernosum (CC). The aim of this study was to investigate the oral efficacy of mirodenafil in an acute spinal cord-injured rabbit model. Mirodenafil or sildenafil citrate was given orally to male rabbits with a surgical transection of the spinal cord at the L2-L4 lumbar vertebra or ischemic-reperfusion spinal cord injury (SCI). Erections were evaluated in a time-course manner by measuring the length of the uncovered penile mucosa. In the transection SCI model, penile erections were induced at 0.3, 1 and 3 mg/kg of mirodenafil but sildenafil only showed an erectile response at 3 mg/kg. The effects of 1 and 3 mg/kg of mirodenafil were significantly increased by intravenous injection of sodium nitroprusside (SNP), a nitric oxide donor. In the ischemic-reperfusion injury model, 3 mg/kg of either mirodenafil or sildenafil produced a penile erection response. After injection of SNP, the lengths of immediate penile erections were significantly increased in the 1 and 3 mg/kg mirodenafil and 3 mg/kg sildenafil groups. The onset of erectile activity was faster with mirodenafil than with sildenafil citrate. These results demonstrate that mirodenafil may be useful for treating erectile dysfunction in patients with a spinal cord injury.

  14. Gene therapy approaches for spinal cord injury

    NASA Astrophysics Data System (ADS)

    Bright, Corinne

    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.

  15. Beneficial effects of melatonin combined with exercise on endogenous neural stem/progenitor cells proliferation after spinal cord injury.

    PubMed

    Lee, Youngjeon; Lee, Seunghoon; Lee, Sang-Rae; Park, Kanghui; Hong, Yunkyung; Lee, Minkyung; Park, Sookyoung; Jin, Yunho; Chang, Kyu-Tae; Hong, Yonggeun

    2014-01-01

    Endogenous neural stem/progenitor cells (eNSPCs) proliferate and differentiate into neurons and glial cells after spinal cord injury (SCI). We have previously shown that melatonin (MT) plus exercise (Ex) had a synergistic effect on functional recovery after SCI. Thus, we hypothesized that combined therapy including melatonin and exercise might exert a beneficial effect on eNSPCs after SCI. Melatonin was administered twice a day and exercise was performed on a treadmill for 15 min, six days per week for 3 weeks after SCI. Immunohistochemistry and RT-PCR analysis were used to determine cell population for late response, in conjunction with histological examination and motor function test. There was marked improvement in hindlimb function in SCI+MT+Ex group at day 14 and 21 after injury, as documented by the reduced size of the spinal lesion and a higher density of dendritic spines and axons; such functional improvements were associated with increased numbers of BrdU-positive cells. Furthermore, MAP2 was increased in the injured thoracic segment, while GFAP was increased in the cervical segment, along with elevated numbers of BrdU-positive nestin-expressing eNSPCs in the SCI+MT+Ex group. The dendritic spine density was augmented markedly in SCI+MT and SCI+MT+Ex groups.These results suggest a synergistic effect of SCI+MT+Ex might create a microenvironment to facilitate proliferation of eNSPCs to effectively replace injured cells and to improve regeneration in SCI.

  16. Spinal Cord Injury Map

    MedlinePlus

    ... on the severity of the injury. Tap this spinal column to see how the level of injury affects loss of function and control. Learn more about spinal cord injuries. A spinal cord injury affects the ...

  17. Effect of abdominal binding on respiratory mechanics during exercise in athletes with cervical spinal cord injury.

    PubMed

    West, Christopher R; Goosey-Tolfrey, Victoria L; Campbell, Ian G; Romer, Lee M

    2014-07-01

    We asked whether elastic binding of the abdomen influences respiratory mechanics during wheelchair propulsion in athletes with cervical spinal cord injury (SCI). Eight Paralympic wheelchair rugby players with motor-complete SCI (C5-C7) performed submaximal and maximal incremental exercise tests on a treadmill, both with and without abdominal binding. Measurements included pulmonary function, pressure-derived indices of respiratory mechanics, operating lung volumes, tidal flow-volume data, gas exchange, blood lactate, and symptoms. Residual volume and functional residual capacity were reduced with binding (77 ± 18 and 81 ± 11% of unbound, P < 0.05), vital capacity was increased (114 ± 9%, P < 0.05), whereas total lung capacity was relatively well preserved (99 ± 5%). During exercise, binding introduced a passive increase in transdiaphragmatic pressure, due primarily to an increase in gastric pressure. Active pressures during inspiration were similar across conditions. A sudden, sustained rise in operating lung volumes was evident in the unbound condition, and these volumes were shifted downward with binding. Expiratory flow limitation did not occur in any subject and there was substantial reserve to increase flow and volume in both conditions. V̇o2 was elevated with binding during the final stages of exercise (8-12%, P < 0.05), whereas blood lactate concentration was reduced (16-19%, P < 0.05). V̇o2/heart rate slopes were less steep with binding (62 ± 35 vs. 47 ± 24 ml/beat, P < 0.05). Ventilation, symptoms, and work rates were similar across conditions. The results suggest that abdominal binding shifts tidal breathing to lower lung volumes without influencing flow limitation, symptoms, or exercise tolerance. Changes in respiratory mechanics with binding may benefit O2 transport capacity by an improvement in central circulatory function.

  18. The effects of maternal anxiety during pregnancy on IGF2/H19 methylation in cord blood.

    PubMed

    Mansell, T; Novakovic, B; Meyer, B; Rzehak, P; Vuillermin, P; Ponsonby, A-L; Collier, F; Burgner, D; Saffery, R; Ryan, J

    2016-01-01

    Compelling evidence suggests that maternal mental health in pregnancy can influence fetal development. The imprinted genes, insulin-like growth factor 2 (IGF2) and H19, are involved in fetal growth and each is regulated by DNA methylation. This study aimed to determine the association between maternal mental well-being during pregnancy and differentially methylated regions (DMRs) of IGF2 (DMR0) and the IGF2/H19 imprinting control region (ICR) in newborn offspring. Maternal depression, anxiety and perceived stress were assessed at 28 weeks of pregnancy in the Barwon Infant Study (n=576). DNA methylation was measured in purified cord blood mononuclear cells using the Sequenom MassArray Platform. Maternal anxiety was associated with a decrease in average ICR methylation (Δ=-2.23%; 95% CI=-3.68 to -0.77%), and across all six of the individual CpG units in anxious compared with non-anxious groups. Birth weight and sex modified the association between prenatal anxiety and infant methylation. When stratified into lower (⩽3530 g) and higher (>3530 g) birth weight groups using the median birth weight, there was a stronger association between anxiety and ICR methylation in the lower birth weight group (Δ=-3.89%; 95% CI=-6.06 to -1.72%), with no association in the higher birth weight group. When stratified by infant sex, there was a stronger association in female infants (Δ=-3.70%; 95% CI=-5.90 to -1.51%) and no association in males. All the linear regression models were adjusted for maternal age, smoking and folate intake. These findings show that maternal anxiety in pregnancy is associated with decreased IGF2/H19 ICR DNA methylation in progeny at birth, particularly in female, low birth weight neonates. ICR methylation may help link poor maternal mental health and adverse birth outcomes, but further investigation is needed. PMID:27023171

  19. Sexuality Counseling with Clients Who Have Spinal Cord Injuries.

    ERIC Educational Resources Information Center

    Farrow, Jeff

    1990-01-01

    Examines effects of spinal cord injury on sexuality. Discusses areas of sexual concern. Provides suggestions for treating clients with spinal cord injuries experiencing sexual difficulties. Concludes that major goal in working with clients with spinal cord injuries who have sexual difficulties should be the facilitation of a creative and…

  20. Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats

    PubMed Central

    Calatrava-Ferreras, Lucía; Gonzalo-Gobernado, Rafael; Herranz, Antonio S.; Reimers, Diana; Montero Vega, Teresa; Jiménez-Escrig, Adriano; Richart López, Luis Alberto; Bazán, Eulalia

    2012-01-01

    Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs) have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP) rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders. PMID:23150735

  1. Effects of serum, tissue extract, conditioned medium, and culture substrata on neurite appearance from spinal cord explants of chick embryo.

    PubMed

    Tanaka, H; Sakai, M; Obata, K

    1982-07-01

    The effects of serum, tissue extracts, conditioned medium, (CM), and culture substrata on neurite appearance from spinal cord explants of 6- to 8-day-old chick embryos were investigated. In Eagle's minimum essential medium (MEM) with no supplement neurites from explants did not appear on collagen coating but on polyornithine coating (PORN). It is concluded that cell-to-substratum interaction is important in neurite appearance. CM, serum and tissue extract potentiated neurite appearance, but their activities were highly dependent on the coating. The amount of collagen was also crucial. On collagen, neurite appearance was observed only when promoting substances were present. CM and serum contained at least two components; one affected neurite appearance after deposition on collagen and the other affected neurite appearance when present in the culture medium. The former was included also in tissue extracts. Both of adsorbable and non-adsorbable components from any origin were necessary for effective induction of neurite appearance. Heat treatment and dialysis differentiated these active components. On PORN, CM highly potentiated neurite appearance. The activity of the CM was reproduced by its low molecular weight fraction. Serum also promoted neurite appearance, but to a lesser extent than CM. The effect of tissue extract was not remarkable.

  2. Transrectal electroejaculation combined with in-vitro fertilization: effective treatment of anejaculatory infertility due to spinal cord injury.

    PubMed

    Brinsden, P R; Avery, S M; Marcus, S; Macnamee, M C

    1997-12-01

    Infertility due to spinal cord injury (SCI) in young men is a frequent complication of their injury. When the simpler methods of management of the erectile and ejaculatory dysfunction that invariably follow the more severe types of SCI are not effective, then semen production by transrectal electroejaculation (TREE) combined with in-vitro fertilization (IVF) and embryo transfer is effective. A retrospective analysis is presented of data on the treatment and outcome of 35 couples who wished to have a family but in whom the male partner had suffered SCI. These 35 couples had 71 attempts at IVF with spermatozoa obtained following TREE. Normal fertilization and cleavage of the embryos occurred in 48.2% of the oocytes. Fresh embryos were transferred in 54 cycles and frozen-thawed embryos in 14 cycles. In all, 18 clinical pregnancies were achieved in 54 fresh and 14 frozen embryo transfer cycles, with a live birth rate of 16.5% (14/85) per treatment cycle started, 20.6% (14/68) per transfer cycle and 40.0% (14/35) per couple who started treatment, in a mean of 1.9 transfer cycles. We conclude that TREE combined with IVF and embryo transfer is an effective treatment for the infertility problems associated with SCI.

  3. Effects of the combination of methylprednisolone with aminoguanidine on functional recovery in rats following spinal cord injury

    PubMed Central

    LI, ZONGSHU; DU, JUAN; SUN, HONGXIA; MANG, JING; HE, JINTING; WANG, JIAOQI; LIU, HONGYU; XU, ZHONGXIN

    2014-01-01

    Methylprednisolone (MP), a synthetic glucocorticoid, has been widely used as a standard therapeutic agent for the treatment of spinal cord injury (SCI). The combination of MP and other pharmacological agents aimed at enhancing functional recovery is desirable as the beneficial effects of MP are controversial, due to a variety of side-effects. Aminoguanidine (AG), a small water-soluble compound, is potentially useful in the treatment of acute SCI. The aim of the present study was to determine the effects of MP and AG, administered in combination, following SCI in adult rats. In rats with SCI, the combination therapy group treated with AG (75 mg/kg) and MP (0.75 mg/kg) exhibited significantly reduced levels of cytokine expression and cell apoptosis compared with those in the control group. In addition, the data demonstrated that the combination therapy significantly enhanced the recovery of limb function. These data clearly suggest that treatment with a combination of MP and AG represents a promising strategy of clinically applicable pharmacological therapy for the rapid initiation of neuroprotection following SCI. PMID:24926352

  4. Spinal Cord Injuries

    MedlinePlus

    ... your body and your brain. A spinal cord injury disrupts the signals. Spinal cord injuries usually begin with a blow that fractures or ... bone disks that make up your spine. Most injuries don't cut through your spinal cord. Instead, ...

  5. Late Effects after Umbilical Cord Blood Transplantation in Very Young Children after Busulfan-Based, Myeloablative Conditioning.

    PubMed

    Allewelt, Heather; El-Khorazaty, Jill; Mendizabal, Adam; Taskindoust, Mahsa; Martin, Paul L; Prasad, Vinod; Page, Kristin; Sanders, Jean; Kurtzberg, Joanne

    2016-09-01

    Infants and young children who undergo allogeneic cord blood transplantation (CBT) are at increased risk for late effects because of exposure of developing organs to chemotherapy and radiation therapy typically used in transplant conditioning regimens. Busulfan (Bu)-based myeloablative regimens were developed to eliminate radiation exposure in these young children with the hope that late effects would be minimized. We now describe the late effects in 102 consecutive patients surviving a minimum of 5 years (median follow-up, 12.9 years) post-CBT. Patients were conditioned with high-dose chemotherapy using Bu-containing regimens. No patient received total body irradiation. The median age at transplant was 1 year (range, .1 to 2). Diagnoses included inherited metabolic diseases (59.8%), leukemia (17.6%), congenital immune deficiency (20.2%), bone marrow failure/myelodysplastic syndrome (3.9%), and hemoglobinopathy (2%). Among patients surviving 5 years, the overall survival rate at 10 years post-CBT was 93% (95% CI, 84.9 to 96.8). Virtually all patients (98%) experienced at least 1 significant late effect. Most (83.3%) experienced 2 or more late effects, and more than half of the patients (64.7%) experienced 3 or more late effects. The most commonly observed late effects included dental problems (92.2%), short stature (55.9%), cognitive deficits (53.6%), pulmonary dysfunction (18.6%), and abnormal pubertal development (27.9%). This is the first report of late effects of Bu-based conditioning in a cohort of very young patients at the time of transplant. These results will inform clinical care guidelines for long-term follow-up and add to the growing information regarding outcomes of hematopoietic stem cell transplantation. PMID:27264632

  6. The effects of maternal anxiety during pregnancy on IGF2/H19 methylation in cord blood

    PubMed Central

    Mansell, T; Novakovic, B; Meyer, B; Rzehak, P; Vuillermin, P; Ponsonby, A-L; Collier, F; Burgner, D; Saffery, R; Ryan, J; Vuillermin, Peter; Ponsonby, Anne-Louise; Carlin, John B; Allen, Katie J; Tang, Mimi L; Saffery, Richard; Ranganathan, Sarath; Burgner, David; Dwyer, Terry; Jachno, Kim; Sly, Peter

    2016-01-01

    Compelling evidence suggests that maternal mental health in pregnancy can influence fetal development. The imprinted genes, insulin-like growth factor 2 (IGF2) and H19, are involved in fetal growth and each is regulated by DNA methylation. This study aimed to determine the association between maternal mental well-being during pregnancy and differentially methylated regions (DMRs) of IGF2 (DMR0) and the IGF2/H19 imprinting control region (ICR) in newborn offspring. Maternal depression, anxiety and perceived stress were assessed at 28 weeks of pregnancy in the Barwon Infant Study (n=576). DNA methylation was measured in purified cord blood mononuclear cells using the Sequenom MassArray Platform. Maternal anxiety was associated with a decrease in average ICR methylation (Δ=−2.23% 95% CI=−3.68 to −0.77%), and across all six of the individual CpG units in anxious compared with non-anxious groups. Birth weight and sex modified the association between prenatal anxiety and infant methylation. When stratified into lower (⩽3530 g) and higher (>3530 g) birth weight groups using the median birth weight, there was a stronger association between anxiety and ICR methylation in the lower birth weight group (Δ=−3.89% 95% CI=−6.06 to −1.72%), with no association in the higher birth weight group. When stratified by infant sex, there was a stronger association in female infants (Δ=−3.70% 95% CI=−5.90 to −1.51%) and no association in males. All the linear regression models were adjusted for maternal age, smoking and folate intake. These findings show that maternal anxiety in pregnancy is associated with decreased IGF2/H19 ICR DNA methylation in progeny at birth, particularly in female, low birth weight neonates. ICR methylation may help link poor maternal mental health and adverse birth outcomes, but further investigation is needed. PMID:27023171

  7. Repair of spinal cord injury by chitosan scaffold with glioma ECM and SB216763 implantation in adult rats.

    PubMed

    Jian, Rao; Yixu, Yang; Sheyu, Lin; Jianhong, Shen; Yaohua, Yan; Xing, Su; Qingfeng, Huang; Xiaojian, Lu; Lei, Zhang; Yan, Zhen; Fangling, Xiong; Huasong, Gao; Yilu, Gao

    2015-10-01

    The loss of spinal cord tissue and the cavity formation are major obstacles to the repair of spinal cord injury (SCI). In the study, the scaffold of chitosan+ECM+SB216763 was fabricated and used for the repair of injured spinal cord injury. First, the biocompatibility of the scaffold was analyzed and results showed that the scaffold had a good compatibility with the neural stem cells. Especially, the processes of differentiated neural stem cell embedded in the scaffold were found in the experiment. At the same time, we also investigated the effect of scaffold on the differentiation of neural stem cell. The results showed that the scaffold of chitosan+ECM+SB216763 could significantly promote the differentiation of neural stem cells into neurons, astrocytes, and oligodendrocytes relative to those in other groups. In order to probe the application of scaffold in vivo, the rat models of spinal cord hemisection were set up and scaffolds were implanted into transected gap. Then the electrophysiology and BBB score were evaluated and results showed that the amplitude, latency period and BBB score in chitosan+ECM+SB216763 group were dramatically better than those in other groups. In addition, the differentiation of neural stem cells into nerve cells was also assayed and the results revealed that the number of neural stem cells differentiating into neuron, astrocytes and oligodendrocytes in chitosan+ECM+SB216763 group was significantly bigger than those in other groups. All these data suggested that the scaffold of chitosan+ECM+SB216763 would be a promising medium for the repair of injured spinal cord.

  8. A Noninvasive Neuroprosthesis Augments Hand Grasp Force in Individuals with Cervical Spinal Cord Injury: The Functional and Therapeutic Effects

    PubMed Central

    Dalla Costa, Davide; Chiaramonte, Sara; Binda, Luca; Beghi, Ettore; Redaelli, Tiziana; Occhi, Eugenio

    2013-01-01

    Objectives. The primary purpose of this study was to evaluate myoelectrically controlled functional electrical stimulation (MeCFES) for enhancing the tenodesis grip in people with tetraplegia. The second aim was to estimate the potential number of candidates for the MeCFES device. The application of MeCFES provides the user with direct control of the grasp force as opposed to triggered FES systems. Methods. Screening 253 medical records of C5 to C7 spinal cord injury resulted in 27 participants who trained activities of daily living for 12 × 2 hours, using the MeCFES. Hand function was evaluated by the Action Research Arm Test (ARAT). Primary outcome was the ARAT change score with/without the device, before/after the intervention period. Secondary outcome was the number of positive or clinically relevant change scores with respect to the cohort. Results. The MeCFES improved hand test score in 63% of the subjects at first application. Training resulted in a significant therapeutic effect, which resulted in an overall increase of hand function in 89% of the participants and 30% experienced a clinically relevant change (6 points or more). Conclusions. Clinical relevance was found both as an assistive aid and as a therapeutic tool in rehabilitation. The therapeutic effect deserves further investigation in clinical studies. PMID:24489513

  9. Effects of lysergic acid diethylamide (LSD) and adjuvant-induced inflammation on desensitization to and metabolism of substance P in the mouse spinal cord.

    PubMed

    Larson, A A; Igwe, O J; Seybold, V S

    1989-06-01

    We have previously shown that the caudally directed biting and scratching response to repeated intrathecal (i.t.) injections of substance P (SP) is decreased by the third injection of SP and that this apparent desensitization to SP is less pronounced in mice pretreated with Freund's adjuvant. This study was designed to study the mechanism of this desensitization to SP and to examine the effect of lysergic acid diethylamide tartrate (LSD) on desensitization. Our results indicate that while 25 micrograms of LSD/kg body weight i.p. in naive mice had no effect on the response to a single injection of SP, LSD decreased the development of desensitization to SP-induced behaviors. In contrast, identical injections of LSD in adjuvant-pretreated mice not only failed to prevent desensitization but enhanced the degree of apparent desensitization to SP. Tolerance developed to the effects of LSD on desensitization to SP-induced behaviors in both adjuvant- and saline-pretreated mice. When injected i.t. with SP, LSD failed to alter the degree of desensitization to SP-induced behaviors, suggesting that the effect of LSD is not produced at the spinal cord level. Separation and quantification of SP and its metabolites in the spinal cord using high performance liquid chromatography (HPLC) techniques indicated that either a single injection of LSD or pretreatment with Freund's adjuvant produced similar patterns of changes in the concentrations of SP-related peptides in mouse spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Advance in spinal cord ischemia reperfusion injury: Blood-spinal cord barrier and remote ischemic preconditioning.

    PubMed

    Yu, Qijing; Huang, Jinxiu; Hu, Ji; Zhu, Hongfei

    2016-06-01

    The blood-spinal cord barrier (BSCB) is the physiological and metabolic substance diffusion barrier between blood circulation and spinal cord tissues. This barrier plays a vital role in maintaining the microenvironment stability of the spinal cord. When the spinal cord is subjected to ischemia/reperfusion (I/R) injury, the structure and function of the BSCB is disrupted, further destroying the spinal cord homeostasis and ultimately leading to neurological deficit. Remote ischemic preconditioning (RIPC) is an approach in which interspersed cycles of preconditioning ischemia is followed by reperfusion to tissues/organs to protect the distant target tissues/organs against subsequent lethal ischemic injuries. RIPC is an innovation of the treatment strategies that protect the organ from I/R injury. In this study, we review the morphological structure and function of the BSCB, the injury mechanism of BSCB resulting from spinal cord I/R, and the effect of RIPC on it.

  11. Mesenchymal Stem Cells and Mononuclear Cells From Cord Blood: Cotransplantation Provides a Better Effect in Treating Myocardial Infarction.

    PubMed

    Chen, Gecai; Yue, Aihuan; Yu, Hong; Ruan, Zhongbao; Yin, Yigang; Wang, Ruzhu; Ren, Yin; Zhu, Li

    2016-03-01

    The aim of this study was to evaluate the effect of cotransplanting mononuclear cells from cord blood (CB-MNCs) and mesenchymal stem cells (MSCs) as treatment for myocardial infarction (MI). Transplanting CD34+ cells or MSCs separately has been shown effective in treating MI, but the effect of cotransplanting CB-MNCs and MSCs is not clear. In this study, MSCs were separated by their adherence to the tissue culture. The morphology, immunophenotype, and multilineage potential of MSCs were analyzed. CB-MNCs were separated in lymphocyte separation medium 1.077. CD34+ cell count and viability were analyzed by flow cytometry. Infarcted male Sprague-Dawley rats in a specific-pathogen-free grade were divided into four treatment groups randomly: group I, saline; group II, CB-MNCs; group III, MSCs; and group IV, CB-MNCs plus MSCs. The saline, and CB-MNCs and/or MSCs were injected intramyocardially in infarcted rats. Their cardiac function was evaluated by echocardiography. The myocardial capillary density was analyzed by immunohistochemistry. Both cell types induced an improvement in the left ventricular cardiac function and increased tissue cell proliferation in myocardial tissue and neoangiogenesis. However, CB-MNCs plus MSCs were more effective in reducing the infarct size and preventing ventricular remodeling. Scar tissue was reduced significantly in the CB-MNCs plus MSCs group. MSCs facilitate engraftment of CD34+ cells and immunomodulation after allogeneic CD34+ cell transplantation. Cotransplanting MSCs and CB-MNCs might be more effective than transplanting MSCs or CB-MNCs separately for treating MI. This study contributes knowledge toward effective treatment strategies for MI.

  12. Effects of Tramadol on Substantia Gelatinosa Neurons in the Rat Spinal Cord: An In Vivo Patch-Clamp Analysis

    PubMed Central

    Yamasaki, Hiroyuki; Funai, Yusuke; Funao, Tomoharu; Mori, Takashi; Nishikawa, Kiyonobu

    2015-01-01

    Tramadol is thought to modulate synaptic transmissions in the spinal dorsal horn mainly by activating µ-opioid receptors and by inhibiting the reuptake of monoamines in the CNS. However, the precise mode of modulation remains unclear. We used an in vivo patch clamp technique in urethane-anesthetized rats to determine the antinociceptive mechanism of tramadol. In vivo whole-cell recordings of spontaneous inhibitory postsynaptic currents (sIPSCs) and spontaneous excitatory postsynaptic currents (sEPSCs) were made from substantia gelatinosa (SG) neurons (lamina II) at holding potentials of 0 mV and -70 mV, respectively. The effects of intravenous administration (0.5, 5, 15 mg/kg) of tramadol were evaluated. The effects of superfusion of tramadol on the surface of the spinal cord and of a tramadol metabolite (M1) were further analyzed. Intravenous administration of tramadol at doses >5 mg/kg decreased the sEPSCs and increased the sIPSCs in SG neurons. These effects were not observed following naloxone pretreatment. Tramadol superfusion at a clinically relevant concentration (10 µM) had no effect, but when administered at a very high concentration (100 µM), tramadol decreased sEPSCs, produced outward currents, and enhanced sIPSCs. The effects of M1 (1, 5 mg/kg intravenously) on sEPSCs and sIPSCs were similar to those of tramadol at a corresponding dose (5, 15 mg/kg). The present study demonstrated that systemically administered tramadol indirectly inhibited glutamatergic transmission, and enhanced GABAergic and glycinergic transmissions in SG neurons. These effects were mediated primarily by the activation of μ-opioid receptors. M1 may play a key role in the antinociceptive mechanisms of tramadol. PMID:25933213

  13. Spinal cord contusion models.

    PubMed

    Young, Wise

    2002-01-01

    Most human spinal cord injuries involve contusions of the spinal cord. Many investigators have long used weight-drop contusion animal models to study the pathophysiology and genetic responses of spinal cord injury. All spinal cord injury therapies tested to date in clinical trial were validated in such models. In recent years, the trend has been towards use of rats for spinal cord injury studies. The MASCIS Impactor is a well-standardized rat spinal cord contusion model that produces very consistent graded spinal cord damage that linearly predicts 24-h lesion volumes, 6-week white matter sparing, and locomotor recovery in rats. All aspects of the model, including anesthesia for male and female rats, age rather than body weight criteria, and arterial blood gases were empirically selected to enhance the consistency of injury. PMID:12440371

  14. BMPR1a and BMPR1b Signaling Exert Opposing Effects on Gliosis after Spinal Cord Injury

    PubMed Central

    Sahni, Vibhu; Mukhopadhyay, Abhishek; Tysseling, Vicki; Hebert, Amy; Birch, Derin; Mcguire, Tammy L.; Stupp, Samuel I.; Kessler, John A.

    2011-01-01

    Astrogliosis following spinal cord injury (SCI) involves an early hypertrophic response that is beneficial and a subsequent formation of a dense scar. We investigated the role of bone morphogenetic protein (BMP) signaling in gliosis after SCI and find that BMPR1a and BMPR1b signaling exerts opposing effects on hypertrophy. Conditional ablation of BMPR1a from glial fibrillary acidic protein (GFAP)-expressing cells leads to defective astrocytic hypertrophy, increased infiltration by inflammatory cells, and reduced axon density. BMPR1b-null mice conversely develop “hyperactive” reactive astrocytes and consequently have smaller lesion volumes. The effects of ablation of either receptor are reversed in the double knock-out animals. These findings indicate that BMPR1a and BMPR1b exert directly opposing effects on the initial reactive astrocytic hypertrophy. Also, BMPR1b knock-out mice have an attenuated glial scar in the chronic stages following injury, suggesting that it has a greater role in glial scar progression. To elucidate the differing roles of the two receptors in astrocytes, we examined the effects of ablation of either receptor in serum-derived astrocytes in vitro. We find that the two receptors exert opposing effects on the posttranscriptional regulation of astrocytic microRNA-21. Further, overexpression of microRNA-21 in wild-type serum-derived astrocytes causes a dramatic reduction in cell size accompanied by reduction in GFAP levels. Hence, regulation of microRNA-21 by BMP signaling provides a novel mechanism for regulation of astrocytic size. Targeting specific BMPR subunits for therapeutic purposes may thus provide an approach for manipulating gliosis and enhancing functional outcomes after SCI. PMID:20130193

  15. Time to implement delayed cord clamping.

    PubMed

    McAdams, Ryan M

    2014-03-01

    Immediate umbilical cord clamping after delivery is routine in the United States despite little evidence to support this practice. Numerous trials in both term and preterm neonates have demonstrated the safety and benefit of delayed cord clamping. In premature neonates, delayed cord clamping has been shown to stabilize transitional circulation, lessening needs for inotropic medications and reducing blood transfusions, necrotizing enterocolitis, and intraventricular hemorrhage. In term neonates, delayed cord clamping has been associated with decreased iron-deficient anemia and increased iron stores with potential valuable effects that extend beyond the newborn period, including improvements in long-term neurodevelopment. The failure to more broadly implement delayed cord clamping in neonates ignores published benefits of increased placental blood transfusion at birth and may represent an unnecessary harm for vulnerable neonates.

  16. Regenerative treatment in spinal cord injury.

    PubMed

    Ozdemir, Mevci; Attar, Ayhan; Kuzu, Isinsu

    2012-09-01

    Spinal cord injury is a devastating, traumatic event, and experienced mainly among young people. Until the modern era, spinal cord injury was so rapidly fatal that no seriously injured persons would survive long enough for regeneration to occur. Treatment of spinal cord injury can be summarized as follows: prevent further cord injury, maintain blood flow, relieve spinal cord compression, and provide secure vertebral stabilization so as to allow mobilization and rehabilitation, none of which achieves functional recovery. Previous studies have focused on analyzing the pathogenesis of secondary injury that extends from the injury epicenter to the periphery, as well as the tissue damage and neural cell death associated with secondary injury. Now, there are hundreds of current experimental and clinical regenerative treatment studies. One of the most popular treatment method is cell transplantation in injured spinal cord. For this purpose bone marrow stromal cells, mononuclear stem cells, mesenchymal stem cells, embryonic stem cells, neural stem cells, and olfactory ensheathing cells can be used. As a result, cell transplantation has become a promising therapeutic option for spinal cord injury patients. In this paper we discuss the effectiveness of stem cell therapy in spinal cord injury.

  17. Effect of adjusting pulse durations of functional electrical stimulation cycling on energy expenditure and fatigue after spinal cord injury.

    PubMed

    Gorgey, Ashraf S; Poarch, Hunter J; Dolbow, David D; Castillo, Teodoro; Gater, David R

    2014-01-01

    The purpose of the current study was to determine the effects of three different pulse durations (200, 350, and 500 microseconds [P200, P350, and P500, respectively]) on oxygen uptake (VO2), cycling performance, and energy expenditure (EE) percentage of fatigue of the knee extensor muscle group immediately and 48 to 72 h after cycling in persons with spinal cord injury (SCI). A convenience sample of 10 individuals with motor complete SCI participated in a repeated-measures design using a functional electrical stimulation (FES) cycle ergometer over a 3 wk period. There was no difference among the three FES protocols on relative VO2 or cycling EE. Delta EE between exercise and rest was 42% greater in both P500 and P350 compared with P200 (p = 0.07), whereas recovery VO2 was 23% greater in P350 compared with P200 (p = 0.03). There was no difference in the outcomes of the three pulse durations on muscle fatigue. Knee extensor torque significantly decreased immediately after (p < 0.001) and 48 to 72 h after (p < 0.001) FES leg cycling. Lengthening pulse duration did not affect submaximal or relative VO2 or EE, total EE, and time to fatigue. Greater recovery VO2 and delta EE were noted in P350 and P500 compared with P200. An acute bout of FES leg cycling resulted in torque reduction that did not fully recover 48 to 72 h after cycling.

  18. Mixed-Reality Exercise Effects on Participation of Individuals with Spinal Cord Injuries and Developmental Disabilities: A Pilot Study

    PubMed Central

    Baumgardner, Chad A.; McLachlan, Leslie; Bodine, Cathy

    2014-01-01

    Objective: The purpose of this pilot study was to investigate the effectiveness of a mixed-reality (MR) exercise environment on engagement and enjoyment levels of individuals with spinal cord injury (SCI) and intellectual and developmental disabilities (IDD). Methods: Six people participated in this cross-sectional, observational pilot study involving one MR exercise trial. The augmented reality environment was based on a first-person perspective video of a scenic biking/walking trail in Colorado. Males and females (mean age, 43.3 ± 13.7 years) were recruited from a research database for their participation in previous clinical studies. Of the 6 participants, 2 had SCI, 2 had IDD, and 2 were without disability. The primary outcome measurement of this pilot study was the self-reported engagement and enjoyment level of each participant after the exercise trial. Results: All participants reported increased levels of engagement, enjoyment, and immersion involving the MR exercise environment as well as positive feedback recommending this type of exercise approach to peers with similar disabilities. All the participants reported higher than normal levels of enjoyment and 66.7% reported higher than normal levels of being on a real trail. Conclusion: Participants’ feedback suggested that the MR environment could be entertaining, motivating, and engaging for users with disabilities, resulting in a foundation for further development of this technology for use in individuals with cognitive and physical disabilities. PMID:25477747

  19. Monocytes are Essential for the Neuroprotective Effect of Human Cord Blood Cells Following Middle Cerebral Artery Occlusion in Rat

    PubMed Central

    Womble, T. A.; Green, S.; Shahaduzzaman, M.; Grieco, J.; Sanberg, P. R.; Pennypacker, K. R.; Willing, A. E.

    2014-01-01

    Systemic administration of human umbilical cord blood (HUCB) mononuclear cells (MNC) following middle cerebral artery occlusion (MCAO) in the rat reduces infarct size and, more importantly, restores motor function. The HUCB cell preparation is composed of immature T-cells, B-cells, monocytes and stem cells. In this study we examined whether the beneficial effects of HUCB injection were attributable to one of these cell types. Male Sprague Dawley rats underwent permanent MCAO followed 48 hours later by intravenous administration of HUCB MNC preparations depleted of either CD14+ monocytes, CD133+ stem cells, CD2+ T-cells or CD19+ B cells. Motor function was measured prior to MCAO and 30 days post-stroke. When CD14+ monocytes were depleted from the HUCB MNC, activity and motor asymmetry were similar to the MCAO only treated animals. Monocyte depletion prevented HUCB cell treatment from reducing infarct size while monocyte enrichment was sufficient to reduce infarct size. Administration of monocyte-depleted HUCB cells did not suppress Iba1 labeling of microglia in the infarcted area relative to treatment with the whole HUCB preparation. These data demonstrate that the HUCB monocytes provide the majority of the efficacy in reducing infarct volume and promoting functional recovery. PMID:24472845

  20. Neuronal activity significantly reduces water displacement: DWI of a vital rat spinal cord with no hemodynamic effect.

    PubMed

    Tirosh, Nitzan; Nevo, Uri

    2013-08-01

    Changes in the diffusion weighted MRI (DWI) signal were observed to be correlated with neuronal activity during chemically induced brain activity, epileptic seizures, or visual stimulation. These changes suggest a possible reduction in water displacement that accompanies neuronal activity, but were possibly affected by other physiological mechanisms such as blood oxygenation level and blood flow. We developed an imaging experiment of an excised and vital newborn rat spinal cord to examine the effect of neuronal function on the displacement of water molecules as measured by DWI signal. This approach provides a DWI experiment of a vital mammalian CNS tissue in the absence of some of the systemic sources of noise. We detected a significant and reproducible drop with an average value of 19.5 ± 1.6% (mean ± SE) upon activation. The drop repeated itself in three orthogonal directions. ADC values corresponded to an oblate anisotropy. This result was validated by high resolution DWI of a fixed tissue, imaged with an ultra-high field MRI. The results support our working hypothesis that water displacement is affected by neuronal activation. These results further imply that water displacement might serve as a potential marker for brain function, and that, although commonly viewed as wholly electrochemical, neuronal activity includes a significant mechanical dimension that affects water displacement.

  1. Effect of adjusting pulse durations of functional electrical stimulation cycling on energy expenditure and fatigue after spinal cord injury.

    PubMed

    Gorgey, Ashraf S; Poarch, Hunter J; Dolbow, David D; Castillo, Teodoro; Gater, David R

    2014-01-01

    The purpose of the current study was to determine the effects of three different pulse durations (200, 350, and 500 microseconds [P200, P350, and P500, respectively]) on oxygen uptake (VO2), cycling performance, and energy expenditure (EE) percentage of fatigue of the knee extensor muscle group immediately and 48 to 72 h after cycling in persons with spinal cord injury (SCI). A convenience sample of 10 individuals with motor complete SCI participated in a repeated-measures design using a functional electrical stimulation (FES) cycle ergometer over a 3 wk period. There was no difference among the three FES protocols on relative VO2 or cycling EE. Delta EE between exercise and rest was 42% greater in both P500 and P350 compared with P200 (p = 0.07), whereas recovery VO2 was 23% greater in P350 compared with P200 (p = 0.03). There was no difference in the outcomes of the three pulse durations on muscle fatigue. Knee extensor torque significantly decreased immediately after (p < 0.001) and 48 to 72 h after (p < 0.001) FES leg cycling. Lengthening pulse duration did not affect submaximal or relative VO2 or EE, total EE, and time to fatigue. Greater recovery VO2 and delta EE were noted in P350 and P500 compared with P200. An acute bout of FES leg cycling resulted in torque reduction that did not fully recover 48 to 72 h after cycling. PMID:25803753

  2. Chitosan produces potent neuroprotection and physiological recovery following traumatic spinal cord injury.

    PubMed

    Cho, Youngnam; Shi, Riyi; Borgens, Richard B

    2010-05-01

    Chitosan, a non-toxic biodegradable polycationic polymer with low immunogenicity, has been extensively investigated in various biomedical applications. In this work, chitosan has been demonstrated to seal compromised nerve cell membranes thus serving as a potent neuroprotector following acute spinal cord trauma. Topical application of chitosan after complete transection or compression of the guinea pig spinal cord facilitated sealing of neuronal membranes in ex vivo tests, and restored the conduction of nerve impulses through the length of spinal cords in vivo, using somatosensory evoked potential recordings. Moreover, chitosan preferentially targeted damaged tissues, served as a suppressor of reactive oxygen species (free radical) generation, and the resultant lipid peroxidation of membranes, as shown in ex vivo spinal cord samples. These findings suggest a novel medical approach to reduce the catastrophic loss of behavior after acute spinal cord and brain injury.

  3. [Effect of different cytokine combinations on the expression of CD49d and CXCR4 and ex vivo expansion of umbilical cord blood mononuclear cells].

    PubMed

    Mao, Ping; Xu, Li; Mo, Wen-Jian; Yin, Yi; Xu, Yan-Li; Lin, Xiu-Mei

    2006-04-01

    This study was purposed to explore the effect of different cytokine combinations on the expansion of the mononuclear cells drived from umbilical cord blood (CB) ex vivo and expression of CXCR4 and CD49d on CD34+ cells after expansion. Human fresh CB mononuclear cells were cultured in serum-free and stroma-free medium containing different combinations of cytokine for 7 days. At day o and 7, the total cells were counted, CD34+ cells and CD34+CXCR4+, CD34+CD49d+ cells were assayed by flow cytometry, and CFU were determined. According to the different combinations of cytokine, experiments were divided into four groups: control, SF group (SCF + FL), SFT group (SCF + FL + TPO) and SFT6 group (SCF + FL + TPO + IL-6). The results showed that the SF (SF group) combination supported only low expansion of total cells, CD34+ cells and CFU. The addition of TPO in SF group restored UCB stem/progenitors expansion to a higher level than that in SF group, while there was no difference between groups SFT and SFT6 (P > 0.05). The cytokine combinations in groups SF, SFT and SFT6 all could upregulate the expression levels of CD49d and CXCR4 on expanded cord blood CD34+ cells, but there were no significant differences between groups SF, SFT and SFT6 (P > 0.05). It is concluded that SCF + FL has no strong synergistic effects on primitive hematopoietic cells. TPO plays an important role in enhancing expansion of umbilical cord blood hematopoietic cells, while IL-6 only shows a neutral effect on it. SCF + FL + TPO combination not only promotes progenitor cells expansion but also upregulates the expression of CD49d and CXCR4 on CD34+ cells from cord blood.

  4. Spinal cord injury increases the reactivity of rat tail artery to angiotensin II

    PubMed Central

    Al Dera, Hussain; Brock, James A.

    2015-01-01

    Studies in individuals with spinal cord injury (SCI) suggest the vasculature is hyperreactive to angiotensin II (Ang II). In the present study, the effects of SCI on the reactivity of the rat tail and mesenteric arteries to Ang II have been investigated. In addition, the effects of SCI on the facilitatory action of Ang II on nerve-evoked contractions of these vessels were determined. Isometric contractions of artery segments from T11 (tail artery) or T4 (mesenteric arteries) spinal cord-transected rats and sham-operated rats were compared 6–7 weeks postoperatively. In both tail and mesenteric arteries, SCI increased nerve-evoked contractions. In tail arteries, SCI also greatly increased Ang II-evoked contractions and the facilitatory effect of Ang II on nerve-evoked contractions. By contrast, SCI did not detectably change the responses of mesenteric arteries to Ang II. These findings provide the first direct evidence that SCI increases the reactivity of arterial vessels to Ang II. In addition, in tail artery, the findings indicate that Ang II may contribute to modifying their responses following SCI. PMID:25610365

  5. 4. The transectional structure of society: the basic societal functions.

    PubMed

    2014-05-01

    For the purposes of research and/or evaluation, a society is organised into 13 basic societal functions (BSFs) within an overall Coordination and Control system. This organisation facilitates transectional descriptions of society or a component of a society for assessment at any given time across the longitudinal phases of a disaster. An assessment results in a picture or description of function(s) limited to the point in time of the assessment. Together with simultaneous assessments of the functional status of all, some, or one of the other BSFs, such assessments deliver a transectional picture of the situation of a society. Since no function operates in isolation from the other functions, information of the concomitant status of several BSFs is crucial to gain a better understanding of functional losses and of the effects and side effects of an intervention. The 13 BSFs include: (1) Public Health (dominantly preventive); (2) Medical Care (dominantly curative); (3) Water and Sanitation; (4) Shelter and Clothing; (5) Food and Nutrition; (6) Energy Supplies; (7) Public Works and Engineering; (8) Social Structure; (9) Logistics And Transportation; (10) Security; (11) Communications; (12); Economy; and (13) Education. These BSFs relate with each other through the Coordination and Control function. Many functions of the BSFs and their respective subfunctions and elements overlap (they share some common subfunctions and elements). However, for the purposes of research/evaluation, it is necessary to assign subfunctions and elements to only one of the BSFs. Just as in the practice of clinical medicine, the sum of assessments provides the transectional description of the status of each of these BSFs at a given time. From this information, compared to the pre-event description of the society, interventions are selected that are likely to meet the defined objectives and their overarching goal(s), and respective plans are developed and implemented. The effects of each

  6. G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice.

    PubMed

    Cheng, Qiang; Meng, Jia; Wang, Xin-Shang; Kang, Wen-Bo; Tian, Zhen; Zhang, Kun; Liu, Gang; Zhao, Jian-Ning

    2016-08-01

    Spinal cord injury (SCI) always occurs accidently and leads to motor dysfunction because of biochemical and pathological events. Estrogen has been shown to be neuroprotective against SCI through estrogen receptors (ERs), but the underlying mechanisms have not been fully elucidated. In the present study, we investigated the role of a newly found membrane ER, G protein-coupled estrogen receptor 1 (GPR30 or GPER1), and discussed the feasibility of a GPR30 agonist as an estrogen replacement. Forty adult female C57BL/6J mice (10-12 weeks old) were divided randomly into vehicle, G-1, E2, G-1 + G-15 and E2 + G-15 groups. All mice were subjected to SCI using a crushing injury approach. The specific GPR30 agonist, G-1, mimicked the effects of E2 treatment by preventing SCI-induced apoptotic cell death and enhancing motor functional recovery after injury. GPR30 activation regulated phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK/extracellular signal-regulated kinase (ERK) signalling pathways, increased GPR30 and anti-apoptosis proteins Bcl-2 and brain derived neurotrophic factor (BDNF), but decreased the pro-apoptosis factor Bax and cleaved caspase-3. However, the neuroprotective effects of G-1 and E2 were blocked by the specific GPR30 antagonist, G-15. Thus, GPR30 rather than classic ERs is required to induce estrogenic neuroprotective effects. Given that estrogen replacement therapy may cause unexpected side effects, especially on the reproductive system, GPR30 agonists may represent a potential therapeutic approach for treating SCI. PMID:27407175

  7. The effects of electrical stimulation on body composition and metabolic profile after spinal cord injury – Part II

    PubMed Central

    Gorgey, Ashraf S.; Dolbow, David R.; Dolbow, James D.; Khalil, Refka K.; Gater, David R.

    2015-01-01

    Diet and exercise are cornerstones in the management of obesity and associated metabolic complications, including insulin resistance, type 2 diabetes, and disturbances in the lipid profile. However, the role of exercise in managing body composition adaptations and metabolic disorders after spinal cord injury (SCI) is not well established. The current review summarizes evidence about the efficacy of using neuromuscular electrical stimulation or functional electrical stimulation in exercising the paralytic lower extremities to improve body composition and metabolic profile after SCI. There are a number of trials that investigated the effects on muscle cross-sectional area, fat-free mass, and glucose/lipid metabolism. The duration of the intervention in these trials varied from 6 weeks to 24 months. Training frequency ranged from 2 to 5 days/week. Most studies documented significant increases in muscle size but no noticeable changes in adipose tissue. While increases in skeletal muscle size after twice weekly training were greater than those trials that used 3 or 5 days/week, other factors such as differences in the training mode, i.e. resistance versus cycling exercise and pattern of muscle activation may be responsible for this observation. Loading to evoke muscle hypertrophy is a key component in neuromuscular training after SCI. The overall effects on lean mass were modest and did not exceed 10% and the effects of training on trunk or pelvic muscles remain unestablished. Most studies reported improvement in glucose metabolism with the enhancement of insulin sensitivity being the major factor following training. The effect on lipid profile is unclear and warrants further investigation. PMID:25001669

  8. G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice

    PubMed Central

    Cheng, Qiang; Meng, Jia; Wang, Xin-shang; Kang, Wen-bo; Tian, Zhen; Zhang, Kun; Liu, Gang; Zhao, Jian-ning

    2016-01-01

    Spinal cord injury (SCI) always occurs accidently and leads to motor dysfunction because of biochemical and pathological events. Estrogen has been shown to be neuroprotective against SCI through estrogen receptors (ERs), but the underlying mechanisms have not been fully elucidated. In the present study, we investigated the role of a newly found membrane ER, G protein-coupled estrogen receptor 1 (GPR30 or GPER1), and discussed the feasibility of a GPR30 agonist as an estrogen replacement. Forty adult female C57BL/6J mice (10–12 weeks old) were divided randomly into vehicle, G-1, E2, G-1 + G-15 and E2 + G-15 groups. All mice were subjected to SCI using a crushing injury approach. The specific GPR30 agonist, G-1, mimicked the effects of E2 treatment by preventing SCI-induced apoptotic cell death and enhancing motor functional recovery after injury. GPR30 activation regulated phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK/extracellular signal-regulated kinase (ERK) signalling pathways, increased GPR30 and anti-apoptosis proteins Bcl-2 and brain derived neurotrophic factor (BDNF), but decreased the pro-apoptosis factor Bax and cleaved caspase-3. However, the neuroprotective effects of G-1 and E2 were blocked by the specific GPR30 antagonist, G-15. Thus, GPR30 rather than classic ERs is required to induce estrogenic neuroprotective effects. Given that estrogen replacement therapy may cause unexpected side effects, especially on the reproductive system, GPR30 agonists may represent a potential therapeutic approach for treating SCI. PMID:27407175

  9. Behavioral and histological outcomes following graded spinal cord contusion injury in the C57Bl/6 mouse.

    PubMed

    Ma, M; Basso, D M; Walters, P; Stokes, B T; Jakeman, L B

    2001-06-01

    A computer-controlled electromagnetic spinal cord injury device (ESCID) has been adapted to develop a mouse model of spinal cord contusion injury. In the present study, we have extended this model in C57Bl/6 mice with behavioral and histopathological outcome assessment. Three groups of mice received a laminectomy at the T(9) vertebral level followed by a contusion injury from a predetermined starting load of 1500 dynes. Contusion was produced by rapid displacement of the spinal cord to a peak distance of 0.3, 0.5, or 0.8 mm, with the entire injury and retraction procedure completed over a 23-ms epoch. Control groups received laminectomy alone or complete transection. Functional recovery was examined for 9 weeks after injury using the BBB locomotor rating scale, grid walking, and footprint analysis. Distinct patterns of locomotor recovery were evident across the five groups. Measurements of spared white matter at the epicenter, lesion length, and cross-sectional area of fibronectin-immunopositive scar tissue were also significantly different between injury groups. The severity of injury corresponded with the biomechanical measures recorded at the time of impact as well as with behavioral and histological parameters. The results demonstrate that graded contusion injuries can be produced reliably in mice using the ESCID. The data provide a thorough and quantitative analysis of the effects of contusion injury on long-term behavioral and histological outcome measures in this strain and species.

  10. Effect of intra-cisternal application of kainic acid on the spinal cord and locomotor activity in rats

    PubMed Central

    Mitra, Nilesh K; Goh, Tiffanie EW; Bala Krishnan, Thalisha; Nadarajah, Vishna D; Vasavaraj, Arun K; Soga, Tomoko

    2013-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease of idiopathic etiology. Glutamate excitotoxicity is one of the proposed hypotheses causing progressive death of motor neurons. We aimed to develop an experimental animal model of this disease to enhance the knowledge of pathophysiological mechanism of ALS. Male Wistar rats were infused with Kainic acid (KA) intra-cisternally for 5 days at the dosage of 50 fmol/day and 150 fmol/day. Locomotor activity, sensory function and histological changes in cervical and lumbar sections of spinal cord were evaluated. Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Protein (NFP) were used as immunohistochemical marker for reactive astrogliosis and neuronal damage respectively. Specific Superoxide Dismutase (SOD) activity of spinal cord was estimated. The locomotor activity in the parameter of observed mean action time remained reduced on 14th day after administration of KA. Spinal motor neurons under Nissl stain showed pyknosis of nucleus and vacuolation of neuropil. GFAP expression increased significantly in the lumbar section of the spinal cord with high dose of KA treatment (p<0.05). NFP was expressed in axonal fibres around the neurons in KA-treated rats. A significant increase in specific SOD activity in both cervical and lumbar sections of the spinal cord was found with low dose of KA treatment (p<0.05). This study concludes that spinal cord damage with some features similar to ALS can be produced by low dose intra-cisternal administration of KA. PMID:23923068

  11. Effects of microtubule-associated protein tau expression on neural stem cell migration after spinal cord injury

    PubMed Central

    Qi, Zhi-ping; Wang, Guo-xiang; Xia, Peng; Hou, Ting-ting; Zhou, Hong-li; Wang, Tie-jun; Yang, Xiao-yu

    2016-01-01

    Our preliminary proteomics analysis suggested that expression of microtubule-associated protein tau is elevated in the spinal cord after injury. Therefore, the first aim of the present study was to examine tau expression in the injured spinal cord. The second aim was to determine whether tau can regulate neural stem cell migration, a critical factor in the successful treatment of spinal cord injury. We established rat models of spinal cord injury and injected them with mouse hippocampal neural stem cells through the tail vein. We used immunohistochemistry to show that the expression of tau protein and the number of migrated neural stem cells were markedly increased in the injured spinal cord. Furthermore, using a Transwell assay, we showed that neural stem cell migration was not affected by an elevated tau concentration in the outer chamber, but it was decreased by changes in intracellular tau phosphorylation state. These results demonstrate that neural stem cells have targeted migration capability at the site of injury, and that although tau is not a chemokine for targeted migration of neural stem cells, intracellular tau phosphorylation/dephosphorylation can inhibit cell migration. PMID:27073389

  12. Learning about time within the spinal cord: evidence that spinal neurons can abstract and store an index of regularity

    PubMed Central

    Lee, Kuan H.; Turtle, Joel D.; Huang, Yung-Jen; Strain, Misty M.; Baumbauer, Kyle M.; Grau, James W.

    2015-01-01

    Prior studies have shown that intermittent noxious stimulation has divergent effects on spinal cord plasticity depending upon whether it occurs in a regular (fixed time, FT) or irregular (variable time, VT) manner: In spinally transected animals, VT stimulation to the tail or hind leg impaired spinal learning whereas an extended exposure to FT stimulation had a restorative/protective effect. These observations imply that lower level systems are sensitive to temporal relations. Using spinally transected rats, it is shown that the restorative effect of FT stimulation emerges after 540 shocks; fewer shocks generate a learning impairment. The transformative effect of FT stimulation is related to the number of shocks administered, not the duration of exposure. Administration of 360 FT shocks induces a learning deficit that lasts 24 h. If a second bout of FT stimulation is given a day after the first, it restores the capacity to learn. This savings effect implies that the initial training episode had a lasting (memory-like) effect. Two bouts of shock have a transformative effect when applied at different locations or at difference frequencies, implying spinal systems abstract and store an index of regularity (rather than a specific interval). Implications of the results for step training and rehabilitation after injury are discussed. PMID:26539090

  13. The effects of particulate ambient air pollution on the murine umbilical cord and its vessels: a quantitative morphological and immunohistochemical study.

    PubMed

    Veras, Mariana Matera; Guimarães-Silva, Rosane Maria; Caldini, Elia Garcia; Saldiva, Paulo H N; Dolhnikoff, Marisa; Mayhew, Terry M

    2012-12-01

    Previous studies have shown that particulate matter (PM) compromise birth weight and placental morphology. We hypothesized that exposing mice to ambient PM would affect umbilical cord (UC) morphology. To test this, mice were kept in paired open-top exposure chambers at the same location and ambient conditions but, in one chamber, the air was filtered (F) and, in the other, it was not (NF). UCs were analysed stereologically and by immunohistochemistry to localize isoprostane and endothelin receptors. The cords of mice from NF chambers were smaller in volume due to loss of mucoid connective tissue and decrease in volume of collagen. These structural changes and in umbilical vessels were associated with greater volumes of regions immunostained for isoprostane, ET(A)R and ET(B)R. Findings indicate that the adverse effects of PM on birth weight may be mediated in part by alterations in UC structure or imbalances in the endogenous regulators of vascular tone and oxidative stress.

  14. Characteristics and rehabilitation for patients with spinal cord stab injury.

    PubMed

    Wang, Fangyong; Zhang, Junwei; Tang, Hehu; Li, Xiang; Jiang, Shudong; Lv, Zhen; Liu, Shujia; Chen, Shizheng; Liu, Jiesheng; Hong, Yi

    2015-12-01

    [Purpose] The objective of the study was to compare the incidence, diagnosis, treatment, and prognosis of patients with spinal cord stab injury to those with the more common spinal cord contusion injury. [Subjects] Of patients hospitalized in China Rehabilitation Research Center from 1994 to 2014, 40 of those having a spinal cord stab injury and 50 with spinal cord contusion were selected. [Methods] The data of all patients were analyzed retrospectively. The cases were evaluated by collecting admission and discharge ASIA (American Spinal Injury Association) and ADL (activity of daily living) scores. [Results] After a comprehensive rehabilitation program, ASIA and ADL scores of patients having both spinal cord stab injury and spinal cord contusion significantly increase. However, the increases were noted to be higher in patients having a spinal cord stab injury than those having spinal cord contusion. [Conclusion] Comprehensive rehabilitation is effective both for patients having spinal cord stab injury and those with spinal cord contusion injury. However, the prognosis of patients having spinal cord stab injury is better than that of patients with spinal cord contusion.

  15. Nanoparticles Exacerbate Both Ubiquitin and Heat Shock Protein Expressions in Spinal Cord Injury: Neuroprotective Effects of the Proteasome Inhibitor Carfilzomib and the Antioxidant Compound H-290/51.

    PubMed

    Sharma, Hari S; Muresanu, Dafin F; Lafuente, Jose V; Sjöquist, Per-Ove; Patnaik, Ranjana; Sharma, Aruna

    2015-10-01

    Increased levels of ubiquitin and heat shock protein (HSP) 72 kD are often seen in spinal cord injury (SCI). However, their roles in cell injury or survival are not well known. Thus, we have investigated the possible relationship between ubiquitin and HSP expressions in relation to cell injury in healthy animals, or following nanoparticle (NP) intoxication in SCI animals. A focal SCI was inflicted on the T10-11 segments over the right dorsal horn; animals were allowed to survive from 5 to 8 h after trauma. Separate groups of rats were exposed to SiO2, Ag, or Cu NPs for 7 days and subjected to SCI on the eighth day. A marked increase in ubiquitin or HSP immunoreactive cells occurred in the T9 to T12 segments 5 h after the injury, which further extended to the T4 and L5 after 8 h of survival. At this time, a marked increase in blood-spinal cord barrier (BSCB) permeability to Evans blue and radioiodine, accompanied by an intense edema formation, was observed. Changes were further exacerbated in NP-treated traumatized rats. The most marked expressions of ubiquitin and HSP in SCI were seen in rats treated with SiO2, followed by Ag, and Cu NPs. Treatment with H-290/51 (50 mg/kg p.o., 30 to 60 min after injury) or carfilzomib (1 mg/kg, i.v., 30 to 60 min after trauma) significantly reduced the ubiquitin or HSP expressions, as well as the BSCB breakdown, the edema formation, and the cell injury in the cord both 5 and 8 h after the injury, in normal animals. However, a double dose of H-290/51 (100 mg/kg) or carfilzomib (2 mg/kg) is needed to reduce cord pathology or ubiquitin and HSP expressions in traumatized animals treated with NPs. H-290/51 showed superior beneficial effects in reducing cord pathology in SCI than carfilzomib. These observations are the first to demonstrate that (i) NP-treated traumatized animals induce a widespread BSCB leakage, edema formation, and cord pathology as well as an overexpression of ubiquitin and HSP, (ii) high doses of antioxidant

  16. Effects of magnetic nanoparticle-incorporated human bone marrow-derived mesenchymal stem cells exposed to pulsed electromagnetic fields on injured rat spinal cord.

    PubMed

    Cho, Hyunjin; Choi, Yun-Kyong; Lee, Dong Heon; Park, Hee Jung; Seo, Young-Kwon; Jung, Hyun; Kim, Soo-Chan; Kim, Sung-Min; Park, Jung-Keug

    2013-01-01

    Transplanting mesenchymal stem cells into injured lesions is currently under study as a therapeutic approach for spinal cord injury. In this study, the effects of a pulsed electromagnetic field (PEMF) on injured rat spinal cord were investigated in magnetic nanoparticle (MNP)-incorporated human bone marrow-derived mesenchymal stem cells (hBM-MSCs). A histological analysis revealed significant differences in MNP-incorporated cell distribution near the injured site under the PEMF in comparison with that in the control group. We confirmed that MNP-incorporated cells were widely distributed in the lesions under PEMF. The results suggest that MNP-incorporated hBM-MSCs were guided by the PEMF near the injured site, and that PEMF exposure for 8 H per day over 4 weeks promoted behavioral recovery in spinal cord injured rats. The results show that rats with MNP-incorporated hBM-MSCs under a PEMF were more effective on the Basso, Beattie, and Bresnahan behavioral test and suggest that the PEMF enhanced the action of transplanted cells for recovery of the injured lesion.

  17. Human Umbilical Cord Wharton's Jelly Stem Cell Conditioned Medium Induces Tumoricidal Effects on Lymphoma Cells Through Hydrogen Peroxide Mediation.

    PubMed

    Lin, Hao Daniel; Fong, Chui-Yee; Biswas, Arijit; Choolani, Mahesh; Bongso, Ariff

    2016-09-01

    Several groups have reported that human umbilical cord Wharton's jelly stem cells (hWJSCs) possess unique tumoricidal properties against many cancers. However, the exact mechanisms as to how hWJSCs inhibit tumor growth are not known. Recent evidence suggests that exposure of cancer cells to high hydrogen peroxide (H2 O2 ) levels from H2 O2 -releasing drugs causes their death. We therefore explored whether the tumoricidal effect of hWJSCs on lymphoma cells was mediated via H2 O2 . We first exposed lymphoma cells to six different molecular weight cut-off (MWCO) concentrates of hWJSC-conditioned medium (hWJSC-CM) (3, 5, 10, 30, 50, 100 kDa) for 48 h. Since, the 3 kDa-MWCO concentrate showed the greatest cell inhibition we then investigated whether the tumoricidal effect of the specific 3 kDa-MWCO concentrate on two different lymphoma cell lines (Ramos and Toledo) was mediated via accumulation of H2 O2 . We used a battery of assays (MTT, propidium iodide, mitochondria membrane potential, apoptosis, cell cycle, oxidative stress enzymes, hydrogen peroxide, mitochondrial superoxide, hydroxyl radical, peroxynitrile anion, and lipid peroxidation) to test this mechanism. The hWJSC-CM-3 kDa MWCO concentrate significantly decreased cell viability and mitochondrial membrane potential and increased cell death and apoptosis in both lymphoma cell lines. There were significant increases in superoxide dismutase with concomitant decreases in glutathione peroxidase, catalase, and thioredoxin peroxidase activities. H2 O2 levels, mitochondrial superoxide, hydroxyl radical, peroxynitrile anion, and lipid peroxidation were also significantly increased in both lymphoma cell lines. The results suggested that the hWJSC-CM-3 kDa MWCO concentrate regulates cellular H2 O2 leading to a tumoricidal effect and may thus be a promising anti-lymphoma agent. J. Cell. Biochem. 117: 2045-2055, 2016. © 2016 Wiley Periodicals, Inc. PMID:27392313

  18. Chronic Contusion Spinal Cord Injury Impairs Ejaculatory Reflexes in Male Rats: Partial Recovery by Systemic Infusions of Dopamine D3 Receptor Agonist 7OHDPAT.

    PubMed

    Kozyrev, Natalie; Staudt, Michael D; Brown, Arthur; Coolen, Lique M

    2016-05-15

    Chronic spinal cord injury (SCI) causes major disruption of ejaculatory function in men. Ejaculation is a reflex and the spinal generator for ejaculatory reflexes in the rat has been located in the lumbosacral spinal cord. The effects of SCI on the rat spinal ejaculation generator and ejaculatory reflexes remain understudied. The first goal of the current study was to establish the effects of chronic SCI on the function of the spinal ejaculation generator. Male rats received a contusion injury of the spinal cord at spinal level T6-T7. Ejaculatory reflexes elicited by electrical stimulation of the dorsal penile nerve (DPN) were evaluated in injured and control rats at 4-6 weeks following SCI. SCI males demonstrated significant reductions in bursting of the bulbocavernosus muscle (BCM), an indicator for expulsion phase of ejaculation, and in seminal vesicle pressure (SVP) increases, an indicator for the emission phase of ejaculation, following DPN stimulation. Thus, contusion SCI resulted in long-term impairment of ejaculatory reflexes. The D3 agonist 7-hydroxy-2-(di-N-propylamino) tetralin (7OHDPAT) facilitates ejaculation in spinal cord intact rats, thus the second goal of the current study was to test whether subcutaneous infusions of 7OHDPAT can facilitate ejaculatory reflexes in rats with chronic SCI. Male rats received a contusion injury at T6-T7 and effects of systemic administration of 7OHDPAT (1 mg/kg) were tested 4-5 weeks following injury. Results showed that 7OHDPAT administration facilitated ejaculatory reflexes in SCI males with or without DPN stimulation, provided that supraspinal inputs to the lumbar cord were severed by transection just prior to evaluating the reflex. Thus, 7OHDPAT administration in SCI males was able to overcome the detrimental effects of SCI on ejaculatory reflexes.

  19. Positively Charged Oligo[Poly(Ethylene Glycol) Fumarate] Scaffold Implantation Results in a Permissive Lesion Environment after Spinal Cord Injury in Rat

    PubMed Central

    Hakim, Jeffrey S.; Esmaeili Rad, Melika; Grahn, Peter J.; Chen, Bingkun K.; Knight, Andrew M.; Schmeichel, Ann M.; Isaq, Nasro A.; Dadsetan, Mahrokh; Yaszemski, Michael J.

    2015-01-01

    Positively charged oligo[poly(ethylene glycol) fumarate] (OPF+) scaffolds loaded with Schwann cells bridge spinal cord injury (SCI) lesions and support axonal regeneration in rat. The regeneration achieved is not sufficient for inducing functional recovery. Attempts to increase regeneration would benefit from understanding the effects of the scaffold and transplanted cells on lesion environment. We conducted morphometric and stereological analysis of lesions in rats implanted with OPF+ scaffolds with or without loaded Schwann cells 1, 2, 3, 4, and 8 weeks after thoracic spinal cord transection. No differences were found in collagen scarring, cyst formation, astrocyte reactivity, myelin debris, or chondroitin sulfate proteoglycan (CSPG) accumulation. However, when scaffold-implanted animals were compared with animals with transection injuries only, these barriers to regeneration were significantly reduced, accompanied by increased activated macrophages/microglia. This distinctive and regeneration permissive tissue reaction to scaffold implantation was independent of Schwann cell transplantation. Although the tissue reaction was beneficial in the short term, we observed a chronic fibrotic host response, resulting in scaffolds surrounded by collagen at 8 weeks. This study demonstrates that an appropriate biomaterial scaffold improves the environment for regeneration. Future targeting of the host fibrotic response may allow increased axonal regeneration and functional recovery. PMID:25891264

  20. Effects of human umbilical cord mesenchymal stem cell transplantation combined with minimally invasive hematoma aspiration on intracerebral hemorrhage in rats

    PubMed Central

    Zhang, Qinghua; Shang, Xiao; Hao, Maolin; Zheng, Maoyong; Li, Yanxia; Liang, Zhigang; Cui, Yuanxiao; Liu, Zhenhua

    2015-01-01

    This study is to investigate the effects of human umbilical cord-mesenchymal stem cells (HUC-MSCs) transplantation combined with minimally invasive hematoma aspiration on neural functional recovery and p53 gene expression in rats with intracerebral hemorrhage (ICH). Collagenase type-IV was injected to the caudate nucleus of the rats to make ICH models. One hundred and twenty Sprague-Dawley rats with successful modeling were randomly divided into 4 groups, including the ICH group, hematoma aspiration group, HUC-MSCs transplantation group and HUC-MSCs transplantation combined with hematoma aspiration group (combination group). Neural functional status of the rats was assessed by modified neurological severity score (mNSS). Expression of p53 in the cerebral tissues surrounding ICH was detected by immunohistochemical assays. The scores of mNSS and the expression of p53 gene in the hematoma aspiration group, the HUC-MSCs transplantation group and the combination group were significantly lower than those in the ICH group at each indicated time point (p < 0.05). Intriguingly, mNSS scores and p53 expression in the combination group were significantly lower than those in the hematoma aspiration group on day 7, 14 and 30 (p < 0.05), and significantly lower than those in the HUC-MSCs transplantation group on day 14 and 30 (p < 0.05). HUC-MSCs transplantation combined with minimally invasive hematoma aspiration is more effective than either therapy alone in rats with ICH and could distinctly reduce the damage of nerve cells. PMID:26807166

  1. Effects of Aerobic Exercise Training on Fitness and Walking Related Outcomes in Ambulatory Individuals with Chronic Incomplete Spinal Cord Injury

    PubMed Central

    DiPiro, Nicole D.; Embry, Aaron E.; Fritz, Stacy L.; Middleton, Addie; Krause, James S.; Gregory, Chris M.

    2015-01-01

    Study Design Single group, pretest-posttest study. Objectives To determine the effects of a non-task-specific, voluntary, progressive aerobic exercise training (AET) intervention on fitness and walking-related outcomes in ambulatory adults with chronic motor-incomplete SCI. Setting Rehabilitation research center. Methods Ten ambulatory individuals (50% female; 57.94 ± 9.33 years old; 11.11 ± 9.66 years post injury) completed voluntary, progressive moderate-to-vigorous intensity AET on a recumbent stepper three days per week for six weeks. The primary outcome measures were aerobic capacity (VO2peak) and self-selected overground walking speed (OGWS). Secondary outcome measures included: walking economy, six-minute walk test (6MWT), daily step counts, Walking Index for Spinal Cord Injury (WISCI-II), Dynamic Gait Index (DGI), and Berg Balance Scale (BBS). Results Nine participants completed all testing and training. Significant improvements in aerobic capacity (P=0.011), OGWS (P=0.023), the percentage of VO2peak utilized while walking at self-selected speed (P=0.03), and daily step counts (P=0.025) resulted following training. Conclusions The results indicate that total-body, voluntary, progressive AET is safe, feasible, and effective for improving aerobic capacity, walking speed, and select walking-related outcomes in an exclusively ambulatory SCI sample. This study suggests the potential for non-task-specific aerobic exercise to improve walking following incomplete SCI and builds a foundation for further investigation aimed at the development of exercise based rehabilitation strategies to target functionally limiting impairments in ambulatory individuals with chronic SCI. PMID:26666508

  2. Effects of intravenous administration of umbilical cord blood CD34(+) cells in a mouse model of neonatal stroke.

    PubMed

    Tsuji, M; Taguchi, A; Ohshima, M; Kasahara, Y; Sato, Y; Tsuda, H; Otani, K; Yamahara, K; Ihara, M; Harada-Shiba, M; Ikeda, T; Matsuyama, T

    2014-03-28

    Neonatal stroke occurs in approximately 1/4000 live births and results in life-long neurological impairments: e.g., cerebral palsy. Currently, there is no evidence-based specific treatment for neonates with stroke. Several studies have reported the benefits of umbilical cord blood (UCB) cell treatment in rodent models of neonatal brain injury. However, all of the studies examined the effects of administering either the UCB mononuclear cell fraction or UCB-derived mesenchymal stem cells in neonatal rat models. The objective of this study was to examine the effects of human UCB CD34(+) cells (hematopoietic stem cell/endothelial progenitor cells) in a mouse model of neonatal stroke, which we recently developed. On postnatal day 12, immunocompromized (SCID) mice underwent permanent occlusion of the left middle cerebral artery (MCAO). Forty-eight hours after MCAO, human UCB CD34(+) cells (1×10(5)cells) were injected intravenously into the mice. The area in which cerebral blood flow (CBF) was maintained was temporarily larger in the cell-treated group than in the phosphate-buffered saline (PBS)-treated group at 24h after treatment. With cell treatment, the percent loss of ipsilateral hemispheric volume was significantly ameliorated (21.5±1.9%) compared with the PBS group (25.6±5.1%) when assessed at 7weeks after MCAO. The cell-treated group did not exhibit significant differences from the PBS group in either rotarod (238±46s in the sham-surgery group, 175±49s in the PBS group, 203±54s in the cell-treated group) or open-field tests. The intravenous administration of human UCB CD34(+) cells modestly reduced histological ischemic brain damage after neonatal stroke in mice, with a transient augmentation of CBF in the peri-infarct area. PMID:24444827

  3. Characterizing scale-specific environmental factors affecting soil organic carbon along two landscape transects.

    PubMed

    She, Dongli; Cao, Yutong; Chen, Qian; Yu, Shuang'en

    2016-09-01

    Soil organic carbon (SOC) is one of the most important soil properties affecting many other soil and environmental properties and processes. In order to understand and manage SOC effectively, it is important to identify the scale-specific main factors affecting SOC distributions, which in this study occurred in a watershed on the Loess Plateau. Two transects were selected that passed along the upper slopes on each side of the main gully of the Liudaogou watershed. Transect 1 (3411-m length) had 27 sampling sites at 131-m intervals; transect 2 (3597 m length) had 30 sampling sites at 124-m intervals. The two transects were chosen in order to compare landscape patterns of differing complexity that were in close proximity, which reduced the effects of factors that would be caused by different locations. The landscape of transect 1 was more complex due to the greater diversity in cultivation. Multivariate empirical mode decomposition (MEMD) decomposed the total variation in SOC and five selected environmental factors into four intrinsic mode functions (IMFs) and a residual according to the scale of occurrence. Scale-specific correlation analysis was used to identify significant relationships between SOC and the environmental factors. The dominant scales were those that were the largest contributors to the total SOC variance; for transect 1, this was the IMF 1 (scale of 403 m), whereas for transect 2, it was the medium scale of the IMF 2 (scale of 688 m). For both transects, vegetation properties (vegetation cover and aboveground biomass) were the main factors affecting SOC distributions at their respective dominant scales. At each scale, the main effective factors could be identified although at the larger scales, their contributions to the overall variance were almost negligible. The distributions of SOC and the factors affecting it were found to be scale dependent. The results of this study highlighted the suitability of the MEMD method in revealing the main scale

  4. Anti-inflammatory and anti-apoptotic effect of combined treatment with methylprednisolone and amniotic membrane mesenchymal stem cells after spinal cord injury in rats.

    PubMed

    Gao, Shan; Ding, Jie; Xiao, Hai-Jun; Li, Zhi-Qiang; Chen, Yan; Zhou, Xing-Sheng; Wang, Jing-E; Wu, Jiang; Shi, Wei-Ze

    2014-08-01

    This study was undertaken to investigate the synergistic effects of methylprednisolone (MP) administration and transplantation of amniotic membrane mesenchymal stem cells (AM-MSCs) following T11 spinal cord clip compressive injury in rats. The combination treatment with MP (50 mg/kg) and delayed transplantation of AM-MSCs after rat spinal cord injury, significantly reduced (1) myeloperoxidase activity, (2) the proinflammatory cytokines: tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-17, interferon-γ and (3) the cell apoptosis [terminal deoxynucleotidyl transferase, dUTP nick end labeling (TUNEL) staining, and caspase-3, Bax and Bcl-2 expressions]; increased: (1) the levels of the anti-inflammatory cytokines (IL-10 and transforming growth factor-β1) and (2) the survival rate of AM-MSCs in the injury site. The combination therapy significantly ameliorated the recovery of limb function (evaluated by Basso, Beattie and Bresnahan score). Taken together, our results demonstrate that MP in combination with AM-MSCs transplantation is a potential strategy for reducing secondary damage and promoting functional recovery following spinal cord injury.

  5. 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.

  6. Staging Childhood Brain and Spinal Cord Tumors

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Childhood brain and spinal cord tumors ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. These are ...

  7. DOM along the Continuum from River to Reservoir: a Comparison of Freshwater and Saline Transects

    NASA Astrophysics Data System (ADS)

    Minor, E. C.; Stephens, B.

    2009-04-01

    Dissolved organic matter (DOM) plays key roles in aquatic ecosystems: as an organic carbon (energy) link between terrestrial and aquatic systems, a food source for biota, a reactant in photochemical reactions, and a sunscreen/competitor for light for aquatic organisms. The composition as well as the concentration of aquatic DOM is believed to determine DOM's efficacy in these roles. The transport and alteration of DOM in river/estuarine systems are significant processes in determining the concentration and composition of DOM in the receiving lake or ocean system (especially in productive and economically important coastal regions). Therefore this study provides a preliminary comparison of the dissolved organic carbon (DOC) concentration, DOM optical properties, and chemical composition of high molecular weight DOM (HMW DOM) on two river-to-receiving-basin transects, one freshwater (St. Louis River/Lake Superior, Minnesota, USA) and the other with a salinity gradient (Elizabeth River/lower Chesapeake Bay/coastal Atlantic, Virginia, USA). Both transects share optical property ranges and general downstream trends toward lower DOC concentrations, less aromaticity, and lower molecular weight DOM, however, there is a stronger downstream decrease in DOC concentration in the saline transect. In HMW DOM, there is more retention of carboxylic signals downstream in the freshwater transect, relative to a downstream shift toward more proteinaceous material in the saline transect. These observed DOM differences most likely result from variations in biological activity, photochemistry, and ionic strength in the two transects. Ionic strength effects include in situ processes (e.g. flocculation) and interactions affecting DOM isolation and analysis.

  8. 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

    2015-05-01

    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.

  9. 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

  10. Effects of retractor application on cuff pressure and vocal cord function in patients undergoing anterior cervical discectomy and fusion.

    PubMed

    Garg, Rakesh; Rath, Girija P; Bithal, Parmod K; Prabhakar, Hemanshu; Marda, Manish K

    2010-07-01

    Anterior cervical discectomy and fusion is a commonly performed procedure for prolapse of cervical intervertebral disc. It involves retraction of soft tissue of neck for adequate exposure of anterior spinal canal. Increased cuff pressure with retractor application may affect the postoperative vocal cord function. Cuff pressures of tracheal tube were measured continuously in 37 patients using air-filled pressure transducer connected to the pilot balloon. Changes of pressure from baseline values were noted after application of cervical retractor. At the end of procedure, vocal cord movement was observed using fibreoptic bronchoscope. Significant increase in cuff pressure (168% of baseline values) and airway pressure of tracheal tube during cervical retraction was observed. The vocal cord function was assessed using fibreoptic laryngoscope. One patient developed right vocal cord palsy (2.7%) and two patients had postoperative hoarseness of voice (5.4%). All these complications improved over a period of time. It is suggested that the cuff of tracheal tube should be inflated to achieve 'just seal', with adequate cuff pressure monitoring. Intermittent release of cervical retraction may help to prevent laryngeal morbidities.

  11. Effects of retractor application on cuff pressure and vocal cord function in patients undergoing anterior cervical discectomy and fusion

    PubMed Central

    Garg, Rakesh; Rath, Girija P; Bithal, Parmod K; Prabhakar, Hemanshu; Marda, Manish K

    2010-01-01

    Anterior cervical discectomy and fusion is a commonly performed procedure for prolapse of cervical intervertebral disc. It involves retraction of soft tissue of neck for adequate exposure of anterior spinal canal. Increased cuff pressure with retractor application may affect the postoperative vocal cord function. Cuff pressures of tracheal tube were measured continuously in 37 patients using air-filled pressure transducer connected to the pilot balloon. Changes of pressure from baseline values were noted after application of cervical retractor. At the end of procedure, vocal cord movement was observed using fibreoptic bronchoscope. Significant increase in cuff pressure (168% of baseline values) and airway pressure of tracheal tube during cervical retraction was observed. The vocal cord function was assessed using fibreoptic laryngoscope. One patient developed right vocal cord palsy (2.7%) and two patients had postoperative hoarseness of voice (5.4%). All these complications improved over a period of time. It is suggested that the cuff of tracheal tube should be inflated to achieve ‘just seal’, with adequate cuff pressure monitoring. Intermittent release of cervical retraction may help to prevent laryngeal morbidities. PMID:20882169

  12. The Effects of Secretion Factors from Umbilical Cord Derived Mesenchymal Stem Cells on Osteogenic Differentiation of Mesenchymal Stem Cells

    PubMed Central

    Wang, Kui-Xing; Xu, Liang-Liang; Rui, Yun-Feng; Huang, Shuo; Lin, Si-En; Xiong, Jiang-Hui; Li, Ying-Hui; Lee, Wayne Yuk-Wai; Li, Gang

    2015-01-01

    Factors synthesized by mesenchymal stem cells (MSCs) contain various growth factors, cytokines, exosomes and microRNAs, which may affect the differentiation abilities of MSCs. In the present study, we investigated the effects of secretion factors of human umbilical cord derived mesenchymal stem cells (hUCMSCs) on osteogenesis of human bone marrow derived MSCs (hBMSCs). The results showed that 20 μg/ml hUCMSCs secretion factors could initiate osteogenic differentiation of hBMSCs without osteogenic induction medium (OIM), and the amount of calcium deposit (stained by Alizarin Red) was significantly increased after the hUCMSCs secretion factors treatment. Real time quantitative reverse transcription-polymerase chain reaction (real time qRT-PCR) demonstrated that the expression of osteogenesis-related genes including ALP, BMP2, OCN, Osterix, Col1α and Runx2 were significantly up-regulated following hUCMSCs secretion factors treatment. In addition, we found that 10 μg hUCMSCs secretion factors together with 2×105 hBMSCs in the HA/TCP scaffolds promoted ectopic bone formation in nude mice. Local application of 10 μg hUCMSCs secretion factors with 50 μl 2% hyaluronic acid hydrogel and 1×105 rat bone marrow derived MSCs (rBMSCs) also significantly enhanced the bone repair of rat calvarial bone critical defect model at both 4 weeks and 8 weeks. Moreover, the group that received the hUCMSCs secretion factors treatment had more cartilage and bone regeneration in the defect areas than those in the control group. Taken together, these findings suggested that hUCMSCs secretion factors can initiate osteogenesis of bone marrow MSCs and promote bone repair. Our study indicates that hUCMSCs secretion factors may be potential sources for promoting bone regeneration. PMID:25799169

  13. Effect of chronic activity-based therapy on bone mineral density and bone turnover in persons with spinal cord injury

    PubMed Central

    Harness, Eric T.; Witzke, Kara A.

    2014-01-01

    Purpose Osteoporosis is a severe complication of spinal cord injury (SCI). Many exercise modalities are used to slow bone loss, yet their efficacy is equivocal. This study examined the effect of activity-based therapy (ABT) targeting the lower extremities on bone health in individuals with SCI. Methods Thirteen men and women with SCI (age and injury duration = 29.7 ± 7.8 and 1.9 ± 2.7 years) underwent 6 months of ABT. At baseline and after 3 and 6 months of training, blood samples were obtained to assess bone formation (serum procollagen type 1 N propeptide (PINP) and bone resorption (serum C-terminal telopeptide of type I collagen (CTX), and participants underwent dual-energy X-ray absorptiometry scans to obtain total body and regional estimates of bone mineral density (BMD). Results Results demonstrated significant increases (p < 0.05) in spine BMD (+4.8 %; 1.27 ± 0.22–1.33 ± 0.24 g/cm2) and decreases (p < 0.01) in total hip BMD (−6.1 %; 0.98 ± 0.18–0.91 ± 0.16 g/cm2) from 0 to 6 months of training. BMD at the bilateral distal femur (−7.5 to −11.0 %) and proximal tibia (− 8.0 to −11.2 %) declined but was not different (p > 0.05) versus baseline. Neither PINP nor CTX was altered (p> 0.05) with training. Conclusions Chronic activity-based therapy did not reverse bone loss typically observed soon after injury, yet reductions in BMD were less than the expected magnitude of decline in lower extremity BMD in persons with recent SCI. PMID:24097172

  14. Effect of Spinal Cord Injury on Quality of Life of Affected Soldiers in India: A Cross-Sectional Study

    PubMed Central

    Gupta, Bhawna

    2016-01-01

    Study Design A prospective cross-sectional study with convenience sampling approach was done to assess quality of life (QoL) in 100 soldiers and veterans affected by spinal cord injury (SCI). Purpose SCI affects almost every aspect of the life of an affected individual. This study was done to measure the impact of SCI on QoL of affected soldiers and veterans using the WHOQOL-BREF questionnaire. Overview of Literature The devastating effect of SCI on QoL is well known. However, this study is unique in that it includes soldiers and veterans, who constitute a large, but excluded, cohort in most demographic studies. Methods A cross-sectional study was done at two SCI rehabilitation centres of the Indian armed forces. Data was collected by face-to-face interviews from 100 patients, which included both sociodemographic data as well as all the questions included in WHOQOL-BREF questionnaire. Statistical analysis was performed using SPSS software. Results Age and marital status did not have any influence on QoL. Level of injury (paraplegic or quadriplegic), level of education and presence of other medical co-morbidities had the most significant influence on QoL. Presence of other medical co-morbidities had a negative influence on QoL. Conclusions Identification of factors having a positive and negative influence on QoL help in formulating measures and policies that positively influence the QoL following SCI in soldiers. Future longitudinal studies with larger sample sizes and assessment of additional variables in addition to WHOQOL-BREF, like presence/absence of secondary complications, are required to bring about policy changes to provide SCI patients with additional support and increased access to equipment or lifestyle interventions. PMID:27114767

  15. Beneficial effect of the oxygen free radical scavenger amifostine (WR-2721) on spinal cord ischemia/reperfusion injury in rabbits

    PubMed Central

    Chronidou, Fany; Apostolakis, Efstratios; Papapostolou, Ioannis; Grintzalis, Konstantinos; Georgiou, Christos D; Koletsis, Efstratios N; Karanikolas, Menelaos; Papathanasopoulos, Panagiotis; Dougenis, Dimitrios

    2009-01-01

    Background Paraplegia is the most devastating complication of thoracic or thoraco-abdominal aortic surgery. During these operations, an ischemia-reperfusion process is inevitable and the produced radical oxygen species cause severe oxidative stress for the spinal cord. In this study we examined the influence of Amifostine, a triphosphate free oxygen scavenger, on oxidative stress of spinal cord ischemia-reperfusion in rabbits. Methods Eighteen male, New Zealand white rabbits were anesthetized and spinal cord ischemia was induced by temporary occlusion of the descending thoracic aorta by a coronary artery balloon catheter, advanced through the femoral artery. The animals were randomly divided in 3 groups. Group I functioned as control. In group II the descending aorta was occluded for 30 minutes and then reperfused for 75 min. In group III, 500 mg Amifostine was infused into the distal aorta during the second half-time of ischemia period. At the end of reperfusion all animals were sacrificed and spinal cord specimens were examined for superoxide radicals by an ultra sensitive fluorescent assay. Results Superoxide radical levels ranged, in group I between 1.52 and 1.76 (1.64 ± 0.10), in group II between 1.96 and 2.50 (2.10 ± 0.23), and in group III (amifostine) between 1.21 and 1.60 (1.40 ± 0.19) (p = 0.00), showing a decrease of 43% in the Group of Amifostine. A lipid peroxidation marker measurement ranged, in group I between 0.278 and 0.305 (0.296 ± 0.013), in group II between 0.427 and 0.497 (0.463 ± 0.025), and in group III (amifostine) between 0.343 and 0.357 (0.350 ± 0.007) (p < 0.00), showing a decrease of 38% after Amifostine administration. Conclusion By direct and indirect methods of measuring the oxidative stress of spinal cord after ischemia/reperfusion, it is suggested that intra-aortic Amifostine infusion during spinal cord ischemia phase, significantly attenuated the spinal cord oxidative injury in rabbits. PMID:19758462

  16. Description of the POLAR Profile transect display

    NASA Astrophysics Data System (ADS)

    Von Knorring, M.; Lund, C.-E.

    1989-05-01

    The POLAR Profile Transect Display attempts to integrate all the existing aeromagnetic, gravimetric, geological and geochemical investigations with the results of the deep seismic and electromagnetic studies carried out along the POLAR Profile. Our description is based on the stage of joint interpretation reached at the Second Earth Science Study Centre. The nearly 440-km long, NE-SW-trending POLAR Profile traverses Archaean and Early Proterozoic parts of the Baltic Shield. The thickness of the crust varies between 40 and 50 km and consists of three distinct crustal layers. A geological interpretation based on the various geophysical results is given for the uppermost 10-14 km thick layer. In the central part of the profile, the overthrust Early Proterozoic Lapland Granulite Belt forms a wedge-shaped body reaching the middle crust. The upper crust is underlain by a transparent layer 16-18 km thick with a smooth increase in velocity and density. A reflective lowermost 10-21-km thick layer has a high-velocity gradient. The crust-mantle has a pronounced topography.

  17. Phosphatase activity against neurofilament proteins from bovine spinal cord: effect of aluminium and neuropsychoactive drugs.

    PubMed

    Shetty, K T; Veeranna; Guru, S C

    1992-03-16

    Protein phosphatase activity associated with neurofilament (NF) rich (Triton X-100 insoluble) fraction was extracted and partially characterised by using known inhibitors of protein phosphatases such as vanadate and fluoride. Protein phosphatase activity was demonstrated with reference to the dephosphorylation of endogenous substrate, NF protein and exogenous protein substrates, casein and phosvitin. Phosphoamino acids and beta-glycerophosphate were found to be poor substrates. Further, new observations have been made regarding the in vitro inhibitory effect of aluminium and the differential effects of some of the neuropsychoactive drugs. The findings could possibly lead to studies explaining the biochemical basis of aluminium induced neurotoxicity as well as the side effects associated with the long term medication of neuropsychoactive drugs. PMID:1320755

  18. Nanomedicine for Treating Spinal Cord Injury

    PubMed Central

    Tyler, Jacqueline Y.; Xu, Xiao-Ming; Cheng, Ji-Xin

    2015-01-01

    Spinal cord injury results in significant mortality and morbidity, lifestyle changes, and difficult rehabilitation. Treatment of spinal cord injury is challenging because the spinal cord is both complex to treat acutely and difficult to regenerate. Nanomaterials can be used to provide effective treatments; their unique properties can facilitate drug delivery to the injury site, enact as neuroprotective agents, or provide platforms to stimulate regrowth of damaged tissues. We review recent uses of nanomaterials including nanowires, micelles, nanoparticles, liposomes, and carbon-based nanomaterials for neuroprotection in the acute phase. We also review the design and neural regenerative application of electrospun scaffolds, conduits, and self-assembling peptide scaffolds. PMID:23945984

  19. Nanomedicine for treating spinal cord injury

    NASA Astrophysics Data System (ADS)

    Tyler, Jacqueline Y.; Xu, Xiao-Ming; Cheng, Ji-Xin

    2013-09-01

    Spinal cord injury results in significant mortality and morbidity, lifestyle changes, and difficult rehabilitation. Treatment of spinal cord injury is challenging because the spinal cord is both complex to treat acutely and difficult to regenerate. Nanomaterials can be used to provide effective treatments; their unique properties can facilitate drug delivery to the injury site, enact as neuroprotective agents, or provide platforms to stimulate regrowth of damaged tissues. We review recent uses of nanomaterials including nanowires, micelles, nanoparticles, liposomes, and carbon-based nanomaterials for neuroprotection in the acute phase. We also review the design and neural regenerative application of electrospun scaffolds, conduits, and self-assembling peptide scaffolds.

  20. Developmental and Functional Effects of Steroid Hormones on the Neuroendocrine Axis and Spinal Cord.

    PubMed

    Zubeldia-Brenner, L; Roselli, C E; Recabarren, S E; Gonzalez Deniselle, M C; Lara, H E

    2016-07-01

    This review highlights the principal effects of steroid hormones at central and peripheral levels in the neuroendocrine axis. The data discussed highlight the principal role of oestrogens and testosterone in hormonal programming in relation to sexual orientation, reproductive and metabolic programming, and the neuroendocrine mechanism involved in the development of polycystic ovary syndrome phenotype. Moreover, consistent with the wide range of processes in which steroid hormones take part, we discuss the protective effects of progesterone on neurodegenerative disease and the signalling mechanism involved in the genesis of oestrogen-induced pituitary prolactinomas. PMID:27262161

  1. In Vivo Neuroprotective Effect of Histidine-Tryptophan-Ketoglutarate Solution in an Ischemia/Reperfusion Spinal Cord Injury Animal Model

    PubMed Central

    Kang, Shin Kwang; Kang, Min-Woong; Rhee, Youn Ju; Kim, Cuk-Seong; Jeon, Byeong Hwa; Han, Sung Joon; Cho, Hyun Jin; Na, Myung Hoon; Yu, Jae-Hyeon

    2016-01-01

    Background Paraplegia is a devastating complication following operations on the thoracoabdominal aorta. We investigated whether histidine-tryptophan-ketoglutarate (HTK) solution could reduce the extent of ischemia/reperfusion (IR) spinal cord injuries in a rat model using a direct delivery method. Methods Twenty-four Sprague-Dawley male rats were randomly divided into four groups. The sham group (n=6) underwent a sham operation, the IR group (n=6) underwent only an aortic occlusion, the saline infusion group (saline group, n=6) underwent an aortic occlusion and direct infusion of cold saline into the occluded aortic segment, and the HTK infusion group (HTK group, n=6) underwent an aortic occlusion and direct infusion of cold HTK solution into the occluded aortic segment. An IR spinal cord injury was induced by transabdominal clamping of the aorta distally to the left renal artery and proximally to the aortic bifurcation for 60 minutes. A neurological evaluation of locomotor function was performed using the modified Tarlov score after 48 hours of reperfusion. The spinal cord was harvested for histopathological and immunohistochemical examinations. Results The spinal cord IR model using direct drug delivery in rats was highly reproducible. The Tarlov score was 4.0 in the sham group, 1.17±0.75 in the IR group, 1.33±1.03 in the saline group, and 2.67±0.81 in the HTK group (p=0.04). The histopathological analysis of the HTK group showed reduced neuronal cell death. Conclusion Direct infusion of cold HTK solution into the occluded aortic segment may reduce the extent of spinal cord injuries in an IR model in rats. PMID:27525231

  2. Explosive cord

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Device, jetcord, is metal-clad linear explosive of sufficient flexibility to allow forming into intricate shapes. Total effect is termed ''cutting'' with jetcord consistently ''cutting'' a target of greater thickness than can be penetrated. Applications include sheet metal working, pipe cutting and fire-fighting.

  3. Effects of ethanol on glycinergic synaptic currents in mouse spinal cord neurons

    PubMed Central

    Mariqueo, Trinidad A.; Agurto, Adolfo; Muñoz, Braulio; San Martin, Loreto; Coronado, Cesar; Fernández-Pérez, Eduardo J.; Murath, Pablo; Sánchez, Andrea; Homanics, Gregg E.

    2014-01-01

    Ethanol increased the frequency of miniature glycinergic currents [miniature inhibitory postsynaptic currents (mIPSCs)] in cultured spinal neurons. This effect was dependent on intracellular calcium augmentation, since preincubation with BAPTA (an intracellular calcium chelator) or thapsigargin [a sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) pump inhibitor] significantly attenuated this effect. Similarly, U73122 (a phospholipase C inhibitor) or 2-aminoethoxydiphenyl borate [2-APB, an inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) inhibitor] reduced this effect. Block of ethanol action was also achieved after preincubation with Rp-cAMPS, inhibitor of the adenylate cyclase (AC)/PKA signaling pathway. These data suggest that there is a convergence at the level of IP3R that accounts for presynaptic ethanol effects. At the postsynaptic level, ethanol increased the decay time constant of mIPSCs in a group of neurons (30 ± 10% above control, n = 13/26 cells). On the other hand, the currents activated by exogenously applied glycine were consistently potentiated (55 ± 10% above control, n = 11/12 cells), which suggests that ethanol modulates synaptic and nonsynaptic glycine receptors (GlyRs) in a different fashion. Supporting the role of G protein modulation on ethanol responses, we found that a nonhydrolyzable GTP analog [guanosine 5′-O-(3-thiotriphosphate) (GTPγS)] increased the decay time constant in ∼50% of the neurons (28 ± 12%, n = 11/19 cells) but potentiated the glycine-activated Cl− current in most of the neurons examined (83 ± 29%, n = 7/9 cells). In addition, confocal microscopy showed that α1-containing GlyRs colocalized with Gβ and Piccolo (a presynaptic cytomatrix protein) in ∼40% of synaptic receptor clusters, suggesting that colocalization of Gβγ and GlyRs might account for the difference in ethanol sensitivity at the postsynaptic level. PMID:24572089

  4. Effects of umbilical cord tissue mesenchymal stem cells (UCX®) on rat sciatic nerve regeneration after neurotmesis injuries

    PubMed Central

    Gärtner, A; Pereira, T; Armada-da-Silva, PAS; Amado, S; Veloso, AP; Amorim, I; Ribeiro, J; Santos, JD; Bárcia, RN; Cruz, P; Cruz, H; Luís, AL; Santos, JM; Geuna, S; Maurício, AC

    2014-01-01

    Peripheral nerves have the intrinsic capacity of self-regeneration after traumatic injury but the extent of the regeneration is often very poor. Increasing evidence demonstrates that mesenchymal stem/stromal cells (MSCs) may play an important role in tissue regeneration through the secretion of soluble trophic factors that enhance and assist in repair by paracrine activation of surrounding cells. In the present study, the therapeutic value of a population of umbilical cord tissue-derived MSCs, obtained by a proprietary method (UCX®), was evaluated on end-to-end rat sciatic nerve repair. Furthermore, in order to promote both, end-to-end nerve fiber contacts and MSC cell-cell interaction, as well as reduce the flush away effect of the cells after administration, a commercially available haemostatic sealant, Floseal®, was used as vehicle. Both, functional and morphologic recoveries were evaluated along the healing period using extensor postural thrust (EPT), withdrawal reflex latency (WRL), ankle kinematics analysis, and either histological analysis or stereology, in the hyper-acute, acute and chronic phases of healing. The histological analysis of the hyper-acute and acute phase studies revealed that in the group treated with UCX® alone the Wallerian degeneration was improved for the subsequent process of regeneration, the fiber organization was higher, and the extent of fibrosis was lower. The chronic phase experimental groups revealed that treatment with UCX® induced an increased number of regenerated fibers and thickening of the myelin sheet. Kinematics analysis showed that the ankle joint angle determined for untreated animals was significantly different from any of the treated groups at the instant of initial contact (IC). At opposite toe off (OT) and heel rise (HR), differences were found between untreated animals and the groups treated with either uCx® alone or UCX® administered with Floseal®. Overall, the UCX® application presented positive effects in

  5. Effects of umbilical cord tissue mesenchymal stem cells (UCX®) on rat sciatic nerve regeneration after neurotmesis injuries.

    PubMed

    Gärtner, A; Pereira, T; Armada-da-Silva, Pas; Amado, S; Veloso, Ap; Amorim, I; Ribeiro, J; Santos, Jd; Bárcia, Rn; Cruz, P; Cruz, H; Luís, Al; Santos, Jm; Geuna, S; Maurício, Ac

    2014-01-01

    Peripheral nerves have the intrinsic capacity of self-regeneration after traumatic injury but the extent of the regeneration is often very poor. Increasing evidence demonstrates that mesenchymal stem/stromal cells (MSCs) may play an important role in tissue regeneration through the secretion of soluble trophic factors that enhance and assist in repair by paracrine activation of surrounding cells. In the present study, the therapeutic value of a population of umbilical cord tissue-derived MSCs, obtained by a proprietary method (UCX(®)), was evaluated on end-to-end rat sciatic nerve repair. Furthermore, in order to promote both, end-to-end nerve fiber contacts and MSC cell-cell interaction, as well as reduce the flush away effect of the cells after administration, a commercially available haemostatic sealant, Floseal(®), was used as vehicle. Both, functional and morphologic recoveries were evaluated along the healing period using extensor postural thrust (EPT), withdrawal reflex latency (WRL), ankle kinematics analysis, and either histological analysis or stereology, in the hyper-acute, acute and chronic phases of healing. The histological analysis of the hyper-acute and acute phase studies revealed that in the group treated with UCX(®) alone the Wallerian degeneration was improved for the subsequent process of regeneration, the fiber organization was higher, and the extent of fibrosis was lower. The chronic phase experimental groups revealed that treatment with UCX(®) induced an increased number of regenerated fibers and thickening of the myelin sheet. Kinematics analysis showed that the ankle joint angle determined for untreated animals was significantly different from any of the treated groups at the instant of initial contact (IC). At opposite toe off (OT) and heel rise (HR), differences were found between untreated animals and the groups treated with either uCx(®) alone or UCX(®) administered with Floseal(®). Overall, the UCX(®) application presented

  6. Somatosensory inputs by application of KinesioTaping: effects on spasticity, balance, and gait in chronic spinal cord injury

    PubMed Central

    Tamburella, Federica; Scivoletto, Giorgio; Molinari, Marco

    2014-01-01

    Introduction: Leg paralysis, spasticity, reduced interlimb coordination, and impaired balance are the chief limitations to overground ambulation in subjects with incomplete spinal cord injury (SCI). In recent years, the application of KinesioTaping (KT) has been proposed to enhance sensory inputs, decreasing spasticity by proprioception feedback and relieving abnormal muscle tension. Because no studies have examined KT-based techniques in SCI subjects, our goal was to analyze the effects of ankle joint KT on spasticity, balance, and gait. Materials and Methods: A randomized crossover case control design was used to compare the effects of KT and conventional nonelastic silk tape (ST) in 11 chronic SCI subjects, AIS level D, with soleus/gastrocnemius (S/G) muscle spasticity and balance and gait impairments. Treatment: 48 h of treatment with KT or ST was followed by 48 h with the other technique after 1 week. A single Y-strip of Cure© tape (KT) and ST was to the S and G muscles with 0% stretch. Before and 48 h after of application of KT and ST, clinical data on the range of motion (ROM), spasticity, clonus, pain, balance, and gait were collected. Stabilometric platform assessment of center of pressure (COP) movements; bidimensional gait analysis; and recording of electromyographic (EMG) activity of the S, G, and tibialis anterior and extensor hallucis lungus muscles were also performed. Results: Only KT had significant effects on spasticity (p < 0.05), clonus (p < 0.001) and COP movements (p < 0.05), kinematic gait parameters (p < 0.001), and EMG activity (p < 0.001). Comparison between ST and KT improvements pointed out significant differences as concerns ROM (p < 0.001), spasticity (p < 0.001), clonus (p < 0.001), pain (p < 0.001), COP parameters (p < 0.05), and most kinematic gait data (p < 0.05). Discussion: Short-term application of KT reduces spasticity and pain and improves balance and gait in chronic SCI subjects. Although these data are promising, they

  7. Effects of receptor-selective neurokinin agonists and a neurokinin antagonist on the electrical activity of spinal cord neurones in culture.

    PubMed Central

    Wienrich, M.; Reuss, K.; Harting, J.

    1989-01-01

    1. Rat spinal cord neurones grown in tissue culture were used to examine the electrophysiological effects of the neurokin in (NK)-selective agonists (pGlu6, Pro9) substance P(6-11) (septide; NK1, 10(-6)M) and (pGlu5, MePhe8, MeGly9)SP(1-7) (DiMe-C7; NK3, 10(-6)M). In addition, the effect of the neurokinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP (10(-5)M) on the neurokinin-evoked responses was investigated. 2. Neurokinin-evoked responses consisted of an increase in neuronal activity with or without long-lasting (mean: 50s) depolarizations of the membrane potential of up to 25mV. The latter also occurred in the presence of tetrodotoxin (10(-7)M) (direct response). 3. In a number of spinal cord neurones (n = 17) only septide induced a membrane depolarization while DiMe-C7 elicited no response. On the other hand, in 2 neurones a response was exclusively evoked by DiMe-C7. 4. The neurokinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP had no effect of its own but blocked the septide- and DiMe-C7-induced depolarizations. It had no effect on the glutamate (10(-5)M)-evoked depolarization. 5. It is concluded that by the use of neurokinin receptor-selective agonists, subpopulations of spinal cord neurones in primary dissociated cell culture can be differentiated which express the NK1 or the NK3 receptor. Cells expressing only the NK1 receptor outnumber those expressing only the NK3 receptor subtype. Both receptors can be blocked by the neurokinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP. PMID:2480170

  8. Fimbria-fornix (FF)-transected hippocampal extracts induce the activation of astrocytes in vitro.

    PubMed

    Zou, Linqing; Li, Haoming; Jin, Guohua; Tian, Meiling; Qin, Jianbing; Zhao, Heyan

    2014-03-01

    Hippocampus is one of the neurogenesis areas in adult mammals, but the function of astrocytes in this area is still less known. In our previous study, the fimbria-fornix (FF)-transected hippocampal extracts promoted the proliferation and neuronal differentiation of radial glial cells in vitro. To explore the effects of hippocampal extracts on gliogenesis, the hippocampal astrocytes were treated by normal or ff-transected hippocampal extracts in vitro. The cells were immunostained by brain lipid-binding protein (BLBP), nestin, and SOX2 to assess their state of activation. The effects of astrocyte-conditioned medium on the neuronal differentiation of hippocampal neural stem cells (NSCs) were also investigated. After treatment of FF-transected hippocampal extracts, the number of BLBP, nestin, and Sox-positive cells were obviously more than the cells which treated by normal hippocampal extracts, these cells maintained a state of activation and the activated astrocyte-conditioned medium also promoted the differentiation of NSCs into more neurons. These findings suggest that the astrocytes can be activated by FF-transected hippocampal extracts and these activated cells also can promote the neuronal differentiation of hippocampal NSCs in vitro.

  9. Spinal Cord Diseases

    MedlinePlus

    ... damages the vertebrae or other parts of the spine, this can also injure the spinal cord. Other spinal cord problems include Tumors Infections such as meningitis and polio Inflammatory diseases Autoimmune diseases Degenerative diseases such as amyotrophic lateral sclerosis and spinal ...

  10. Effects of spinal cord injury and hindlimb immobilization on sublesional and supralesional bones in young growing rats.

    PubMed

    Liu, Da; Zhao, Chang-Qing; Li, Hai; Jiang, Sheng-Dan; Jiang, Lei-Sheng; Dai, Li-Yang

    2008-07-01

    Both spinal cord injury (SCI) and hindlimb cast immobilization (HCI) cause reduction in maturation-related bone gain in young rats, but the effects of the two interventions on bone pathophysiology may be different. The objective of this study was to compare the effects of SCI and HCI on the sublesional/supralesional bones and bone turnover indicators in young rats. Forty male Sprague-Dawley rats (six-week-old) were randomized into four groups, with ten rats in each group. The groups were classified as follows: base-line control, age-matched intact control, HCI, and SCI groups. Bone tissues, blood, and urine samples were studied at 4 weeks after treatments. The tibial dry weights and ash weights in SCI were remarkably reduced by 7.5% (dry weights) and 8.2% (ash weights) compared with HCI. SCI rats showed lower areal bone mineral density in the proximal tibiae compared with HCI rats (- 14%). Cortical thickness and cortical area of the tibial midshaft in SCI were lower than HCI (- 23%,