Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury

PubMed Central

Kasten, M.R.; Sunshine, M.D.; Secrist, E.S.; Horner, P.J.; Moritz, C.T.

2013-01-01

Objective Intraspinal microstimulation (ISMS) is a promising method for activating the spinal cord distal to an injury. The objectives of this study were to examine the ability of chronically implanted stimulating wires within the cervical spinal cord to (1) directly produce forelimb movements, and (2) assess whether ISMS stimulation improved subsequent volitional control of paretic extremities following injury. Approach We developed a technique for implanting intraspinal stimulating electrodes within the cervical spinal cord segments C6-T1 of Long-Evans rats. Beginning 4 weeks after a severe cervical contusion injury at C4–C5, animals in the treatment condition received therapeutic ISMS 7 hours/day, 5 days/week for the following 12 weeks. Main Results Over 12 weeks of therapeutic ISMS, stimulus-evoked forelimb movements were relatively stable. We also explored whether therapeutic ISMS promotes recovery of forelimb reaching movements. Animals receiving daily therapeutic ISMS performed significantly better than unstimulated animals during behavioral tests conducted without stimulation. Quantitative video analysis of forelimb movements showed that stimulated animals performed better in the movements reinforced by stimulation, including extending the elbow to advance the forelimb and opening the digits. While threshold current to elicit forelimb movement gradually increased over time, no differences were observed between chronically stimulated and unstimulated electrodes suggesting that no additional tissue damage was produced by the electrical stimulation. Significance The results indicate that therapeutic intraspinal stimulation delivered via chronic microwire implants within the cervical spinal cord confers benefits extending beyond the period of stimulation, suggesting future strategies for neural devices to promote sustained recovery after injury. PMID:23715242

Cervical spinal demyelination with ethidium bromide impairs respiratory (phrenic) activity and forelimb motor behavior in rats

PubMed Central

Nichols, Nicole L.; Punzo, Antonio M.; Duncan, Ian D.; Mitchell, Gordon S.; Johnson, Rebecca A.

2012-01-01

Although respiratory complications are a major cause of morbidity/mortality in many neural injuries or diseases, little is known concerning mechanisms whereby deficient myelin impairs breathing, or how patients compensate for such changes. Here, we tested the hypothesis that respiratory and forelimb motor function are impaired in a rat model of focal dorsolateral spinal demyelination (ethidium bromide, EB). Ventilation, phrenic nerve activity and horizontal ladder walking were performed 7-14 days post-C2 injection of EB or vehicle (SHAM). EB caused dorsolateral demyelination at C2-C3 followed by signficant spontaneous remyelination at 14 days post-EB. Although ventilation did not differ between groups, ipsilateral integrated phrenic nerve burst amplitude was significantly reduced versus SHAM during chemoreceptor activation at 7 days post-EB but recovered by 14 days. The ratio of ipsi- to contralateral phrenic nerve amplitude correlated with cross-sectional lesion area. This ratio was significantly reduced 7 days post-EB versus SHAM during baseline conditions, and versus SHAM and 14 day groups during chemoreceptor activation. Limb function ipsilateral to EB was impaired 7 days post-EB and partially recovered by 14 days post-EB. EB provides a reversible model of focal, spinal demyelination, and may be a useful model to study mechanisms of functional impairment and recovery via motor plasticity, or the efficacy of new therapeutic interventions to reduce severity or duration of disease. PMID:23159317

Activity-Based Therapies To Promote Forelimb Use after a Cervical Spinal Cord Injury

PubMed Central

Dai, Haining; MacArthur, Linda; McAtee, Marietta; Hockenbury, Nicole; Tidwell, J. Lille; McHugh, Brian; Mansfield, Kevin; Finn, Tom; Hamers, Frank P.T.

2009-01-01

Abstract Significant interest exists in strategies for improving forelimb function following spinal cord injury. We investigated the effect of enriched housing combined with skilled training on the recovery of skilled and automatic forelimb function after a cervical spinal cord injury in adult rats. All animals were pretrained in skilled reaching, gridwalk crossing, and overground locomotion. Some received a cervical over-hemisection lesion at C4-5, interrupting the right side of the spinal cord and dorsal columns bilaterally, and were housed in standard housing alone or enriched environments with daily training. A subset of animals received rolipram to promote neuronal plasticity. Animals were tested weekly for 4 weeks to measure reaching, errors on the gridwalk, locomotion, and vertical exploration. Biotinylated dextran amine was injected into the cortex to label the corticospinal tract. Enriched environments/daily training significantly increased the number and success of left reaches compared to standard housing. Animals also made fewer errors on the gridwalk, a measure of coordinated forelimb function. However, there were no significant improvements in forelimb use during vertical exploration or locomotion. Likewise, rolipram did not improve any of the behaviors tested. Both enriched housing and rolipram increased plasticity of the corticospinal tract rostral to the lesion. These studies indicate that skilled training after a cervical spinal cord injury improves recovery of skilled forelimb use (reaching) and coordinated limb function (gridwalk) but does not improve automatic forelimb function (locomotion and vertical exploration). These studies suggest that rehabilitating forelimb function after spinal cord injury will require separate strategies for descending and segmental pathways. PMID:19317604

Coordination strategies for limb forces during weight-bearing locomotion in normal rats, and in rats spinalized as neonates

PubMed Central

Giszter, Simon F; Davies, Michelle R; Graziani, Virginia

2010-01-01

Some rats spinally transected as neonates (ST rats) achieve weight-supporting independent locomotion. The mechanisms of coordinated hindlimb weight support in such rats are not well understood. To examine these in such ST rats and normal rats, rats with better than 60% of weight supported steps on a treadmill as adults were trained to cross an instrumented runway. Ground reaction forces, coordination of hindlimb and forelimb forces and the motions of the center of pressure were assessed. Normal rats crossed the runway with a diagonal trot. On average hindlimbs bore about 80% of the vertical load carried by forelimbs, although this varied. Forelimbs and hindlimb acted synergistically to generate decelerative and propulsive rostrocaudal forces, which averaged 15% of body weight with maximums of 50% . Lateral forces were very small (<8% of body weight). Center of pressure progressed in jumps along a straight line with mean lateral deviations <1 cm. ST rats hindlimbs bore about 60% of the vertical load of forelimbs, significantly less compared to intact (p<0.05). ST rats showed similar mean rostrocaudal forces, but with significantly larger maximum fluctuations of up to 80% of body weight (p<0.05). Joint force-plate recordings showed forelimbs and hindlimb rostrocaudal forces in ST rats were opposing and significantly different from intact rats (p<0.05). Lateral forces were ~20% of body weight and significantly larger than in normal rats (p<0.05). Center of pressure zig-zagged, with mean lateral deviations of ~ 2cm and a significantly larger range (p<0.05). The haunches were also observed to roll more than normal rats. The locomotor strategy of injured rats using limbs in opposition was presumably less efficient but their complex gait was statically stable. Because forelimbs and hindlimbs acted in opposition, the trunk was held compressed. Force coordination was likely managed largely by the voluntary control in forelimbs and trunk. PMID:18612631

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

PubMed Central

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

2009-01-01

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

The Irvine, Beatties, and Bresnahan (IBB) Forelimb Recovery Scale: An Assessment of Reliability and Validity

PubMed Central

Irvine, Karen-Amanda; Ferguson, Adam R.; Mitchell, Kathleen D.; Beattie, Stephanie B.; Lin, Amity; Stuck, Ellen D.; Huie, J. Russell; Nielson, Jessica L.; Talbott, Jason F.; Inoue, Tomoo; Beattie, Michael S.; Bresnahan, Jacqueline C.

2014-01-01

The IBB scale is a recently developed forelimb scale for the assessment of fine control of the forelimb and digits after cervical spinal cord injury [SCI; (1)]. The present paper describes the assessment of inter-rater reliability and face, concurrent and construct validity of this scale following SCI. It demonstrates that the IBB is a reliable and valid scale that is sensitive to severity of SCI and to recovery over time. In addition, the IBB correlates with other outcome measures and is highly predictive of biological measures of tissue pathology. Multivariate analysis using principal component analysis (PCA) demonstrates that the IBB is highly predictive of the syndromic outcome after SCI (2), and is among the best predictors of bio-behavioral function, based on strong construct validity. Altogether, the data suggest that the IBB, especially in concert with other measures, is a reliable and valid tool for assessing neurological deficits in fine motor control of the distal forelimb, and represents a powerful addition to multivariate outcome batteries aimed at documenting recovery of function after cervical SCI in rats. PMID:25071704

Intrastriatal administration of botulinum neurotoxin A normalizes striatal D2 R binding and reduces striatal D1 R binding in male hemiparkinsonian rats.

PubMed

Wedekind, Franziska; Oskamp, Angela; Lang, Markus; Hawlitschka, Alexander; Zilles, Karl; Wree, Andreas; Bauer, Andreas

2018-01-01

Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to improve disease-specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT-A on striatal dopamine receptor expression using in vitro and in vivo imaging techniques (positron emission tomography and quantitative autoradiography, respectively). Seventeen male Wistar rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and assigned to two treatment groups 7 weeks later: 10 rats were treated ipsilaterally with an intrastriatal injection of 1 ng BoNT-A, while the others received vehicle (n = 7). All animals were tested for asymmetric motor behavior (apomorphine-induced rotations and forelimb usage) and for striatal expression of dopamine receptors and transporters (D 1 R, D 2 R, and DAT). The striatal D 2 R availability was also quantified longitudinally (1.5, 3, and 5 months after intervention) in 5 animals per treatment group. The 6-OHDA lesion alone induced a unilateral PD-like phenotype and a 13% increase of striatal D 2 R. BoNT-A treatment reduced the asymmetry in both apomorphine-induced rotational behavior and D 2 R expression, with the latter returning to normal values 5 months after intervention. D 1 R expression was significantly reduced, while DAT concentrations showed no alteration. Independent of the treatment, higher interhemispheric symmetry in raclopride binding to D 2 R was generally associated with reduced forelimb akinesia. Our findings indicate that striatal BoNT-A treatment diminishes motor impairment and induces changes in D 1 and D 2 binding site density in the 6-OHDA rat model of PD. © 2017 Wiley Periodicals, Inc.

Mild Contralesional Hypothermia Reduces Use of the Unimpaired Forelimb in a Skilled Reaching Task After Motor Cortex Injury in Rats.

PubMed

Klahr, Ana C; Fagan, Kelly; Aziz, Jasmine R; John, Roseleen; Colbourne, Frederick

2018-06-01

Therapeutic hypothermia (TH) mitigates neuronal injury in models of ischemic stroke. Although this therapy is meant for injured tissue, most protocols cool the whole body, including the contralesional hemisphere. Neuroplasticity responses within this hemisphere can affect functional outcome. Thus, cooling the contralesional hemisphere serves no clear neuroprotective function and may instead be detrimental. In this study, we cooled the contralesional hemisphere to determine whether this harms behavioral recovery after cortical injury in rats. All rats were trained on skilled reaching and walking tasks. Rats then received a motor cortex insult contralateral to their dominant paw after which they were randomly assigned to focal contralesional TH (∼33°C) for 1-48, 1-97, or 48-96 hours postinjury, or to a normothermic control group. Contralesional cooling did not impact lesion volume (p = 0.371) and had minimal impact on neurological outcome of the impaired limb. However, rats cooled early were significantly less likely to shift paw preference to the unimpaired paw (p ≤ 0.043), suggesting that cooling reduced learned nonuse. In a second experiment, we tested whether cooling impaired learning of the skilled reaching task in naive rats. Localized TH applied to the hemisphere contralateral or ipsilateral to the preferred paw did not impair learning (p ≥ 0.677) or dendritic branching/length in the motor cortex (p ≥ 0.105). In conclusion, localized TH did not impair learning or plasticity in the absence of neural injury, but contralesional TH may reduce unwanted shifts in limb preference after stroke.

Ergonomic task reduction prevents bone osteopenia in a rat model of upper extremity overuse

PubMed Central

BARBE, Mary F.; JAIN, Nisha X.; MASSICOTTE, Vicky S.; POPOFF, Steven N.; BARR-GILLESPIE, Ann E.

2015-01-01

We evaluated the effectiveness of ergonomic workload reduction of switching rats from a high repetition high force (HRHF) lever pulling task to a reduced force and reach rate task for preventing task-induced osteopenic changes in distal forelimb bones. Distal radius and ulna trabecular structure was examined in young adult rats performing one of three handle-pulling tasks for 12 wk: 1) HRHF, 2) low repetition low force (LRLF); or 3) HRHF for 4 wk and than LRLF thereafter (HRHF-to-LRLF). Results were compared to age-matched controls rats. Distal forelimb bones of 12-wk HRHF rats showed increased trabecular resorption and decreased volume, as control rats. HRHF-to-LRLF rats had similar trabecular bone quality as control rats; and decreased bone resorption (decreased trabecular bone volume and serum CTX1), increased bone formation (increased mineral apposition, bone formation rate, and serum osteocalcin), and decreased osteoclasts and inflammatory cytokines, than HRHF rats. Thus, an ergonomic intervention of HRHF-to-LRLF prevented loss of trabecular bone volume occurring with prolonged performance of a repetitive upper extremity task. These findings support the idea of reduced workload as an effective approach to management of work-related musculoskeletal disorders, and begin to define reach rate and load level boundaries for such interventions. PMID:25739896

Varieties of paw and digit movement during spontaneous food handling in rats: postures, bimanual coordination, preferences, and the effect of forelimb cortex lesions.

PubMed

Whishaw, I Q; Coles, B L

1996-05-01

This study describes how rats use their paws and digits when handling a wide range of foodstuffs, including food pellets, grapes, sunflower seeds, shelled and unshelled peanuts, and different sized pastas, etc. Analysis of videorecordings show that the rats display digit postures that include variations in the spacing of the digits, differences in the relative use of different digits, and interlimb differences in paw and digit posture. The rats also display limb preferences in that one paw is used in a supporting function while the other rotates, flips, or pushes the food as is required by the shape of the item. There is a significant correlation between the paw used for manipulation and food items of similar shape but no correlation between the limb used for manipulation and that used for skilled reaching. Small unilateral lesions to the forepaw area of somatic sensorimotor cortex produced impairments in use of the paw contralateral to the lesions. These results: (1) reveal a surprising complexity in the way in which rats use their paws and digits in manipulating food; (2) show that rats have limb preferences in spontaneous food handling; and (3) show that manipulatory dexterity is dependent upon the integrity of the forelimb area of motor cortex. The results are discussed in relation to the evolution of motor skill, the use of rats for investigating questions of motor system organization, neural plasticity, and recovery of function after brain damage.

The comparative anatomy of the forelimb veins of primates.

PubMed Central

Thiranagama, R; Chamberlain, A T; Wood, B A

1989-01-01

One hundred and thirteen forelimbs taken from 62 individuals belonging to 17 primate genera were dissected to reveal the entire course of the superficial venous system. The course of the deep venous system was also documented in at least one forelimb of each primate genus, and the number and location of perforating veins was recorded in 18 human and 45 non-human primate limbs. In Pan, Gorilla and in about 25% of human specimens the lateral superficial vein was confined to the forearm, while in all other primates, and in the majority of humans, this vein extended from the carpus to the clavicular region. Only Pongo and humans exhibited a second main superficial vein on the medial side of the forearm. In all primates the deep veins of the forelimb usually accompanied the arteries. Thus variation in the deep venous system reflected the different arterial patterns exhibited by these primates. The number of perforating veins in the forelimb was related to the length of the limb. Primate genera with longer forelimbs had more perforators, though not as many as would be expected if the number of perforators scaled linearly with limb length. PMID:2514175

Tbx5 Buffers Inherent Left/Right Asymmetry Ensuring Symmetric Forelimb Formation

PubMed Central

Nishimoto, Satoko; Kucharska, Anna; Newbury-Ecob, Ruth; Logan, Malcolm P. O.

2016-01-01

The forelimbs and hindlimbs of vertebrates are bilaterally symmetric. The mechanisms that ensure symmetric limb formation are unknown but they can be disrupted in disease. In Holt-Oram Syndrome (HOS), caused by mutations in TBX5, affected individuals have left-biased upper/forelimb defects. We demonstrate a role for the transcription factor Tbx5 in ensuring the symmetric formation of the left and right forelimb. In our mouse model, bilateral hypomorphic levels of Tbx5 produces asymmetric forelimb defects that are consistently more severe in the left limb than the right, phenocopying the left-biased limb defects seen in HOS patients. In Tbx hypomorphic mutants maintained on an INV mutant background, with situs inversus, the laterality of defects is reversed. Our data demonstrate an early, inherent asymmetry in the left and right limb-forming regions and that threshold levels of Tbx5 are required to overcome this asymmetry to ensure symmetric forelimb formation. PMID:27992425

Vagus Nerve Stimulation Delivered During Motor Rehabilitation Improves Recovery in a Rat Model of Stroke

PubMed Central

Khodaparast, Navid; Hays, Seth A.; Sloan, Andrew M.; Fayyaz, Tabbassum; Hulsey, Daniel R.; Rennaker, Robert L.; Kilgard, Michael P.

2014-01-01

Neural plasticity is widely believed to support functional recovery following brain damage. Vagus nerve stimulation paired with different forelimb movements causes long-lasting map plasticity in rat primary motor cortex that is specific to the paired movement. We tested the hypothesis that repeatedly pairing vagus nerve stimulation with upper forelimb movements would improve recovery of motor function in a rat model of stroke. Rats were separated into three groups: vagus nerve stimulation during rehab, vagus nerve stimulation after rehab, and rehab alone. Animals underwent 4 training stages: shaping (motor skill learning), pre-lesion training, post-lesion training, and therapeutic training. Rats were given a unilateral ischemic lesion within motor cortex and implanted with a left vagus nerve cuff. Animals were allowed one week of recovery before post-lesion baseline training. During the therapeutic training stage, rats received vagus nerve stimulation paired with each successful trial. All seventeen trained rats demonstrated significant contralateral forelimb impairment when performing a bradykinesia assessment task. Forelimb function was recovered completely to pre-lesion levels when vagus nerve stimulation was delivered during rehab training. Alternatively, intensive rehab training alone (without stimulation) failed to restore function to pre-lesion levels. Delivering the same amount of stimulation after rehab training did not yield improvements compared to rehab alone. These results demonstrate that vagus nerve stimulation repeatedly paired with successful forelimb movements can improve recovery after motor cortex ischemia and may be a viable option for stroke rehabilitation. PMID:24553102

Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats

PubMed Central

Wen, Tong-Chun; Lall, Sophia; Pagnotta, Corey; Markward, James; Gupta, Disha; Ratnadurai-Giridharan, Shivakeshavan; Bucci, Jacqueline; Greenwald, Lucy; Klugman, Madelyne; Hill, N. Jeremy; Carmel, Jason B.

2018-01-01

After injury to the corticospinal tract (CST) in early development there is large-scale adaptation of descending motor pathways. Some studies suggest the uninjured hemisphere controls the impaired forelimb, while others suggest that the injured hemisphere does; these pathways have never been compared directly. We tested the contribution of each motor cortex to the recovery forelimb function after neonatal injury of the CST. We cut the left pyramid (pyramidotomy) of postnatal day 7 rats, which caused a measurable impairment of the right forelimb. We used pharmacological inactivation of each motor cortex to test its contribution to a skilled reach and supination task. Rats with neonatal pyramidotomy were further impaired by inactivation of motor cortex in both the injured and the uninjured hemispheres, while the forelimb of uninjured rats was impaired only from the contralateral motor cortex. Thus, inactivation demonstrated motor control from each motor cortex. In contrast, physiological and anatomical interrogation of these pathways support adaptations only in the uninjured hemisphere. Intracortical microstimulation of motor cortex in the uninjured hemisphere of rats with neonatal pyramidotomy produced responses from both forelimbs, while stimulation of the injured hemisphere did not elicit responses from either forelimb. Both anterograde and retrograde tracers were used to label corticofugal pathways. There was no increased plasticity from the injured hemisphere, either from cortex to the red nucleus or the red nucleus to the spinal cord. In contrast, there were very strong CST connections to both halves of the spinal cord from the uninjured motor cortex. Retrograde tracing produced maps of each forelimb within the uninjured hemisphere, and these were partly segregated. This suggests that the uninjured hemisphere may encode separate control of the unimpaired and the impaired forelimbs of rats with neonatal pyramidotomy. PMID:29706871

Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats.

PubMed

Wen, Tong-Chun; Lall, Sophia; Pagnotta, Corey; Markward, James; Gupta, Disha; Ratnadurai-Giridharan, Shivakeshavan; Bucci, Jacqueline; Greenwald, Lucy; Klugman, Madelyne; Hill, N Jeremy; Carmel, Jason B

2018-01-01

After injury to the corticospinal tract (CST) in early development there is large-scale adaptation of descending motor pathways. Some studies suggest the uninjured hemisphere controls the impaired forelimb, while others suggest that the injured hemisphere does; these pathways have never been compared directly. We tested the contribution of each motor cortex to the recovery forelimb function after neonatal injury of the CST. We cut the left pyramid (pyramidotomy) of postnatal day 7 rats, which caused a measurable impairment of the right forelimb. We used pharmacological inactivation of each motor cortex to test its contribution to a skilled reach and supination task. Rats with neonatal pyramidotomy were further impaired by inactivation of motor cortex in both the injured and the uninjured hemispheres, while the forelimb of uninjured rats was impaired only from the contralateral motor cortex. Thus, inactivation demonstrated motor control from each motor cortex. In contrast, physiological and anatomical interrogation of these pathways support adaptations only in the uninjured hemisphere. Intracortical microstimulation of motor cortex in the uninjured hemisphere of rats with neonatal pyramidotomy produced responses from both forelimbs, while stimulation of the injured hemisphere did not elicit responses from either forelimb. Both anterograde and retrograde tracers were used to label corticofugal pathways. There was no increased plasticity from the injured hemisphere, either from cortex to the red nucleus or the red nucleus to the spinal cord. In contrast, there were very strong CST connections to both halves of the spinal cord from the uninjured motor cortex. Retrograde tracing produced maps of each forelimb within the uninjured hemisphere, and these were partly segregated. This suggests that the uninjured hemisphere may encode separate control of the unimpaired and the impaired forelimbs of rats with neonatal pyramidotomy.

Evaluation of forelimb horseshoe characteristics of thoroughbreds racing on dirt surfaces.

PubMed

Gross, Diane K; Stover, Susan M; Hill, Ashley E; Gardner, Ian A

2004-07-01

To describe forelimb horseshoe characteristics of horses racing on dirt surfaces and determine whether these characteristics vary with region of California, season, horse characteristics, and race-related factors. 5,730 Thoroughbred racehorses. From June 17, 2000, to June 16, 2001, the characteristics of 1 forelimb horseshoe of horses that raced on dirt surfaces at 5 major racetracks in California were recorded. These characteristics included shoe type; toe grab height; and presence of a rim, pad, and heel traction devices (jar caulks, heel stickers, heel blocks, and special nails). Horse and race information was obtained from commercial records. One race/horse was randomly selected. 99% of forelimb horseshoes were aluminum racing plates, 35% had a pad, 23% had a rim, and 8% had a heel traction device. A toe grab was observed on 75% of forelimb horseshoes (14% very low [< or = 2 mm], 30% low [> 2 and < or = 4 mm], 30% regular [> 4 and < or = 6 mm], and 1% high [> 6 and < or = 8 mm]). Forelimb horseshoe characteristics varied with region of California, season, age and sex of the horse, race purse and distance, and track surface condition. Log-linear modeling revealed that all of these factors were significantly interrelated. Complex interrelationships among forelimb horseshoe characteristics and region, season, age and sex of the horse, and race-related factors need to be considered when evaluating the relationships between injury and horseshoe characteristics in Thoroughbred racehorses.

High-order motor cortex in rats receives somatosensory inputs from the primary motor cortex via cortico-cortical pathways.

PubMed

Kunori, Nobuo; Takashima, Ichiro

2016-12-01

The motor cortex of rats contains two forelimb motor areas; the caudal forelimb area (CFA) and the rostral forelimb area (RFA). Although the RFA is thought to correspond to the premotor and/or supplementary motor cortices of primates, which are higher-order motor areas that receive somatosensory inputs, it is unknown whether the RFA of rats receives somatosensory inputs in the same manner. To investigate this issue, voltage-sensitive dye (VSD) imaging was used to assess the motor cortex in rats following a brief electrical stimulation of the forelimb. This procedure was followed by intracortical microstimulation (ICMS) mapping to identify the motor representations in the imaged cortex. The combined use of VSD imaging and ICMS revealed that both the CFA and RFA received excitatory synaptic inputs after forelimb stimulation. Further evaluation of the sensory input pathway to the RFA revealed that the forelimb-evoked RFA response was abolished either by the pharmacological inactivation of the CFA or a cortical transection between the CFA and RFA. These results suggest that forelimb-related sensory inputs would be transmitted to the RFA from the CFA via the cortico-cortical pathway. Thus, the present findings imply that sensory information processed in the RFA may be used for the generation of coordinated forelimb movements, which would be similar to the function of the higher-order motor cortex in primates. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Clawed forelimbs allow northern seals to eat like their ancient ancestors

NASA Astrophysics Data System (ADS)

Hocking, David P.; Marx, Felix G.; Sattler, Renae; Harris, Robert N.; Pollock, Tahlia I.; Sorrell, Karina J.; Fitzgerald, Erich M. G.; McCurry, Matthew R.; Evans, Alistair R.

2018-04-01

Streamlined flippers are often considered the defining feature of seals and sea lions, whose very name `pinniped' comes from the Latin pinna and pedis, meaning `fin-footed'. Yet not all pinniped limbs are alike. Whereas otariids (fur seals and sea lions) possess stiff streamlined forelimb flippers, phocine seals (northern true seals) have retained a webbed yet mobile paw bearing sharp claws. Here, we show that captive and wild phocines routinely use these claws to secure prey during processing, enabling seals to tear large fish by stretching them between their teeth and forelimbs. `Hold and tear' processing relies on the primitive forelimb anatomy displayed by phocines, which is also found in the early fossil pinniped Enaliarctos. Phocine forelimb anatomy and behaviour therefore provide a glimpse into how the earliest seals likely fed, and indicate what behaviours may have assisted pinnipeds along their journey from terrestrial to aquatic feeding.

Clawed forelimbs allow northern seals to eat like their ancient ancestors.

PubMed

Hocking, David P; Marx, Felix G; Sattler, Renae; Harris, Robert N; Pollock, Tahlia I; Sorrell, Karina J; Fitzgerald, Erich M G; McCurry, Matthew R; Evans, Alistair R

2018-04-01

Streamlined flippers are often considered the defining feature of seals and sea lions, whose very name 'pinniped' comes from the Latin pinna and pedis , meaning 'fin-footed'. Yet not all pinniped limbs are alike. Whereas otariids (fur seals and sea lions) possess stiff streamlined forelimb flippers, phocine seals (northern true seals) have retained a webbed yet mobile paw bearing sharp claws. Here, we show that captive and wild phocines routinely use these claws to secure prey during processing, enabling seals to tear large fish by stretching them between their teeth and forelimbs. 'Hold and tear' processing relies on the primitive forelimb anatomy displayed by phocines, which is also found in the early fossil pinniped Enaliarctos . Phocine forelimb anatomy and behaviour therefore provide a glimpse into how the earliest seals likely fed, and indicate what behaviours may have assisted pinnipeds along their journey from terrestrial to aquatic feeding.

Contralesional Axonal Remodeling of the Corticospinal System in Adult Rats After Stroke and Bone Marrow Stromal Cell Treatment

PubMed Central

Liu, Zhongwu; Li, Yi; Zhang, Xueguo; Savant-Bhonsale, Smita; Chopp, Michael

2008-01-01

Background and Purpose Motor recovery after stroke is associated with neuronal reorganization in bilateral hemispheres. We investigated contralesional corticospinal tract remodeling in the brain and spinal cord in rats after stroke and treatment of bone marrow stromal cells. Methods Adult male Wistar rats were subjected to permanent right middle cerebral artery occlusion. Phosphate-buffered saline or bone marrow stromal cells were injected into a tail vein 1 day postischemia. An adhesive removal test was performed weekly to monitor functional recovery. Threshold currents of intracortical microstimulation on the left motor cortex for evoking bilateral forelimb movements were measured 6 weeks after stroke. When intracortical microstimulation was completed, biotinylated dextran amine was injected into the left motor cortex to anterogradely label the corticospinal tract. At 4 days before euthanization, pseudorabies virus-152-EGFP and 614-mRFP were injected into left or right forelimb extensor muscles, respectively. All animals were euthanized 8 weeks after stroke. Results In normal rats (n=5), the corticospinal tract showed a unilateral innervation pattern. In middle cerebral artery occlusion rats (n=8), our data demonstrated that: 1) stroke reduced the stimulation threshold evoking ipsilateral forelimb movement; 2) EGFP-positive pyramidal neurons were increased in the left intact cortex, which were labeled from the left stroke-impaired forelimb; and 3) biotinylated dextran amine-labeled contralesional axons sprouted into the denervated spinal cord. Bone marrow stromal cells significantly enhanced all 3 responses (n=8, P<0.05). Conclusions Our data demonstrated that corticospinal tract fibers originating from the contralesional motor cortex sprout into the denervated spinal cord after stroke and bone marrow stromal cells treatment, which may contribute to functional recovery. PMID:18617661

Clawed forelimbs allow northern seals to eat like their ancient ancestors

PubMed Central

Sattler, Renae; Harris, Robert N.; Pollock, Tahlia I.; Sorrell, Karina J.; Fitzgerald, Erich M. G.; McCurry, Matthew R.

2018-01-01

Streamlined flippers are often considered the defining feature of seals and sea lions, whose very name ‘pinniped’ comes from the Latin pinna and pedis, meaning ‘fin-footed’. Yet not all pinniped limbs are alike. Whereas otariids (fur seals and sea lions) possess stiff streamlined forelimb flippers, phocine seals (northern true seals) have retained a webbed yet mobile paw bearing sharp claws. Here, we show that captive and wild phocines routinely use these claws to secure prey during processing, enabling seals to tear large fish by stretching them between their teeth and forelimbs. ‘Hold and tear’ processing relies on the primitive forelimb anatomy displayed by phocines, which is also found in the early fossil pinniped Enaliarctos. Phocine forelimb anatomy and behaviour therefore provide a glimpse into how the earliest seals likely fed, and indicate what behaviours may have assisted pinnipeds along their journey from terrestrial to aquatic feeding. PMID:29765684

Causal Link between the Cortico-Rubral Pathway and Functional Recovery through Forced Impaired Limb Use in Rats with Stroke

PubMed Central

Ishida, Akimasa; Isa, Kaoru; Umeda, Tatsuya; Kobayashi, Kazuto; Kobayashi, Kenta; Hida, Hideki

2016-01-01

Intensive rehabilitation is believed to induce use-dependent plasticity in the injured nervous system; however, its causal relationship to functional recovery is unclear. Here, we performed systematic analysis of the effects of forced use of an impaired forelimb on the recovery of rats after lesioning the internal capsule with intracerebral hemorrhage (ICH). Forced limb use (FLU) group rats exhibited better recovery of skilled forelimb functions and their cortical motor area with forelimb representation was restored and enlarged on the ipsilesional side. In addition, abundant axonal sprouting from the reemerged forelimb area was found in the ipsilateral red nucleus after FLU. To test the causal relationship between the plasticity in the cortico-rubral pathway and recovery, loss-of-function experiments were conducted using a double-viral vector technique, which induces selective blockade of the target pathway. Blockade of the cortico-rubral tract resulted in deficits of the recovered forelimb function in FLU group rats. These findings suggest that the cortico-rubral pathway is a substrate for recovery induced by intensive rehabilitation after ICH. SIGNIFICANCE STATEMENT The research aimed at determining the causal linkage between reorganization of the motor pathway induced by intensive rehabilitative training and recovery after stroke. We clarified the expansion of the forelimb representation area of the ipsilesional motor cortex by forced impaired forelimb use (FLU) after lesioning the internal capsule with intracerebral hemorrhaging (ICH) in rats. Anterograde tracing showed robust axonal sprouting from the forelimb area to the red nucleus in response to FLU. Selective blockade of the cortico-rubral pathway by the novel double-viral vector technique clearly revealed that the increased cortico-rubral axonal projections had causal linkage to the recovery of reaching movements induced by FLU. Our data demonstrate that the cortico-rubral pathway is responsible for the

Rehabilitative skilled forelimb training enhances axonal remodeling in the corticospinal pathway but not the brainstem-spinal pathways after photothrombotic stroke in the primary motor cortex.

PubMed

Okabe, Naohiko; Himi, Naoyuki; Maruyama-Nakamura, Emi; Hayashi, Norito; Narita, Kazuhiko; Miyamoto, Osamu

2017-01-01

Task-specific rehabilitative training is commonly used for chronic stroke patients. Axonal remodeling is believed to be one mechanism underlying rehabilitation-induced functional recovery, and significant roles of the corticospinal pathway have previously been demonstrated. Brainstem-spinal pathways, as well as the corticospinal tract, have been suggested to contribute to skilled motor function and functional recovery after brain injury. However, whether axonal remodeling in the brainstem-spinal pathways is a critical component for rehabilitation-induced functional recovery is not known. In this study, rats were subjected to photothrombotic stroke in the caudal forelimb area of the primary motor cortex and received rehabilitative training with a skilled forelimb reaching task for 4 weeks. After completion of the rehabilitative training, the retrograde tracer Fast blue was injected into the contralesional lower cervical spinal cord. Fast blue-positive cells were counted in 32 brain areas located in the cerebral cortex, hypothalamus, midbrain, pons, and medulla oblongata. Rehabilitative training improved motor performance in the skilled forelimb reaching task but not in the cylinder test, ladder walk test, or staircase test, indicating that rehabilitative skilled forelimb training induced task-specific recovery. In the histological analysis, rehabilitative training significantly increased the number of Fast blue-positive neurons in the ipsilesional rostral forelimb area and secondary sensory cortex. However, rehabilitative training did not alter the number of Fast blue-positive neurons in any areas of the brainstem. These results indicate that rehabilitative skilled forelimb training enhances axonal remodeling selectively in the corticospinal pathway, which suggests a critical role of cortical plasticity, rather than brainstem plasticity, in task-specific recovery after subtotal motor cortex destruction.

Rehabilitative skilled forelimb training enhances axonal remodeling in the corticospinal pathway but not the brainstem-spinal pathways after photothrombotic stroke in the primary motor cortex

PubMed Central

Himi, Naoyuki; Maruyama-Nakamura, Emi; Hayashi, Norito; Narita, Kazuhiko; Miyamoto, Osamu

2017-01-01

Task-specific rehabilitative training is commonly used for chronic stroke patients. Axonal remodeling is believed to be one mechanism underlying rehabilitation-induced functional recovery, and significant roles of the corticospinal pathway have previously been demonstrated. Brainstem-spinal pathways, as well as the corticospinal tract, have been suggested to contribute to skilled motor function and functional recovery after brain injury. However, whether axonal remodeling in the brainstem-spinal pathways is a critical component for rehabilitation-induced functional recovery is not known. In this study, rats were subjected to photothrombotic stroke in the caudal forelimb area of the primary motor cortex and received rehabilitative training with a skilled forelimb reaching task for 4 weeks. After completion of the rehabilitative training, the retrograde tracer Fast blue was injected into the contralesional lower cervical spinal cord. Fast blue-positive cells were counted in 32 brain areas located in the cerebral cortex, hypothalamus, midbrain, pons, and medulla oblongata. Rehabilitative training improved motor performance in the skilled forelimb reaching task but not in the cylinder test, ladder walk test, or staircase test, indicating that rehabilitative skilled forelimb training induced task-specific recovery. In the histological analysis, rehabilitative training significantly increased the number of Fast blue-positive neurons in the ipsilesional rostral forelimb area and secondary sensory cortex. However, rehabilitative training did not alter the number of Fast blue-positive neurons in any areas of the brainstem. These results indicate that rehabilitative skilled forelimb training enhances axonal remodeling selectively in the corticospinal pathway, which suggests a critical role of cortical plasticity, rather than brainstem plasticity, in task-specific recovery after subtotal motor cortex destruction. PMID:29095902

Paws for thought: comparative radiologic anatomy of the mammalian forelimb.

PubMed

Gough-Palmer, Antony L; Maclachlan, Jody; Routh, Andrew

2008-01-01

All mammals share a remarkably similar skeleton based on a common template. This commonality is particularly well illustrated by the versatile pentadactyl limb, upon which all mammalian limbs are based. For most mammals, the primary function of the forelimb is locomotion. The forelimb has been successfully adapted in mammals of all sizes and in terrestrial, arboreal, aquatic, and airborne environments. In primates, the forelimbs have developed such that speed and stamina have been sacrificed for an increased range of movement, which in turn has provided increased manual dexterity. For instance, chimpanzee hands are pronated and the fingers are flexed, and the phalanges are longer and exhibit much more robust insertion areas for flexor tendons. Ungulates (hoofed mammals), on the other hand, have evolved to maximize speed and stamina in quadrupedal locomotion. The two main orders of ungulates have elongated phalanges and metacarpals; all ungulates have lost the first metacarpal. The cat family represents some of the most highly evolved predators. Cats' forelimbs are designed for speed, power, and acceleration rather than for stamina; they maintain all five metacarpals and phalanges, although the first digit is relatively small. (c) RSNA, 2008

Enhanced Thalamic Functional Connectivity with No fMRI Responses to Affected Forelimb Stimulation in Stroke-Recovered Rats.

PubMed

Shim, Woo H; Suh, Ji-Yeon; Kim, Jeong K; Jeong, Jaeseung; Kim, Young R

2016-01-01

Neurological recovery after stroke has been extensively investigated to provide better understanding of neurobiological mechanism, therapy, and patient management. Recent advances in neuroimaging techniques, particularly functional MRI (fMRI), have widely contributed to unravel the relationship between the altered neural function and stroke-affected brain areas. As results of previous investigations, the plastic reorganization and/or gradual restoration of the hemodynamic fMRI responses to neural stimuli have been suggested as relevant mechanisms underlying the stroke recovery process. However, divergent study results and modality-dependent outcomes have clouded the proper interpretation of variable fMRI signals. Here, we performed both evoked and resting state fMRI (rs-fMRI) to clarify the link between the fMRI phenotypes and post-stroke functional recovery. The experiments were designed to examine the altered neural activity within the contra-lesional hemisphere and other undamaged brain regions using rat models with large unilateral stroke, which despite the severe injury, exhibited nearly full recovery at ∼6 months after stroke. Surprisingly, both blood oxygenation level-dependent and blood volume-weighted (CBVw) fMRI activities elicited by electrical stimulation of the stroke-affected forelimb were completely absent, failing to reveal the neural origin of the behavioral recovery. In contrast, the functional connectivity maps showed highly robust rs-fMRI activity concentrated in the contra-lesional ventromedial nucleus of thalamus (VM). The negative finding in the stimuli-induced fMRI study using the popular rat middle cerebral artery model denotes weak association between the fMRI hemodynamic responses and neurological improvement. The results strongly caution the indiscreet interpretation of stroke-affected fMRI signals and demonstrate rs-fMRI as a complementary tool for efficiently characterizing stroke recovery.

Load redistribution in walking and trotting Beagles with induced forelimb lameness.

PubMed

Abdelhadi, Jalal; Wefstaedt, Patrick; Galindo-Zamora, Vladimir; Anders, Alexandra; Nolte, Ingo; Schilling, Nadja

2013-01-01

To evaluate the load redistribution mechanisms in walking and trotting dogs with induced forelimb lameness. 7 healthy adult Beagles. Dogs walked and trotted on an instrumented treadmill to determine control values for peak and mean vertical force as well as vertical impulse for all 4 limbs. A small sphere was attached to the ventral pad of the right forelimb paw to induce a reversible lameness, and recordings were repeated for both gaits. Additionally, footfall patterns were assessed to test for changes in temporal gait variables. During walking and trotting, peak and mean vertical force as well as vertical impulse were decreased in the ipsilateral forelimb, increased in the contralateral hind limb, and remained unchanged in the ipsilateral hind limb after lameness was induced. All 3 variables were increased in the contralateral forelimb during trotting, whereas only mean vertical force and vertical impulse were increased during walking. Stance phase duration increased in the contralateral forelimb and hind limb during walking but not during trotting. Analysis of the results suggested that compensatory load redistribution mechanisms in dogs depend on the gait. All 4 limbs should be evaluated in basic research and clinical studies to determine the effects of lameness on the entire body. Further studies are necessary to elucidate specific mechanisms for unloading of the affected limb and to determine the long-term effects of load changes in animals with chronic lameness.

Peripheral Nerve Injury in Developing Rats Reorganizes Representation Pattern in Motor Cortex

NASA Astrophysics Data System (ADS)

Donoghue, John P.; Sanes, Jerome N.

1987-02-01

We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stimuli activated shoulder and trunk muscles in experimental animals. In addition, an expanded cortical representation of intact body parts was present and there was an absence of a distinct portion of motor cortex. These data demonstrate that representation patterns in motor cortex can be altered by peripheral nerve injury during development.

A Three-Dimensional Analysis of Morphological Evolution and Locomotor Performance of the Carnivoran Forelimb

PubMed Central

Martín-Serra, Alberto; Figueirido, Borja; Palmqvist, Paul

2014-01-01

In this study, three-dimensional landmark-based methods of geometric morphometrics are used for estimating the influence of phylogeny, allometry and locomotor performance on forelimb shape in living and extinct carnivorans (Mammalia, Carnivora). The main objective is to investigate morphological convergences towards similar locomotor strategies in the shape of the major forelimb bones. Results indicate that both size and phylogeny have strong effects on the anatomy of all forelimb bones. In contrast, bone shape does not correlate in the living taxa with maximum running speed or daily movement distance, two proxies closely related to locomotor performance. A phylomorphospace approach showed that shape variation in forelimb bones mainly relates to changes in bone robustness. This indicates the presence of biomechanical constraints resulting from opposite demands for energetic efficiency in locomotion –which would require a slender forelimb– and resistance to stress –which would be satisfied by a robust forelimb–. Thus, we interpret that the need of maintaining a trade-off between both functional demands would limit shape variability in forelimb bones. Given that different situations can lead to one or another morphological solution, depending on the specific ecology of taxa, the evolution of forelimb morphology represents a remarkable “one-to-many mapping” case between anatomy and ecology. PMID:24454891

Comparative kinematics of the forelimb during swimming in red-eared slider (Trachemys scripta) and spiny softshell (Apalone spinifera) turtles.

PubMed

Pace, C M; Blob, R W; Westneat, M W

2001-10-01

Softshell turtles (Family Trionychidae) possess extensive webbing between the digits of the manus, suggesting that the forelimb may serve as an effective thrust generator during aquatic locomotion. However, the hindlimb has previously been viewed as the dominant propulsive organ in swimming freshwater turtles. To evaluate the potential role of the forelimb in thrust production during swimming in freshwater turtles, we compared the forelimb morphology and three-dimensional forelimb kinematics of a highly aquatic trionychid turtle, the spiny softshell Apalone spinifera, and a morphologically generalized emydid turtle, the red-eared slider Trachemys scripta. Spiny softshells possess nearly twice as much forelimb surface area as sliders for generating drag-based thrust. In addition, although both species use drag-based propulsion, several aspects of forelimb kinematics differ significantly between these species. During the thrust phase of the forelimb cycle, spiny softshells hold the elbow and wrist joints significantly straighter than sliders, thereby further increasing the surface area of the limb that can move water posteriorly and increasing the velocity of the distal portion of the forelimb. These aspects of swimming kinematics in softshells should increase forelimb thrust production and suggest that the forelimbs make more substantial contributions to forward thrust in softshell turtles than in sliders. Spiny softshells also restrict forelimb movements to a much narrower dorsoventral and anteroposterior range than sliders throughout the stroke, thereby helping to minimize limb movements potentially extraneous to forward thrust production. These comparisons demonstrate considerable diversity in the forelimb kinematics of turtles that swim using rowing motions of the limbs and suggest that the evolution of turtle forelimb mechanics produced a variety of contrasting solutions for aquatic specialization.

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

PubMed

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

2016-10-19

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

Output Properties of the Cortical Hindlimb Motor Area in Spinal Cord-Injured Rats.

PubMed

Frost, Shawn B; Dunham, Caleb L; Barbay, Scott; Krizsan-Agbas, Dora; Winter, Michelle K; Guggenmos, David J; Nudo, Randolph J

2015-11-01

The purpose of this study was to examine neuronal activity levels in the hindlimb area of motor cortex following spinal cord injury (SCI) in rats and compare the results with measurements in normal rats. Fifteen male Fischer-344 rats received a 200 Kdyn contusion injury in the thoracic cord at level T9-T10. After a minimum of 4 weeks following SCI, intracortical microstimulation (ICMS) and single-unit recording techniques were used in both the forelimb and hindlimb motor areas (FLA, HLA) under ketamine anesthesia. Although movements could be evoked using ICMS in the forelimb area with relatively low current levels, no movements or electromyographical responses could be evoked from ICMS in the HLA in any of the injured rats. During the same procedure, electrophysiological recordings were obtained with a single-shank, 16-channel Michigan probe (Neuronexus) to monitor activity. Neural spikes were discriminated using principle component analysis. Neural activity (action potentials) was collected and digitized for a duration of 5 min. Despite the inability to evoke movement from stimulation of cortex, robust single-unit activity could be recorded reliably from hindlimb motor cortex in SCI rats. Activity in the motor cortex of SCI rats was significantly higher compared with uninjured rats, and increased in hindlimb and forelimb motor cortex by similar amounts. These results demonstrate that in a rat model of thoracic SCI, an increase in single-unit cortical activity can be reliably recorded for several weeks post-injury.

Output Properties of the Cortical Hindlimb Motor Area in Spinal Cord-Injured Rats

PubMed Central

Dunham, Caleb L.; Barbay, Scott; Krizsan-Agbas, Dora; Winter, Michelle K.; Guggenmos, David J.; Nudo, Randolph J.

2015-01-01

Abstract The purpose of this study was to examine neuronal activity levels in the hindlimb area of motor cortex following spinal cord injury (SCI) in rats and compare the results with measurements in normal rats. Fifteen male Fischer-344 rats received a 200 Kdyn contusion injury in the thoracic cord at level T9–T10. After a minimum of 4 weeks following SCI, intracortical microstimulation (ICMS) and single-unit recording techniques were used in both the forelimb and hindlimb motor areas (FLA, HLA) under ketamine anesthesia. Although movements could be evoked using ICMS in the forelimb area with relatively low current levels, no movements or electromyographical responses could be evoked from ICMS in the HLA in any of the injured rats. During the same procedure, electrophysiological recordings were obtained with a single-shank, 16-channel Michigan probe (Neuronexus) to monitor activity. Neural spikes were discriminated using principle component analysis. Neural activity (action potentials) was collected and digitized for a duration of 5 min. Despite the inability to evoke movement from stimulation of cortex, robust single-unit activity could be recorded reliably from hindlimb motor cortex in SCI rats. Activity in the motor cortex of SCI rats was significantly higher compared with uninjured rats, and increased in hindlimb and forelimb motor cortex by similar amounts. These results demonstrate that in a rat model of thoracic SCI, an increase in single-unit cortical activity can be reliably recorded for several weeks post-injury. PMID:26406381

Grasp-Based Functional Coupling Between Reach- and Grasp-Related Components of Forelimb Muscle Activity

PubMed Central

Geed, Shashwati; van Kan, Peter L. E.

2017-01-01

How are appropriate combinations of forelimb muscles selected during reach-to-grasp movements in the presence of neuromotor redundancy and important task-related constraints? The authors tested whether grasp type or target location preferentially influence the selection and synergistic coupling between forelimb muscles during reach-to-grasp movements. Factor analysis applied to 14–20 forelimb electromyograms recorded from monkeys performing reach-to-grasp tasks revealed 4–6 muscle components that showed transport/preshape- or grasp-related features. Weighting coefficients of transport/preshape-related components demonstrated strongest similarities for reaches that shared the same grasp type rather than the same target location. Scaling coefficients of transport/preshape- and grasp-related components showed invariant temporal coupling. Thus, grasp type influenced strongly both transport/preshape- and grasp-related muscle components, giving rise to grasp-based functional coupling between forelimb muscles. PMID:27589010

Reflex-based grasping, skilled forelimb reaching, and electrodiagnostic evaluation for comprehensive analysis of functional recovery-The 7-mm rat median nerve gap repair model revisited.

PubMed

Stößel, Maria; Rehra, Lena; Haastert-Talini, Kirsten

2017-10-01

The rat median nerve injury and repair model gets increasingly important for research on novel bioartificial nerve grafts. It allows follow-up evaluation of the recovery of the forepaw functional ability with several sensitive techniques. The reflex-based grasping test, the skilled forelimb reaching staircase test, as well as electrodiagnostic recordings have been described useful in this context. Currently, no standard values exist, however, for comparison or comprehensive correlation of results obtained in each of the three methods after nerve gap repair in adult rats. Here, we bilaterally reconstructed 7-mm median nerve gaps with autologous nerve grafts (ANG) or autologous muscle-in-vein grafts (MVG), respectively. During 8 and 12 weeks of observation, functional recovery of each paw was separately monitored using the grasping test (weekly), the staircase test, and noninvasive electrophysiological recordings from the thenar muscles (both every 4 weeks). Evaluation was completed by histomorphometrical analyses at 8 and 12 weeks postsurgery. The comprehensive evaluation detected a significant difference in the recovery of forepaw functional motor ability between the ANG and MVG groups. The correlation between the different functional tests evaluated precisely displayed the recovery of distinct levels of forepaw functional ability over time. Thus, this multimodal evaluation model represents a valuable preclinical model for peripheral nerve reconstruction approaches.

Comparative anatomy, evolution, and homologies of tetrapod hindlimb muscles, comparison with forelimb muscles, and deconstruction of the forelimb-hindlimb serial homology hypothesis.

PubMed

Diogo, Rui; Molnar, Julia

2014-06-01

For more than two centuries, the idea that the forelimb and hindlimb are serially homologous structures has been accepted without serious question. This study presents the first detailed analysis of the evolution and homologies of all hindlimb muscles in representatives of each major tetrapod group and proposes a unifying nomenclature for these muscles. These data are compared with information obtained previously about the forelimb muscles of tetrapods and the muscles of other gnathostomes in order to address one of the most central and enigmatic questions in evolutionary and comparative anatomy: why are the pelvic and pectoral appendages of gnathostomes generally so similar to each other? An integrative analysis of the new myological data, combined with a review of recent paleontological, developmental, and genetic works and of older studies, does not support serial homology between the structures of these appendages. For instance, many of the strikingly similar forelimb and hindlimb muscles found in each major extant tetrapod taxon were acquired at different geological times and/or have different embryonic origins. These similar muscles are not serial homologues, but the result of evolutionary parallelism/convergence due to a complex interplay of ontogenetic, functional, topological, and phylogenetic constraints/factors. Copyright © 2014 Wiley Periodicals, Inc.

Forelimb posture in dinosaurs and the evolution of the avian flapping flight-stroke.

PubMed

Nudds, Robert L; Dyke, Gareth J

2009-04-01

Ontogenetic and behavioral studies using birds currently do not document the early evolution of flight because birds (including juveniles) used in such studies employ forelimb oscillation frequencies over 10 Hz, forelimb stroke-angles in excess of 130 degrees , and possess uniquely avian flight musculatures. Living birds are an advanced morphological stage in the development of flapping flight. To gain insight into the early stages of flight evolution (i.e., prebird), in the absence of a living analogue, a new approach using Strouhal number was used. Strouhal number is a nondimensional number that describes the relationship between wing-stroke amplitude (A), wing-beat frequency (f), and flight speed (U). Calculations indicated that even moderate wing movements are enough to generate rudimentary thrust and that a propulsive flapping flight-stroke could have evolved via gradual incremental changes in wing movement and wing morphology. More fundamental to the origin of the avian flapping flight-stroke is the question of how a symmetrical forelimb posture-required for gliding and flapping flight-evolved from an alternating forelimb motion, evident in all extant bipeds when running except birds.

Motor Skills Training Enhances α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptor Subunit mRNA Expression in the Ipsilateral Sensorimotor Cortex and Striatum of Rats Following Intracerebral Hemorrhage.

PubMed

Tamakoshi, Keigo; Ishida, Kazuto; Kawanaka, Kentaro; Takamatsu, Yasuyuki; Tamaki, Hiroyuki

2017-10-01

We investigated the effects of acrobatic training (AT) on expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits in the sensorimotor cortex and striatum after intracerebral hemorrhage (ICH). Male Wistar rats were divided into 4 groups: ICH without AT (ICH), ICH with AT (ICH + AT), sham operation without AT (SHAM), and sham operation with AT (SHAM + AT). ICH was induced by collagenase injection into the left striatum. The ICH + AT group performed 5 acrobatic tasks daily on days 4-28 post ICH. Forelimb sensorimotor function was evaluated using the forelimb placing test. On days 14 and 29, mRNA expression levels of AMPAR subunits GluR1-4 were measured by real-time reverse transcription-polymerase chain reaction. Forelimb placing test scores were significantly higher in the ICH + AT group than in the ICH group. Expression levels of all AMPAR subunit mRNAs were significantly higher in the ipsilateral sensorimotor cortex of rats in the ICH + AT group than in that of rats in the ICH group on day 29. GluR3 and GluR4 expression levels were reduced in the ipsilateral striatum of rats in the ICH group compared with that of rats in the SHAM group on day 14. These changes may play a critical role in motor skills training-induced recovery after ICH. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Forelimbs of Tyrannosaurus Rex: A pathetic vestigial organ or an integral part of a fearsome predator?

NASA Astrophysics Data System (ADS)

Lee, Scott A.; Thomas, Joshua D.

2014-12-01

In this paper, we examine a first-year torque and angular acceleration problem to address a possible use of the forelimbs of Tyrannosaurus rex. A 1/40th-scale model (see Fig. 1) is brought to the classroom to introduce the students to the quandary: given that the forelimbs of T. rex were too short to reach its mouth, what function did the forelimbs serve? This issue crosses several scientific disciplines including paleontology, ecology, and physics, making it a great starting point for thinking "outside the box." Noted paleontologist Kenneth Carpenter has suggested that the forelimbs of T. rex were an integral part of its predatory behavior. Given the large teeth of T. rex, it is assumed that they killed with their teeth. Lipkin and Carpenter1 have suggested that the forelimbs were used to hold a struggling victim (which had not been dispatched with the first bite) while the final, lethal bite was applied. If that is the case, then the forelimbs must be capable of large angular accelerations α in order to grab the animal attempting to escape. The concepts of the typical first-year physics course are sufficient to test this hypothesis by solving α =τ /I . Naturally, students love solving any problem related to Tyrannosaurus rex!

Morphology and function of the forelimb in arboreal frogs: specializations for grasping ability?

PubMed Central

Manzano, Adriana S; Abdala, Virginia; Herrel, Anthony

2008-01-01

Frogs are characterized by a unique morphology associated with their saltatory lifestyle. Although variation in the form and function of the pelvic girdle and associated appendicular system related to specialized locomotor modes such as swimming or burrowing has been documented, the forelimbs have typically been viewed as relatively unspecialized. Yet, previous authors have noted versatility in forelimb function among arboreal frogs associated with feeding. Here we study the morphology and function of the forelimb and hand during locomotion in two species of arboreal frogs (Litoria caerulea and Phyllomedusa bicolor). Our data show a complex arrangement of the distal forelimb and hand musculature with some notable differences between species. Analyses of high-speed video and video fluoroscopy recordings show that forelimbs are used in alternating fashion in a diagonal sequence footfall pattern and that the position of the hand is adjusted when walking on substrates of different diameters. Electromyographic recordings show that the flexors of the hand are active during substrate contact, suggesting the use of gripping to generate a stabilizing torque. Measurements of grasping forces in vivo and during stimulation experiments show that both species, are capable of executing a so-called power grip but also indicates marked differences between species, in the magnitude of forces generated. Stimulation experiments showed an increased control of digit flexion in the more specialized of the two species, allowing it to execute a precision grip paralleled only by that seen in primates. PMID:18565111

Morphology and function of the forelimb in arboreal frogs: specializations for grasping ability?

PubMed

Manzano, Adriana S; Abdala, Virginia; Herrel, Anthony

2008-09-01

Frogs are characterized by a unique morphology associated with their saltatory lifestyle. Although variation in the form and function of the pelvic girdle and associated appendicular system related to specialized locomotor modes such as swimming or burrowing has been documented, the forelimbs have typically been viewed as relatively unspecialized. Yet, previous authors have noted versatility in forelimb function among arboreal frogs associated with feeding. Here we study the morphology and function of the forelimb and hand during locomotion in two species of arboreal frogs (Litoria caerulea and Phyllomedusa bicolor). Our data show a complex arrangement of the distal forelimb and hand musculature with some notable differences between species. Analyses of high-speed video and video fluoroscopy recordings show that forelimbs are used in alternating fashion in a diagonal sequence footfall pattern and that the position of the hand is adjusted when walking on substrates of different diameters. Electromyographic recordings show that the flexors of the hand are active during substrate contact, suggesting the use of gripping to generate a stabilizing torque. Measurements of grasping forces in vivo and during stimulation experiments show that both species, are capable of executing a so-called power grip but also indicates marked differences between species, in the magnitude of forces generated. Stimulation experiments showed an increased control of digit flexion in the more specialized of the two species, allowing it to execute a precision grip paralleled only by that seen in primates.

Extreme Modification of the Tetrapod Forelimb in a Triassic Diapsid Reptile.

PubMed

Pritchard, Adam C; Turner, Alan H; Irmis, Randall B; Nesbitt, Sterling J; Smith, Nathan D

2016-10-24

The tetrapod forelimb is one of the most versatile structures in vertebrate evolution, having been co-opted for an enormous array of functions. However, the structural relationships between the bones of the forelimb have remained largely unchanged throughout the 375 million year history of Tetrapoda, with a radius and ulna made up of elongate, paralleling shafts contacting a series of shorter carpal bones. These features are consistent across nearly all known tetrapods, suggesting that the morphospace encompassed by these taxa is limited by some sort of constraint(s). Here, we report on a series of three-dimensionally preserved fossils of the small-bodied (<1 m) Late Triassic diapsid reptile Drepanosaurus, from the Chinle Formation of New Mexico, USA, which dramatically diverge from this pattern. Along with the crushed type specimen from Italy, these specimens have a flattened, crescent-shaped ulna with a long axis perpendicular to that of the radius and hyperelongate, shaft-like carpal bones contacting the ulna that are proximodistally longer than the radius. The second digit supports a massive, hooked claw. This condition has similarities to living "hook-and-pull" digging mammals and demonstrates that specialized, modern ecological roles had developed during the Triassic Period, over 200 million years ago. The forelimb bones in Drepanosaurus represent previously unknown morphologies for a tetrapod and, thus, a dramatic expansion of known tetrapod forelimb morphospace. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recovery of Breathing and Forelimb Function after Prolonged Exposure to Repetitive Acute Intermittent Hypoxia

DTIC Science & Technology

2017-03-01

breathing capacity (Aim 1) and forelimb function (Aim 2), without systemic hypertension or hippocampal pathology (Aim 3). SPECIFIC AIMS Aim 1 (Florida...benefits. On the other hand, there was no evidence for pathology ( hypertension or hippocampal pathology). We were not able to perform time-series... hypertension or hippocampal (CA1) pathology. However, we did see striking (and surprising) preliminary evidence that prolonged rAIH: 1) reduced volume of the

Bilateral Cervical Contusion Spinal Cord Injury in Rats

PubMed Central

Anderson, Kim D.; Sharp, Kelli G.; Steward, Oswald

2009-01-01

There is increasing motivation to develop clinically relevant experimental models for cervical SCI in rodents and techniques to assess deficits in forelimb function. Here we describe a bilateral cervical contusion model in rats. Female Sprague-Dawley rats received mild or moderate cervical contusion injuries (using the Infinite Horizons device) at C5, C6, or C7/8. Forelimb motor function was assessed using a Grip Strength Meter (GSM); sensory function was assessed by the von Frey hair test; the integrity of the corticospinal tract (CST) was assessed by biotinylated dextran amine (BDA) tract tracing. Mild contusions caused primarily dorsal column (DC) and gray matter (GM) damage while moderate contusions produced additional damage to lateral and ventral tissue. Forelimb and hindlimb function was severely impaired immediately post-injury, but all rats regained the ability to use their hindlimbs for locomotion. Gripping ability was abolished immediately after injury but recovered partially, depending upon the spinal level and severity of the injury. Rats exhibited a loss of sensation in both fore- and hindlimbs that partially recovered, and did not exhibit allodynia. Tract tracing revealed that the main contingent of CST axons in the DC was completely interrupted in all but one animal whereas the dorsolateral CST (dlCST) was partially spared, and dlCST axons gave rise to axons that arborized in the GM caudal to the injury. Our data demonstrate that rats can survive significant bilateral cervical contusion injuries at or below C5 and that forepaw gripping function recovers after mild injuries even when the main component of CST axons in the dorsal column is completely interrupted. PMID:19559699

Vertical movement symmetry of the withers in horses with induced forelimb and hindlimb lameness at trot.

PubMed

Rhodin, M; Persson-Sjodin, E; Egenvall, A; Serra Bragança, F M; Pfau, T; Roepstorff, L; Weishaupt, M A; Thomsen, M H; van Weeren, P R; Hernlund, E

2018-04-15

The main criteria for lameness assessment in horses are head movement for forelimb lameness and pelvic movement for hindlimb lameness. However, compensatory head nod in horses with primary hindlimb lameness is a well-known phenomenon. This compensatory head nod movement can be easily misinterpreted as a sign of primary ipsilateral forelimb lameness. Therefore, discriminating compensatory asymmetries from primary directly pain-related movement asymmetries is a prerequisite for successful lameness assessment. To investigate the association between head, withers and pelvis movement asymmetry in horses with induced forelimb and hindlimb lameness. Experimental study. In 10 clinically sound Warmblood riding horses, forelimb and hindlimb lameness were induced using a sole pressure model. The horses were then trotted on a treadmill. Three-dimensional optical motion capture was used to collect kinematic data from reflective markers attached to the poll, withers and tubera sacrale. The magnitude and side (left or right) of the following symmetry parameters, vertical difference in minimum position, maximum position and range-up were calculated for head, withers, and pelvis. Mixed models were used to analyse data from induced forelimb and hindlimb lameness. For each mm increase in pelvic asymmetry in response to hindlimb lameness induction, withers movement asymmetry increased by 0.35-0.55 mm, but towards the contralateral side. In induced forelimb lameness, for each mm increase in head movement asymmetry, withers movement asymmetry increased by 0.05-0.10 mm, in agreement with the head movement asymmetry direction, both indicating lameness in the induced forelimb. Results must be confirmed in clinically lame horses trotting overground. The vertical asymmetry pattern of the withers discriminated a head nod associated with true forelimb lameness from the compensatory head movement asymmetry caused by primary hindlimb lameness. Measuring movement symmetry of the withers may, thus

Sensorimotor restriction affects complex movement topography and reachable space in the rat motor cortex.

PubMed

Budri, Mirco; Lodi, Enrico; Franchi, Gianfranco

2014-01-01

Long-duration intracortical microstimulation (ICMS) studies with 500 ms of current pulses suggest that the forelimb area of the motor cortex is organized into several spatially distinct functional zones that organize movements into complex sequences. Here we studied how sensorimotor restriction modifies the extent of functional zones, complex movements, and reachable space representation in the rat forelimb M1. Sensorimotor restriction was achieved by means of whole-forelimb casting of 30 days duration. Long-duration ICMS was carried out 12 h and 14 days after cast removal. Evoked movements were measured using a high-resolution 3D optical system. Long-term cast caused: (i) a reduction in the number of sites where complex forelimb movement could be evoked; (ii) a shrinkage of functional zones but no change in their center of gravity; (iii) a reduction in movement with proximal/distal coactivation; (iv) a reduction in maximal velocity, trajectory and vector length of movement, but no changes in latency or duration; (v) a large restriction of reachable space. Fourteen days of forelimb freedom after casting caused: (i) a recovery of the number of sites where complex forelimb movement could be evoked; (ii) a recovery of functional zone extent and movement with proximal/distal coactivation; (iii) an increase in movement kinematics, but only partial restoration of control rat values; (iv) a slight increase in reachability parameters, but these remained far below baseline values. We pose the hypothesis that specific aspects of complex movement may be stored within parallel motor cortex re-entrant systems.

Sensorimotor restriction affects complex movement topography and reachable space in the rat motor cortex

PubMed Central

Budri, Mirco; Lodi, Enrico; Franchi, Gianfranco

2014-01-01

Long-duration intracortical microstimulation (ICMS) studies with 500 ms of current pulses suggest that the forelimb area of the motor cortex is organized into several spatially distinct functional zones that organize movements into complex sequences. Here we studied how sensorimotor restriction modifies the extent of functional zones, complex movements, and reachable space representation in the rat forelimb M1. Sensorimotor restriction was achieved by means of whole-forelimb casting of 30 days duration. Long-duration ICMS was carried out 12 h and 14 days after cast removal. Evoked movements were measured using a high-resolution 3D optical system. Long-term cast caused: (i) a reduction in the number of sites where complex forelimb movement could be evoked; (ii) a shrinkage of functional zones but no change in their center of gravity; (iii) a reduction in movement with proximal/distal coactivation; (iv) a reduction in maximal velocity, trajectory and vector length of movement, but no changes in latency or duration; (v) a large restriction of reachable space. Fourteen days of forelimb freedom after casting caused: (i) a recovery of the number of sites where complex forelimb movement could be evoked; (ii) a recovery of functional zone extent and movement with proximal/distal coactivation; (iii) an increase in movement kinematics, but only partial restoration of control rat values; (iv) a slight increase in reachability parameters, but these remained far below baseline values. We pose the hypothesis that specific aspects of complex movement may be stored within parallel motor cortex re-entrant systems. PMID:25565987

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

PubMed Central

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

2016-01-01

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

Opiate modification of amygdaloid-kindled seizures in rats.

PubMed

Stone, W S; Eggleton, C E; Berman, R F

1982-05-01

Male Long-Evans rats were stereotaxically implanted bilaterally with bipolar electrodes in the central amygdala. Rats were then kindled once daily for 1 sec until 3 consecutive Stage V [25] kindled seizures were elicited. On the following day, animals were injected (IP) with either saline, naloxone (10 mg/kg), naltrexone (10mg/kg) or morphine sulfate (10 mg/kg) and again stimulated at the kindling stimulation parameters. Saline injected animals continued to show long bilateral AD's and behaviors (i.e., forelimb clonus, rearing, falling) typical of Stage V kindled animals. In contrast, rats injected with naloxone or naltrexone showed reduced behavioral seizures. Potentiation of post-ictal spiking by morphine in amygdaloid-kindled rats was also observed supporting previous reports [7,21]. In a second experiment, the reduction of kindled seizure serverity by naloxone was systematically replicated. It is concluded that opiates can significantly modify amygdaloid-kindled seizures, and that brain endorphins may play a role in the development or maintenance of an amygdaloid-kindled seizure focus.

The forelimb of Tyrannosaurus rex: a pathetic vestigial organ or an integral part of a fearsome predator?

NASA Astrophysics Data System (ADS)

Lee, Scott A.; Thomas, Joshua

2014-03-01

The function of the forelimb of Tyrannosaurus rex remains a controversial topic since it was too short to transfer food directly to the mouth. Since Tyrannosaurus rex was bipedal, the forelimb was not involved in locomotion. Suggestions for its possible use include providing an initial push for a laying animal to stand or to hold position during mating. We report numerical calculations performed to determine the moment of inertia of the forearm and the torques generated by the muscles of the arm, based on three-dimensional representations of the forelimb. Our results imply that the forelimb was capable of very high angular accelerations, on the order of 130 radians/s2. This corresponds to a tangential acceleration of the manus on the order of 90 m/s2 or about 9g, indicating that the manus could be moved extremely quickly to control a struggling prey animal immediately before the death blow was delivered by the teeth of Tyrannosaurus rex. Rather than a pathetic vestigial organ, these calculations suggest that the forelimbs were an integral part of the predation tactics of Tyrannosaurus rex.

Cervical intraspinal microstimulation evokes robust forelimb movements before and after injury

NASA Astrophysics Data System (ADS)

Sunshine, Michael D.; Cho, Frances S.; Lockwood, Danielle R.; Fechko, Amber S.; Kasten, Michael R.; Moritz, Chet T.

2013-06-01

Objective. Intraspinal microstimulation (ISMS) is a promising method for reanimating paralyzed limbs following neurological injury. ISMS within the cervical and lumbar spinal cord is capable of evoking a variety of highly-functional movements prior to injury, but the ability of ISMS to evoke forelimb movements after cervical spinal cord injury is unknown. Here we examine the forelimb movements and muscles activated by cervical ISMS both before and after contusion injury. Approach. We documented the forelimb muscles activated and movements evoked via systematic stimulation of the rodent cervical spinal cord both before injury and three, six and nine weeks following a moderate C4/C5 lateralized contusion injury. Animals were anesthetized with isoflurane to permit construction of somatotopic maps of evoked movements and quantify evoked muscle synergies between cervical segments C3 and T1. Main results. When ISMS was delivered to the cervical spinal cord, a variety of responses were observed at 68% of locations tested, with a spatial distribution that generally corresponded to the location of motor neuron pools. Stimulus currents required to achieve movement and the number of sites where movements could be evoked were unchanged by spinal cord injury. A transient shift toward extension-dominated movements and restricted muscle synergies were observed at three and six weeks following injury, respectively. By nine weeks after injury, however, ISMS-evoked patterns were similar to spinally-intact animals. Significance. The results demonstrate the potential for cervical ISMS to reanimate hand and arm function following spinal cord injury. Robust forelimb movements can be evoked both before and during the chronic stages of recovery from a clinically relevant and sustained cervical contusion injury.

Forelimb preferences in quadrupedal marsupials and their implications for laterality evolution in mammals

PubMed Central

2013-01-01

Background Acquisition of upright posture in evolution has been argued to facilitate manual laterality in primates. Owing to the high variety of postural habits marsupials can serve as a suitable model to test whether the species-typical body posture shapes forelimb preferences in non-primates or this phenomenon emerged only in the course of primate evolution. In the present study we aimed to explore manual laterality in marsupial quadrupeds and compare them with the results in the previously studied bipedal species. Forelimb preferences were assessed in captive grey short-tailed opossum (Monodelphis domestica) and sugar glider (Petaurus breviceps) in four different types of unimanual behaviour per species, which was not artificially evoked. We examined the possible effects of sex, age and task, because these factors have been reported to affect motor laterality in placental mammals. Results In both species the direction of forelimb preferences was strongly sex-related. Male grey short-tailed opossums showed right-forelimb preference in most of the observed unimanual behaviours, while male sugar gliders displayed only a slight, not significant rightward tendency. In contrast, females in both species exhibited consistent group-level preference of the left forelimb. We failed to reveal significant differences in manual preferences between tasks of potentially differing complexity: reaching a stable food item and catching live insects, as well as between the body support and food manipulation. No influence of subjects’ age on limb preferences was found. Conclusions The direction of sex-related differences in the manual preferences found in quadrupedal marsupials seems to be not typical for placental mammals. We suggest that the alternative way of interhemispheric connection in absence of corpus callosum may result in a fundamentally distinct mechanism of sex effect on limb preferences in marsupials compared to placentals. Our data confirm the idea that non

Forelimb preferences in quadrupedal marsupials and their implications for laterality evolution in mammals.

PubMed

Giljov, Andrey; Karenina, Karina; Malashichev, Yegor

2013-03-06

Acquisition of upright posture in evolution has been argued to facilitate manual laterality in primates. Owing to the high variety of postural habits marsupials can serve as a suitable model to test whether the species-typical body posture shapes forelimb preferences in non-primates or this phenomenon emerged only in the course of primate evolution. In the present study we aimed to explore manual laterality in marsupial quadrupeds and compare them with the results in the previously studied bipedal species. Forelimb preferences were assessed in captive grey short-tailed opossum (Monodelphis domestica) and sugar glider (Petaurus breviceps) in four different types of unimanual behaviour per species, which was not artificially evoked. We examined the possible effects of sex, age and task, because these factors have been reported to affect motor laterality in placental mammals. In both species the direction of forelimb preferences was strongly sex-related. Male grey short-tailed opossums showed right-forelimb preference in most of the observed unimanual behaviours, while male sugar gliders displayed only a slight, not significant rightward tendency. In contrast, females in both species exhibited consistent group-level preference of the left forelimb. We failed to reveal significant differences in manual preferences between tasks of potentially differing complexity: reaching a stable food item and catching live insects, as well as between the body support and food manipulation. No influence of subjects' age on limb preferences was found. The direction of sex-related differences in the manual preferences found in quadrupedal marsupials seems to be not typical for placental mammals. We suggest that the alternative way of interhemispheric connection in absence of corpus callosum may result in a fundamentally distinct mechanism of sex effect on limb preferences in marsupials compared to placentals. Our data confirm the idea that non-primate mammals differ from primates in

Organization of the sympathetic innervation of the forelimb resistance vessels in the cat.

PubMed

Backman, S B; Stein, R D; Polosa, C

1999-02-01

Detailed information on the outflow pathway of sympathetic vasoconstrictor fibers to the upper extremity is lacking. We studied the organization of the sympathetic innervation of the forelimb resistance vessels and of the sinoatrial (SA) node in the decerebrated, artificially respirated cat. The distal portion of sectioned individual rami T1-8 and the sympathetic chain immediately caudal to T8 on the right side were electrically stimulated while the right forelimb perfusion pressure (forelimb perfused at constant flow) and heart rate were recorded. Increases in perfusion pressure were evoked by stimulation of T2-8 (maximal response T7: 55 +/- 2.3 mm Hg). Responses were still evoked by stimulation of the sympathetic chain immediately caudal to T8 (44 +/- 15 mm Hg). Increases in heart rate were evoked by the stimulation of more rostral rami (T1-5; maximal response T3: 55.2 +/- 8 bpm). These vasoconstrictor and cardioacceleratory responses were blocked by the cholinergic antagonists hexamethonium and scopolamine. Sectioning of the vertebral nerve and the T1 ramus abolished the vasoconstrictor response. Stimulation of the vertebral nerve and of the proximal portion of the sectioned T1 ramus increased perfusion pressure (69 +/- 9 and 34 +/- 14 mm Hg, respectively), which was unaffected by ganglionic cholinergic block. These data suggest that forelimb resistance vessel control is subserved by sympathetic preganglionic neurons located mainly in the middle to caudal thoracic spinal segments. Some of the postganglionic axons subserving vasomotor function course through the T1 ramus, in addition to the vertebral nerve. Forelimb vasculature is controlled by sympathetic preganglionic neurons located in middle to caudal thoracic spinal segments and by postganglionic axons carried in the T1 ramus and vertebral nerve. This helps to provide the anatomical substrate of interruption of sympathetic outflow to the upper extremity produced by major conduction anesthesia of the stellate

Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats

PubMed Central

Combs, Hannah L.; Jones, Theresa A.; Kozlowski, Dorothy A.

2016-01-01

Abstract Cortical reorganization subsequent to post-stroke motor rehabilitative training (RT) has been extensively examined in animal models and humans. However, similar studies focused on the effects of motor training after traumatic brain injury (TBI) are lacking. We previously reported that after a moderate/severe TBI in adult male rats, functional improvements in forelimb use were accomplished only with a combination of skilled forelimb reach training and aerobic exercise, with or without nonimpaired forelimb constraint. Thus, the current study was designed to examine the relationship between functional motor cortical map reorganization after experimental TBI and the behavioral improvements resulting from this combinatorial rehabilitative regime. Adult male rats were trained to proficiency on a skilled reaching task, received a unilateral controlled cortical impact (CCI) over the forelimb area of the caudal motor cortex (CMC). Three days post-CCI, animals began RT (n = 13) or no rehabilitative training (NoRT) control procedures (n = 13). The RT group participated in daily skilled reach training, voluntary aerobic exercise, and nonimpaired forelimb constraint. This RT regimen significantly improved impaired forelimb reaching success and normalized reaching strategies, consistent with previous findings. RT also enlarged the area of motor cortical wrist representation, derived by intracortical microstimulation, compared to NoRT. These findings indicate that sufficient RT can greatly improve motor function and improve the functional integrity of remaining motor cortex after a moderate/severe CCI. When compared with findings from stroke models, these findings also suggest that more intense RT may be needed to improve motor function and remodel the injured cortex after TBI. PMID:26421759

Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats.

PubMed

Combs, Hannah L; Jones, Theresa A; Kozlowski, Dorothy A; Adkins, DeAnna L

2016-04-15

Cortical reorganization subsequent to post-stroke motor rehabilitative training (RT) has been extensively examined in animal models and humans. However, similar studies focused on the effects of motor training after traumatic brain injury (TBI) are lacking. We previously reported that after a moderate/severe TBI in adult male rats, functional improvements in forelimb use were accomplished only with a combination of skilled forelimb reach training and aerobic exercise, with or without nonimpaired forelimb constraint. Thus, the current study was designed to examine the relationship between functional motor cortical map reorganization after experimental TBI and the behavioral improvements resulting from this combinatorial rehabilitative regime. Adult male rats were trained to proficiency on a skilled reaching task, received a unilateral controlled cortical impact (CCI) over the forelimb area of the caudal motor cortex (CMC). Three days post-CCI, animals began RT (n = 13) or no rehabilitative training (NoRT) control procedures (n = 13). The RT group participated in daily skilled reach training, voluntary aerobic exercise, and nonimpaired forelimb constraint. This RT regimen significantly improved impaired forelimb reaching success and normalized reaching strategies, consistent with previous findings. RT also enlarged the area of motor cortical wrist representation, derived by intracortical microstimulation, compared to NoRT. These findings indicate that sufficient RT can greatly improve motor function and improve the functional integrity of remaining motor cortex after a moderate/severe CCI. When compared with findings from stroke models, these findings also suggest that more intense RT may be needed to improve motor function and remodel the injured cortex after TBI.

Electroacupuncture reduces the evoked responses of the spinal dorsal horn neurons in ankle-sprained rats

PubMed Central

Kim, Jae Hyo; Kim, Hee Young; Chung, Kyungsoon

2011-01-01

Acupuncture is shown to be effective in producing analgesia in ankle sprain pain in humans and animals. To examine the underlying mechanisms of the acupuncture-induced analgesia, the effects of electroacupuncture (EA) on weight-bearing forces (WBR) of the affected foot and dorsal horn neuron activities were examined in a rat model of ankle sprain. Ankle sprain was induced manually by overextending ligaments of the left ankle in the rat. Dorsal horn neuron responses to ankle movements or compression were recorded from the lumbar spinal cord using an in vivo extracellular single unit recording setup 1 day after ankle sprain. EA was applied to the SI-6 acupoint on the right forelimb (contralateral to the sprained ankle) by trains of electrical pulses (10 Hz, 1-ms pulse width, 2-mA intensity) for 30 min. After EA, WBR of the sprained foot significantly recovered and dorsal horn neuron activities were significantly suppressed in ankle-sprained rats. However, EA produced no effect in normal rats. The inhibitory effect of EA on hyperactivities of dorsal horn neurons of ankle-sprained rats was blocked by the α-adrenoceptor antagonist phentolamine (5 mg/kg ip) but not by the opioid receptor antagonist naltrexone (10 mg/kg ip). These data suggest that EA-induced analgesia in ankle sprain pain is mediated mainly by suppressing dorsal horn neuron activities through α-adrenergic descending inhibitory systems at the spinal level. PMID:21389301

Acute alcohol administration improves skilled reaching success in intact but not 6-OHDA dopamine depleted rats: a subsystems analysis of the motoric and anxiolytic effects of alcohol.

PubMed

Metz, Gerlinde A; Gonzalez, Claudia L R; Piecharka, Dionne M; Whishaw, Ian Q

2003-06-16

Low doses of alcohol impair movement and reduce anxiety. Most assessments of movement under ethyl alcohol (alcohol) in the rat have been tests of whole body movements, however. There has been no examination of the effects of alcohol on skilled limb movements, such as reaching for food with a forelimb. This was the purpose of the present study. Rats were trained to reach through a slot of a box with a forelimb in order to obtain a food pellet located on an external shelf. Once asymptotic performance was achieved, rats were given alcohol (20 ml of 8, 12 or 20% (v/v) solution) in separate tests to establish a relationship between alcohol ingestion and skilled reaching performance. Acute treatment with all doses of alcohol impaired postural support, but doses of 8 and 12% alcohol improved skilled reaching success. Qualitative analysis of the movements used for reaching at doses of 8 and 12% indicated that some limb components of the reaching movement were also impaired, perhaps secondarily due to impaired posture. In contrast, the reaching success of rats with unilateral dopamine depletion, induced with the neurotoxin 6-hydroxydopamine (6-OHDA) in the nigrostriatal bundle, was impaired by the same dose of alcohol that improved reaching success in control rats. The finding of improved success in reaching associated with reduced postural support in normal rats suggests a differential action of alcohol on movement subsystems underlying posture relative to skilled movement that depends upon an intact dopaminergic system. The results are also discussed with respect to the relationship of subsystems of movement and anxiety.

Complete reorganization of the motor cortex of adult rats following long-term spinal cord injuries.

PubMed

Tandon, Shashank; Kambi, Niranjan; Mohammed, Hisham; Jain, Neeraj

2013-07-01

Understanding brain reorganization following long-term spinal cord injuries is important for optimizing recoveries based on residual function as well as developing brain-controlled assistive devices. Although it has been shown that the motor cortex undergoes partial reorganization within a few weeks after peripheral and spinal cord injuries, it is not known if the motor cortex of rats is capable of large-scale reorganization after longer recovery periods. Here we determined the organization of the rat (Rattus norvegicus) motor cortex at 5 or more months after chronic lesions of the spinal cord at cervical levels using intracortical microstimulation. The results show that, in the rats with the lesions, stimulation of neurons in the de-efferented forelimb motor cortex no longer evokes movements of the forelimb. Instead, movements of the body parts in the adjacent representations, namely the whiskers and neck were evoked. In addition, at many sites, movements of the ipsilateral forelimb were observed at threshold currents. The extent of representations of the eye, jaw and tongue movements was unaltered by the lesion. Thus, large-scale reorganization of the motor cortex leads to complete filling-in of the de-efferented cortex by neighboring representations following long-term partial spinal cord injuries at cervical levels in adult rats. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The scaling of postcranial muscles in cats (Felidae) I: forelimb, cervical, and thoracic muscles.

PubMed

Cuff, Andrew R; Sparkes, Emily L; Randau, Marcela; Pierce, Stephanie E; Kitchener, Andrew C; Goswami, Anjali; Hutchinson, John R

2016-07-01

The body masses of cats (Mammalia, Carnivora, Felidae) span a ~300-fold range from the smallest to largest species. Despite this range, felid musculoskeletal anatomy remains remarkably conservative, including the maintenance of a crouched limb posture at unusually large sizes. The forelimbs in felids are important for body support and other aspects of locomotion, as well as climbing and prey capture, with the assistance of the vertebral (and hindlimb) muscles. Here, we examine the scaling of the anterior postcranial musculature across felids to assess scaling patterns between different species spanning the range of felid body sizes. The muscle architecture (lengths and masses of the muscle-tendon unit components) for the forelimb, cervical and thoracic muscles was quantified to analyse how the muscles scale with body mass. Our results demonstrate that physiological cross-sectional areas of the forelimb muscles scale positively with increasing body mass (i.e. becoming relatively larger). Many significantly allometric variables pertain to shoulder support, whereas the rest of the limb muscles become relatively weaker in larger felid species. However, when phylogenetic relationships were corrected for, most of these significant relationships disappeared, leaving no significantly allometric muscle metrics. The majority of cervical and thoracic muscle metrics are not significantly allometric, despite there being many allometric skeletal elements in these regions. When forelimb muscle data were considered in isolation or in combination with those of the vertebral muscles in principal components analyses and MANOVAs, there was no significant discrimination among species by either size or locomotory mode. Our results support the inference that larger felid species have relatively weaker anterior postcranial musculature compared with smaller species, due to an absence of significant positive allometry of forelimb or vertebral muscle architecture. This difference in strength

Cerebellar Modulation of Cortically Evoked Complex Movements in Rats.

PubMed

Viaro, Riccardo; Bonazzi, Laura; Maggiolini, Emma; Franchi, Gianfranco

2017-07-01

Intracortical microstimulation (ICMS) delivered to the motor cortex (M1) via long- or short-train duration (long- or short-duration ICMS) can evoke coordinated complex movements or muscle twitches, respectively. The role of subcortical cerebellar input in M1 output, in terms of long- and short-duration ICMS-evoked movement and motor skill performance, was evaluated in rats with bilateral lesion of the deep cerebellar nuclei. After the lesion, distal forelimb movements were seldom observed, and almost 30% of proximal forelimb movements failed to match criteria defining the movement class observed under control conditions. The classifiable movements could be evoked in different cortical regions with respect to control and many kinematic variables were strongly affected. Furthermore, movement endpoints within the rat's workspace shrunk closer to the body, while performance in the reaching/grasping task worsened. Surprisingly, neither the threshold current values for evoking movements nor the overall size of forelimb movement representation changed with respect to controls in either long- or short-duration ICMS. We therefore conclude that cerebellar input via the motor thalamus is crucial for expressing the basic functional features of the motor cortex. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Spinal cord projections of the rat main forelimb nerves, studied by transganglionic transport of WGA-HRP and by the disappearance of acid phosphatase.

PubMed

Castro-Lopes, J M; Coimbra, A

1991-03-01

The spinal cord projections of the 3 main forelimb nerves-median, radial and ulnar, were studied in the rat dorsal horn with transganglionic transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP), or using the disappearance of fluoride resistant acid phosphatase (FRAP) after nerve section. The projection patterns in lamina II were similar following the two procedures. The median and the radial nerve fibers projected to the medial and the intermediate thirds, respectively, of the dorsal horn lamina II in spinal cord segments C4-C8. The ulnar nerve projected to segments C6-C8 between the areas occupied by the other two nerves. The FRAP method also showed that the lateral part of lamina II, which was not filled by radial nerve fibers, received the projections from the dorsal cutaneous branches of cervical spinal nerves. In addition, FRAP disappeared from the medial end of segment T1 after skin incisions extending from the medial brachium to the axilla, which seemed due to severance of the cutaneous branchlets of the lateral anterior thoracic nerve. The FRAP procedure is thus sensitive enough to detect fibers in lamina II arising from small peripheral nerves, and may be used as an alternative to the anterograde tracing methods whenever there are no overlapping projections.

Swim stress reduces chronic pain in mice through an opioid mechanism.

PubMed

Carmody, J; Cooper, K

1987-03-09

Chronic nociception has been studied in male mice by means of the formalin test in which forelimb motor behaviour is scored after subcutaneous formalin injection. The rating remained above 2.0 for 30 min after the injection (scale range 0-3). The magnitude of the nociception has been compared with that reported in other animal types. Mice are more sensitive than rats, cats and monkeys. The stress of a swim of 3 min has been found to reduce nociception by up to 25%. This analgesia is wholly opioid in nature, being abolished by a moderate dose of naloxone (1 mg/kg).

Forelimbs of "Tyrannosaurus Rex": A Pathetic Vestigial Organ or an Integral Part of a Fearsome Predator?

ERIC Educational Resources Information Center

Lee, Scott A.; Thomas, Joshua D.

2014-01-01

In this paper, we examine a first-year torque and angular acceleration problem to address a possible use of the forelimbs of "Tyrannosaurus rex." A 1/40th-scale model (see Fig. 1) is brought to the classroom to introduce the students to the quandary: given that the forelimbs of "T. rex" were too short to reach its mouth, what…

Whisker and Nose Tactile Sense Guide Rat Behavior in a Skilled Reaching Task

PubMed Central

Parmiani, Pierantonio; Lucchetti, Cristina; Franchi, Gianfranco

2018-01-01

Skilled reaching is a complex movement in which a forelimb is extended to grasp food for eating. Video-recordings analysis of control rats enables us to distinguish several components of skilled reaching: Orient, approaching the front wall of the reaching box and poking the nose into the slot to locate the food pellet; Transport, advancing the forelimb through the slot to reach-grasp the pellet; and Withdrawal of the grasped food to eat. Although food location and skilled reaching is guided by olfaction, the importance of whisker/nose tactile sense in rats suggests that this too could play a role in reaching behavior. To test this hypothesis, we studied skilled reaching in rats trained in a single-pellet reaching task before and after bilateral whisker trimming and bilateral infraorbital nerve (ION) severing. During the task, bilaterally trimmed rats showed impaired Orient with respect to controls. Specifically, they detected the presence of the wall by hitting it with their nose (rather than their whiskers), and then located the slot through repetitive nose touches. The number of nose touches preceding poking was significantly higher in comparison to controls. On the other hand, macrovibrissae trimming resulted in no change in reaching/grasping or withdrawal components of skilled reaching. Bilaterally ION-severed rats, displayed a marked change in the structure of their skilled reaching. With respect to controls, in ION-severed rats: (a) approaches to the front wall were significantly reduced at 3–5 and 6–8 days; (b) nose pokes were significantly reduced at 3–5 days, and the slot was only located after many repetitive nose touches; (c) the reaching-grasping-retracting movement never appeared at 3–5 days; (d) explorative paw movements, equal to zero in controls, reached significance at 9–11 days; and (e) the restored reaching-grasping-retracting sequence was globally slower than in controls, but the success rate was the same. These findings strongly

The effect of ambient temperature on infrared thermographic images of joints in the distal forelimbs of healthy racehorses.

PubMed

Soroko, Maria; Howell, Kevin; Dudek, Krzysztof

2017-05-01

The aim of the study was to describe the dependence on ambient temperature of distal joint temperature at the forelimbs of racehorses. The study also investigated the influence of differing ambient temperatures on the temperature difference between joints: this was measured ipsilaterally (i.e. between the carpal and fetlock joints along each forelimb) and contralaterally (i.e. between the same joints of the left and right forelimbs). Sixty-four healthy racehorses were monitored over 10 months. At each session, three thermographic images were taken of the dorsal, lateral and medial aspects of the distal forelimbs. Temperature measurements were made from regions of interest (ROIs) covering the carpal and fetlock joints. There was a strong correlation between ambient temperature and absolute joint temperature at all ROIs. The study also observed a moderate correlation between ambient temperature and the ipsilateral temperature differences between joints when measured from the medial and lateral aspects. No significant correlation was noted when measured dorsally. The mean contralateral temperature differences between joints were all close to 0°C. The data support previous reports that the temperature distribution between the forelimbs of the healthy equine is generally symmetric, although some horses differ markedly from the average findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

From fish to modern humans--comparative anatomy, homologies and evolution of the pectoral and forelimb musculature.

PubMed

Diogo, R; Abdala, V; Aziz, M A; Lonergan, N; Wood, B A

2009-05-01

In a recent study Diogo & Abdala [(2007) J Morphol 268, 504-517] reported the results of the first part of a research project on the comparative anatomy, homologies and evolution of the pectoral muscles of osteichthyans (bony fish and tetrapods). That report mainly focused on actinopterygian fish but also compared these fish with certain non-mammalian sarcopterygians. This study, which reports the second part of the research project, focuses mainly on sarcopterygians and particularly on how the pectoral and forelimb muscles have evolved during the transitions from sarcopterygian fish and non-mammalian tetrapods to monotreme and therian mammals and humans. The data obtained by our own dissections of all the pectoral and forelimb muscles of representative members of groups as diverse as sarcopterygian fish, amphibians, reptiles, monotremes and therian mammals such as rodents, tree-shrews, colugos and primates, including humans, are compared with the information available in the literature. Our observations and comparisons clearly stress that, with regard to the number of pectoral and forelimb muscles, the most striking transition within sarcopterygian evolutionary history was that leading to the origin of tetrapods. Whereas extant sarcopterygian fish have an abductor and adductor of the fin and a largely undifferentiated hypaxial and epaxial musculature, extant salamanders such as Ambystoma have more than 40 pectoral and forelimb muscles. There is no clear increase in the number of pectoral and forelimb muscles within the evolutionary transition that led to the origin of mammals and surely not to that leading to the origin of primates and humans.

Delta-9-tetrahydrocannabinol (THC) affects forelimb motor map expression but has little effect on skilled and unskilled behavior.

PubMed

Scullion, K; Guy, A R; Singleton, A; Spanswick, S C; Hill, M N; Teskey, G C

2016-04-05

It has previously been shown in rats that acute administration of delta-9-tetrahydrocannabinol (THC) exerts a dose-dependent effect on simple locomotor activity, with low doses of THC causing hyper-locomotion and high doses causing hypo-locomotion. However the effect of acute THC administration on cortical movement representations (motor maps) and skilled learned movements is completely unknown. It is important to determine the effects of THC on motor maps and skilled learned behaviors because behaviors like driving place people at a heightened risk. Three doses of THC were used in the current study: 0.2mg/kg, 1.0mg/kg and 2.5mg/kg representing the approximate range of the low to high levels of available THC one would consume from recreational use of cannabis. Acute peripheral administration of THC to drug naïve rats resulted in dose-dependent alterations in motor map expression using high resolution short duration intracortical microstimulation (SD-ICMS). THC at 0.2mg/kg decreased movement thresholds and increased motor map size, while 1.0mg/kg had the opposite effect, and 2.5mg/kg had an even more dramatic effect. Deriving complex movement maps using long duration (LD)-ICMS at 1.0mg/kg resulted in fewer complex movements. Dosages of 1.0mg/kg and 2.5mg/kg THC reduced the number of reach attempts but did not affect percentage of success or the kinetics of reaching on the single pellet skilled reaching task. Rats that received 2.5mg/kg THC did show an increase in latency of forelimb removal on the bar task, while dose-dependent effects of THC on unskilled locomotor activity using the rotorod and horizontal ladder tasks were not observed. Rats may be employing compensatory strategies after receiving THC, which may account for the robust changes in motor map expression but moderate effects on behavior. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Motor cortex stimulation does not lead to functional recovery after experimental cortical injury in rats.

PubMed

Schönfeld, Lisa-Maria; Jahanshahi, Ali; Lemmens, Evi; Bauwens, Matthias; Hescham, Sarah-Anna; Schipper, Sandra; Lagiere, Melanie; Hendrix, Sven; Temel, Yasin

2017-01-01

Motor impairments are among the major complications that develop after cortical damage caused by either stroke or traumatic brain injury. Motor cortex stimulation (MCS) can improve motor functions in animal models of stroke by inducing neuroplasticity. In the current study, the therapeutic effect of chronic MCS was assessed in a rat model of severe cortical damage. A controlled cortical impact (CCI) was applied to the forelimb area of the motor cortex followed by implantation of a flat electrode covering the lesioned area. Forelimb function was assessed using the Montoya staircase test and the cylinder test before and after a period of chronic MCS. Furthermore, the effect of MCS on tissue metabolism and lesion size was measured using [18F]-fluorodesoxyglucose (FDG) μPET scanning. CCI caused a considerable lesion at the level of the motor cortex and dorsal striatum together with a long-lasting behavioral phenotype of forelimb impairment. However, MCS applied to the CCI lesion did not lead to any improvement in limb functioning when compared to non-stimulated control rats. Also, MCS neither changed lesion size nor distribution of FDG. The use of MCS as a standalone treatment did not improve motor impairments in a rat model of severe cortical damage using our specific treatment modalities.

Progressive motor cortex functional reorganization following 6-hydroxydopamine lesioning in rats.

PubMed

Viaro, Riccardo; Morari, Michele; Franchi, Gianfranco

2011-03-23

Many studies have attempted to correlate changes of motor cortex activity with progression of Parkinson's disease, although results have been controversial. In the present study we used intracortical microstimulation (ICMS) combined with behavioral testing in 6-hydroxydopamine hemilesioned rats to evaluate the impact of dopamine depletion on movement representations in primary motor cortex (M1) and motor behavior. ICMS allows for motor-effective stimulation of corticofugal neurons in motor areas so as to obtain topographic movements representations based on movement type, area size, and threshold currents. Rats received unilateral 6-hydroxydopamine in the nigrostriatal bundle, causing motor impairment. Changes in M1 were time dependent and bilateral, although stronger in the lesioned than the intact hemisphere. Representation size and threshold current were maximally impaired at 15 d, although inhibition was still detectable at 60-120 d after lesion. Proximal forelimb movements emerged at the expense of the distal ones. Movement lateralization was lost mainly at 30 d after lesion. Systemic L-3,4-dihydroxyphenylalanine partially attenuated motor impairment and cortical changes, particularly in the caudal forelimb area, and completely rescued distal forelimb movements. Local application of the GABA(A) antagonist bicuculline partially restored cortical changes, particularly in the rostral forelimb area. The local anesthetic lidocaine injected into the M1 of the intact hemisphere restored movement lateralization in the lesioned hemisphere. This study provides evidence for motor cortex remodeling after unilateral dopamine denervation, suggesting that cortical changes were associated with dopamine denervation, pathogenic intracortical GABA inhibition, and altered interhemispheric activity.

Fore-Aft Ground Force Adaptations to Induced Forelimb Lameness in Walking and Trotting Dogs

PubMed Central

Abdelhadi, Jalal; Wefstaedt, Patrick; Nolte, Ingo; Schilling, Nadja

2012-01-01

Animals alter their locomotor mechanics to adapt to a loss of limb function. To better understand their compensatory mechanisms, this study evaluated the changes in the fore-aft ground forces to forelimb lameness and tested the hypothesis that dogs unload the affected limb by producing a nose-up pitching moment via the exertion of a net-propulsive force when the lame limb is on the ground. Seven healthy Beagles walked and trotted at steady speed on an instrumented treadmill while horizontal force data were collected before and after a moderate lameness was induced. Peak, mean and summed braking and propulsive forces as well as the duration each force was exerted and the time to reach maximum force were evaluated for both the sound and the lame condition. Compared with the sound condition, a net-propulsive force was produced by the lame diagonal limbs due to a reduced braking force in the affected forelimb and an increased propulsive force in the contralateral hindlimb when the dogs walked and trotted. To regain pitch stability and ensure steady speed for a given locomotor cycle, the dogs produced a net-braking force when the sound diagonal limbs were on the ground by exerting greater braking forces in both limbs during walking and additionally reducing the propulsive force in the hindlimb during trotting. Consistent with the proposed mechanism, dogs maximize their double support phases when walking. Likely associated with the fore-aft force adaptations to lameness are changes in muscle recruitment that potentially result in short- and long-term effects on the limb and trunk muscles. PMID:23300614

Postnatal Maturation of the Red Nucleus Motor Map Depends on Rubrospinal Connections with Forelimb Motor Pools

PubMed Central

Williams, Preston T. J. A.; Kim, Sangsoo

2014-01-01

The red nucleus (RN) and rubrospinal tract (RST) are important for forelimb motor control. Although the RST is present postnatally in cats, nothing is known about when rubrospinal projections could support motor functions or the relation between the development of the motor functions of the rubrospinal system and the corticospinal system, the other major system for limb control. Our hypothesis is that the RN motor map is present earlier in development than the motor cortex (M1) map, to support early forelimb control. We investigated RN motor map maturation with microstimulation and RST cervical enlargement projections using anterograde tracers between postnatal week 3 (PW3) and PW16. Microstimulation and tracer injection sites were verified histologically to be located within the RN. Microstimulation at PW4 evoked contralateral wrist, elbow, and shoulder movements. The number of sites producing limb movement increased and response thresholds decreased progressively through PW16. From the outset, all forelimb joints were represented. At PW3, RST projections were present within the cervical intermediate zone, with a mature density of putative synapses. In contrast, beginning at PW5 there was delayed and age-dependent development of forelimb motor pool projections and putative rubromotoneuronal synapses. The RN has a more complete forelimb map early in development than previous studies showed for M1, supporting our hypothesis of preferential rubrospinal rather than corticospinal control for early movements. Remarkably, development of the motor pool, not intermediate zone, RST projections paralleled RN motor map development. The RST may be critical for establishing the rudiments of motor skills that subsequently become refined with further CST development. PMID:24647962

Comparison of hand use and forelimb posture during vertical climbing in mountain gorillas (Gorilla beringei beringei) and chimpanzees (Pan troglodytes).

PubMed

Neufuss, Johanna; Robbins, Martha M; Baeumer, Jana; Humle, Tatyana; Kivell, Tracy L

2017-12-01

Studies on grasping and limb posture during arboreal locomotion in great apes in their natural environment are scarce and thus, attempts to correlate behavioral and habitat differences with variation in morphology are limited. The aim of this study is to compare hand use and forelimb posture during vertical climbing in wild, habituated mountain gorillas (Gorilla beringei beringei) and semi-free-ranging chimpanzees (Pan troglodytes) to assess differences in the climbing styles that may relate to variation in hand or forelimb morphology and body size. We investigated hand use and forelimb posture during both ascent and descent vertical climbing in 15 wild mountain gorillas and eight semi-free-ranging chimpanzees, using video records obtained ad libitum. In both apes, forelimb posture was correlated with substrate size during both ascent and descent climbing. While climbing, both apes used power grips and diagonal power grips, including three different thumb postures. Mountain gorillas showed greater ulnar deviation of the wrist during vertical descent than chimpanzees, and the thumb played an important supportive role when gorillas vertically descended lianas. We found that both apes generally had the same grip preferences and used similar forelimb postures on supports of a similar size, which is consistent with their overall similarity in hard and soft tissue morphology of the hand and forelimb. However, some species-specific differences in morphology appear to elicit slightly different grasping strategies during vertical climbing between mountain gorillas and chimpanzees. © 2017 Wiley Periodicals, Inc.

Forelimb anatomy and the discrimination of the predatory behavior of carnivorous mammals: the thylacine as a case study.

PubMed

Janis, Christine M; Figueirido, Borja

2014-12-01

Carnivorous mammals use their forelimbs in different ways to capture their prey. Most terrestrial carnivores have some cursorial (running) adaptations, but ambush predators retain considerable flexibility in their forelimb movement, important for grappling with their prey. In contrast, predators that rely on pursuit to run down their prey have sacrificed some of this flexibility for locomotor efficiency, in the greater restriction of the forelimb motion to the parasagittal plane. In this article, we measured aspects of the forelimb anatomy (44 linear measurements) in 36 species of carnivorous mammals of known predatory behavior, and used multivariate analyses to investigate how well the forelimb anatomy reflects the predatory mode (ambush, pursuit, or pounce-pursuit). A prime intention of this study was to establish morphological correlates of behavior that could then be applied to fossil mammals: for this purpose, five individuals of the recently extinct thylacine (Thylacinus cynocephalus) were also included as unknowns. We show that the three different types of predators can be distinguished by their morphology, both in analyses where all the forelimb bones are included together, and in the separate analyses of each bone individually. Of particular interest is the ability to distinguish between the two types of more cursorial predators, pursuit and pounce-pursuit, which have previously been considered as primarily size-based categories. Despite a prior consideration of the thylacine as a "pounce-pursuit" or an "ambush" type of predator, the thylacines did not consistently cluster with any type of predatory carnivores in our analyses. Rather, the thylacines appeared to be more generalized in their morphology than any of the extant carnivores. The absence of a large diversity of large carnivorous mammals in Australia, past and present, may explain the thylacine's generalized morphology. © 2014 Wiley Periodicals, Inc.

The phylogeny of the red panda (Ailurus fulgens): evidence from the forelimb

PubMed Central

Fisher, Rebecca E; Adrian, Brent; Barton, Michael; Holmgren, Jennifer; Tang, Samuel Y

2009-01-01

Within the order Carnivora, the phylogeny of the red panda (Ailurus fulgens) is contentious, with morphological and molecular studies supporting a wide range of possible relationships, including close ties to procyonids, ursids, mustelids and mephitids. This study provides additional morphological data, including muscle maps, for the forelimb of Ailurus, based on the dissection of four cadavers from the National Zoological Park, Washington, DC, USA. The red panda forelimb is characterized by a number of primitive features, including the lack of m. rhomboideus profundus, a humeral insertion for m. cleidobrachialis, the presence of mm. brachioradialis, articularis humeri and coracobrachialis, a single muscle belly for m. extensor digitorum lateralis with tendons to digits III–V, four mm. lumbricales, and the presence of mm. flexor digitorum brevis manus, adductores digiti I, II and V, and abductor digiti I and V. Red pandas resemble Ailuropoda, mustelids and some procyonids in possessing a soft tissue origin of m. flexor digitorum superficialis. In addition, red pandas are similar to ursids and procyonids in having a variable presence of m. biceps brachii caput breve. Furthermore, Ailurus and some ursids lack m. rhomboideus capitis. The forelimb muscle maps from this study represent a valuable resource for analyzing the functional anatomy of fossil ailurids and some notes on the Miocene ailurid, Simocyon batalleri, are presented. PMID:19930516

The phylogeny of the red panda (Ailurus fulgens): evidence from the forelimb.

PubMed

Fisher, Rebecca E; Adrian, Brent; Barton, Michael; Holmgren, Jennifer; Tang, Samuel Y

2009-12-01

Within the order Carnivora, the phylogeny of the red panda (Ailurus fulgens) is contentious, with morphological and molecular studies supporting a wide range of possible relationships, including close ties to procyonids, ursids, mustelids and mephitids. This study provides additional morphological data, including muscle maps, for the forelimb of Ailurus, based on the dissection of four cadavers from the National Zoological Park, Washington, DC, USA. The red panda forelimb is characterized by a number of primitive features, including the lack of m. rhomboideus profundus, a humeral insertion for m. cleidobrachialis, the presence of mm. brachioradialis, articularis humeri and coracobrachialis, a single muscle belly for m. extensor digitorum lateralis with tendons to digits III-V, four mm. lumbricales, and the presence of mm. flexor digitorum brevis manus, adductores digiti I, II and V, and abductor digiti I and V. Red pandas resemble Ailuropoda, mustelids and some procyonids in possessing a soft tissue origin of m. flexor digitorum superficialis. In addition, red pandas are similar to ursids and procyonids in having a variable presence of m. biceps brachii caput breve. Furthermore, Ailurus and some ursids lack m. rhomboideus capitis. The forelimb muscle maps from this study represent a valuable resource for analyzing the functional anatomy of fossil ailurids and some notes on the Miocene ailurid, Simocyon batalleri, are presented.

Grizzly bear (Ursus arctos horribilis) locomotion: forelimb joint mechanics across speed in the sagittal and frontal planes.

PubMed

Shine, Catherine L; Robbins, Charles T; Nelson, O Lynne; McGowan, Craig P

2017-04-01

The majority of terrestrial locomotion studies have focused on parasagittal motion and paid less attention to forces or movement in the frontal plane. Our previous research has shown that grizzly bears produce higher medial ground reaction forces (lateral pushing from the animal) than would be expected for an upright mammal, suggesting frontal plane movement may be an important aspect of their locomotion. To examine this, we conducted an inverse dynamics analysis in the sagittal and frontal planes, using ground reaction forces and position data from three high-speed cameras of four adult female grizzly bears. Over the speed range collected, the bears used walks, running walks and canters. The scapulohumeral joint, wrist and the limb overall absorb energy (average total net work of the forelimb joints, -0.97 W kg -1 ). The scapulohumeral joint, elbow and total net work of the forelimb joints have negative relationships with speed, resulting in more energy absorbed by the forelimb at higher speeds (running walks and canters). The net joint moment and power curves maintain similar patterns across speed as in previously studied species, suggesting grizzly bears maintain similar joint dynamics to other mammalian quadrupeds. There is no significant relationship with net work and speed at any joint in the frontal plane. The total net work of the forelimb joints in the frontal plane was not significantly different from zero, suggesting that, despite the high medial ground reaction forces, the forelimb acts as a strut in that plane. © 2017. Published by The Company of Biologists Ltd.

From fish to modern humans – comparative anatomy, homologies and evolution of the pectoral and forelimb musculature

PubMed Central

Diogo, R; Abdala, V; Aziz, M A; Lonergan, N; Wood, B A

2009-01-01

In a recent study Diogo & Abdala [(2007) JMorphol268, 504–517] reported the results of the first part of a research project on the comparative anatomy, homologies and evolution of the pectoral muscles of osteichthyans (bony fish and tetrapods). That report mainly focused on actinopterygian fish but also compared these fish with certain non-mammalian sarcopterygians. This study, which reports the second part of the research project, focuses mainly on sarcopterygians and particularly on how the pectoral and forelimb muscles have evolved during the transitions from sarcopterygian fish and non-mammalian tetrapods to monotreme and therian mammals and humans. The data obtained by our own dissections of all the pectoral and forelimb muscles of representative members of groups as diverse as sarcopterygian fish, amphibians, reptiles, monotremes and therian mammals such as rodents, tree-shrews, colugos and primates, including humans, are compared with the information available in the literature. Our observations and comparisons clearly stress that, with regard to the number of pectoral and forelimb muscles, the most striking transition within sarcopterygian evolutionary history was that leading to the origin of tetrapods. Whereas extant sarcopterygian fish have an abductor and adductor of the fin and a largely undifferentiated hypaxial and epaxial musculature, extant salamanders such as Ambystoma have more than 40 pectoral and forelimb muscles. There is no clear increase in the number of pectoral and forelimb muscles within the evolutionary transition that led to the origin of mammals and surely not to that leading to the origin of primates and humans. PMID:19438764

Genetic regulation of canine skeletal traits: trade-offs between the hind limbs and forelimbs in the fox and dog

PubMed Central

Kharlamova, Anastasia V.; Trut, Lyudmila N.; Carrier, David R.; Chase, Kevin; Lark, Karl G.

2008-01-01

Synopsis Genetic variation in functionally integrated skeletal traits can be maintained over 10 million years despite bottlenecks and stringent selection. Here, we describe an analysis of the genetic architecture of the canid axial skeleton using populations of the Portuguese Water Dog Canis familiaris) and silver fox (Vulpes vulpes). Twenty-one skeletal metrics taken from radiographs of the forelimbs and hind limbs of the fox and dog were used to construct separate anatomical principal component (PC) matrices of the two species. In both species, 15 of the 21 PCs exhibited significant heritability, ranging from 25% to 70%. The second PC, in both species, represents a trade-off in which limb-bone width is inversely correlated with limb-bone length. PC2 accounts for approximately 15% of the observed skeletal variation, ~30% of the variation in shape. Many of the other significant PCs affect very small amounts of variation (e.g., 0.2–2%) along trade-off axes that partition function between the forelimbs and hind limbs. These PCs represent shape axes in which an increase in size of an element of the forelimb is associated with a decrease in size of an element of the hind limb and vice versa. In most cases, these trade-offs are heritable in both species and genetic loci have been identified in the Portuguese Water Dog for many of these. These PCs, present in both the dog and the fox, include ones that affect lengths of the forelimb versus the hind limb, length of the forefoot versus that of the hind foot, muscle moment (i.e., lever) arms of the forelimb versus hind limb, and cortical thickness of the bones of the forelimb versus hind limb. These inverse relationships suggest that genetic regulation of the axial skeleton results, in part, from the action of genes that influence suites of functionally integrated traits. Their presence in both dogs and foxes suggests that the genes controlling the regulation of these PCs of the forelimb versus hind limb may be found in

Motor Skills Training Improves Sensorimotor Dysfunction and Increases Microtubule-Associated Protein 2 mRNA Expression in Rats with Intracerebral Hemorrhage.

PubMed

Tamakoshi, Keigo; Kawanaka, Kentaro; Onishi, Hideaki; Takamatsu, Yasuyuki; Ishida, Kazuto

2016-08-01

In this study, we examined the effects of motor skills training on the sensorimotor function and the expression of genes associated with synaptic plasticity after intracerebral hemorrhage (ICH) in rats. Male Wistar rats were subjected to ICH or sham operation. ICH was caused by the injection of collagenase into the left striatum. Rats were randomly assigned to no training, acrobatic training, and sham groups. The acrobatic group performed 5 types of acrobatic tasks from 4 to 28 days after surgery. The forelimb sensorimotor function was evaluated over time using forepaw grasping, forelimb placing, and postural instability tests. At 14 and 29 days after the lesion, we analyzed the mRNA expression levels of microtubule-associated protein 2 (MAP2), brain-derived neurotrophic factor, and growth-associated protein 43 in the bilateral sensorimotor cortex (forelimb area) by real-time reverse transcription-polymerase chain reaction. Motor skills training in ICH rats improved the sensorimotor dysfunction significantly from the early phase. The mRNA expression level of MAP2 was upregulated in the ipsilesional sensorimotor cortex by motor skills training at 29 days after the lesion. Our results suggest that sensorimotor functional recovery following motor skills training after ICH is promoted by dendritic growth in the ipsilesional sensorimotor cortex. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Forelimb muscle and joint actions in Archosauria: insights from Crocodylus johnstoni (Pseudosuchia) and Mussaurus patagonicus (Sauropodomorpha)

PubMed Central

Allen, Vivian

2017-01-01

Many of the major locomotor transitions during the evolution of Archosauria, the lineage including crocodiles and birds as well as extinct Dinosauria, were shifts from quadrupedalism to bipedalism (and vice versa). Those occurred within a continuum between more sprawling and erect modes of locomotion and involved drastic changes of limb anatomy and function in several lineages, including sauropodomorph dinosaurs. We present biomechanical computer models of two locomotor extremes within Archosauria in an analysis of joint ranges of motion and the moment arms of the major forelimb muscles in order to quantify biomechanical differences between more sprawling, pseudosuchian (represented the crocodile Crocodylus johnstoni) and more erect, dinosaurian (represented by the sauropodomorph Mussaurus patagonicus) modes of forelimb function. We compare these two locomotor extremes in terms of the reconstructed musculoskeletal anatomy, ranges of motion of the forelimb joints and the moment arm patterns of muscles across those ranges of joint motion. We reconstructed the three-dimensional paths of 30 muscles acting around the shoulder, elbow and wrist joints. We explicitly evaluate how forelimb joint mobility and muscle actions may have changed with postural and anatomical alterations from basal archosaurs to early sauropodomorphs. We thus evaluate in which ways forelimb posture was correlated with muscle leverage, and how such differences fit into a broader evolutionary context (i.e. transition from sprawling quadrupedalism to erect bipedalism and then shifting to graviportal quadrupedalism). Our analysis reveals major differences of muscle actions between the more sprawling and erect models at the shoulder joint. These differences are related not only to the articular surfaces but also to the orientation of the scapula, in which extension/flexion movements in Crocodylus (e.g. protraction of the humerus) correspond to elevation/depression in Mussaurus. Muscle action is highly

Effects of microRNA-21 on Nerve Cell Regeneration and Neural Function Recovery in Diabetes Mellitus Combined with Cerebral Infarction Rats by Targeting PDCD4.

PubMed

Guo, Yun-Bao; Ji, Tie-Feng; Zhou, Hong-Wei; Yu, Jin-Lu

2018-03-01

We aimed to determine the effect and mechanism of microRNA-21 (miR-21) on nerve cell regeneration and nerve functional recovery in diabetes mellitus combined with cerebral infarction (DM + CI) rats by targeting PDCD4. A total of 125 male Wistar rats were selected for DM + CI rat model construction and assigned into the blank, miR-21 mimics, mimics control, miR-21 inhibitor, inhibitor control, miR-21 inhibitor + si-PDCD4 and si-PDCD4 groups. And, 20 healthy rats were selected for the normal group. Triphenylterazolium chloride (TTC) staining and HE staining were used for determination of the area of CI and pathological changes, respectively. Behaviors of rats in the eight groups were determined by forelimb placement test and balance beam walking test. Immunohistochemical staining, double immunofluorescence staining assay, Western blotting, and qRT-PCR were used to detect expressions of miR-21, PDCD4, HNA, Nestin, NeuN, β-III-Tub, PTEN, FasL, and GFAP. DNA laddering and TUNEL staining was used for cell apoptosis. TTC and HE staining confirmed that 87.5% rats were induced into CI + DM models successfully. Results of forelimb placement test and balance beam walking test showed that miR-21 mimics, and si-PCDC4 improved the nerve defect of model rats. Comparing with the blank group at the same time, rats in the miR-21 inhibitor group displayed significant decrease in the forelimb placement test score, significant increase in the balance beam walking test score, and exacerbation of nerve defect, while rats in the miR-21 mimics and si-PCDC4 groups displayed significant increase in forelimb placement test score and significant decrease in the balance beam walking test score and improvement of nerve defect situation. The HNA, Nestin, and PDCD4 expressions were decreased and the NeuN, β-III-Tub, and GFAP expressions were increased in the miR-21 mimics and si-PDCD4 groups comparing with the blank group. The results of miR-21 inhibitor group were on the contrary. In

Assessing Forelimb Function after Unilateral Cervical SCI using Novel Tasks: Limb Step-alternation, Postural Instability and Pasta Handling

PubMed Central

Schallert, Timothy; Schmidt, Christine E.

2013-01-01

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority of the spinal cord injuries in humans occur at the cervical levels. Therefore, developing cervical injury models and developing relevant and sensitive behavioral tests is of great importance. Here we describe the use of a newly developed forelimb step-alternation test after cervical spinal cord injury in rats. In addition, we describe two behavioral tests that have not been used after spinal cord injury: a postural instability test (PIT), and a pasta-handling test. All three behavioral tests are highly sensitive to injury and are easy to use. Therefore, we feel that these behavioral tests can be instrumental in investigating therapeutic strategies after cSCI. PMID:24084700

Assessing forelimb function after unilateral cervical SCI using novel tasks: limb step-alternation, postural instability and pasta handling.

PubMed

Khaing, Zin Z; Geissler, Sydney A; Schallert, Timothy; Schmidt, Christine E

2013-09-16

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority of the spinal cord injuries in humans occur at the cervical levels. Therefore, developing cervical injury models and developing relevant and sensitive behavioral tests is of great importance. Here we describe the use of a newly developed forelimb step-alternation test after cervical spinal cord injury in rats. In addition, we describe two behavioral tests that have not been used after spinal cord injury: a postural instability test (PIT), and a pasta-handling test. All three behavioral tests are highly sensitive to injury and are easy to use. Therefore, we feel that these behavioral tests can be instrumental in investigating therapeutic strategies after cSCI.

A Method for Immobilizing the Forelimbs of Rabbits.

PubMed

Thunder, Richard M.; Chang, James; Broome, Rosemary L.; Most, Daniel

1998-09-01

Immobilizing the forelimbs of rabbits after surgical procedures is necessary to allow healing, yet it often can be difficult, because rabbits are often able to pull the repaired limb from its cast soon after surgery and well before adequate tissue repair has taken place. We describe here a method of immobilization that uses 3 layers of cast material combined with flexion of the radiocarpal and radiohumeral joints. This method resulted in successful immobilization in 97% of the rabbits on which it was used.

Do constraints associated with the locomotor habitat drive the evolution of forelimb shape? A case study in musteloid carnivorans

PubMed Central

Fabre, Anne-Claire; Cornette, Raphael; Goswami, Anjali; Peigné, Stéphane

2015-01-01

Convergence in morphology can result from evolutionary adaptations in species living in environments with similar selective pressures. Here, we investigate whether the shape of the forelimb long bones has converged in environments imposing similar functional constraints, using musteloid carnivores as a model. The limbs of quadrupeds are subjected to many factors that may influence their shape. They need to support body mass without collapsing or breaking, yet at the same time resist the stresses and strains induced by locomotion. This likely imposes strong constraints on their morphology. Our geometric morphometric analyses show that locomotion, body mass and phylogeny all influence the shape of the forelimb. Furthermore, we find a remarkable convergence between: (i) aquatic and semi-fossorial species, both displaying a robust forelimb, with a shape that improves stability and load transfer in response to the physical resistance imposed by the locomotor environment; and (ii) aquatic and arboreal/semi-arboreal species, with both groups displaying a broad capitulum. This augments the degree of pronation/supination, an important feature for climbing as well as grasping and manipulation ability, behaviors common to aquatic and arboreal species. In summary, our results highlight how musteloids with different locomotor ecologies show differences in the anatomy of their forelimb bones. Yet, functional demands for limb movement through dense media also result in convergence in forelimb long-bone shape between diverse groups, for example, otters and badgers. PMID:25994128

Do constraints associated with the locomotor habitat drive the evolution of forelimb shape? A case study in musteloid carnivorans.

PubMed

Fabre, Anne-Claire; Cornette, Raphael; Goswami, Anjali; Peigné, Stéphane

2015-06-01

Convergence in morphology can result from evolutionary adaptations in species living in environments with similar selective pressures. Here, we investigate whether the shape of the forelimb long bones has converged in environments imposing similar functional constraints, using musteloid carnivores as a model. The limbs of quadrupeds are subjected to many factors that may influence their shape. They need to support body mass without collapsing or breaking, yet at the same time resist the stresses and strains induced by locomotion. This likely imposes strong constraints on their morphology. Our geometric morphometric analyses show that locomotion, body mass and phylogeny all influence the shape of the forelimb. Furthermore, we find a remarkable convergence between: (i) aquatic and semi-fossorial species, both displaying a robust forelimb, with a shape that improves stability and load transfer in response to the physical resistance imposed by the locomotor environment; and (ii) aquatic and arboreal/semi-arboreal species, with both groups displaying a broad capitulum. This augments the degree of pronation/supination, an important feature for climbing as well as grasping and manipulation ability, behaviors common to aquatic and arboreal species. In summary, our results highlight how musteloids with different locomotor ecologies show differences in the anatomy of their forelimb bones. Yet, functional demands for limb movement through dense media also result in convergence in forelimb long-bone shape between diverse groups, for example, otters and badgers. © 2015 Anatomical Society.

A three-dimensional morphometric analysis of upper forelimb morphology in the enigmatic tapir (Perissodactyla: Tapirus) hints at subtle variations in locomotor ecology.

PubMed

MacLaren, Jamie A; Nauwelaerts, Sandra

2016-11-01

Forelimb morphology is an indicator for terrestrial locomotor ecology. The limb morphology of the enigmatic tapir (Perissodactyla: Tapirus) has often been compared to that of basal perissodactyls, despite the lack of quantitative studies comparing forelimb variation in modern tapirs. Here, we present a quantitative assessment of tapir upper forelimb osteology using three-dimensional geometric morphometrics to test whether the four modern tapir species are monomorphic in their forelimb skeleton. The shape of the upper forelimb bones across four species (T. indicus; T. bairdii; T. terrestris; T. pinchaque) was investigated. Bones were laser scanned to capture surface morphology and 3D landmark analysis was used to quantify shape. Discriminant function analyses were performed to reveal features which could be used for interspecific discrimination. Overall our results show that the appendicular skeleton contains notable interspecific differences. We demonstrate that upper forelimb bones can be used to discriminate between species (>91% accuracy), with the scapula proving the most diagnostic bone (100% accuracy). Features that most successfully discriminate between the four species include the placement of the cranial angle of the scapula, depth of the humeral condyle, and the caudal deflection of the olecranon. Previous studies comparing the limbs of T. indicus and T. terrestris are corroborated by our quantitative findings. Moreover, the mountain tapir T. pinchaque consistently exhibited the greatest divergence in morphology from the other three species. Despite previous studies describing tapirs as functionally mediportal in their locomotor style, we find osteological evidence suggesting a spectrum of locomotor adaptations in the tapirs. We conclude that modern tapir forelimbs are neither monomorphic nor are tapirs as conserved in their locomotor habits as previously described. J. Morphol. 277:1469-1485, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals

The effect of caloric restriction on the forelimb skeletal muscle fibers of the hypertrophic myostatin null mice.

PubMed

Elashry, Mohamed I; Matsakas, Antonios; Wenisch, Sabine; Arnhold, Stefan; Patel, Ketan

2017-06-01

Skeletal muscle mass loss has a broad impact on body performance and physical activity. Muscle wasting occurs due to genetic mutation as in muscular dystrophy, age-related muscle loss (sarcopenia) as well as in chronic wasting disorders as in cancer cachexia. Food restriction reduces muscle mass underpinned by increased muscle protein break down. However the influence of dietary restriction on the morphometry and phenotype of forelimb muscles in a genetically modified myostatin null mice are not fully characterized. The effect of a five week dietary limitation on five anatomically and structurally different forelimb muscles was examined. C57/BL6 wild type (Mstn +/+ ) and myostatin null (Mstn -/- ) mice were either given a standard rodent normal daily diet ad libitum (ND) or 60% food restriction (FR) for a 5 week period. M. triceps brachii Caput laterale (T.lateral), M. triceps brachii Caput longum (T.long), M. triceps brachii Caput mediale (T.medial), M. extensor carpi ulnaris (ECU) and M. flexor carpi ulnaris (FCU) were dissected, weighted and processed for immunohistochemistry. Muscle mass, fibers cross sectional areas (CSA) and myosin heavy chain types IIB, IIX, IIA and type I were analyzed. We provide evidence that caloric restriction results in muscle specific weight reduction with the fast myofibers being more prone to atrophy. We show that slow fibers are less liable to dietary restriction induced muscle atrophy. The effect of dietary restriction was more pronounced in Mstn -/- muscles to implicate the oxidative fibers compared to Mstn +/+ . Furthermore, peripherally located myofibers are more susceptible to dietary induced reduction compared to deep fibers. We additionally report that dietary restriction alters the glycolytic phenotype of the Mstn -/- into the oxidative form in a muscle dependent manner. In summary our study shows that calorie restriction alters muscle fiber profile of forelimb muscles of Myostatin null mice. Copyright © 2017 Elsevier Gmb

Does the Morphology of the Forelimb Flexor Muscles Differ Between Lizards Using Different Habitats?

PubMed

Lowie, Aurélien; Herrel, Anthony; Abdala, Virginia; Manzano, Adriana S; Fabre, Anne-Claire

2018-03-01

Lizards are an interesting group to study how habitat use impacts the morphology of the forelimb because they occupy a great diversity of ecological niches. In this study, we specifically investigated whether habitat use impacts the morphology of the forelimb flexor muscles in lizards. To do so, we performed dissections and quantified the physiological cross sectional area (PCSA), the fiber length, and the mass of four flexor muscles in 21 different species of lizards. Our results show that only the PCSA of the m. flexor carpi radialis is different among lizards with different ecologies (arboreal versus non-arboreal). This difference disappeared, however, when taking phylogeny into account. Arboreal species have a higher m. flexor carpi radialis cross sectional area likely allowing them to flex the wrist more forcefully which may allow them climb and hold on to branches better. In contrast, other muscles are not different between arboreal and non-arboreal species. Further studies focusing on additional anatomical features of the lizard forelimb as well as studies documenting how lizards use the arboreal niche are needed to fully understand how an arboreal life style may constrain limb morphology in lizards. Anat Rec, 301:424-433, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Distinct cortical circuit mechanisms for complex forelimb movement and motor map topography.

PubMed

Harrison, Thomas C; Ayling, Oliver G S; Murphy, Timothy H

2012-04-26

Cortical motor maps are the basis of voluntary movement, but they have proven difficult to understand in the context of their underlying neuronal circuits. We applied light-based motor mapping of Channelrhodopsin-2 mice to reveal a functional subdivision of the forelimb motor cortex based on the direction of movement evoked by brief (10 ms) pulses. Prolonged trains of electrical or optogenetic stimulation (100-500 ms) targeted to anterior or posterior subregions of motor cortex evoked reproducible complex movements of the forelimb to distinct positions in space. Blocking excitatory cortical synaptic transmission did not abolish basic motor map topography, but the site-specific expression of complex movements was lost. Our data suggest that the topography of movement maps arises from their segregated output projections, whereas complex movements evoked by prolonged stimulation require intracortical synaptic transmission. Copyright © 2012 Elsevier Inc. All rights reserved.

Expression of a hindlimb-determining factor Pitx1 in the forelimb of the lizard Pogona vitticeps during morphogenesis.

PubMed

Melville, Jane; Hunjan, Sumitha; McLean, Felicity; Mantziou, Georgia; Boysen, Katja; Parry, Laura J

2016-10-01

With over 9000 species, squamates, which include lizards and snakes, are the largest group of reptiles and second-largest order of vertebrates, spanning a vast array of appendicular skeletal morphology. As such, they provide a promising system for examining developmental and molecular processes underlying limb morphology. Using the central bearded dragon (Pogona vitticeps) as the primary study model, we examined limb morphometry throughout embryonic development and characterized the expression of three known developmental genes (GHR, Pitx1 and Shh) from early embryonic stage through to hatchling stage via reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). In this study, all genes were found to be transcribed in both the forelimbs and hindlimbs of P. vitticeps. While the highest level of GHR expression occurred at the hatchling stage, Pitx1 and Shh expression was greatest earlier during embryogenesis, which coincides with the onset of the differentiation between forelimb and hindlimb length. We compared our finding of Pitx1 expression-a hindlimb-determining gene-in the forelimbs of P. vitticeps to that in a closely related Australian agamid lizard, Ctenophorus pictus, where we found Pitx1 expression to be more highly expressed in the hindlimb compared with the forelimb during early and late morphogenesis-a result consistent with that found across other tetrapods. Expression of Pitx1 in forelimbs has only rarely been documented, including via in situ hybridization in a chicken and a frog. Our findings from both RT-qPCR and IHC indicate that further research across a wider range of tetrapods is needed to more fully understand evolutionary variation in molecular processes underlying limb morphology. © 2016 The Authors.

Functional anatomy of the cheetah (Acinonyx jubatus) forelimb

PubMed Central

Hudson, Penny E; Corr, Sandra A; Payne-Davis, Rachel C; Clancy, Sinead N; Lane, Emily; Wilson, Alan M

2011-01-01

Despite the cheetah being the fastest living land mammal, we know remarkably little about how it attains such high top speeds (29 m s−1). Here we aim to describe and quantify the musculoskeletal anatomy of the cheetah forelimb and compare it to the racing greyhound, an animal of similar mass, but which can only attain a top speed of 17 m s−1. Measurements were made of muscle mass, fascicle length and moment arms, enabling calculations of muscle volume, physiological cross-sectional area (PCSA), and estimates of joint torques and rotational velocities. Bone lengths, masses and mid-shaft cross-sectional areas were also measured. Several species differences were observed and have been discussed, such as the long fibred serratus ventralis muscle in the cheetah, which we theorise may translate the scapula along the rib cage (as has been observed in domestic cats), thereby increasing the cheetah's effective limb length. The cheetah's proximal limb contained many large PCSA muscles with long moment arms, suggesting that this limb is resisting large ground reaction force joint torques and therefore is not functioning as a simple strut. Its structure may also reflect a need for control and stabilisation during the high-speed manoeuvring in hunting. The large digital flexors and extensors observed in the cheetah forelimb may be used to dig the digits into the ground, aiding with traction when galloping and manoeuvring. PMID:21332715

Functional anatomy of the cheetah (Acinonyx jubatus) forelimb.

PubMed

Hudson, Penny E; Corr, Sandra A; Payne-Davis, Rachel C; Clancy, Sinead N; Lane, Emily; Wilson, Alan M

2011-04-01

Despite the cheetah being the fastest living land mammal, we know remarkably little about how it attains such high top speeds (29 m s(-1)). Here we aim to describe and quantify the musculoskeletal anatomy of the cheetah forelimb and compare it to the racing greyhound, an animal of similar mass, but which can only attain a top speed of 17 m s(-1). Measurements were made of muscle mass, fascicle length and moment arms, enabling calculations of muscle volume, physiological cross-sectional area (PCSA), and estimates of joint torques and rotational velocities. Bone lengths, masses and mid-shaft cross-sectional areas were also measured. Several species differences were observed and have been discussed, such as the long fibred serratus ventralis muscle in the cheetah, which we theorise may translate the scapula along the rib cage (as has been observed in domestic cats), thereby increasing the cheetah's effective limb length. The cheetah's proximal limb contained many large PCSA muscles with long moment arms, suggesting that this limb is resisting large ground reaction force joint torques and therefore is not functioning as a simple strut. Its structure may also reflect a need for control and stabilisation during the high-speed manoeuvring in hunting. The large digital flexors and extensors observed in the cheetah forelimb may be used to dig the digits into the ground, aiding with traction when galloping and manoeuvring. © 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society of Great Britain and Ireland.

Locomotor function of forelimb protractor and retractor muscles of dogs: evidence of strut-like behavior at the shoulder.

PubMed

Carrier, David R; Deban, Stephen M; Fischbein, Timna

2008-01-01

The limbs of running mammals are thought to function as inverted struts. When mammals run at constant speed, the ground reaction force vector appears to be directed near the point of rotation of the limb on the body such that there is little or no moment at the joint. If this is true, little or no external work is done at the proximal joints during constant-speed running. This possibility has important implications to the energetics of running and to the coupling of lung ventilation to the locomotor cycle. To test if the forelimb functions as an inverted strut at the shoulder during constant-speed running and to characterize the locomotor function of extrinsic muscles of the forelimb, we monitored changes in the recruitment of six muscles that span the shoulder (the m. pectoralis superficialis descendens, m. pectoralis profundus, m. latissimus dorsi, m. omotransversarius, m. cleidobrachialis and m. trapezius) to controlled manipulations of locomotor forces and moments in trotting dogs (Canis lupus familiaris Linnaeus 1753). Muscle activity was monitored while the dogs trotted at moderate speed (approximately 2 m s(-1)) on a motorized treadmill. Locomotor forces were modified by (1) adding mass to the trunk, (2) inclining the treadmill so that the dogs ran up- and downhill (3) adding mass to the wrists or (4) applying horizontally directed force to the trunk through a leash. When the dogs trotted at constant speed on a level treadmill, the primary protractor muscles of the forelimb exhibited activity during the last part of the ipsilateral support phase and the beginning of swing phase, a pattern that is consistent with the initiation of swing phase but not with active protraction of the limb during the beginning of support phase. Results of the force manipulations were also consistent with the protractor muscles initiating swing phase and contributing to active braking via production of a protractor moment on the forelimb when the dogs decelerate. A similar

Nomenclatural review of long digital forelimb flexors in carnivores.

PubMed

Spoor, C F; Badoux, D M

1986-12-01

A hitherto-unknown atavistic muscle in the dog initiated a review of the literature on the homologies and nomenclature of the forelimb flexors in carnivores and man. A consequence is that we recommend a revision of the nomenclature in the Nomina Anatomica Veterinaria (Ithaca, New York, 1983) so that it is in agreement with the Nomina Anatomica (Wilkins, Baltimore, 1983). This revision mainly consists of the incorporation of the terms M. palmaris longus and Mm. flexores breves manus.

Effective intracortical microstimulation parameters applied to primary motor cortex for evoking forelimb movements to stable spatial end points

PubMed Central

Van Acker, Gustaf M.; Amundsen, Sommer L.; Messamore, William G.; Zhang, Hongyu Y.; Luchies, Carl W.; Kovac, Anthony

2013-01-01

High-frequency, long-duration intracortical microstimulation (HFLD-ICMS) applied to motor cortex is recognized as a useful and informative method for corticomotor mapping by evoking natural-appearing movements of the limb to consistent stable end-point positions. An important feature of these movements is that stimulation of a specific site in motor cortex evokes movement to the same spatial end point regardless of the starting position of the limb. The goal of this study was to delineate effective stimulus parameters for evoking forelimb movements to stable spatial end points from HFLD-ICMS applied to primary motor cortex (M1) in awake monkeys. We investigated stimulation of M1 as combinations of frequency (30–400 Hz), amplitude (30–200 μA), and duration (0.5–2 s) while concurrently recording electromyographic (EMG) activity from 24 forelimb muscles and movement kinematics with a motion capture system. Our results suggest a range of parameters (80–140 Hz, 80–140 μA, and 1,000-ms train duration) that are effective and safe for evoking forelimb translocation with subsequent stabilization at a spatial end point. The mean time for stimulation to elicit successful movement of the forelimb to a stable spatial end point was 475.8 ± 170.9 ms. Median successful frequency and amplitude were 110 Hz and 110 μA, respectively. Attenuated parameters resulted in inconsistent, truncated, or undetectable movements, while intensified parameters yielded no change to movement end points and increased potential for large-scale physiological spread and adverse focal motor effects. Establishing cortical stimulation parameters yielding consistent forelimb movements to stable spatial end points forms the basis for a systematic and comprehensive mapping of M1 in terms of evoked movements and associated muscle synergies. Additionally, the results increase our understanding of how the central nervous system may encode movement. PMID:23741044

Aging reduces the neuroprotective capacity, VEGF secretion, and metabolic activity of rat choroid plexus epithelial cells.

PubMed

Emerich, Dwaine F; Schneider, Patricia; Bintz, Briannan; Hudak, Jebecka; Thanos, Christopher G

2007-01-01

Delivery of neurotrophic molecules to the brain has potential for preventing neuronal loss in neurodegenerative disorders. Choroid plexus (CP) epithelial cells secrete numerous neurotrophic factors, and encapsulated CP transplants are neuroprotective in models of stroke and Huntington's disease (HD). To date, all studies examining the neuroprotective potential of CP transplants have used cells isolated from young donor animals. Because the aging process significantly impacts the cytoarchitecture and function of the CP the following studies determined whether age-related impairments occur in its neuroprotective capacity. CP was isolated from either young (3-4 months) or aged (24 months) rats. In vitro, young CP epithelial cells secreted more VEGF and were metabolically more active than aged CP epithelial cells. Additionally, conditioned medium from cultured aged CP was less potent than young CP at enhancing the survival of serum-deprived neurons. Finally, encapsulated CP was tested in an animal model of HD. Cell-loaded or empty alginate capsules (control group) were transplanted unilaterally into the rat striatum. Seven days later, the animals received an injection of quinolinic acid (QA; 225 nmol) adjacent to the implant site. Animals were tested for motor function 28 days later. In the control group, QA lesions severely impaired function of the contralateral forelimb. Implants of young CP were potently neuroprotective as rats receiving CP transplants were not significantly impaired when tested for motor function. In contrast, implants of CP from aged rats were only modestly effective and were much less potent than young CP transplants. These data are the first to directly link aging with diminished neuroprotective capacity of CP epithelial cells.

Morphological integration in the forelimb of musteloid carnivorans

PubMed Central

Fabre, Anne-Claire; Goswami, Anjali; Peigné, Stéphane; Cornette, Raphaël

2014-01-01

The forelimb forms a functional unit that allows a variety of behaviours and needs to be mobile, yet at the same time stable. Both mobility and stability are controlled, amongst others, at the level of the elbow joint. This joint is composed of the humero-ulnar articulation, mainly involved during parasagittal movements; and the radio-ulnar articulation, mainly allowing rotation. In contrast, the humero-radial articulation allows both movements of flexion–extension and rotation. Here, we study the morphological integration between each bone of the forelimb at the level of the entire arm, as well as at the elbow joint, in musteloid carnivorans. To do so, we quantitatively test shape co-variation using surface 3D geometric morphometric data. Our results show that morphological integration is stronger for bones that form functional units. Different results are obtained depending on the level of investigation: for the entire arm, results show a greater degree of shape co-variation between long bones of the lower arm than between the humerus and either bone of the lower arm. Thus, at this level the functional unit of the lower arm is comprised of the radius and ulna, permitting rotational movements of the lower arm. At the level of the elbow, results display a stronger shape co-variation between bones allowing flexion and stability (humerus and ulna) than between bones allowing mobility (ulna and radius and humerus and radius). Thus, the critical functional unit appears to be the articulation between the humerus and ulna providing the stability of the joint. PMID:24836555

Elbow joint adductor moment arm as an indicator of forelimb posture in extinct quadrupedal tetrapods

PubMed Central

Fujiwara, Shin-ichi; Hutchinson, John R.

2012-01-01

Forelimb posture has been a controversial aspect of reconstructing locomotor behaviour in extinct quadrupedal tetrapods. This is partly owing to the qualitative and subjective nature of typical methods, which focus on bony articulations that are often ambiguous and unvalidated postural indicators. Here we outline a new, quantitatively based forelimb posture index that is applicable to a majority of extant tetrapods. By determining the degree of elbow joint adduction/abduction mobility in several tetrapods, the carpal flexor muscles were determined to also play a role as elbow adductors. Such adduction may play a major role during the stance phase in sprawling postures. This role is different from those of upright/sagittal and sloth-like creeping postures, which, respectively, depend more on elbow extensors and flexors. Our measurements of elbow muscle moment arms in 318 extant tetrapod skeletons (Lissamphibia, Synapsida and Reptilia: 33 major clades and 263 genera) revealed that sprawling, sagittal and creeping tetrapods, respectively, emphasize elbow adductor, extensor and flexor muscles. Furthermore, scansorial and non-scansorial taxa, respectively, emphasize flexors and extensors. Thus, forelimb postures of extinct tetrapods can be qualitatively classified based on our quantitative index. Using this method, we find that Triceratops (Ceratopsidae), Anhanguera (Pterosauria) and desmostylian mammals are categorized as upright/sagittally locomoting taxa. PMID:22357261

Influence of Muscle-Tendon Wrapping on Calculations of Joint Reaction Forces in the Equine Distal Forelimb

PubMed Central

Merritt, Jonathan S.; Davies, Helen M. S.; Burvill, Colin; Pandy, Marcus G.

2008-01-01

The equine distal forelimb is a common location of injuries related to mechanical overload. In this study, a two-dimensional model of the musculoskeletal system of the region was developed and applied to kinematic and kinetic data from walking and trotting horses. The forces in major tendons and joint reaction forces were calculated. The components of the joint reaction forces caused by wrapping of tendons around sesamoid bones were found to be of similar magnitude to the reaction forces between the long bones at each joint. This finding highlighted the importance of taking into account muscle-tendon wrapping when evaluating joint loading in the equine distal forelimb. PMID:18509485

Forelimb kinematics and motor patterns of swimming loggerhead sea turtles (Caretta caretta): are motor patterns conserved in the evolution of new locomotor strategies?

PubMed

Rivera, Angela R V; Wyneken, Jeanette; Blob, Richard W

2011-10-01

Novel functions in animals may evolve through changes in morphology, muscle activity or a combination of both. The idea that new functions or behavior can arise solely through changes in structure, without concurrent changes in the patterns of muscle activity that control movement of those structures, has been formalized as the neuromotor conservation hypothesis. In vertebrate locomotor systems, evidence for neuromotor conservation is found across evolutionary transitions in the behavior of terrestrial species, and in evolutionary transitions from terrestrial species to flying species. However, evolutionary transitions in the locomotion of aquatic species have received little comparable study to determine whether changes in morphology and muscle function were coordinated through the evolution of new locomotor behavior. To evaluate the potential for neuromotor conservation in an ancient aquatic system, we quantified forelimb kinematics and muscle activity during swimming in the loggerhead sea turtle, Caretta caretta. Loggerhead forelimbs are hypertrophied into wing-like flippers that produce thrust via dorsoventral forelimb flapping. We compared kinematic and motor patterns from loggerheads with previous data from the red-eared slider, Trachemys scripta, a generalized freshwater species exhibiting unspecialized forelimb morphology and anteroposterior rowing motions during swimming. For some forelimb muscles, comparisons between C. caretta and T. scripta support neuromotor conservation; for example, the coracobrachialis and the latissimus dorsi show similar activation patterns. However, other muscles (deltoideus, pectoralis and triceps) do not show neuromotor conservation; for example, the deltoideus changes dramatically from a limb protractor/elevator in sliders to a joint stabilizer in loggerheads. Thus, during the evolution of flapping in sea turtles, drastic restructuring of the forelimb was accompanied by both conservation and evolutionary novelty in limb motor

Task-specific compensation and recovery following focal motor cortex lesion in stressed rats.

PubMed

Kirkland, Scott W; Smith, Lori K; Metz, Gerlinde A

2012-03-01

One reason for the difficulty to develop effective therapies for stroke is that intrinsic factors, such as stress, may critically influence pathological mechanisms and recovery. In cognitive tasks, stress can both exaggerate and alleviate functional loss after focal ischemia in rodents. Using a comprehensive motor assessment in rats, this study examined if chronic stress and corticosterone treatment affect skill recovery and compensation in a task-specific manner. Groups of rats received daily restraint stress or oral corticosterone supplementation for two weeks prior to a focal motor cortex lesion. After lesion, stress and corticosterone treatments continued for three weeks. Motor performance was assessed in two skilled reaching tasks, skilled walking, forelimb inhibition, forelimb asymmetry and open field behavior. The results revealed that persistent stress and elevated corticosterone levels mainly limit motor recovery. Treated animals dropped larger amounts of food in successful reaches and showed exaggerated loss of forelimb inhibition early after lesion. Stress also caused a moderate, but non-significant increase in infarct size. By contrast, stress and corticosterone treatments promoted reaching success and other quantitative measures in the tray reaching task. Comparative analysis revealed that improvements are due to task-specific development of compensatory strategies. These findings suggest that stress and stress hormones may partially facilitate task-specific and adaptive compensatory movement strategies. The observations support the notion that hypothalamic-pituitary-adrenal axis activation may be a key determinant of recovery and motor system plasticity after ischemic stroke.

Impaired limb reaction to displacement of center of gravity in rats with unilateral striatal ischemic injury.

PubMed

Nobile, Cameron W; Palmateer, Julie M; Kane, Jackie; Hurn, Patricia D; Schallert, Timothy; Adkins, DeAnna L

2014-10-01

Clinical stroke often results in impaired balance and increased vulnerability to severe injuries due to falling. To evaluate potential preclinical treatments that might target these deficits, it will be important to include tests capable of assessing these impairments chronically in animal models. Previously, we developed a postural instability test (PIT) that revealed chronic, unilateral impairments in postural stability in rat models of hemi-Parkinson's disease (PD) and of unilateral cervical spinal cord injury. Here, we investigated whether this test was also capable of revealing long-term stroke-induced impairments in postural support in rats. Additionally, we examined the ability of more common tests of sensorimotor function to detect chronic impairments. We found that the PIT detected chronic deficits in postural stability/balance enduring for up to 6 weeks post-stroke, outlasting impairments detected in other tests of forelimb sensorimotor function, including asymmetries in upright postural support (cylinder test) and vibrissae-evoked forelimb placing.

Single pellet grasping following cervical spinal cord injury in adult rat using an automated full-time training robot

PubMed Central

Fenrich, Keith K.; May, Zacincte; Torres-Espín, Abel; Forero, Juan; Bennett, David J.; Fouad, Karim

2016-01-01

Task specific motor training is a common form of rehabilitation therapy in individuals with spinal cord injury (SCI). The single pellet grasping (SPG) task is a skilled forelimb motor task used to evaluate recovery of forelimb function in rodent models of SCI. The task requires animals to obtain food pellets located on a shelf beyond a slit at the front of an enclosure. Manually training and testing rats in the SPG task requires extensive time and often yields results with high outcome variability and small therapeutic windows (i.e., the difference between pre- and post-SCI success rates). Recent advances in automated SPG training using automated pellet presentation (APP) systems allow rats to train ad libitum 24 h a day, 7 days a week. APP trained rats have improved success rates, require less researcher time, and have lower outcome variability compared to manually trained rats. However, it is unclear whether APP trained rats can perform the SPG task using the APP system after SCI. Here we show that rats with cervical SCI can successfully perform the SPG task using the APP system. We found that SCI rats with APP training performed significantly more attempts, had slightly lower and less variable final score success rates, and larger therapeutic windows than SCI rats with manual training. These results demonstrate that APP training has clear advantages over manual training for evaluating reaching performance of SCI rats and represents a new tool for investigating rehabilitative motor training following CNS injury. PMID:26611563

Single pellet grasping following cervical spinal cord injury in adult rat using an automated full-time training robot.

PubMed

Fenrich, Keith K; May, Zacincte; Torres-Espín, Abel; Forero, Juan; Bennett, David J; Fouad, Karim

2016-02-15

Task specific motor training is a common form of rehabilitation therapy in individuals with spinal cord injury (SCI). The single pellet grasping (SPG) task is a skilled forelimb motor task used to evaluate recovery of forelimb function in rodent models of SCI. The task requires animals to obtain food pellets located on a shelf beyond a slit at the front of an enclosure. Manually training and testing rats in the SPG task requires extensive time and often yields results with high outcome variability and small therapeutic windows (i.e., the difference between pre- and post-SCI success rates). Recent advances in automated SPG training using automated pellet presentation (APP) systems allow rats to train ad libitum 24h a day, 7 days a week. APP trained rats have improved success rates, require less researcher time, and have lower outcome variability compared to manually trained rats. However, it is unclear whether APP trained rats can perform the SPG task using the APP system after SCI. Here we show that rats with cervical SCI can successfully perform the SPG task using the APP system. We found that SCI rats with APP training performed significantly more attempts, had slightly lower and less variable final score success rates, and larger therapeutic windows than SCI rats with manual training. These results demonstrate that APP training has clear advantages over manual training for evaluating reaching performance of SCI rats and represents a new tool for investigating rehabilitative motor training following CNS injury. Copyright © 2015 Elsevier B.V. All rights reserved.

Distinct Functional Modules for Discrete and Rhythmic Forelimb Movements in the Mouse Motor Cortex.

PubMed

Hira, Riichiro; Terada, Shin-Ichiro; Kondo, Masashi; Matsuzaki, Masanori

2015-09-30

Movements of animals are composed of two fundamental dynamics: discrete and rhythmic movements. Although the movements with distinct dynamics are thought to be differently processed in the CNS, it is unclear how they are represented in the cerebral cortex. Here, we investigated the cortical representation of movement dynamics by developing prolonged transcranial optogenetic stimulation (pTOS) using awake, channelrhodopsin-2 transgenic mice. We found two domains that induced discrete forelimb movements in the forward and backward directions, and these sandwiched a domain that generated rhythmic forelimb movements. The forward discrete movement had an intrinsic velocity profile and the rhythmic movement had an intrinsic oscillation frequency. Each of the forward discrete and rhythmic domains possessed intracortical synaptic connections within its own domain, independently projected to the spinal cord, and weakened the neuronal activity and movement induction of the other domain. pTOS-induced movements were also classified as ethologically relevant movements. Forepaw-to-mouth movement was mapped in a part of the forward discrete domain, while locomotion-like movement was in a part of the rhythmic domain. Interestingly, photostimulation of the rhythmic domain resulted in a nonrhythmic, continuous lever-pull movement when a lever was present. The motor cortex possesses functional modules for distinct movement dynamics, and these can adapt to environmental constraints for purposeful movements. Significance statement: Animal behavior has discrete and rhythmic components, such as reaching and locomotion. It is unclear how these movements with distinct dynamics are represented in the cerebral cortex. We investigated the dynamics of movements induced by long-duration transcranial photostimulation on the dorsal cortex of awake channelrhodopsin-2 transgenic mice. We found two domains causing forward and backward discrete forelimb movements and a domain for rhythmic forelimb

Schwann cell transplantation improves reticulospinal axon growth and forelimb strength after severe cervical spinal cord contusion.

PubMed

Schaal, S M; Kitay, B M; Cho, K S; Lo, T P; Barakat, D J; Marcillo, A E; Sanchez, A R; Andrade, C M; Pearse, D D

2007-01-01

Schwann cell (SC) implantation alone has been shown to promote the growth of propriospinal and sensory axons, but not long-tract descending axons, after thoracic spinal cord injury (SCI). In the current study, we examined if an axotomy close to the cell body of origin (so as to enhance the intrinsic growth response) could permit supraspinal axons to grow onto SC grafts. Adult female Fischer rats received a severe (C5) cervical contusion (1.1 mm displacement, 3 KDyn). At 1 week postinjury, 2 million SCs ex vivo transduced with lentiviral vector encoding enhanced green fluorescent protein (EGFP) were implanted within media into the injury epicenter; injury-only animals served as controls. Animals were tested weekly using the BBB score for 7 weeks postimplantation and received at end point tests for upper body strength: self-supported forelimb hanging, forearm grip force, and the incline plane. Following behavioral assessment, animals were anterogradely traced bilaterally from the reticular formation using BDA-Texas Red. Stereological quantification revealed a twofold increase in the numbers of preserved NeuN+ neurons rostral and caudal to the injury/graft site in SC implanted animals, corroborating previous reports of their neuroprotective efficacy. Examination of labeled reticulospinal axon growth revealed that while rarely an axon was present within the lesion site of injury-only controls, numerous reticulospinal axons had penetrated the SC implant/lesion milieu. This has not been observed following implantation of SCs alone into the injured thoracic spinal cord. Significant behavioral improvements over injury-only controls in upper limb strength, including an enhanced grip strength (a 296% increase) and an increased self-supported forelimb hanging, accompanied SC-mediated neuroprotection and reticulospinal axon growth. The current study further supports the neuroprotective efficacy of SC implants after SCI and demonstrates that SCs alone are capable of supporting

Dynamic Motor Compensations with Permanent, Focal Loss of Forelimb Force after Cervical Spinal Cord Injury

PubMed Central

López-Dolado, Elisa; Lucas-Osma, Ana M.

2013-01-01

Abstract Incomplete cervical lesion is the most common type of human spinal cord injury (SCI) and causes permanent paresis of arm muscles, a phenomenon still incompletely understood in physiopathological and neuroanatomical terms. We performed spinal cord hemisection in adult rats at the caudal part of the segment C6, just rostral to the bulk of triceps brachii motoneurons, and analyzed the forces and kinematics of locomotion up to 4 months postlesion to determine the nature of motor function loss and recovery. A dramatic (50%), immediate and permanent loss of extensor force occurred in the forelimb but not in the hind limb of the injured side, accompanied by elbow and wrist kinematic impairments and early adaptations of whole-body movements that initially compensated the balance but changed continuously over the follow-up period to allow effective locomotion. Overuse of both contralateral legs and ipsilateral hind leg was evidenced since 5 days postlesion. Ipsilateral foreleg deficits resulted mainly from interruption of axons that innervate the spinal cord segments caudal to the lesion, because chronic loss (about 35%) of synapses was detected at C7 while only 14% of triceps braquii motoneurons died, as assessed by synaptophysin immunohistochemistry and retrograde neural tracing, respectively. We also found a large pool of propriospinal neurons projecting from C2–C5 to C7 in normal rats, with topographical features similar to the propriospinal premotoneuronal system of cats and primates. Thus, concurrent axotomy at C6 of brain descending axons and cervical propriospinal axons likely hampered spontaneous recovery of the focal neurological impairments. PMID:23249275

Ultrasonographic assessment of the proximal digital annular ligament in the equine forelimb.

PubMed

Dik, K J; Boroffka, S; Stolk, P

1994-01-01

Ultrasonography was used with 6 normal cadaver forelimbs of Dutch Warmblood horses to delineate the ultrasonographic anatomy of the palmar pastern region, with emphasis on the proximal digital annular ligament. Using a 5.5 MHz sector scanner, the thin proximal digital annular ligament was not visible on offset sonograms. Only if the digital sheath in the normal limb was distended was the distal border of this ligament outlined. In all normal limbs the palmarodistal thickness of the combined skin-proximal digital annular ligament layer in the mid-pastern region was 2 mm. The flexor tendons and distal sesamoidean ligaments were easily identified as hyperechoic structures. Distension of the digital sheath in the normal limbs clearly outlined the anechoic digital sheath pouches. In 4 lame horses ultrasonography aided the diagnosis of functional proximal digital annular ligament constriction. In all 4 diseased forelimbs ultrasonography demonstrated thickening of the skin-proximal digital annular ligament layer and distension of the digital sheath. In one of these limbs the distended digital sheath was also thickened. The flexor tendons and distal sesamoidean ligaments were normal. There was no radiographic evidence of additional bone or joint lesions.

Bio-functional pickles that reduce blood pressure of rats.

PubMed

Oda, Kohei; Imanishi, Takanori; Yamane, Yoshito; Ueno, Yoshie; Mori, Yoshiharu

2014-01-01

Addition of γ-aminobutyric acid (GABA) and angiotensin converting enzyme (ACE)-inhibitory peptides to the pickles was studied in order to develop a new type of pickles that reduce blood pressure. Based on the outcome of these studies, a new type of fermentation bed composed of rice bran and white miso has been successfully developed. The advantage of such pickles is that they not only contain both GABA and ACE-inhibitory peptides, but also that their taste and flavor are excellent, with colors close to the original ones. The new type of pickles could temporarily reduce blood pressure in two types of rats, spontaneously hypertensive rats and NaCl-sensitive model rats. Thus, the newly developed pickles appear to be beneficial for pickle business.

Treatment with tamoxifen reduces hypoxic-ischemic brain injury in neonatal rats.

PubMed

Feng, Yangzheng; Fratkins, Jonathan D; LeBlanc, Michael H

2004-01-19

Tamoxifen, an estrogen receptor modulator, is neuroprotective in adult rats. Does tamoxifen reduce brain injury in the rat pup? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of hypoxia (8% oxygen). Tamoxifen (10 mg/kg) or vehicle was given i.p. 5 min prior to hypoxia, or 5 min after reoxygenation, with a second dose given 6 h after the first. Brain damage was evaluated by weight deficit of the right hemisphere 22 days following hypoxia and gross and microscopic morphology. Tamoxifen pre-treatment reduced brain weight loss from 21.5+/-4.0% in vehicle pups (n=27) to 2.6+/-2.5% in the treated pups (n=22, P<0.05). Treatment 5 min after reoxygenation reduced brain weight loss from 27.5+/-4.0% in vehicle pups (n=42) to 12.0+/-3.9% in the treated pups (n=30, P<0.05). Tamoxifen reduces brain injury in the neonatal rat.

The effect of airflow on thermographically determined temperature of the distal forelimb of the horse.

PubMed

Westermann, S; Stanek, C; Schramel, J P; Ion, A; Buchner, H H F

2013-09-01

Current literature suggests that thermographic imaging of horses should be performed in a draught-free room. However, studies on the effect of airflow on determined temperature have not been published. To investigate effects of airflow on thermographically determined temperature of horses' forelimbs; to assess the relationship of wind velocity, rectal temperature, ambient temperature and humidity. Thermographic images were obtained for the forelimbs of 6 horses in a draught-free room. Three replicates (R) with defined wind velocities (R1, 0.5-1.0 m/s; R2, 1.3-2.6 m/s; and R3, 3.0-4.0 m/s) were conducted. Each replicate consisted of a baseline image, a 15 min phase with the wind on and a 15 min phase with the wind off. We exposed only the right leg to airflow and determined the temperature by thermography with the wind on and wind off. Temperature differences between baseline and wind on, between wind on and wind off and between different wind velocities were analysed by a general linear model, Student's paired t test and ANOVA. After the onset of wind, the temperature on the right forelimb decreased within 1-3 min (by approximately 0.6°C at R1, 1.5°C at R2 and 2.1°C at R3). With the wind off, the temperature increased within 3 min (by approximately 1.2°C at R1, 1.7°C at R2 and 2.1°C at R3). With increasing wind velocity, the temperature differences between baseline and wind on and between wind on and wind off increased significantly. Barely noticeable wind velocities caused a decrease in thermographically determined temperatures of the forelimbs of the horse. Further research is required to assess the influence of airflow on other parts of the body and at different ambient temperatures, as well as the effect on horses with inflammatory lesions, especially of the distal limbs. It is essential for practitioners to perform thermography on horses in a draught-free environment in order to avoid false-positive or -negative diagnoses. © 2012 EVJ Ltd.

Reducing Peripheral Inflammation with Infliximab Reduces Neuroinflammation and Improves Cognition in Rats with Hepatic Encephalopathy

PubMed Central

Dadsetan, Sherry; Balzano, Tiziano; Forteza, Jerónimo; Cabrera-Pastor, Andrea; Taoro-Gonzalez, Lucas; Hernandez-Rabaza, Vicente; Gil-Perotín, Sara; Cubas-Núñez, Laura; García-Verdugo, José-Manuel; Agusti, Ana; Llansola, Marta; Felipo, Vicente

2016-01-01

Inflammation contributes to cognitive impairment in patients with hepatic encephalopathy (HE). However, the process by which peripheral inflammation results in cognitive impairment remains unclear. In animal models, neuroinflammation and altered neurotransmission mediate cognitive impairment. Taking into account these data, we hypothesized that in rats with HE: (1) peripheral inflammation is a main contributor to neuroinflammation; (2) neuroinflammation in hippocampus impairs spatial learning by altering AMPA and/or NMDA receptors membrane expression; (3) reducing peripheral inflammation with infliximab (anti-TNF-a) would improve spatial learning; (4) this would be associated with reduced neuroinflammation and normalization of the membrane expression of glutamate receptors. The aims of this work were to assess these hypotheses. We analyzed in rats with portacaval shunt (PCS) and control rats, treated or not with infliximab: (a) peripheral inflammation by measuring prostaglandin E2, IL10, IL-17, and IL-6; (b) neuroinflammation in hippocampus by analyzing microglial activation and the content of TNF-a and IL-1b; (c) AMPA and NMDA receptors membrane expression in hippocampus; and (d) spatial learning in the Radial and Morris water mazes. We assessed the effects of treatment with infliximab on peripheral inflammation, on neuroinflammation and AMPA and NMDA receptors membrane expression in hippocampus and on spatial learning and memory. PCS rats show increased serum prostaglandin E2, IL-17, and IL-6 and reduced IL-10 levels, indicating increased peripheral inflammation. PCS rats also show microglial activation and increased nuclear NF-kB and expression of TNF-a and IL-1b in hippocampus. This was associated with altered AMPA and NMDA receptors membrane expression in hippocampus and impaired spatial learning and memory in the radial and Morris water maze. Treatment with infliximab reduces peripheral inflammation in PCS rats, normalizing prostaglandin E2, IL-17, IL-6, and

Functional anatomy of the gibbon forelimb: adaptations to a brachiating lifestyle

PubMed Central

Michilsens, Fana; Vereecke, Evie E; D'Août, Kristiaan; Aerts, Peter

2009-01-01

It has been shown that gibbons are able to brachiate with very low mechanical costs. The conversion of muscle activity into smooth, purposeful movement of the limb depends on the morphometry of muscles and their mechanical action on the skeleton. Despite the gibbon's reputation for excellence in brachiation, little information is available regarding either its gross musculoskeletal anatomy or its more detailed muscle–tendon architecture. We provide quantitative anatomical data on the muscle–tendon architecture (muscle mass, physiological cross-sectional area, fascicle length and tendon length) of the forelimb of four gibbon species, collected by detailed dissections of unfixed cadavers. Data are compared between different gibbon species and with similar published data of non-brachiating primates such as macaques, chimpanzees and humans. No quantitative differences are found between the studied gibbon species. Both their forelimb anatomy and muscle dimensions are comparable when normalized to the same body mass. Gibbons have shoulder flexors, extensors, rotator muscles and elbow flexors with a high power or work-generating capacity and their wrist flexors have a high force-generating capacity. Compared with other primates, the elbow flexors of gibbons are particularly powerful, suggesting that these muscles are particularly important for a brachiating lifestyle. Based on this anatomical study, the shoulder flexors, extensors, rotator muscles, elbow flexors and wrist flexors are expected to contribute the most to brachiation. PMID:19519640

Rat hindlimb muscle responses to suspension hypokinesia/hypodynamia

NASA Technical Reports Server (NTRS)

Musacchia, X. J.; Steffen, J. M.; Deavers, D. R.

1983-01-01

Hypokinetic/hyupodynamic (H/H) whole body suspension of rats eliminates hindlimb load bearing functions while permitting continued use of the forelimbs. Responses of hindlimb muscles were assessed in terms of absolute and relative weights during 1 and 2 weeks of H/H suspension. Muscle mass loss was in the order soleus greater than gastrocnemius equal to plantaris greater than extensor digitorum longus (EDL). The soleus, a postural antigravity muscle composed mainly of slow twitch fibers, was most sensitive, losing 35 and 45 percent of its weight during the first and second weeks, respectively. The gastrocnemius and plantaris showed losses during the first week but no significant loss during the second wee. The EDL showed little or no weight loss. During post suspension recovery all muscles showed a weight gain. H/H suspended rats failed to grow; following removal from suspension they gained weight linearly, comparable to controls. Products of muscle metabolism including urea, ammonia, and 3-methylhistidine increased in the urine during H/H suspension and were significantly reduced approaching control levels during recovery. This suspension model offers considerable promise for comparison with H/H responses during weightlessness.

Red maca (Lepidium meyenii) reduced prostate size in rats

PubMed Central

Gonzales, Gustavo F; Miranda, Sara; Nieto, Jessica; Fernández, Gilma; Yucra, Sandra; Rubio, Julio; Yi, Pedro; Gasco, Manuel

2005-01-01

Background Epidemiological studies have found that consumption of cruciferous vegetables is associated with a reduced risk of prostate cancer. This effect seems to be due to aromatic glucosinolate content. Glucosinolates are known for have both antiproliferative and proapoptotic actions. Maca is a cruciferous cultivated in the highlands of Peru. The absolute content of glucosinolates in Maca hypocotyls is relatively higher than that reported in other cruciferous crops. Therefore, Maca may have proapoptotic and anti-proliferative effects in the prostate. Methods Male rats treated with or without aqueous extracts of three ecotypes of Maca (Yellow, Black and Red) were analyzed to determine the effect on ventral prostate weight, epithelial height and duct luminal area. Effects on serum testosterone (T) and estradiol (E2) levels were also assessed. Besides, the effect of Red Maca on prostate was analyzed in rats treated with testosterone enanthate (TE). Results Red Maca but neither Yellow nor Black Maca reduced significantly ventral prostate size in rats. Serum T or E2 levels were not affected by any of the ecotypes of Maca assessed. Red Maca also prevented the prostate weight increase induced by TE treatment. Red Maca administered for 42 days reduced ventral prostatic epithelial height. TE increased ventral prostatic epithelial height and duct luminal area. These increases by TE were reduced after treatment with Red Maca for 42 days. Histology pictures in rats treated with Red Maca plus TE were similar to controls. Phytochemical screening showed that aqueous extract of Red Maca has alkaloids, steroids, tannins, saponins, and cardiotonic glycosides. The IR spectra of the three ecotypes of Maca in 3800-650 cm (-1) region had 7 peaks representing 7 functional chemical groups. Highest peak values were observed for Red Maca, intermediate values for Yellow Maca and low values for Black Maca. These functional groups correspond among others to benzyl glucosinolate. Conclusions

Forelimb kinematics during swimming in the pig-nosed turtle, Carettochelys insculpta, compared with other turtle taxa: rowing versus flapping, convergence versus intermediacy

PubMed Central

Rivera, Angela R. V.; Rivera, Gabriel; Blob, Richard W.

2013-01-01

SUMMARY Animals that swim using appendages do so by way of rowing and/or flapping motions. Often considered discrete categories, rowing and flapping are more appropriately regarded as points along a continuum. The pig-nosed turtle, Carettochelys insculpta, is unusual in that it is the only freshwater turtle to have limbs modified into flippers and swim via synchronous forelimb motions that resemble dorsoventral flapping, traits that evolved independently from their presence in sea turtles. We used high-speed videography to quantify forelimb kinematics in C. insculpta and a closely related, highly aquatic rower (Apalone ferox). Comparisons of our new data with those previously collected for a generalized freshwater rower (Trachemys scripta) and a flapping sea turtle (Caretta caretta) allow us to: (1) more precisely quantify and characterize the range of limb motions used by flappers versus rowers, and (2) assess whether the synchronous forelimb motions of C. insculpta can be classified as flapping (i.e. whether they exhibit forelimb kinematics and angles of attack more similar to closely related rowing species or more distantly related flapping sea turtles). We found that the forelimb kinematics of previously recognized rowers (T. scripta and A. ferox) were most similar to each other, but that those of C. insculpta were more similar to rowers than to flapping C. caretta. Nevertheless, of the three freshwater species, C. insculpta was most similar to flapping C. caretta. ‘Flapping’ in C. insculpta is achieved through humeral kinematics very different from those in C. caretta, with C. insculpta exhibiting significantly more anteroposterior humeral motion and protraction, and significantly less dorsoventral humeral motion and depression. Based on several intermediate kinematic parameters and angle of attack data, C. insculpta may in fact represent a synchronous rower or hybrid rower-flapper, suggesting that traditional views of C. insculpta as a flapper should be

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

PubMed

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

2015-05-15

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

Simulating certain aspects of hypogravity: Effects on the mandibular incisors of suspended rats (PULEH model)

NASA Technical Reports Server (NTRS)

Simmons, D. J.; Winter, F.; Morey-Holton, E. R.

1984-01-01

The effect of a hypogravity simulating model on the rate of mandibular incisor formation, dentinogenesis and, amelogenesis in laboratory rats was studied. The model is the partial unloading by elevating the hindquarters. In this system, rat hindquarters are elevated 30 to 40 deg from the cage floors to completely unload the hindlimbs, but the animals are free to move about using their forelimbs. This model replicates the fluid sift changes which occur during the weightlessness of spaceflight and produces an osteopenia in the weight bearing skeletons. The histogenesis and/or mineralization rates of the mandibular incisor during the first 19d of PULEH in young growing rats are recorded.

Disorganization of Oligodendrocyte Development in the Layer II/III of the Sensorimotor Cortex Causes Motor Coordination Dysfunction in a Model of White Matter Injury in Neonatal Rats.

PubMed

Ueda, Yoshitomo; Misumi, Sachiyo; Suzuki, Mina; Ogawa, Shino; Nishigaki, Ruriko; Ishida, Akimasa; Jung, Cha-Gyun; Hida, Hideki

2018-01-01

We previously established neonatal white matter injury (WMI) model rat that is made by right common carotid artery dissection at postnatal day 3, followed by 6% hypoxia for 60 min. This model has fewer oligodendrocyte progenitor cells and reduced myelin basic protein (MBP) positive areas in the sensorimotor cortex, but shows no apparent neuronal loss. However, how motor deficits are induced in this model is unclear. To elucidate the relationship between myelination disturbance and concomitant motor deficits, we first performed motor function tests (gait analysis, grip test, horizontal ladder test) and then analyzed myelination patterns in the sensorimotor cortex using transmission electron microscopy (TEM) and Contactin associated protein 1 (Caspr) staining in the neonatal WMI rats in adulthood. Behavioral tests revealed imbalanced motor coordination in this model. Motor deficit scores were higher in the neonatal WMI model, while hindlimb ladder stepping scores and forelimb grasping force were comparable to controls. Prolonged forelimb swing times and decreased hindlimb paw angles on the injured side were revealed by gait analysis. TEM revealed no change in myelinated axon number and the area g-ratio in the layer II/III of the cortex. Electromyographical durations and latencies in the gluteus maximus in response to electrical stimulation of the brain area were unchanged in the model. Caspr staining revealed fewer positive dots in layers II/III of the WMI cortex, indicating fewer and/or longer myelin sheath. These data suggest that disorganization of oligodendrocyte development in layers II/III of the sensorimotor cortex relates to imbalanced motor coordination in the neonatal WMI model rat.

Inferring the use of forelimb suspensory locomotion by extinct primate species via shape exploration of the ulna.

PubMed

Rein, Thomas R; Harvati, Katerina; Harrison, Terry

2015-01-01

Uncovering links between skeletal morphology and locomotor behavior is an essential component of paleobiology because it allows researchers to infer the locomotor repertoire of extinct species based on preserved fossils. In this study, we explored ulnar shape in anthropoid primates using 3D geometric morphometrics to discover novel aspects of shape variation that correspond to observed differences in the relative amount of forelimb suspensory locomotion performed by species. The ultimate goal of this research was to construct an accurate predictive model that can be applied to infer the significance of these behaviors. We studied ulnar shape variation in extant species using principal component analysis. Species mainly clustered into phylogenetic groups along the first two principal components. Upon closer examination, the results showed that the position of species within each major clade corresponded closely with the proportion of forelimb suspensory locomotion that they have been observed to perform in nature. We used principal component regression to construct a predictive model for the proportion of these behaviors that would be expected to occur in the locomotor repertoire of anthropoid primates. We then applied this regression analysis to Pliopithecus vindobonensis, a stem catarrhine from the Miocene of central Europe, and found strong evidence that this species was adapted to perform a proportion of forelimb suspensory locomotion similar to that observed in the extant woolly monkey, Lagothrix lagothricha. Copyright © 2014 Elsevier Ltd. All rights reserved.

Reduced L-Carnitine Transport in Aortic Endothelial Cells from Spontaneously Hypertensive Rats

PubMed Central

Salsoso, Rocío; Guzmán-Gutiérrez, Enrique; Arroyo, Pablo; Salomón, Carlos; Zambrano, Sonia; Ruiz-Armenta, María Victoria; Blanca, Antonio Jesús; Pardo, Fabián; Leiva, Andrea; Mate, Alfonso; Sobrevia, Luis; Vázquez, Carmen María

2014-01-01

Impaired L-carnitine uptake correlates with higher blood pressure in adult men, and L-carnitine restores endothelial function in aortic rings from spontaneously hypertensive rat (SHR). Thus, endothelial dysfunction in hypertension could result from lower L-carnitine transport in this cell type. L-Carnitine transport is mainly mediated by novel organic cation transporters 1 (Octn1, Na+-independent) and 2 (Octn2, Na+-dependent); however, their kinetic properties and potential consequences in hypertension are unknown. We hypothesize that L-carnitine transport kinetic properties will be altered in aortic endothelium from spontaneously hypertensive rats (SHR). L-Carnitine transport was measured at different extracellular pH (pHo 5.5–8.5) in the absence or presence of sodium in rat aortic endothelial cells (RAECs) from non-hypertensive Wistar-Kyoto (WKY) rats and SHR. Octn1 and Octn2 mRNA relative expression was also determined. Dilation of endothelium-intact or denuded aortic rings in response to calcitonine gene related peptide (CGRP, 0.1–100 nmol/L) was measured (myography) in the absence or presence of L-carnitine. Total L-carnitine transport was lower in cells from SHR compared with WKY rats, an effect due to reduced Na+-dependent (Na+ dep) compared with Na+-independent (Na+ indep) transport components. Saturable L-carnitine transport kinetics show maximal velocity (V max), without changes in apparent K m for Na+ indep transport in SHR compared with WKY rats. Total and Na+ dep component of transport were increased, but Na+ indep transport was reduced by extracellular alkalization in WKY rats. However, alkalization reduced total and Na+ indep transport in cells from SHR. Octn2 mRNA was higher than Octn-1 mRNA expression in cells from both conditions. Dilation of artery rings in response to CGRP was reduced in vessels from SHR compared with WKY rats. CGRP effect was endothelium-dependent and restored by L-carnitine. All together these results suggest that reduced

Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats

PubMed Central

Bordia, Tanuja; McIntosh, J. Michael

2012-01-01

Antipsychotics are an important class of drugs for the management of schizophrenia and other psychotic disorders. They act by blocking dopamine receptors; however, because these receptors are present throughout the brain, prolonged antipsychotic use also leads to serious side effects. These include tardive dyskinesia, repetitive abnormal involuntary movements of the face and limbs for which there is little treatment. In this study, we investigated whether nicotine administration could reduce tardive dyskinesia because nicotine attenuates other drug-induced abnormal movements. We used a well established model of tardive dyskinesia in which rats injected with the commonly used antipsychotic haloperidol develop vacuous chewing movements (VCMs) that resemble human orofacial dyskinesias. Rats were first administered nicotine (minipump; 2 mg/kg per day). Two weeks later, they were given haloperidol (1 mg/kg s.c.) once daily. Nicotine treatment reduced haloperidol-induced VCMs by ∼20% after 5 weeks, with a significant ∼60% decline after 13 weeks. There was no worsening of haloperidol-induced catalepsy. To understand the molecular basis for this improvement, we measured the striatal dopamine transporter and nicotinic acetylcholine receptors (nAChRs). Both haloperidol and nicotine treatment decreased the transporter and α6β2* nAChRs (the asterisk indicates the possible presence of other nicotinic subunits in the receptor complex) when given alone, with no further decline with combined drug treatment. By contrast, nicotine alone increased, while haloperidol reduced α4β2* nAChRs in both vehicle and haloperidol-treated rats. These data suggest that molecular mechanisms other than those directly linked to the transporter and nAChRs underlie the nicotine-mediated improvement in haloperidol-induced VCMs in rats. The present results are the first to suggest that nicotine may be useful for improving the tardive dyskinesia associated with antipsychotic use. PMID:22144565

The effect of perineural anesthesia on infrared thermographic images of the forelimb digits of normal horses

PubMed Central

Holmes, Layne C.; Gaughan, Earl M.; Gorondy, Denise A.; Hogge, Steve; Spire, Mark F.

2003-01-01

Infrared thermography is an imaging modality gaining popularity as a diagnostic aid in the evaluation of equine lameness. Anecdotal reports of skin hyperthermia induced by local anesthesia, detected by thermography, have been made; however, no controlled studies have been reported. The purpose of this study was to examine the effects of perineural anesthesia on infrared thermographic images of the forelimb digits in normal horses. After environmental acclimation, infrared thermographs were made at intervals of 0, 5, 10, 15, 30, and 45 min from administration of mepivacaine hydrochloride or phosphate buffered saline in 6 adult horses with no clinical evidence of abnormality of the forelimb digits. The mean limb surface temperatures were compared by 2-factor ANOVA. Results indicated no significant difference between treatments, time after injection, or an interaction of time and treatment. Infrared thermographic imaging apparently can be performed within 45 min of perineural mepivacaine hydrochloride anesthesia without risk of artifactual changes in limb surface temperature. PMID:12757130

Three-dimensional skeletal kinematics of the shoulder girdle and forelimb in walking Alligator

PubMed Central

Baier, David B; Gatesy, Stephen M

2013-01-01

Crocodylians occupy a key phylogenetic position for investigations of archosaur locomotor evolution. Compared to the well-studied hindlimb, relatively little is known about the skeletal movements and mechanics of the forelimb. In this study, we employed manual markerless XROMM (X-ray Reconstruction Of Moving Morphology) to measure detailed 3-D kinematics of the shoulder girdle and forelimb bones of American alligators (Alligator mississippiensis) walking on a treadmill. Digital models of the interclavicle, scapulocoracoid, humerus, radius and ulna were created using a 3-D laser scanner. Models were articulated and aligned to simultaneously recorded frames of fluoroscopic and standard light video to reconstruct and measure joint motion. Joint coordinate systems were established for the coracosternal, glenohumeral and elbow joints. Our analysis revealed that the limb joints only account for about half of fore/aft limb excursion; the remaining excursion results from shoulder girdle movements and lateral bending of the vertebral column. Considerable motion of each scapulocoracoid relative to the vertebral column is consistent with coracosternal mobility. The hemisellar design of the glenohumeral joint permits some additional translation, or sliding in the fore-aft plane, but this movement does not have much of an effect on the distal excursion of the bone. PMID:24102540

Planar Covariation of Hindlimb and Forelimb Elevation Angles during Terrestrial and Aquatic Locomotion of Dogs

PubMed Central

Catavitello, Giovanna; Ivanenko, Yuri P.; Lacquaniti, Francesco

2015-01-01

The rich repertoire of locomotor behaviors in quadrupedal animals requires flexible inter-limb and inter-segmental coordination. Here we studied the kinematic coordination of different gaits (walk, trot, gallop, and swim) of six dogs (Canis lupus familiaris) and, in particular, the planar covariation of limb segment elevation angles. The results showed significant variations in the relative duration of rearward limb movement, amplitude of angular motion, and inter-limb coordination, with gait patterns ranging from a lateral sequence of footfalls during walking to a diagonal sequence in swimming. Despite these differences, the planar law of inter-segmental coordination was maintained across different gaits in both forelimbs and hindlimbs. Notably, phase relationships and orientation of the covariation plane were highly limb specific, consistent with the functional differences in their neural control. Factor analysis of published muscle activity data also demonstrated differences in the characteristic timing of basic activation patterns of the forelimbs and hindlimbs. Overall, the results demonstrate that the planar covariation of inter-segmental coordination has emerged for both fore- and hindlimbs and all gaits, although in a limb-specific manner. PMID:26218076

Unsaturated Fatty Acids Supplementation Reduces Blood Lead Level in Rats

PubMed Central

Skoczyńska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, Łukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

2015-01-01

Some dietary factors could inhibit lead toxicity. The aim of this study was to evaluate the effect of dietary compounds rich in unsaturated fatty acids (FA) on blood lead level, lipid metabolism, and vascular reactivity in rats. Serum metallothionein and organs' lead level were evaluated with the aim of assessing the possible mechanism of unsaturated FA impact on blood lead level. For three months, male Wistar rats that were receiving drinking water with (100 ppm Pb) or without lead acetate were supplemented per os daily with virgin olive oil or linseed oil (0.2 mL/kg b.w.) or egg derived lecithin fraction: “super lecithin” (50 g/kg b.w.). Mesenteric artery was stimulated ex vivo by norepinephrine (NE) administered at six different doses. Lecithin supplementation slightly reduced pressor responses of artery to NE. Lead administered to rats attenuated the beneficial effect of unsaturated FA on lipid metabolism and vascular reactivity to adrenergic stimulation. On the other hand, the super lecithin and linseed oil that were characterized by low omega-6 to omega-3 ratio (about 1) reduced the blood lead concentration. This effect was observed in lead poisoned rats (p < 0.0001) and also in rats nonpoisoned with lead (p < 0.05). PMID:26075218

Unsaturated fatty acids supplementation reduces blood lead level in rats.

PubMed

Skoczyńska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, Łukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

2015-01-01

Some dietary factors could inhibit lead toxicity. The aim of this study was to evaluate the effect of dietary compounds rich in unsaturated fatty acids (FA) on blood lead level, lipid metabolism, and vascular reactivity in rats. Serum metallothionein and organs' lead level were evaluated with the aim of assessing the possible mechanism of unsaturated FA impact on blood lead level. For three months, male Wistar rats that were receiving drinking water with (100 ppm Pb) or without lead acetate were supplemented per os daily with virgin olive oil or linseed oil (0.2 mL/kg b.w.) or egg derived lecithin fraction: "super lecithin" (50 g/kg b.w.). Mesenteric artery was stimulated ex vivo by norepinephrine (NE) administered at six different doses. Lecithin supplementation slightly reduced pressor responses of artery to NE. Lead administered to rats attenuated the beneficial effect of unsaturated FA on lipid metabolism and vascular reactivity to adrenergic stimulation. On the other hand, the super lecithin and linseed oil that were characterized by low omega-6 to omega-3 ratio (about 1) reduced the blood lead concentration. This effect was observed in lead poisoned rats (p < 0.0001) and also in rats nonpoisoned with lead (p < 0.05).

Forelimb kinematics and motor patterns of the slider turtle (Trachemys scripta) during swimming and walking: shared and novel strategies for meeting locomotor demands of water and land

PubMed Central

Rivera, Angela R. V.; W. Blob, Richard

2010-01-01

Turtles use their limbs during both aquatic and terrestrial locomotion, but water and land impose dramatically different physical requirements. How must musculoskeletal function be adjusted to produce locomotion through such physically disparate habitats? We addressed this question by quantifying forelimb kinematics and muscle activity during aquatic and terrestrial locomotion in a generalized freshwater turtle, the red-eared slider (Trachemys scripta), using digital high-speed video and electromyography (EMG). Comparisons of our forelimb data to previously collected data from the slider hindlimb allow us to test whether limb muscles with similar functional roles show qualitatively similar modulations of activity across habitats. The different functional demands of water and air lead to a prediction that muscle activity for limb protractors (e.g. latissimus dorsi and deltoid for the forelimb) should be greater during swimming than during walking, and activity in retractors (e.g. coracobrachialis and pectoralis for the forelimb) should be greater during walking than during swimming. Differences between aquatic and terrestrial forelimb movements are reflected in temporal modulation of muscle activity bursts between environments, and in some cases the number of EMG bursts as well. Although patterns of modulation between water and land are similar between the fore- and hindlimb in T. scripta for propulsive phase muscles (retractors), we did not find support for the predicted pattern of intensity modulation, suggesting that the functional demands of the locomotor medium alone do not dictate differences in intensity of muscle activity across habitats. PMID:20889832

Naloxone and rimonabant reduce the reinforcing properties of exercise in rats.

PubMed

Rasmussen, Erin B; Hillman, Conrad

2011-12-01

Naloxone and rimonabant block neurotransmitter action of some drugs of abuse (such as ethanol, opiates, and nicotine), and thereby reduce drug seeking and self-administration by suppressing the drugs' reinforcing properties. The present study represents an attempt to elucidate whether these drugs may also reduce rewarding properties of other events, in this case, activity-based reinforcement. In Experiment 1, 10 obese and 10 lean Zucker rats pressed a locked door under a progressive ratio schedule of reinforcement that, when unlocked, provided access to a running wheel for 2-min intervals. After baseline breakpoints were established, doses of naloxone (0.3-10 mg/kg) were administered prior to experimental sessions. Obese rats exhibited lower baseline breakpoints for wheel activity, lower response rates, and fewer revolutions compared to lean rats. Naloxone decreased revolutions and response rates for lean and obese rats, but did not reduce breakpoints. In Experiment 2, five Long-Evans rats pressed a door to unlock a wheel for 20 s of wheel activity. Doses of rimonabant (1-10 mg/kg) were administered before some experimental sessions. The highest dose of rimonabant suppressed breakpoints and response rates, but did not affect revolutions. These data suggest that both drugs reduce the reinforcing properties of wheel running, but do so in different manners: naloxone may suppress wheel-based activity (consummatory behavior), but not seeking (appetitive behavior), and rimonabant does the converse. The data also support the role of endocannabinoids in the reinforcing properties of exercise, an implication that is important in terms of CB1 antagonists as a type of pharmacotherapy.

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

PubMed Central

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

2015-01-01

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

Population Coding of Forelimb Joint Kinematics by Peripheral Afferents in Monkeys

PubMed Central

Umeda, Tatsuya; Seki, Kazuhiko; Sato, Masa-aki; Nishimura, Yukio; Kawato, Mitsuo; Isa, Tadashi

2012-01-01

Various peripheral receptors provide information concerning position and movement to the central nervous system to achieve complex and dexterous movements of forelimbs in primates. The response properties of single afferent receptors to movements at a single joint have been examined in detail, but the population coding of peripheral afferents remains poorly defined. In this study, we obtained multichannel recordings from dorsal root ganglion (DRG) neurons in cervical segments of monkeys. We applied the sparse linear regression (SLiR) algorithm to the recordings, which selects useful input signals to reconstruct movement kinematics. Multichannel recordings of peripheral afferents were performed by inserting multi-electrode arrays into the DRGs of lower cervical segments in two anesthetized monkeys. A total of 112 and 92 units were responsive to the passive joint movements or the skin stimulation with a painting brush in Monkey 1 and Monkey 2, respectively. Using the SLiR algorithm, we reconstructed the temporal changes of joint angle, angular velocity, and acceleration at the elbow, wrist, and finger joints from temporal firing patterns of the DRG neurons. By automatically selecting a subset of recorded units, the SLiR achieved superior generalization performance compared with a regularized linear regression algorithm. The SLiR selected not only putative muscle units that were responsive to only the passive movements, but also a number of putative cutaneous units responsive to the skin stimulation. These results suggested that an ensemble of peripheral primary afferents that contains both putative muscle and cutaneous units encode forelimb joint kinematics of non-human primates. PMID:23112841

Use-Dependent Dendritic Regrowth Is Limited after Unilateral Controlled Cortical Impact to the Forelimb Sensorimotor Cortex

PubMed Central

Jones, Theresa A.; Liput, Daniel J.; Maresh, Erin L.; Donlan, Nicole; Parikh, Toral J.; Marlowe, Dana

2012-01-01

Abstract Compensatory neural plasticity occurs in both hemispheres following unilateral cortical damage incurred by seizures, stroke, and focal lesions. Plasticity is thought to play a role in recovery of function, and is important for the utility of rehabilitation strategies. Such effects have not been well described in models of traumatic brain injury (TBI). We examined changes in immunoreactivity for neural structural and plasticity-relevant proteins in the area surrounding a controlled cortical impact (CCI) to the forelimb sensorimotor cortex (FL-SMC), and in the contralateral homotopic cortex over time (3–28 days). CCI resulted in considerable motor deficits in the forelimb contralateral to injury, and increased reliance on the ipsilateral forelimb. The density of dendritic processes, visualized with immunostaining for microtubule-associated protein-2 (MAP-2), were bilaterally decreased at all time points. Synaptophysin (SYN) immunoreactivity increased transiently in the injured hemisphere, but this reflected an atypical labeling pattern, and it was unchanged in the contralateral hemisphere compared to uninjured controls. The lack of compensatory neuronal structural plasticity in the contralateral homotopic cortex, despite behavioral asymmetries, is in contrast to previous findings in stroke models. In the cortex surrounding the injury (but not the contralateral cortex), decreases in dendrites were accompanied by neurodegeneration, as indicated by Fluoro-Jade B (FJB) staining, and increased expression of the growth-inhibitory protein Nogo-A. These studies indicate that, following unilateral CCI, the cortex undergoes neuronal structural degradation in both hemispheres out to 28 days post-injury, which may be indicative of compromised compensatory plasticity. This is likely to be an important consideration in designing therapeutic strategies aimed at enhancing plasticity following TBI. PMID:22352953

Effect of hoof boots and toe-extension shoes on the forelimb kinetics of horses during walking.

PubMed

Amitrano, Fernando N; Gutierrez-Nibeyro, Santiago D; Schaeffer, David J

2016-05-01

OBJECTIVE To determine and compare the effect of hoof boots (HBs) and shoes with a toe extension on stance duration, ground reaction force, and sole length in contact with the ground in nonlame horses during walking. ANIMALS 6 nonlame Standardbreds. PROCEDURES Force plate gait analyses of the forelimbs were performed while the horses were walking barefoot before manipulation of feet (baseline), while the horses were walking fitted with HBs, while the horses were walking shod with toe-extension shoes, and while the horses were walking barefoot after shoe removal. Horses underwent radiography of both forelimb feet to determine the sole length in contact with the ground when barefoot, wearing HBs, and shod with toe-extension shoes. Stance duration, ground reaction force, and sole length were compared among the various walking sessions. RESULTS Compared with baseline findings, stance duration increased significantly when horses were fitted with HBs (7%) or toe-extension shoes (5%). Peak forelimb ground reaction force was similar among walking sessions; however, time of braking force peak was significantly greater during the stance phase only when horses wore HBs. Also, the sole length in contact with the ground was significantly longer in horses fitted with HBs (14.3 cm) or shod with the toe-extension shoes (17.6 cm), compared with that for one of the barefoot hooves (12.7 cm). CONCLUSIONS AND CLINICAL RELEVANCE In nonlame horses, use of HBs prolonged the stance time and time of braking force peak, which is indicative of a slower deceleration phase during limb impact with the ground. Also, the use of HBs prolonged the deceleration phase of the stride and increased the sole length in contact with the ground.

Use-dependent dendritic regrowth is limited after unilateral controlled cortical impact to the forelimb sensorimotor cortex.

PubMed

Jones, Theresa A; Liput, Daniel J; Maresh, Erin L; Donlan, Nicole; Parikh, Toral J; Marlowe, Dana; Kozlowski, Dorothy A

2012-05-01

Compensatory neural plasticity occurs in both hemispheres following unilateral cortical damage incurred by seizures, stroke, and focal lesions. Plasticity is thought to play a role in recovery of function, and is important for the utility of rehabilitation strategies. Such effects have not been well described in models of traumatic brain injury (TBI). We examined changes in immunoreactivity for neural structural and plasticity-relevant proteins in the area surrounding a controlled cortical impact (CCI) to the forelimb sensorimotor cortex (FL-SMC), and in the contralateral homotopic cortex over time (3-28 days). CCI resulted in considerable motor deficits in the forelimb contralateral to injury, and increased reliance on the ipsilateral forelimb. The density of dendritic processes, visualized with immunostaining for microtubule-associated protein-2 (MAP-2), were bilaterally decreased at all time points. Synaptophysin (SYN) immunoreactivity increased transiently in the injured hemisphere, but this reflected an atypical labeling pattern, and it was unchanged in the contralateral hemisphere compared to uninjured controls. The lack of compensatory neuronal structural plasticity in the contralateral homotopic cortex, despite behavioral asymmetries, is in contrast to previous findings in stroke models. In the cortex surrounding the injury (but not the contralateral cortex), decreases in dendrites were accompanied by neurodegeneration, as indicated by Fluoro-Jade B (FJB) staining, and increased expression of the growth-inhibitory protein Nogo-A. These studies indicate that, following unilateral CCI, the cortex undergoes neuronal structural degradation in both hemispheres out to 28 days post-injury, which may be indicative of compromised compensatory plasticity. This is likely to be an important consideration in designing therapeutic strategies aimed at enhancing plasticity following TBI.

Cheap Labor: Myosin fiber type expression and enzyme activity in the forelimb musculature of sloths (Pilosa: Xenarthra).

PubMed

Spainhower, Kyle B; Cliffe, Rebecca N; Metz, Allan K; Barkett, Ernest M; Kiraly, Paije M; Thomas, Dylan R; Kennedy, Sarah J; Avey-Arroyo, Judy; Butcher, Michael T

2018-05-03

Sloths are canopy-dwelling inhabitants of American neotropical rainforests that exhibit suspensory behaviors. These abilities require both strength and muscular endurance to hang for extended periods of time; however, the skeletal muscle mass of sloths is reduced, thus requiring modifications to muscle architecture and leverage for large joint torque. We hypothesize that intrinsic muscle properties also are modified for fatigue resistance and predict a heterogeneous expression of slow/fast myosin heavy chain (MHC) fibers that utilize oxidative metabolic pathways for economic force production. MHC fiber type distribution and energy metabolism in the forelimb muscles of three-toed ( Bradypus variegatus, N=5) and two-toed ( Choloepus hoffmanni, N=4) sloths were evaluated using SDS-PAGE, immunohistochemistry, and enzyme activity assays. The results partially support our hypothesis by a primary expression of the slow MHC-1 isoform as well as moderate expression of fast MHC-2A fibers, while few hybrid MHC-1/2A fibers were found in both species. MHC-1 fibers were larger in cross-sectional area (CSA) than MHC-2A fibers and comprised the greatest %CSA in each muscle sampled. Enzyme assays showed elevated activity for the anaerobic enzymes creatine kinase (CK) and lactate dehydrogenase (LDH) compared to low activity for aerobic markers citrate synthase (CS) and 3- hydroxyacetyl CoA dehydrogenase (3-HAD). These findings suggest that sloth forelimb muscles may rely heavily on rapid ATP resynthesis pathways, and lactate accumulation may be beneficial. The intrinsic properties observed match well with suspensory requirements, and these modifications may have further evolved in unison with low metabolism and slow movement patterns as means to systemically conserve energy.

Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction.

PubMed

Liu, Jing; Wang, Xiaofeng; Liu, Ying; Yang, Na; Xu, Jing; Ren, Xiaotun

2013-08-15

From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12(th) day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction

PubMed Central

Liu, Jing; Wang, Xiaofeng; Liu, Ying; Yang, Na; Xu, Jing; Ren, Xiaotun

2013-01-01

From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain. PMID:25206528

Berberine reduced blood pressure and improved vasodilation in diabetic rats.

PubMed

Ma, Yu-Guang; Liang, Liang; Zhang, Yin-Bin; Wang, Bao-Feng; Bai, Yun-Gang; Dai, Zhi-Jun; Xie, Man-Jiang; Wang, Zhong-Wei

2017-10-01

Hyperglycemia and hypertension are considered to be the two leading risk factors for vascular disease in diabetic patients. However, few pharmacologic agents could provide a combinational therapy for controlling hyperglycemia and hypertension at the same time in diabetes. The objectives of this study are to investigate whether berberine treatment could directly reduce blood pressure and identify the molecular mechanism underlying the vascular protection of berberine in diabetic rats. Berberine was intragastrically administered with different dosages of 50, 100 and 200 mg/kg/day to diabetic rats for 8 weeks since the injection of streptozotocin. The endothelium-dependent/-independent relaxation in middle cerebral arteries was investigated. The activity of large-conductance Ca 2+ -activated K + channel (BK Ca ) was investigated by recording whole-cell currents, analyzing single-channel activities and assessing the expressions of α- and β1-subunit at protein or mRNA levels. Results of the study suggest that chronic administration of 100 mg/kg/day berberine not only lowered blood glucose but also reduced blood pressure and improved vasodilation in diabetic rats. Furthermore, berberine markedly increased the function and expression of BK Ca β1-subunit in cerebral vascular smooth muscle cells (VSMCs) isolated from diabetic rats or when exposed to hyperglycemia condition. The present study provided initial evidences that berberine reduced blood pressure and improved vasodilation in diabetic rats by activation of BK Ca channel in VSMCs, which suggested that berberine might provide a combinational therapy for controlling hyperglycemia and blood pressure in diabetes. Furthermore, our work indicated that activation of BK Ca channel might be the underlying mechanism responsible for the vascular protection of berberine in diabetes. © 2017 Society for Endocrinology.

Type 1 Diabetes in Young Rats Leads to Progressive Trabecular Bone Loss, Cessation of Cortical Bone Growth, and Diminished Whole Bone Strength and Fatigue Life

PubMed Central

Silva, Matthew J.; Brodt, Michael D.; Lynch, Michelle A.; McKenzie, Jennifer A.; Tanouye, Kristi M.; Nyman, Jeffry S.; Wang, Xiaodu

2009-01-01

People with diabetes have increased risk of fracture disproportionate to BMD, suggesting reduced material strength (quality). We quantified the skeletal effects of type 1 diabetes in the rat. Fischer 344 and Sprague-Dawley rats (12 wk of age) were injected with either vehicle (Control) or streptozotocin (Diabetic). Forelimbs were scanned at 0, 4, 8, and 12 wk using pQCT. Rats were killed after 12 wk. We observed progressive osteopenia in diabetic rats. Trabecular osteopenia was caused by bone loss: volumetric BMD decreased progressively with time in diabetic rats but was constant in controls. Cortical osteopenia was caused by premature arrest of cortical expansion: cortical area did not increase after 4–8 wk in diabetic rats but continued to increase in controls. Postmortem μCT showed a 60% reduction in proximal tibial trabecular BV/TV in diabetic versus control rats, whereas moments of inertia of the ulnar and femoral diaphysis were reduced ∼30%. Monotonic bending tests indicated that ulna and femora from diabetic animals were ∼25% less stiff and strong versus controls. Estimates of material properties indicated no changes in elastic modulus or ultimate stress but modest (∼10%) declines in yield stress for diabetic bone. These changes were associated with a ∼50% increase in the nonenzymatic collagen cross-link pentosidine. Last, cyclic testing showed diminished fatigue life in diabetic bones at the structural (force) level but not at the material (stress) level. In summary, type 1 diabetes, left untreated, causes trabecular bone loss and a reduction in diaphyseal growth. Diabetic bone has greatly increased nonenzymatic collagen cross-links but only modestly reduced material properties. The loss of whole bone strength under both monotonic and fatigue loading is attributed mainly to reduced bone size. PMID:19338453

MAG-EPA reduces severity of DSS-induced colitis in rats.

PubMed

Morin, Caroline; Blier, Pierre U; Fortin, Samuel

2016-05-15

Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the intestinal mucosa of the large bowel. Omega-3 (ω3) fatty acid supplementation has been associated with a decreased production of inflammatory cytokines involved in UC pathogenesis. The aim of this study was to determine the preventive and therapeutic potential of eicosapentaenoic acid monoglyceride (MAG-EPA) in an in vivo rats model of UC induced by dextran sulfate sodium (DSS). DSS rats were untreated or treated per os with MAG-EPA. Morphological, histological, and biochemical analyses were performed following MAG-EPA administrations. Morphological and histological analyses revealed that MAG-EPA pretreatment (12 days pre-DSS) and treatment (6 days post-DSS) exhibited strong activity in reducing severity of disease in DSS rats. Following MAG-EPA administrations, tissue levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 were markedly lower compared with rats treated only with DSS. MAG-EPA per os administration decrease neutrophil infiltration in colon tissues, as depicted by myelohyperoxidase activity. Results also revealed a reduced activation of NF-κB pathways correlated with a decreased expression of COX-2 in colon homogenates derived from MAG-EPA-pretreated and treated rats. Tension measurements performed on colon tissues revealed that contractile responses to methacholine and relaxing effect induced by sodium nitroprusside were largely increased following MAG-EPA treatment. The combined treatment of MAG-EPA and vitamin E displayed an antagonistic effect on anti-inflammatory properties of MAG-EPA in DSS rats. Copyright © 2016 the American Physiological Society.

Functional anatomy of the forelimb in Promegantereon* ogygia (Felidae, Machairodontinae, Smilodontini) from the late miocene of spain and the origins of the sabre-toothed felid model.

PubMed

Salesa, Manuel J; Antón, Mauricio; Turner, Alan; Morales, Jorge

2010-03-01

We examine the functional anatomy of the forelimb in the primitive sabre-toothed cat Promegantereon ogygia in comparison with that of the extant pantherins, other felids and canids. The study reveals that this early machairodontine had already developed strong forelimbs and a short and robust thumb, a combination that probably allowed P. ogygia to exert relatively greater forces than extant pantherins. These features can be clearly related to the evolution of the sabre-toothed cat hunting method, in which the rapid killing of prey was achieved with a precise canine shear-bite to the throat. In this early sabre-toothed cat from the Late Miocene, the strong forelimbs and thumb were adapted to achieve the rapid immobilization of prey, thus decreasing the risk of injury and minimizing energy expenditure. We suggest that these were the major evolutionary pressures that led to the appearance of the sabre-toothed cat model from the primitive forms of the Middle Miocene, rather than the hunting of very large prey, although these adaptations reached their highest development in the more advanced sabre-toothed cats of the Plio-Pleistocene, such as Smilodon and Homotherium. Although having very different body proportions, these later animals developed such extremely powerful forelimbs that they were probably able to capture relatively larger prey than extant pantherins.

Record-Breaking Pain: The Largest Number and Variety of Forelimb Bone Maladies in a Theropod Dinosaur.

PubMed

Senter, Phil; Juengst, Sara L

2016-01-01

Bone abnormalities are common in theropod dinosaur skeletons, but before now no specimen was known with more than four afflicted bones of the pectoral girdle and/or forelimb. Here we describe the pathology of a specimen of the theropod dinosaur Dilophosaurus wetherilli with eight afflicted bones of the pectoral girdle and forelimb. On its left side the animal has a fractured scapula and radius and large fibriscesses in the ulna and the proximal thumb phalanx. On its right side the animal has abnormal torsion of the humeral shaft, bony tumors on the radius, a truncated distal articular surface of metacarpal III, and angular deformities of the first phalanx of the third finger. Healing and remodeling indicates that the animal survived for months and possibly years after its ailments began, but its right third finger was permanently deformed and lacked the capability of flexion. The deformities of the humerus and the right third finger may be due to developmental osteodysplasia, a condition known in extant birds but unreported in non-avian dinosaurs before now.

The Role of Endogenous Neurogenesis in Functional Recovery and Motor Map Reorganization Induced by Rehabilitative Therapy after Stroke in Rats.

PubMed

Shiromoto, Takashi; Okabe, Naohiko; Lu, Feng; Maruyama-Nakamura, Emi; Himi, Naoyuki; Narita, Kazuhiko; Yagita, Yoshiki; Kimura, Kazumi; Miyamoto, Osamu

2017-02-01

Endogenous neurogenesis is associated with functional recovery after stroke, but the roles it plays in such recovery processes are unknown. This study aims to clarify the roles of endogenous neurogenesis in functional recovery and motor map reorganization induced by rehabilitative therapy after stroke by using a rat model of cerebral ischemia (CI). Ischemia was induced via photothrombosis in the caudal forelimb area of the rat cortex. First, we examined the effect of rehabilitative therapy on functional recovery and motor map reorganization, using the skilled forelimb reaching test and intracortical microstimulation. Next, using the same approaches, we examined how motor map reorganization changed when endogenous neurogenesis after stroke was inhibited by cytosine-β-d-arabinofuranoside (Ara-C). Rehabilitative therapy for 4 weeks after the induction of stroke significantly improved functional recovery and expanded the rostral forelimb area (RFA). Intraventricular Ara-C administration for 4-10 days after stroke significantly suppressed endogenous neurogenesis compared to vehicle, but did not appear to influence non-neural cells (e.g., microglia, astrocytes, and vascular endothelial cells). Suppressing endogenous neurogenesis via Ara-C administration significantly inhibited (~50% less than vehicle) functional recovery and RFA expansion (~33% of vehicle) induced by rehabilitative therapy after CI. After CI, inhibition of endogenous neurogenesis suppressed both the functional and anatomical markers of rehabilitative therapy. These results suggest that endogenous neurogenesis contributes to functional recovery after CI related to rehabilitative therapy, possibly through its promotion of motor map reorganization, although other additional roles cannot be ruled out. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Resting Orientations of Dinosaur Scapulae and Forelimbs: A Numerical Analysis, with Implications for Reconstructions and Museum Mounts.

PubMed

Senter, Phil; Robins, James H

2015-01-01

The inclination of the scapular blade and the resting pose of the forelimb in dinosaurs differ among reconstructions and among skeletal mounts. For most dinosaurian taxa, no attempt has previously been made to quantify the correct resting positions of these elements. Here, we used data from skeletons preserved in articulation to quantify the resting orientations of the scapula and forelimb in dinosaurs. Specimens were included in the study only if they were preserved lying on their sides; for each specimen the angle between forelimb bones at a given joint was included in the analysis only if the joint was preserved in articulation. Using correlation analyses of the angles between the long axis of the sacrum, the first dorsal centrum, and the scapular blade in theropods and Eoraptor, we found that vertebral hyperextension does not influence scapular orientation in saurischians. Among examined taxa, the long axis of the scapular blade was found to be most horizontal in bipedal saurischians, most vertical in basal ornithopods, and intermediate in hadrosauroids. We found that in bipedal dinosaurs other than theropods with semilunate carpals, the resting orientation of the elbow is close to a right angle and the resting orientation of the wrist is such that the hand exhibits only slight ulnar deviation from the antebrachium. In theropods with semilunate carpals the elbow and wrist are more flexed at rest, with the elbow at a strongly acute angle and with the wrist approximately at a right angle. The results of our study have important implications for correct orientations of bones in reconstructions and skeletal mounts. Here, we provide recommendations on bone orientations based on our results.

Memantine reduces alcohol drinking but not relapse in alcohol-dependent rats.

PubMed

Alaux-Cantin, Stéphanie; Buttolo, Romain; Houchi, Hakim; Jeanblanc, Jérôme; Naassila, Mickaël

2015-09-01

Alcoholism is a chronic relapsing disorder with consequences on health and that requires more effective treatments. Among alternative therapies, the therapeutic potential of the non-competitive N-methyl-D-aspartate receptor antagonist memantine has been suggested. Despite promising results, its efficiency in the treatment of alcoholism remains controversial. Currently, there is no pre-clinical data regarding its effects on the motivation for ethanol in post-dependent (PD) animals exposed to intermittent ethanol vapor, a validated model of alcoholism. Thus, the objectives of this study were to evaluate the effects of acute injections of memantine (0, 12.5, 25 and 50 mg/kg) on operant ethanol self-administration in non-dependent (ND) and PD rats tested either during acute withdrawal or relapse after protracted abstinence. Our results showed that memantine (25 mg/kg) abolished ethanol self-administration in ND rats and reduced by half the one of PD rats during acute withdrawal. While this effect was observed only 6 hours after treatment in ND rats, it was long lasting in PD rats (at least 30 hours after injection). Furthermore, our results indicated that memantine did not modify the breaking point for ethanol. This suggests that memantine probably act by potentiating the pharmacological effect of ethanol but not by reducing motivation for ethanol. Finally, memantine was also ineffective in reducing relapse after protracted abstinence. Altogether, our pre-clinical results highlighted a potential therapeutic use of memantine that may be used as a replacement therapy drug but not as relapse-preventing drug. © 2014 Society for the Study of Addiction.

Azilsartan improves glycemic status and reduces kidney damage in zucker diabetic fatty rats.

PubMed

Hye Khan, Md Abdul; Neckář, Jan; Haines, Jasmine; Imig, John D

2014-08-01

Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, demonstrates antihypertensive and organ protective effects in hypertension. We investigated the efficacy of AZL-M to ameliorate metabolic syndrome and kidney damage associated with type 2 diabetes using Zucker diabetic fatty (ZDF) rats. ZDF rats were treated with vehicle or AZL-M for 8 weeks. Zucker diabetic lean (ZDL) rats were used as controls. Urine and plasma samples were collected for biochemical analysis, and kidney tissues were used for histopathological and immunohistopathological examination at the end of the 8-week protocol. ZDF rats were diabetic with hyperglycemia and impaired glucose tolerance, and AZL-M ameliorated the diabetic phenotype. ZDF rats were hypertensive compared with ZDL rats (181±6 vs. 129±7mm Hg), and AZL-M decreased blood pressure in ZDF rats (116±7mm Hg). In ZDF rats, there was marked renal damage with elevated proteinuria, albuminuria, nephrinuria, 2-4-fold higher tubular cast formation, and glomerular injury compared with ZDL rats. AZL-M treatment reduced renal damage in ZDF rats. ZDF rats demonstrated renal inflammation and oxidative stress with elevated urinary monocyte chemoattractant protein 1 excretion, renal infiltration of macrophages, and elevated kidney malondialdehyde levels. AZL-M reduced oxidative stress and inflammation in ZDF rats. Overall, we demonstrate that AZL-M attenuates kidney damage in type 2 diabetes. We further demonstrate that anti-inflammatory and antioxidative activities of AZL-M contribute to its kidney protective action. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Sepiapterin reduces postischemic injury in the rat heart.

PubMed

Tiefenbacher, Christiane P; Lee, Ching-Hua; Kapitza, Jolanthe; Dietz, Volker; Niroomand, Feraydoon

2003-10-01

A reduced availability of tetrahydrobiopterin (BH4), an essential cofactor for NO-synthesis, is causally involved in the development of endothelial dysfunction associated with ischemia/reperfusion. We, therefore, investigated the effect of sepiapterin, a substrate for BH4 synthesis, on postischemic injury in myocardial infarction and myocardial stunning. In rats, myocardial stunning was induced by repetitive ischemia (5 x 10-min ligature of the left coronary artery, 5 x 20-min reperfusion) and myocardial infarction by 50-min ligature and 60-min reperfusion. Myocardial blood flow was determined by H2-clearance, regional myocardial function by pulsed Doppler and infarct size by tetrazolium staining. Myeloperoxidase (MPO) activity was measured as a marker of neutrophil extravasation. cGMP was determined in rat serum as an indicator of increased NO synthesis. In animals treated with sepiapterin, regional myocardial function was significantly improved in both myocardial stunning and infarction and infarct size was significantly reduced. MPO activity decreased with sepiapterin treatment in both models. The systemic level of cGMP was reduced both following myocardial stunning and myocardial infarction in the control group. Pretreatment with sepiapterin induced a significant increase of cGMP level at the end of the protocol in both models. Substitution of sepiapterin reduces postischemic injury both in myocardial stunning and infarction apparently by ameliorating the availability of NO, thereby attenuating the activation of neutrophils in ischemia/reperfusion.

Fructo-oligosaccharides reduce energy intake but do not affect adiposity in rats fed a low-fat diet but increase energy intake and reduce fat mass in rats fed a high-fat diet.

PubMed

Hadri, Zouheyr; Rasoamanana, Rojo; Fromentin, Gilles; Azzout-Marniche, Dalila; Even, Patrick C; Gaudichon, Claire; Darcel, Nicolas; Bouras, Abdelkader Dilmi; Tomé, Daniel; Chaumontet, Catherine

2017-12-01

The ingestion of low or high lipid diets enriched with fructo-oligosaccharide (FOS) affects energy homeostasis. Ingesting protein diets also induces a depression of energy intake and decreases body weight. The goal of this study was to investigate the ability of FOS, combined or not with a high level of protein (P), to affect energy intake and body composition when included in diets containing different levels of lipids (L). We performed two studies of similar design over a period of 5weeks. During the first experiment (exp1), after a 3-week period of adaptation to a normal protein-low fat diet, the rats received one of the following four diets for 5weeks (6 rats per group): (i) normal protein (14% P/E (Energy) low fat (10% L/E) diet, (ii) normal protein, low fat diet supplemented with 10% FOS, (iii) high protein (55%P/E) low fat diet, and (iv) high protein, low fat diet supplemented with 10% FOS. In a second experiment (exp2) after the 3-week period of adaptation to a normal protein-high fat diet, the rats received one of the following 4 diets for 5weeks (6 rats per group): (i) normal protein, high fat diet (35% of fat), (ii) normal protein, high fat diet supplemented with 10% FOS, (iii) high protein high fat diet and (iv) high protein high fat diet supplemented with 10% FOS. In low-fat fed rats, FOS did not affect lean body mass (LBM) and fat mass but the protein level reduced fat mass and tended to reduce adiposity. In high-fat fed rats, FOS did not affect LBM but reduced fat mass and adiposity. No additive or antagonistic effects between FOS and the protein level were observed. FOS reduced energy intake in low-fat fed rats, did not affect energy intake in normal-protein high-fat fed rats but surprisingly, and significantly, increased energy intake in high-protein high-fat fed rats. The results thus showed that FOS added to a high-fat diet reduced body fat and body adiposity. Published by Elsevier Inc.

Combined SCI and TBI: Recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement

PubMed Central

Inoue, Tomoo; Lin, Amity; Ma, Xiaokui; McKenna, Stephen L.; Creasey, Graham H.; Manley, Geoffrey T.; Ferguson, Adam R.; Bresnahan, Jacqueline C.; Beattie, Michael S.

2015-01-01

A significant proportion (estimates range from 16–74%) of patients with spinal cord injury (SCI) have concomitant traumatic brain injury (TBI), and the combination often produces difficulties in planning and implementing rehabilitation strategies and drug therapies. For example, many of the drugs used to treat SCI may interfere with cognitive rehabilitation, and conversely drugs that are used to control seizures in TBI patients may undermine locomotor recovery after SCI. The current paper presents an experimental animal model for combined SCI and TBI to help drive mechanistic studies of dual diagnosis. Rats received a unilateral SCI (75 kdyn) at C5 vertebral level, a unilateral TBI (2.0 mm depth, 4.0 m/s velocity impact on the forelimb sensori-motor cortex), or both SCI + TBI. TBI was placed either contralateral or ipsilateral to the SCI. Behavioral recovery was examined using paw placement in a cylinder, grooming, open field locomotion, and the IBB cereal eating test. Over 6 weeks, in the paw placement test, SCI + contralateral TBI produced a profound deficit that failed to recover, but SCI + ipsilateral TBI increased the relative use of the paw on the SCI side. In the grooming test, SCI + contralateral TBI produced worse recovery than either lesion alone even though contralateral TBI alone produced no observable deficit. In the IBB forelimb test, SCI + contralateral TBI revealed a severe deficit that recovered in 3 weeks. For open field locomotion, SCI alone or in combination with TBI resulted in an initial deficit that recovered in 2 weeks. Thus, TBI and SCI affected forelimb function differently depending upon the test, reflecting different neural substrates underlying, for example, exploratory paw placement and stereotyped grooming. Concurrent SCI and TBI had significantly different effects on outcomes and recovery, depending upon laterality of the two lesions. Recovery of function after cervical SCI was retarded by the addition of a moderate TBI in the

Combined SCI and TBI: recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement.

PubMed

Inoue, Tomoo; Lin, Amity; Ma, Xiaokui; McKenna, Stephen L; Creasey, Graham H; Manley, Geoffrey T; Ferguson, Adam R; Bresnahan, Jacqueline C; Beattie, Michael S

2013-10-01

A significant proportion (estimates range from 16 to 74%) of patients with spinal cord injury (SCI) have concomitant traumatic brain injury (TBI), and the combination often produces difficulties in planning and implementing rehabilitation strategies and drug therapies. For example, many of the drugs used to treat SCI may interfere with cognitive rehabilitation, and conversely drugs that are used to control seizures in TBI patients may undermine locomotor recovery after SCI. The current paper presents an experimental animal model for combined SCI and TBI to help drive mechanistic studies of dual diagnosis. Rats received a unilateral SCI (75 kdyn) at C5 vertebral level, a unilateral TBI (2.0 mm depth, 4.0 m/s velocity impact on the forelimb sensori-motor cortex), or both SCI+TBI. TBI was placed either contralateral or ipsilateral to the SCI. Behavioral recovery was examined using paw placement in a cylinder, grooming, open field locomotion, and the IBB cereal eating test. Over 6weeks, in the paw placement test, SCI+contralateral TBI produced a profound deficit that failed to recover, but SCI+ipsilateral TBI increased the relative use of the paw on the SCI side. In the grooming test, SCI+contralateral TBI produced worse recovery than either lesion alone even though contralateral TBI alone produced no observable deficit. In the IBB forelimb test, SCI+contralateral TBI revealed a severe deficit that recovered in 3 weeks. For open field locomotion, SCI alone or in combination with TBI resulted in an initial deficit that recovered in 2 weeks. Thus, TBI and SCI affected forelimb function differently depending upon the test, reflecting different neural substrates underlying, for example, exploratory paw placement and stereotyped grooming. Concurrent SCI and TBI had significantly different effects on outcomes and recovery, depending upon laterality of the two lesions. Recovery of function after cervical SCI was retarded by the addition of a moderate TBI in the contralateral

Short-term glycemic control is effective in reducing surgical site infection in diabetic rats.

PubMed

Kroin, Jeffrey S; Buvanendran, Asokumar; Li, Jinyuan; Moric, Mario; Im, Hee-Jeong; Tuman, Kenneth J; Shafikhani, Sasha H

2015-06-01

Patients and animals with diabetes exhibit enhanced vulnerability to bacterial surgical infections. Despite multiple retrospective studies demonstrating the benefits associated with glycemic control in reducing bacterial infection after cardiac surgery, there are fewer guidelines on the use of glycemic control for noncardiac surgeries. In the current study, we investigated whether long-term (begun 2 weeks before surgery) or immediate (just before surgery) glycemic controls, continued postoperatively, can reduce surgical site infection in type 1 diabetic-induced rats. Rats were injected with streptozotocin to induce type 1 diabetes. Four groups of animals underwent surgery and thigh muscle Staphylococcus aureus bacteria challenge (1 × 10 colony forming units) at the time of surgery. Group 1 diabetic rats received insulin treatment just before surgery and continued until the end of study (short-term glycemic control group). Group 2 diabetic rats received insulin treatment 2 weeks before surgery and continued until the end of study (long-term glycemic control). Group 3 diabetic rats received no insulin treatment (no glycemic control group). Group 4 nondiabetic rats served as a healthy control group. Rats were euthanized at 3 or 6 days after surgery. Blood glucose and muscle bacterial burden were measured at 3 or 6 days after surgery. Glycemic control was achieved in both long- and short-term insulin-treated diabetic rats. Compared with untreated diabetic rats, the bacterial burden in muscle was significantly lower in both groups of glycemic controlled diabetic rats at 3 (all P < 0.003) and 6 (all P < 0.0001) days after surgery. A short-term glycemic control regimen, initiated just before surgery and bacterial exposure, was as effective in reducing surgical site infection as a long-term glycemic control in type 1 diabetic rats. These data suggest that immediately implementing glycemic control in type 1 diabetic surgical patients before undergoing noncardiac surgery

Human bone marrow-derived clonal mesenchymal stem cells inhibit inflammation and reduce acute pancreatitis in rats.

PubMed

Jung, Kyung Hee; Song, Sun U; Yi, Tacghee; Jeon, Myung-Shin; Hong, Sang-Won; Zheng, Hong-Mei; Lee, Hee-Seung; Choi, Myung-Joo; Lee, Don-Haeng; Hong, Soon-Sun

2011-03-01

Acute pancreatitis (AP) has a high mortality rate; repetitive AP induces chronic AP and pancreatic adenocarcinoma. Mesenchymal stem cells (MSCs) have immunoregulatory effects and reduce inflammation. We developed a protocol to isolate human bone marrow-derived clonal MSCs (hcMSCs) from bone marrow aspirate and investigated the effects of these cells in rat models of mild and severe AP. Mild AP was induced in Sprague-Dawley rats by 3 intraperitoneal injections of cerulein (100 μg/kg), given at 2-hour intervals; severe AP was induced by intraparenchymal injection of 3% sodium taurocholate solution. hcMSCs were labeled with CM-1,1'-dioctadecyl-3,3,3'-tetramethylindo-carbocyanine perchloride and administered to rats through the tail vein. hcMSCs underwent self-renewal and had multipotent differentiation capacities and immunoregulatory functions. Greater numbers of infused hcMSCs were detected in pancreas of rats with mild and severe AP than of control rats. Infused hcMSCs reduced acinar-cell degeneration, pancreatic edema, and inflammatory cell infiltration in each model of pancreatitis. The hcMSCs reduced expression of inflammation mediators and cytokines in rats with mild and severe AP. hcMSCs suppressed the mixed lymphocyte reaction and increased expression of Foxp3(+) (a marker of regulatory T cells) in cultured rat lymph node cells. Rats with mild or severe AP that were given infusions of hcMSCs had reduced numbers of CD3(+) T cells and increased expression of Foxp3(+) in pancreas tissues. hcMSCs reduced inflammation and damage to pancreatic tissue in a rat model of AP; they reduced levels of cytokines and induced numbers of Foxp3(+) regulatory T cells. hcMSCs might be developed as a cell therapy for pancreatitis. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Development of a universal measure of quadrupedal forelimb-hindlimb coordination using digital motion capture and computerised analysis.

PubMed

Hamilton, Lindsay; Franklin, Robin J M; Jeffery, Nick D

2007-09-18

Clinical spinal cord injury in domestic dogs provides a model population in which to test the efficacy of putative therapeutic interventions for human spinal cord injury. To achieve this potential a robust method of functional analysis is required so that statistical comparison of numerical data derived from treated and control animals can be achieved. In this study we describe the use of digital motion capture equipment combined with mathematical analysis to derive a simple quantitative parameter - 'the mean diagonal coupling interval' - to describe coordination between forelimb and hindlimb movement. In normal dogs this parameter is independent of size, conformation, speed of walking or gait pattern. We show here that mean diagonal coupling interval is highly sensitive to alterations in forelimb-hindlimb coordination in dogs that have suffered spinal cord injury, and can be accurately quantified, but is unaffected by orthopaedic perturbations of gait. Mean diagonal coupling interval is an easily derived, highly robust measurement that provides an ideal method to compare the functional effect of therapeutic interventions after spinal cord injury in quadrupeds.

Adult neurogenesis is reduced in the dorsal hippocampus of rats displaying learned helplessness behavior.

PubMed

Ho, Y C; Wang, S

2010-11-24

Clinical and preclinical studies suggest that the hippocampus has a role in the pathophysiology of major depression. In the learned helplessness (LH) animal model of depression after inescapable shocks (ISs) animals that display LH behavior have reduced cell proliferation in the hippocampus; this effect can be reversed by antidepressant treatment. Using this model, we compared rats that displayed LH behavior and rats that did not show LH behavior (NoLH) after ISs to determine whether reduced hippocampal cell proliferation is associated with the manifestation of LH behavior or is a general response to stress. Specifically, we examined cell proliferation, neurogenesis, and synaptic function in dorsal and ventral hippocampus of LH and NoLH animals and control rats that were not shocked. The LH rats had showed reduced cell proliferation, neurogenesis, and synaptic transmission in the dorsal hippocampus, whereas no changes were seen in the ventral hippocampus. These changes were not observed in the NoLH animals. In a group of NoLH rats that received the same amount of electrical shock as the LH rats to control for the unequal shocks received in these two groups, we observed changes in Ki-67(+) cells associated with acute stress. We conclude that reduced hippocampal cell proliferation and neurogenesis are associated with the manifestation of LH behavior and that the dorsal hippocampus is the most affected area. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Hawthorn extract reduces infarct volume and improves neurological score by reducing oxidative stress in rat brain following middle cerebral artery occlusion.

PubMed

Elango, Chinnasamy; Jayachandaran, Kasevan Sawaminathan; Niranjali Devaraj, S

2009-12-01

In our present investigation the neuroprotective effect of alcoholic extract of Hawthorn (Crataegus oxycantha) was evaluated against middle cerebral artery occlusion induced ischemia/reperfusion injury in rats. Male Sprague-Dawley rats were pretreated with 100 mg/kg body weight of the extract by oral gavage for 15 days. The middle cerebral artery was then occluded for 75 min followed by 24 h of reperfusion. The pretreated rats showed significantly improved neurological behavior with reduced brain infarct when compared to vehicle control rats. The glutathione level in brain was found to be significantly (p<0.05) low in vehicle control rats after 24 h of reperfusion when compared to sham operated animals. However, in Hawthorn extract pretreated rats the levels were found to be close to that of sham. Malondialdehyde levels in brain of sham and pretreated group were found to be significantly lower than the non-treated vehicle group (p<0.05). The nitric oxide levels in brain were measured and found to be significantly (p<0.05) higher in vehicle than in sham or extract treated rats. Our results suggest that Hawthorn extract which is a well known prophylactic for cardiac conditions may very well protect the brain against ischemia-reperfusion. The reduced brain damage and improved neurological behavior after 24 h of reperfusion in Hawthorn extract pretreated group may be attributed to its antioxidant property which restores glutathione levels, circumvents the increase in lipid peroxidation and nitric oxide levels thereby reducing peroxynitrite formation and free radical induced brain damage.

Improved single pellet grasping using automated ad libitum full-time training robot.

PubMed

Fenrich, Keith K; May, Zacnicte; Hurd, Caitlin; Boychuk, Carolyn E; Kowalczewski, Jan; Bennett, David J; Whishaw, Ian Q; Fouad, Karim

2015-03-15

The single pellet grasping (SPG) task is a skilled forelimb motor task commonly used to evaluate reaching and grasp kinematics and recovery of forelimb function in rodent models of CNS injuries and diseases. To train rats in the SPG task, the animals are usually food restricted then placed in an SPG task enclosure and presented food pellets on a platform located beyond a slit located at the front of the task enclosure for 10-30 min, normally every weekday for several weeks. When the SPG task is applied in studies involving various experimental groups, training quickly becomes labor intensive, and can yield results with significant day-to-day variability. Furthermore, training is frequently done during the animals' light-cycle, which for nocturnal rodents such as mice and rats could affect performance. Here we describe an automated pellet presentation (APP) robotic system to train and test rats in the SPG task that reduces some of the procedural weaknesses of manual training. We found that APP trained rats performed significantly more trials per 24 h period, and had higher success rates with less daily and weekly variability than manually trained rats. Moreover, the results show that success rates are positively correlated with the number of dark-cycle trials, suggesting that dark-cycle training has a positive effect on success rates. These results demonstrate that automated training is an effective method for evaluating and training skilled reaching performance of rats, opening up the possibility for new approaches to investigating the role of motor systems in enabling skilled forelimb use and new approaches to investigating rehabilitation following CNS injury. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of different captive bolt lengths and breed influence upon post-stun hind limb and forelimb activity in fed cattle at a commercial slaughter facility.

PubMed

Martin, Miriam S; Kline, Helen C; Wagner, Dana R; Alexander, Lacey R; Edwards-Callaway, Lily N; Grandin, Temple

2018-05-03

The objective of this study was to assess the effects of captive bolt length and breed type on post-stun leg activity in cattle. A total of 2850 Holstein (HOL) and non-Holstein British/Continental bred (NHOL) steers and heifers were observed post-stunning at a large commercial slaughter facility. A pneumatically powered penetrating captive bolt stunner was used with three different bolt lengths: CON, 15.24 cm; MED, 16.51 cm; and LON, 17.78 cm. Hind limb kicking, forelimb activity, take away belt stops, carcass swing and number of knife sticks during exsanguination were recorded for each animal from video recording. Hind limb and forelimb kicks observed ranged from 0 to 25 and 0 to 8, respectively. Analysis of post-stun hind limb and forelimb activity indicated that increasing pneumatically powered penetrating captive bolt length does not decrease post-stun leg activity. There was a higher percentage of cattle experiencing take away belt stops and carcass swing in HOL as compared with NHOL. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

The locus of origin of augmenting and reducing of visual evoked potentials in rat brain.

PubMed

Siegel, J; Gayle, D; Sharma, A; Driscoll, P

1996-07-01

Humans who are high sensation seekers and cats who demonstrate comparable behavioral traits show increasing amplitudes of the early components of the cortical visual evoked potential (VEP) to increasing intensities of light flash; low sensation seekers show VEP reducing. Roman high-avoidance (RHA) and Roman low-avoidance (RLA) rats have behavioral traits comparable to human and cat high and low sensation seekers, respectively. Previously, we showed that RHA and RLA rats are cortical VEP augmenters and reducers, respectively. The goal of this study was to determine if augmenting-reducing is in fact a property of the visual cortex or if it originates at the lateral geniculate nucleus and is merely reflected in recordings from the cortex. EPs to five flash intensities were recorded from the visual cortex and dorsal lateral geniculate of RHA and RLA rats. As in the previous study, the slope of the first cortical component as a function of flash intensity was greater in the RHA than in the RLA rats. The amplitude of the geniculate component that has a latency shorter than the first cortical component was no different in the two lines of rats. The finding from the cortex confirms the earlier finding of augmenting and reducing in RHA and RLA rats, respectively. The major new finding is that the augmenting-reducing difference recorded at the cortex does not occur at the thalamus, indicating that it is truly a cortical phenomenon.

Early growth hormone (GH) treatment promotes relevant motor functional improvement after severe frontal cortex lesion in adult rats.

PubMed

Heredia, Margarita; Fuente, A; Criado, J; Yajeya, J; Devesa, J; Riolobos, A S

2013-06-15

A number of studies, in animals and humans, describe the positive effects of the growth hormone (GH) treatment combined with rehabilitation on brain reparation after brain injury. We examined the effect of GH treatment and rehabilitation in adult rats with severe frontal motor cortex ablation. Thirty-five male rats were trained in the paw-reaching-for-food task and the preferred forelimb was recorded. Under anesthesia, the motor cortex contralateral to the preferred forelimb was aspirated or sham-operated. Animals were then treated with GH (0.15 mg/kg/day, s.c) or vehicle during 5 days, commencing immediately or 6 days post-lesion. Rehabilitation was applied at short- and long-term after GH treatment. Behavioral data were analized by ANOVA following Bonferroni post hoc test. After sacrifice, immunohistochemical detection of glial fibrillary acid protein (GFAP) and nestin were undertaken in the brain of all groups. Animal group treated with GH immediately after the lesion, but not any other group, showed a significant improvement of the motor impairment induced by the motor lesion, and their performances in the motor test were no different from sham-operated controls. GFAP immunolabeling and nestin immunoreactivity were observed in the perilesional area in all injured animals; nestin immunoreactivity was higher in GH-treated injured rats (mainly in animals GH-treated 6 days post-lesion). GFAP immunoreactivity was similar among injured rats. Interestingly, nestin re-expression was detected in the contralateral undamaged motor cortex only in GH-treated injured rats, being higher in animals GH-treated immediately after the lesion than in animals GH-treated 6 days post-lesion. Early GH treatment induces significant recovery of the motor impairment produced by frontal cortical ablation. GH effects include increased neurogenesis for reparation (perilesional area) and for increased brain plasticity (contralateral motor area). Copyright © 2013 Elsevier B.V. All rights

Extract of Adenanthera pavonina L. seed reduces development of diabetic nephropathy in streptozotocin-induced diabetic rats

PubMed Central

Pandhare, Ramdas; Sangameswaran, Balakrishnan

2012-01-01

Objective: The aim of the present study was to investigate the renal protective effect of Adenanthera pavonina (A. pavonina) seed aqueous extract (APSAE), in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: The renal protective effect of A. pavonina seed aqueous extract (APSAE) was studied in STZ-induced diabetic rats. APSAE (50, 100 and 200 mg/kg per day) was given daily to diabetic rats for 13 weeks. Blood glucose, serum parameters such as albumin, creatinine, total protein, urea, lipid profile, glycated haemoglobin (HbA1c), and urine parameters such as urine protein and albumin were examined. Kidney histopathology was also done. Results: After 13 weeks of treatment, in STZ-induced diabetic rats, severe hyperglycemia was developed, with marked increase in proteinuria and albuminuria. However, APSAE treatment significantly reduced proteinuria, albuminuria, lipid levels, and HbA1c deposition in diabetic rats. Conclusion: These results suggested that APSAE has reduced development of diabetic nephropathy in streptozotocin-induced diabetic rats and could have beneficial effect in reducing the progression of diabetic nephropathy. PMID:25050253

A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia.

PubMed

Pannérec, Alice; Springer, Margherita; Migliavacca, Eugenia; Ireland, Alex; Piasecki, Mathew; Karaz, Sonia; Jacot, Guillaume; Métairon, Sylviane; Danenberg, Esther; Raymond, Frédéric; Descombes, Patrick; McPhee, Jamie S; Feige, Jerome N

2016-04-01

Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process.

Reorganization of Motor Cortex by Vagus Nerve Stimulation Requires Cholinergic Innervation.

PubMed

Hulsey, Daniel R; Hays, Seth A; Khodaparast, Navid; Ruiz, Andrea; Das, Priyanka; Rennaker, Robert L; Kilgard, Michael P

2016-01-01

Vagus nerve stimulation (VNS) paired with forelimb training drives robust, specific reorganization of movement representations in the motor cortex. The mechanisms that underlie VNS-dependent enhancement of map plasticity are largely unknown. The cholinergic nucleus basalis (NB) is a critical substrate in cortical plasticity, and several studies suggest that VNS activates cholinergic circuitry. We examined whether the NB is required for VNS-dependent enhancement of map plasticity in the motor cortex. Rats were trained to perform a lever pressing task and then received injections of the immunotoxin 192-IgG-saporin to selectively lesion cholinergic neurons of the NB. After lesion, rats underwent five days of motor training during which VNS was paired with successful trials. At the conclusion of behavioral training, intracortical microstimulation was used to document movement representations in motor cortex. VNS paired with forelimb training resulted in a substantial increase in the representation of proximal forelimb in rats with an intact NB compared to untrained controls. NB lesions prevent this VNS-dependent increase in proximal forelimb area and result in representations similar to untrained controls. Motor performance was similar between groups, suggesting that differences in forelimb function cannot account for the difference in proximal forelimb representation. Together, these findings indicate that the NB is required for VNS-dependent enhancement of plasticity in the motor cortex and may provide insight into the mechanisms that underlie the benefits of VNS therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Bat Accelerated Regions Identify a Bat Forelimb Specific Enhancer in the HoxD Locus

PubMed Central

Mason, Mandy K.; VanderMeer, Julia E.; Zhao, Jingjing; Eckalbar, Walter L.; Logan, Malcolm; Illing, Nicola; Pollard, Katherine S.; Ahituv, Nadav

2016-01-01

The molecular events leading to the development of the bat wing remain largely unknown, and are thought to be caused, in part, by changes in gene expression during limb development. These expression changes could be instigated by variations in gene regulatory enhancers. Here, we used a comparative genomics approach to identify regions that evolved rapidly in the bat ancestor, but are highly conserved in other vertebrates. We discovered 166 bat accelerated regions (BARs) that overlap H3K27ac and p300 ChIP-seq peaks in developing mouse limbs. Using a mouse enhancer assay, we show that five Myotis lucifugus BARs drive gene expression in the developing mouse limb, with the majority showing differential enhancer activity compared to the mouse orthologous BAR sequences. These include BAR116, which is located telomeric to the HoxD cluster and had robust forelimb expression for the M. lucifugus sequence and no activity for the mouse sequence at embryonic day 12.5. Developing limb expression analysis of Hoxd10-Hoxd13 in Miniopterus natalensis bats showed a high-forelimb weak-hindlimb expression for Hoxd10-Hoxd11, similar to the expression trend observed for M. lucifugus BAR116 in mice, suggesting that it could be involved in the regulation of the bat HoxD complex. Combined, our results highlight novel regulatory regions that could be instrumental for the morphological differences leading to the development of the bat wing. PMID:27019019

Systemic propranolol acts centrally to reduce conditioned fear in rats without impairing extinction.

PubMed

Rodriguez-Romaguera, Jose; Sotres-Bayon, Francisco; Mueller, Devin; Quirk, Gregory J

2009-05-15

Previous work has implicated noradrenergic beta-receptors in the consolidation and reconsolidation of conditioned fear. Less is known, however, about their role in fear expression and extinction. The beta-receptor blocker propranolol has been used clinically to reduce anxiety. With an auditory fear conditioning task in rats, we assessed the effects of systemic propranolol on the expression and extinction of two measures of conditioned fear: freezing and suppression of bar-pressing. One day after receiving auditory fear conditioning, rats were injected with saline, propranolol, or peripheral beta-receptor blocker sotalol (both 10 mg/kg, IP). Twenty minutes after injection, rats were given either 6 or 12 extinction trials and were tested for extinction retention the following day. The effect of propranolol on the firing rate of neurons in prelimbic (PL) prefrontal cortex was also assessed. Propranolol reduced freezing by more than 50%, an effect that was evident from the first extinction trial. Suppression was also significantly reduced. Despite this, propranolol had no effect on the acquisition or retention of extinction. Unlike propranolol, sotalol did not affect fear expression, although both drugs significantly reduced heart rate. This suggests that propranolol acts centrally to reduce fear. Consistent with this, propranolol reduced the firing rate of PL neurons. Propranolol reduced the expression of conditioned fear, without interfering with extinction learning. Reduced fear with intact extinction suggests a possible use for propranolol in reducing anxiety during extinction-based exposure therapies, without interfering with long-term clinical response.

Morphine reduces social cohesion in rats.

PubMed

Panksepp, J; Najam, N; Soares, F

1979-08-01

The effect of low (1 mg/kg) doses of morphine on maintenance of physical proximity were evaluated in paired rats observed in a 4 square foot test arena. Morphine reliably reduced proximity maintenance time, and this was apparently not due to sedation, since the effect was unmodified by doses of amphetamine which substantially increased motor activity. The effects of naloxone were inconsistent on this measure of social motivation. In general, the results are consistent with the theoretical proposition that a brain neurochemical change which might lead to social attraction is the activation of endogenous opioid systems. When opiate activity is exogenously sustained, animals exhibit a subnormal tendency to be gregarious.

Memory Retrieval before or after Extinction Reduces Recovery of Fear in Adolescent Rats

ERIC Educational Resources Information Center

Baker, Kathryn D.; McNally, Gavan P.; Richardson, Rick

2013-01-01

Adolescent rats exhibit impaired extinction retention compared to pre-adolescent and adult rats. A single nonreinforced exposure to the conditioned stimulus (CS; a retrieval trial) given shortly before extinction has been shown in some circumstances to reduce the recovery of fear after extinction in adult animals. This study investigated whether a…

Trabecular architecture in the forelimb epiphyses of extant xenarthrans (Mammalia).

PubMed

Amson, Eli; Arnold, Patrick; van Heteren, Anneke H; Canoville, Aurore; Nyakatura, John A

2017-01-01

Bone structure has a crucial role in the functional adaptations that allow vertebrates to conduct their diverse lifestyles. Much has been documented regarding the diaphyseal structure of long bones of tetrapods. However, the architecture of trabecular bone, which is for instance found within the epiphyses of long bones, and which has been shown experimentally to be extremely plastic, has received little attention in the context of lifestyle adaptations (virtually only in primates). We therefore investigated the forelimb epiphyses of extant xenarthrans, the placental mammals including the sloths, anteaters, and armadillos. They are characterised by several lifestyles and degrees of fossoriality involving distinct uses of their forelimb. We used micro computed tomography data to acquire 3D trabecular parameters at regions of interest (ROIs) for all extant genera of xenarthrans (with replicates). Traditional, spherical, and phylogenetically informed statistics (including the consideration of size effects) were used to characterise the functional signal of these parameters. Several trabecular parameters yielded functional distinctions. The main direction of the trabeculae distinguished lifestyle categories for one ROI (the radial trochlea). Among the other trabecular parameters, it is the degree of anisotropy (i.e., a preferential alignment of the trabeculae) that yielded the clearest functional signal. For all ROIs, the armadillos, which represent the fully terrestrial and fossorial category, were found as characterised by a greater degree of anisotropy (i.e., more aligned trabeculae). Furthermore, the trabeculae of the humeral head of the most fossorial armadillos were also found to be more anisotropic than in the less fossorial species. Most parameters were marked by an important intraspecific variability and by a size effect, which could, at least partly, be masking the functional signal. But for some parameters, the degree of anisotropy in particular, a clear

Reduced tumorigenicity of rat glioma cells in the brain when mediated by hygromycin phosphotransferase.

PubMed

Hormigo, A; Friedlander, D R; Brittis, P A; Zagzag, D; Grumet, M

2001-04-01

A variant of C6 glioma cells, C6R-G/H cells express hygromycin phosphotransferase (HPT) and appear to have reduced tumorigenicity in the embryonic brain. The goal of this study was to investigate their reduced capacity to generate tumors in the adult rat brain. Cell lines were implanted into rat brains and tumorigenesis was evaluated. After 3 weeks, all rats with C6 cells showed signs of neurological disease, whereas rats with C6R-G/H cells did not and were either killed then or allowed to survive until later. Histological studies were performed to analyze tumor size, malignancy, angiogenesis, and cell proliferation. Cells isolated from rat brain tumors were analyzed for mutation to HPT by testing their sensitivity to hygromycin. The results indicate that HPT suppresses tumor formation. Three weeks after implantation, only 44% of animals implanted with C6R-G/H cells developed tumors, whereas all animals that received C6 glioma cells developed high-grade gliomas. The C6R-G/H cells filled a 20-fold smaller maximal cross-sectional area than the C6 cells, and exhibited less malignant characteristics, including reduced angiogenesis, mitosis, and cell proliferation. Similar results were obtained in the brain of nude rats, indicating that the immune system did not play a significant role in suppressing tumor growth. The combination of green fluorescent protein (GFP) and HPT was more effective in suppressing tumorigenesis than either plasmid by itself, indicating that the GFP may protect against inactivation of the HPT. Interestingly. hygromycin resistance was lost in tumor cells that were recovered from a group of animals in which C6R-G/H cells formed tumors, confirming the correlation of HPT with reduced tumorigenicity.

Electrical stimulation of motor cortex in the uninjured hemisphere after chronic unilateral injury promotes recovery of skilled locomotion through ipsilateral control.

PubMed

Carmel, Jason B; Kimura, Hiroki; Martin, John H

2014-01-08

Partial injury to the corticospinal tract (CST) causes sprouting of intact axons at their targets, and this sprouting correlates with functional improvement. Electrical stimulation of motor cortex augments sprouting of intact CST axons and promotes functional recovery when applied soon after injury. We hypothesized that electrical stimulation of motor cortex in the intact hemisphere after chronic lesion of the CST in the other hemisphere would restore function through ipsilateral control. To test motor skill, rats were trained and tested to walk on a horizontal ladder with irregularly spaced rungs. Eight weeks after injury, produced by pyramidal tract transection, half of the rats received forelimb motor cortex stimulation of the intact hemisphere. Rats with injury and stimulation had significantly improved forelimb control compared with rats with injury alone and achieved a level of proficiency similar to uninjured rats. To test whether recovery of forelimb function was attributable to ipsilateral control, we selectively inactivated the stimulated motor cortex using the GABA agonist muscimol. The dose of muscimol we used produces strong contralateral but no ipsilateral impairments in naive rats. In rats with injury and stimulation, but not those with injury alone, inactivation caused worsening of forelimb function; the initial deficit was reinstated. These results demonstrate that electrical stimulation can promote recovery of motor function when applied late after injury and that motor control can be exerted from the ipsilateral motor cortex. These results suggest that the uninjured motor cortex could be targeted for brain stimulation in people with large unilateral CST lesions.

Asenapine reduces anxiety-related behaviours in rat conditioned fear stress model.

PubMed

Ohyama, Masayo; Kondo, Maho; Yamauchi, Miki; Imanishi, Taiichiro; Koyama, Tsukasa

2016-12-01

Asenapine is an atypical antipsychotic that is currently available for the treatment of schizophrenia and bipolar I disorder. Although the atypical antipsychotics clozapine and olanzapine are effective for depression and anxiety in schizophrenia, as demonstrated by animal model studies, this has not been clarified for asenapine. Therefore, we compared the effects of asenapine in the conditioned fear stress model with those of clozapine and olanzapine. Rats were individually fear conditioned using electrical foot shock in a Skinner box. Approximately 24 h later, individual animals were returned to the same Skinner box (without electrical shock) and their freezing behaviour was observed for 5 min. Animals were treated with asenapine, clozapine, olanzapine, the 5-HT1A receptor partial agonist buspirone, or the 5-HT2C receptor antagonist SB242084 at 30 min before freezing behaviour assessment. The 5-HT1A receptor antagonist WAY100635 or the 5-HT2C receptor agonist Ro60-0175 was also used concomitantly with asenapine. The effects of asenapine, clozapine, and olanzapine on serotonin release in the rat hippocampus were also measured using in vivo microdialysis. Asenapine reduced freezing behaviour, while neither clozapine nor olanzapine reduced freezing behaviour. Buspirone and SB242084 also reduced freezing behaviour. The effect of asenapine in reducing freezing behaviour was not altered by the concomitant administration of WAY100635 or Ro60-0175. Both asenapine and clozapine, but not olanzapine, increased serotonin release in the rat hippocampus. Asenapine may have superior therapeutic effect on anxiety symptoms than other agents, although the underlying mechanism of its anxiolytic activity remains unknown.

Sildenafil reduces polyuria in rats with lithium-induced NDI.

PubMed

Sanches, Talita Rojas; Volpini, Rildo Aparecido; Massola Shimizu, Maria H; Bragança, Ana Carolina de; Oshiro-Monreal, Fabíola; Seguro, Antonio Carlos; Andrade, Lúcia

2012-01-01

Lithium (Li)-treated patients often develop urinary concentrating defect and polyuria, a condition known as nephrogenic diabetes insipidus (NDI). In a rat model of Li-induced NDI, we studied the effect that sildenafil (Sil), a phosphodiesterase 5 (PDE5) inhibitor, has on renal expression of aquaporin-2 (AQP2), urea transporter UT-A1, Na(+)/H(+) exchanger 3 (NHE3), Na(+)-K(+)-2Cl(-) cotransporter (NKCC2), epithelial Na channel (ENaC; α-, β-, and γ-subunits), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase. We also evaluated cGMP levels in medullary collecting duct cells in suspension. For 4 wk, Wistar rats received Li (40 mmol/kg food) or no treatment (control), some receiving, in weeks 2-4, Sil (200 mg/kg food) or Li and Sil (Li+Sil). In Li+Sil rats, urine output and free water clearance were markedly lower, whereas urinary osmolality was higher, than in Li rats. The cGMP levels in the suspensions of medullary collecting duct cells were markedly higher in the Li+Sil and Sil groups than in the control and Li groups. Semiquantitative immunoblotting revealed the following: in Li+Sil rats, AQP2 expression was partially normalized, whereas that of UT-A1, γ-ENaC, and eNOS was completely normalized; and expression of NKCC2 and NHE3 was significantly higher in Li rats than in controls. Inulin clearance was normal in all groups. Mean arterial pressure and plasma arginine vasopressin did not differ among the groups. Sil completely reversed the Li-induced increase in renal vascular resistance. We conclude that, in experimental Li-induced NDI, Sil reduces polyuria, increases urinary osmolality, and decreases free water clearance via upregulation of renal AQP2 and UT-A1.

Tofacitinib attenuates arthritis manifestations and reduces the pathogenic CD4 T cells in adjuvant arthritis rats.

PubMed

Gertel, Smadar; Mahagna, Hussein; Karmon, Gidi; Watad, Abdulla; Amital, Howard

2017-11-01

Rheumatoid arthritis (RA) is an autoimmune disease characterized by pronounced inflammation and leukocyte infiltration in affected joints. Tofacitinib is new agent, a selective inhibitor of Janus kinase (JAK) signaling pathways mediated by JAK1 and JAK3 and inhibits the key transcription factors STAT1 and STAT3. We investigated the action mechanisms of tofacitinib in rats with adjuvant-induced-arthritis (AIA). AIA-rats were treated orally with tofacitinib or with methotrexate. Arthritis severity and serum C-reactive protein (CRP) levels were evaluated, splenic cells were examined by flow cytometry and cytokines were analyzed by real-time PCR. Tofacitinib markedly reduced the clinical status of treated rats in comparison to control group. Reduced joints inflammation and down-regulated serum CRP levels reflected the clinical manifestations of the treated rats. Tofacitinib down-regulated significantly the frequency of CD4 + IFN-γ + T cells and reduced IL-1β mRNA expression levels in the spleen of the treated rats. These results show that tofacitinib attenuated arthritis severity, modified splenic populations and cytokine imbalance. Copyright © 2017. Published by Elsevier Inc.

Two whisker motor areas in the rat cortex: evidence from thalamocortical connections.

PubMed

Mohammed, Hisham; Jain, Neeraj

2014-02-15

In primates, the motor cortex consists of at least seven different areas, which are involved in movement planning, coordination, initiation, and execution. However, for rats, only the primary motor cortex has been well described. A rostrally located second motor area has been proposed, but its extent, organization, and even definitive existence remain uncertain. Only a rostral forelimb area (RFA) has been definitively described, besides few reports of a rostral hindlimb area. We have previously proposed existence of a second whisker area, which we termed the rostral whisker area (RWA), based on its differential response to intracortical microstimulation compared with the caudal whisker area (CWA) in animals under deep anesthesia (Tandon et al. [2008] Eur J Neurosci 27:228). To establish that RWA is distinct from the caudally contiguous CWA, we determined sources of thalamic inputs to the two proposed whisker areas. Sources of inputs to RFA, caudal forelimb area (CFA), and caudal hindlimb region were determined for comparison. The results show that RWA and CWA can be distinguished based on differences in their thalamic inputs. RWA receives major projections from mediodorsal and ventromedial nuclei, whereas the major projections to CWA are from the ventral anterior, ventrolateral, and posterior nuclei. Moreover, the thalamic nuclei that provide major inputs to RWA are the same as for RFA, and the nuclei projecting to CWA are same as for CFA. The results suggest that rats have a second rostrally located motor area with RWA and RFA as its constituents. Copyright © 2013 Wiley Periodicals, Inc.

Parallel changes in cortical neuron biochemistry and motor function in protein-energy malnourished adult rats.

PubMed

Alaverdashvili, Mariam; Hackett, Mark J; Caine, Sally; Paterson, Phyllis G

2017-04-01

While protein-energy malnutrition in the adult has been reported to induce motor abnormalities and exaggerate motor deficits caused by stroke, it is not known if alterations in mature cortical neurons contribute to the functional deficits. Therefore, we explored if PEM in adult rats provoked changes in the biochemical profile of neurons in the forelimb and hindlimb regions of the motor cortex. Fourier transform infrared spectroscopic imaging using a synchrotron generated light source revealed for the first time altered lipid composition in neurons and subcellular domains (cytosol and nuclei) in a cortical layer and region-specific manner. This change measured by the area under the curve of the δ(CH 2 ) band may indicate modifications in membrane fluidity. These PEM-induced biochemical changes were associated with the development of abnormalities in forelimb use and posture. The findings of this study provide a mechanism by which PEM, if not treated, could exacerbate the course of various neurological disorders and diminish treatment efficacy. Copyright © 2017 Elsevier Inc. All rights reserved.

High-dose estrogen treatment at reperfusion reduces lesion volume and accelerates recovery of sensorimotor function after experimental ischemic stroke.

PubMed

Carpenter, Randall S; Iwuchukwu, Ifeanyi; Hinkson, Cyrus L; Reitz, Sydney; Lee, Wonhee; Kukino, Ayaka; Zhang, An; Pike, Martin M; Ardelt, Agnieszka A

2016-05-15

Estrogens have previously been shown to protect the brain against acute ischemic insults, by potentially augmenting cerebrovascular function after ischemic stroke. The current study hypothesized that treatment with sustained release of high-dose 17β-estradiol (E2) at the time of reperfusion from middle cerebral artery occlusion (MCAO) in rats would attenuate reperfusion injury, augment post-stroke angiogenesis and cerebral blood flow, and attenuate lesion volume. Female Wistar rats underwent ovariectomy, followed two weeks later by transient, two-hour right MCAO (tMCAO) and treatment with E2 (n=13) or placebo (P; n=12) pellets starting at reperfusion. E2 treatment resulted in significantly smaller total lesion volume, smaller lesions within striatal and cortical brain regions, and less atrophy of the ipsilateral hemisphere after six weeks of recovery. E2-treated animals exhibited accelerated recovery of contralateral forelimb sensorimotor function in the cylinder test. Magnetic resonance imaging (MRI) showed that E2 treatment reduced the formation of lesion cysts, decreased lesion volume, and increased lesional cerebral blood flow (CBF). K(trans), a measure of vascular permeability, was increased in the lesions. This finding, which represents lesion neovascularization, was not altered by E2 treatment. Ischemic stroke-related angiogenesis and vessel formation was confirmed with immunolabeling of brain tissue and was not altered with E2 treatment. In summary, E2 treatment administered immediately following reperfusion significantly reduced lesion size, cyst formation, and brain atrophy while improving lesional CBF and accelerating recovery of functional deficits in a rat model of ischemic stroke. Copyright © 2016 Elsevier B.V. All rights reserved.

Extraction of motor activity from the cervical spinal cord of behaving rats

NASA Astrophysics Data System (ADS)

Prasad, Abhishek; Sahin, Mesut

2006-12-01

Injury at the cervical region of the spinal cord results in the loss of the skeletal muscle control from below the shoulders and hence causes quadriplegia. The brain-computer interface technique is one way of generating a substitute for the lost command signals in these severely paralyzed individuals using the neural signals from the brain. In this study, we are investigating the feasibility of an alternative method where the volitional signals are extracted from the cervical spinal cord above the point of injury. A microelectrode array assembly was implanted chronically at the C5-C6 level of the spinal cord in rats. Neural recordings were made during the face cleaning behavior with forelimbs as this task involves cyclic forelimb movements and does not require any training. The correlation between the volitional motor signals and the elbow movements was studied. Linear regression technique was used to reconstruct the arm movement from the rectified-integrated version of the principal neural components. The results of this study demonstrate the feasibility of extracting the motor signals from the cervical spinal cord and using them for reconstruction of the elbow movements.

Slow Breathing Can Be Operantly Conditioned in the Rat and May Reduce Sensitivity to Experimental Stressors

PubMed Central

Noble, Donald J.; Goolsby, William N.; Garraway, Sandra M.; Martin, Karmarcha K.; Hochman, Shawn

2017-01-01

In humans, exercises involving slowed respiratory rate (SRR) counter autonomic sympathetic bias and reduce responses to stressors, including in individuals with various degrees of autonomic dysfunction. In the rat, we examined whether operant conditioning could lead to reductions in respiratory rate (RR) and performed preliminary studies to assess whether conditioned SRR was sufficient to decrease physiological and behavioral responsiveness to stressors. RR was continuously monitored during 20 2-h sessions using whole body plethysmography. SRR conditioned, but not yoked control rats, were able to turn off aversive visual stimulation (intermittent bright light) by slowing their breathing below a preset target of 80 breaths/min. SRR conditioned rats greatly increased the incidence of breaths below the target RR over training, with average resting RR decreasing from 92 to 81 breaths/min. These effects were significant as a group and vs. yoked controls. Preliminary studies in a subset of conditioned rats revealed behavioral changes suggestive of reduced reactivity to stressful and nociceptive stimuli. In these same rats, intermittent sessions without visual reinforcement and a post-training priming stressor (acute restraint) demonstrated that conditioned rats retained reduced RR vs. controls in the absence of conditioning. In conclusion, we present the first successful attempt to operantly condition reduced RR in an animal model. Although further studies are needed to clarify the physio-behavioral concomitants of slowed breathing, the developed model may aid subsequent neurophysiological inquiries on the role of slow breathing in stress reduction. PMID:29163199

Acute and constitutive increases in central serotonin levels reduce social play behaviour in peri-adolescent rats

PubMed Central

Schiepers, Olga J. G.; Schoffelmeer, Anton N. M.; Cuppen, Edwin; Vanderschuren, Louk J. M. J.

2007-01-01

Rationale Serotonin is an important modulator of social behaviour. Individual differences in serotonergic signalling are considered to be a marker of personality that is stable throughout lifetime. While a large body of evidence indicates that central serotonin levels are inversely related to aggression and sexual behaviour in adult rats, the relationship between serotonin and social behaviour during peri-adolescence has hardly been explored. Objective To study the effect of acute and constitutive increases in serotonin neurotransmission on social behaviour in peri-adolescent rats. Materials and methods Social behaviour in peri-adolesent rats (28–35 days old) was studied after genetic ablation of the serotonin transporter, causing constitutively increased extra-neuronal serotonin levels, and after acute treatment with the serotonin reuptake inhibitor fluoxetine or the serotonin releasing agent 3,4-methylenedioxymethamphetamine (MDMA). A distinction was made between social play behaviour that mainly occurs during peri-adolescence, and non-playful social interactions that are abundant during the entire lifespan of rats. Results In serotonin transporter knockout rats, social play behaviour was markedly reduced, while non-playful aspects of social interaction were unaffected. Acute treatment with fluoxetine or MDMA dose-dependently inhibited social play behaviour. MDMA also suppressed non-playful social interaction but at higher doses than those required to reduce social play. Fluoxetine did not affect non-playful social interaction. Conclusions These data show that both acute and constitutive increases in serotonergic neurotransmission reduce social play behaviour in peri-adolescent rats. Together with our previous findings of reduced aggressive and sexual behaviour in adult serotonin transporter knockout rats, these data support the notion that serotonin modulates social behaviour in a trait-like manner. PMID:17661017

Chronic overexpression of angiotensin-(1-7) in rats reduces cardiac reactivity to acute stress and dampens anxious behavior.

PubMed

Moura Santos, Danielle; Ribeiro Marins, Fernanda; Limborço-Filho, Marcelo; de Oliveira, Marilene Luzia; Hamamoto, Daniele; Xavier, Carlos Henrique; Moreira, Fabrício Araújo; Santos, Robson Augusto Souza; Campagnole-Santos, Maria José; Peliky Fontes, Marco Antonio

2017-03-01

Angiotensin II (Ang II) acts as a pro-stress hormone, while other evidence indicates that angiotensin-(1-7) [Ang-(1-7)] attenuates physiological responses to emotional stress. To further test this hypothesis, in groups of 5-6 rats we evaluated autonomic, cardiovascular and behavioral parameters in male Sprague-Dawley (SD) and transgenic TGR(A1-7)3292 (TG) rats chronically overexpressing Ang-(1-7). Compared to SD rats, TG rats showed reduced baseline heart rate (HR; SD 380 ± 16 versus TG 329 ± 9 beats per minute (bpm), mean ± standard error of mean, p < .05) and renal sympathetic discharge (SD 138 ± 4 versus TG 117 ± 5 spikes/second, p < .05). TG rats had an attenuated tachycardic response to acute air-puff stress (ΔHR: SD 51 ± 20 versus TG 1 ± 3 bpm; p < .05), which was reversed by intracerebroventricular injection of the Mas receptor antagonist, A-779 (ΔHR: SD 51 ± 20 versus TG 63 ± 15 bpm). TG rats showed less anxious behavior on the elevated plus maze, as revealed by more entries into open arms (SD 2 ± 2 versus TG 47 ± 5% relative to total entries; p < .05), and more time spent in the open arms (SD 5 ± 4 versus TG 53 ± 9% relative to total time, p < .05). By contrast with SD rats, diazepam (1.5 mg/kg, intraperitoneally) did not further reduce anxious behavior in TG rats, indicating a ceiling anxiolytic effect of Ang-(1-7) overexpression. Ang-(1-7) concentrations in hypothalamus and plasma, measured by mass spectrometry were two- and three-fold greater, respectively, in TG rats than in SD rats. Hence, increased endogenous Ang-(1-7) levels in TG rats diminishes renal sympathetic outflow and attenuates cardiac reactivity to emotional stress, which may be via central Mas receptors, and reduces anxious behavior. Lay summaryWe used a genetically modified rat model that produces above normal amounts of a peptide hormone called angiotensin-(1-7) to test whether this peptide can

Ozonized sunflower oil reduces oxidative damage induced by indomethacin in rat gastric mucosa.

PubMed

Zamora, Z; González, R; Guanche, D; Merino, N; Menéndez, S; Hernández, F; Alonso, Y; Schulz, S

2008-01-01

This study was carried out in order to investigate the potential cytoprotective effects of ozonized sunflower oil (OSO) in the damage of rat gastric mucosa induced by indomethacin and also to elucidate the role of reactive oxygen species (ROS), lipid peroxidation and some constituents of antioxidant defense such as superoxide dismutase (SOD) and catalase (CAT) in these effects. The gastric damage was induced by indomethacin (20 mg/kg) as solution in 0.5% sodium bicarbonate and given intragastrically. Three hours later OSO (4, 12 and 24 mg/kg) and cimetidine 25 mg/kg were administered also by oral route. Four hours thereafter the rats were killed and the stomachs were removed for biochemical analysis and histological study. The gastric ulcer index was reduced by OSO and cimetidine. OSO also reduced TBARS concentration, but it increased SOD activity in gastric mucosa homogenates. In contrast, CAT activity was not significantly modified the treatment. Histological study confirmed the cytoprotective effects of OSO in rat gastric mucosa damaged by indomethacin. It was concluded that cytoprotective effects of OSO in rat gastric mucosa are mediated at least partially by upregulation of the antioxidant system and mainly SOD.

Dietary D-psicose reduced visceral fat mass in high-fat diet-induced obese rats.

PubMed

Chung, Young-Mee; Hyun Lee, Joo; Youl Kim, Deuk; Hwang, Se-Hee; Hong, Young-Ho; Kim, Seong-Bo; Jin Lee, Song; Hye Park, Chi

2012-02-01

D-Psicose, a C-3 epimer of D-fructose, has shown promise in reducing body fat accumulation in normal rats and plasma glucose level in genetic diabetic mice. Effects of D-psicose on diet-induced obesity are not clearly elucidated, and we investigated food intake, body weight, and fat accumulation in rats fed high-fat (HF) diet. Sprague-Dawley rats became obese by feeding HF diet for 4 wk, and were assigned either to normal or HF diet supplemented with or without D-psicose, sucrose, or erythritol for 8 wk. Changing HF to normal diet gained less body weight and adipose tissue due to different energy intake. D-psicose-fed rats exhibited lower weight gain, food efficiency ratio, and fat accumulation than erythritol- and sucrose-fed rats. This effect was more prominent in D-psicose-fed rats with normal diet than with HF diet, suggesting combination of psicose and calorie restriction further reduced obesity. There was no difference in serum cholesterol/high-density lipoprotein (HDL)-C and low-density lipoprotein (LDL)-C/HDL-C ratios between D-psicose group and other groups. Liver weight in 5% psicose group with normal diet was higher than in other groups, but histopathological examination did not reveal any psicose-related change. D-Psicose inhibited the differentiation of mesenchymal stem cell (MSC) to adipose tissue in a concentration-dependent manner. These results demonstrate that D-psicose produces a marked decrease, greater than erythritol, in weight gain and visceral fat in an established obesity model by inhibiting MSC differentiation to adipocyte. Thus, D-psicose can be useful in preventing and reducing obesity as a sugar substitute and food ingredient. We can develop D-psicose as a sugar substitute and food ingredient since it can prevent obesity in normal people, but also suppress adiposity as a sugar substitute or food ingredients with antiobesity effect in obese people. D-psicose can be unique functional sweetener because of its function of reducing visceral

Preoperative carbohydrate-rich beverage reduces hypothermia during general anesthesia in rats.

PubMed

Yatabe, Tomoaki; Kawano, Takashi; Yamashita, Koichi; Yokoyama, Masataka

2011-08-01

Intraoperative hypothermia is associated with several unfavorable events; therefore, it is important to prevent the development of hypothermia. Amino acid consumption and/or infusion have been reported to prevent hypothermia. We hypothesized that preoperative carbohydrate-rich beverage (Arginaid Water™) loading can reduce intraoperative hypothermia in rats under general anesthesia. We divided 18 rats into 3 groups (group A, 8 mL/kg of saline; group B, 8 mL/kg of a carbohydrate-rich beverage; and group C, 21 mL/kg of the carbohydrate-rich beverage). The rats were administered each beverage at the above mentioned doses via an oral gastric tube 30 min before the induction of anesthesia. During the 2-h general anesthesia, rectal temperature was measured at 20-min intervals. Serum ketone body concentration was measured at 0 and 120 min. The baseline temperature was not significantly different among the groups. At the end of the experiment, group A showed a significantly greater decrease in temperature from the baseline (5.4 ± 0.8°C) than group B (3.9 ± 0.7°C, P = 0.01) and group C (3.8 ± 0.8°C, P = 0.01). The temperatures in groups B and C were not significantly different. There was no significant change in the serum ketone body concentration from the baseline at the end of the experiment in group A. However, the serum ketone body concentrations in group B and group C were significantly decreased from the baseline. Preoperative carbohydrate loading reduces hypothermia in rats under general anesthesia.

Pravastatin reduces steroid-induced osteonecrosis of the femoral head in SHRSP rats

PubMed Central

2012-01-01

Background and purpose Although the definite cause of steroid-induced osteonecrosis of the femoral head (ONFH) is unknown, peripheral circulatory failure, lipid metabolism disturbance, and increased oxidative stress are considered to be possible causes. We investigated whether pravastatin as a statin treatment reduces (1) the incidence of ONFH, (2) the adipocyte area, and (3) bone marrow changes in the femoral head. Methods We divided up 81 thirteen-week-old spontaneously hypertensive stroke-prone (SHRSP)/Izm male rats into 4 groups: a control group (group C), a group given pravastatin (group P), a group given steroid (group S), and a group given both pravastatin and steroid (Group PS). The steroid was administered at 15 weeks of age. Pravastatin, as a statin, was administered in the drinking water for 4 weeks. The rats were killed when 17 weeks old. Osteonecrosis was diagnosed based on histopathological examination. Oxidative stress was assessed from immunostaining. Results The incidence of histological osteonecrosis was lower in the groups given pravastatin. The percentage of adipocyte area in the bone marrow was lower in the PS group than in the S group. Immunohistochemical staining for oxidative stress showed that staining was less in the PS group than in the S group. Pravastatin had no effect on the blood-derived biochemical findings on lipid metabolism. However, it reduced the incidence of steroid-induced ONFH in these SHRSP rats. We presume that this occurred by reducing oxidative stress and by reducing the percentage of adipocyte area in the femoral heads. Interpretation Our data suggest that pravastatin may be effective in reducing steroid-induced ONFH. PMID:22313369

Creatine supplementation reduces sleep need and homeostatic sleep pressure in rats.

PubMed

Dworak, Markus; Kim, Tae; Mccarley, Robert W; Basheer, Radhika

2017-06-01

Sleep has been postulated to promote brain energy restoration. It is as yet unknown if increasing the energy availability within the brain reduces sleep need. The guanidine amino acid creatine (Cr) is a well-known energy booster in cellular energy homeostasis. Oral Cr-monohydrate supplementation (CS) increases exercise performance and has been shown to have substantial effects on cognitive performance, neuroprotection and circadian rhythms. The effect of CS on cellular high-energy molecules and sleep-wake behaviour is unclear. Here, we examined the sleep-wake behaviour and brain energy metabolism before and after 4-week-long oral administration of CS in the rat. CS decreased total sleep time and non-rapid eye movement (NREM) sleep significantly during the light (inactive) but not during the dark (active) period. NREM sleep and NREM delta activity were decreased significantly in CS rats after 6 h of sleep deprivation. Biochemical analysis of brain energy metabolites showed a tendency to increase in phosphocreatine after CS, while cellular adenosine triphosphate (ATP) level decreased. Microdialysis analysis showed that the sleep deprivation-induced increase in extracellular adenosine was attenuated after CS. These results suggest that CS reduces sleep need and homeostatic sleep pressure in rats, thereby indicating its potential in the treatment of sleep-related disorders. © 2017 European Sleep Research Society.

A Protein Extract from Chicken Reduces Plasma Homocysteine in Rats.

PubMed

Lysne, Vegard; Bjørndal, Bodil; Vik, Rita; Nordrehaug, Jan Erik; Skorve, Jon; Nygård, Ottar; Berge, Rolf K

2015-06-04

The present study aimed to evaluate effects of a water-soluble protein fraction of chicken (CP), with a low methionine/glycine ratio, on plasma homocysteine and metabolites related to homocysteine metabolism. Male Wistar rats were fed either a control diet with 20% w/w casein as the protein source, or an experimental diet where 6, 14 or 20% w/w of the casein was replaced with the same amount of CP for four weeks. Rats fed CP had reduced plasma total homocysteine level and markedly increased levels of the choline pathway metabolites betaine, dimethylglycine, sarcosine, glycine and serine, as well as the transsulfuration pathway metabolites cystathionine and cysteine. Hepatic mRNA level of enzymes involved in homocysteine remethylation, methionine synthase and betaine-homocysteine S-methyltransferase, were unchanged, whereas cystathionine gamma-lyase of the transsulfuration pathway was increased in the CP treated rats. Plasma concentrations of vitamin B2, folate, cobalamin, and the B-6 catabolite pyridoxic acid were increased in the 20% CP-treated rats. In conclusion, the CP diet was associated with lower plasma homocysteine concentration and higher levels of serine, choline oxidation and transsulfuration metabolites compared to a casein diet. The status of related B-vitamins was also affected by CP.

A Protein Extract from Chicken Reduces Plasma Homocysteine in Rats

PubMed Central

Lysne, Vegard; Bjørndal, Bodil; Vik, Rita; Nordrehaug, Jan Erik; Skorve, Jon; Nygård, Ottar; Berge, Rolf K.

2015-01-01

The present study aimed to evaluate effects of a water-soluble protein fraction of chicken (CP), with a low methionine/glycine ratio, on plasma homocysteine and metabolites related to homocysteine metabolism. Male Wistar rats were fed either a control diet with 20% w/w casein as the protein source, or an experimental diet where 6, 14 or 20% w/w of the casein was replaced with the same amount of CP for four weeks. Rats fed CP had reduced plasma total homocysteine level and markedly increased levels of the choline pathway metabolites betaine, dimethylglycine, sarcosine, glycine and serine, as well as the transsulfuration pathway metabolites cystathionine and cysteine. Hepatic mRNA level of enzymes involved in homocysteine remethylation, methionine synthase and betaine-homocysteine S-methyltransferase, were unchanged, whereas cystathionine gamma-lyase of the transsulfuration pathway was increased in the CP treated rats. Plasma concentrations of vitamin B2, folate, cobalamin, and the B-6 catabolite pyridoxic acid were increased in the 20% CP-treated rats. In conclusion, the CP diet was associated with lower plasma homocysteine concentration and higher levels of serine, choline oxidation and transsulfuration metabolites compared to a casein diet. The status of related B-vitamins was also affected by CP. PMID:26053618

Propolis reduces oxidative stress in l-NAME-induced hypertension rats.

PubMed

Selamoglu Talas, Zeliha

2014-03-01

The inhibition in the synthesis or bioavailability of nitric oxide (NO) has an important role in progress of hypertension. The blocking of nitric oxide synthase activity may cause vasoconstriction with the formation of reactive oxygen species (ROS). Propolis is a resinous substance collected by honey bees from various plants. Propolis has biological and pharmacological properties. The aim of this study was to examine the effect of propolis on catalase (CAT) activity, malondialdehyde (MDA) and NO levels in the testis tissues of hypertensive rats by Nω-nitro-l-arginine methyl ester (l-NAME). Rats have received nitric oxide synthase inhibitor (l-NAME, 40 mg kg(-1) , intraperitoneally) for 15 days to produce hypertension and propolis (200 mg kg(-1) , by gavage) during the last 5 days. MDA level in l-NAME-treated group significantly increased compared with control group (P < 0.01). MDA level of l-NAME + propolis-treated rats significantly reduced (P < 0.01) compared with l-NAME-treated group. CAT activity and NO level significantly reduced (P < 0.01) in l-NAME group compared with control group. There were no statistically significant increases in the CAT activity and NO level of the l-NAME + propolis group compared with the l-NAME-treated group (P > 0.01). These results suggest that propolis changes CAT activity, NO and MDA levels in testis of l-NAME-treated animals, and so it may modulate the antioxidant system. Copyright © 2013 John Wiley & Sons, Ltd.

Hindlimb spasticity after unilateral motor cortex lesion in rats is reduced by contralateral nerve root transfer.

PubMed

Zong, Haiyang; Ma, Fenfen; Zhang, Laiyin; Lu, Huiping; Gong, Jingru; Cai, Min; Lin, Haodong; Zhu, Yizhun; Hou, Chunlin

2016-12-01

Lower extremity spasticity is a common sequela among patients with acquired brain injury. The optimum treatment remains controversial. The aim of our study was to test the feasibility and effectiveness of contralateral nerve root transfer in reducing post stroke spasticity of the affected hindlimb muscles in rats. In our study, we for the first time created a novel animal hindlimb spastic hemiplegia model in rats with photothrombotic lesion of unilateral motor cortex and we established a novel surgical procedure in reducing motor cortex lesion-induced hindlimb spastic hemiplegia in rats. Thirty six rats were randomized into three groups. In group A, rats received sham operation. In group B, rats underwent unilateral hindlimb motor cortex lesion. In group C, rats underwent unilateral hindlimb cortex lesion followed by contralateral L4 ventral root transfer to L5 ventral root of the affected side. Footprint analysis, Hoffmann reflex (H-reflex), cholera toxin subunit B (CTB) retrograde tracing of gastrocnemius muscle (GM) motoneurons and immunofluorescent staining of vesicle glutamate transporter 1 (VGLUT1) on CTB-labelled motoneurons were used to assess spasticity of the affected hindlimb. Sixteen weeks postoperatively, toe spread and stride length recovered significantly in group C compared with group B (P<0.001). H max (H-wave maximum amplitude)/M max (M-wave maximum amplitude) ratio of gastrocnemius and plantaris muscles (PMs) significantly reduced in group C (P<0.01). Average VGLUT1 positive boutons per CTB-labelled motoneurons significantly reduced in group C (P<0.001). We demonstrated for the first time that contralateral L4 ventral root transfer to L5 ventral root of the affected side was effective in relieving unilateral motor cortex lesion-induced hindlimb spasticity in rats. Our data indicated that this could be an alternative treatment for unilateral lower extremity spasticity after brain injury. Therefore, contralateral neurotization may exert a potential

Strychnos nux-vomica extract and its ultra-high dilution reduce voluntary ethanol intake in rats.

PubMed

Sukul, N C; Ghosh, S; Sinhababu, S P; Sukul, A

2001-04-01

To see whether Strychnos nux-vomica extract (mother tincture [MT]), its potency Nux 30c, and its principal alkaloid, strychnine, could reduce voluntary ethanol intake in rats. To analyze the solution structure of Nux MT, Nux 30c, 90% ethanol, and ethanol 30c by means of electronic (ES) and nuclear nuclear magnetic resonance (NMR) spectra. Potentially alcoholic rats were first given 20% ethanol and then kept on a two-choice bottle, one with 20% ethanol and another with tap water. These rats were given the following oral treatments for 15 days: group 1, control; group 2, strychnine at 0.36 mg/kg per day; group 3, ethanolic extract of S. nux-vomica seeds (Nux MT) at 3.6 mg/kg per day; and group 4, Nux 30c at 0.05 mL/d per rat. Nux 30c was prepared by successive dilution of Nux MT and 90% ethanol (1:100) and sonication at 20 kHz for 30 seconds in 30 steps. Both Nux MT and Nux 30c significantly reduced ethanol intake and increased water intake in rats. ES of two dilutions of Nux MT and Nux 30c showed intersections at more than one point suggesting existence of molecular complexes. ES of Nux MT in CCl4 showed a red shift when 90% ethanol was added indicating molecular complexation and charge transfer interaction between ethanol and Nux compounds. NMR spectra of Nux MT, 90% ethanol, ethanol 30c, and Nux 30c indicated a change in solution structure of the medium (90% ethanol) of Nux 30c. Nux MT and Nux 30c could reduce ethanol intake in rats. The altered solution structure of Nux 30c is thought to mimic Nux MT and produce ethanol aversion in rats.

Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats

PubMed Central

Zonta, Yohan Ricci; Martinez, Marcelo; Camargo, Isabel Cristina C.; Domeniconi, Raquel F.; Lupi Júnior, Luiz Antonio; Pinheiro, Patricia Fernanda F.; Reiter, Russel J.; Martinez, Francisco Eduardo; Chuffa, Luiz Gustavo A.

2017-01-01

Angiogenesis is a hallmark of ovarian cancer (OC); the ingrowth of blood vessels promotes rapid cell growth and the associated metastasis. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women. OC was chemically induced with a single injection of 7,12-dimethylbenz(a)anthracene (DMBA) under the ovarian bursa. After the rats developed serous papillary OC, half of the animals received intraperitoneal injections of melatonin (200 µg/100 g body weight/day) for 60 days. Melatonin-treated animals showed a significant reduction in OC size and microvessel density. Serum levels of melatonin were higher following therapy, and the expression of its receptor MT1 was significantly increased in OC-bearing rats, regardless of ethanol intake. TGFβ1, a transforming growth factor-beta1, was reduced only after melatonin treatment. Importantly, vascular endothelial growth factor (VEGF) was severely reduced after melatonin therapy in animals given or not given ethanol. Conversely, the levels of VEGF receptor 1 (VEGFR1) was diminished after ethanol consumption, regardless of melatonin therapy, and VEGFR2 was only reduced following melatonin. Hypoxia-inducible factor (HIF)-1α was augmented with ethanol consumption, and, notably, melatonin significantly reduced their levels. Collectively, our results suggest that melatonin attenuates angiogenesis in OC in an animal model of ethanol consumption; this provides a possible complementary therapeutic opportunity for concurrent OC chemotherapy. PMID:28398226

Decreases in bone blood flow and bone material properties in aging Fischer-344 rats

NASA Technical Reports Server (NTRS)

Bloomfield, Susan A.; Hogan, Harry A.; Delp, Michael D.

2002-01-01

The purpose of this study was to quantify precisely aging-induced changes in skeletal perfusion and bone mechanical properties in a small rodent model. Blood flow was measured in conscious juvenile (2 months old), adult (6 months old), and aged (24 months old) male Fischer-344 rats using radiolabeled microspheres. There were no significant differences in bone perfusion rate or vascular resistance between juvenile and adult rats. However, blood flow was lower in aged versus adult rats in the forelimb bones, scapulas, and femurs. To test for functional effects of this decline in blood flow, bone mineral density and mechanical properties were measured in rats from these two age groups. Bone mineral density and cross-sectional moment of inertia in femoral and tibial shafts and the femoral neck were significantly larger in the aged versus adult rats, resulting in increased (+14%-53%) breaking strength and stiffness. However, intrinsic material properties at midshaft of the long bones were 12% to 25% lower in the aged rats. Although these data are consistent with a potential link between decreased perfusion and focal alterations in bone remodeling activity related to clinically relevant bone loss, additional studies are required to establish the mechanisms for this putative relationship.

Lactobacillus paracasei HII01, xylooligosaccharides, and synbiotics reduce gut disturbance in obese rats.

PubMed

Thiennimitr, Parameth; Yasom, Sakawdaurn; Tunapong, Wannipa; Chunchai, Titikorn; Wanchai, Keerati; Pongchaidecha, Anchalee; Lungkaphin, Anusorn; Sirilun, Sasithorn; Chaiyasut, Chaiyavat; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2018-03-20

The beneficial effects of pro-, pre-, and synbiotics on obesity with insulin resistance have been reported previously. However, the strain-specific effect of probiotics and the combination with various types of prebiotic fiber yield controversial outcomes and limit clinical applications. Our previous study demonstrated that the probiotic Lactobacillus paracasei (L. paracasei) HII01, prebiotic xylooligosaccharide (XOS), and synbiotics share similar efficacy in attenuating cardiac mitochondrial dysfunction in obese-insulin resistant rats. Nonetheless, the roles of HII01 and XOS on gut dysbiosis and gut inflammation under obese-insulin resistant conditions have not yet, to our knowledge, been investigated. Our hypothesis was that pro-, pre-, and synbiotics improve the metabolic parameters in obese-insulin resistant rats by reducing gut dysbiosis and gut inflammation. Male Wistar rats were fed with either a normal or high-fat diet that contained 19.77% and 59.28% energy from fat, respectively, for 12 wk. Then, the high-fat diet rats were fed daily with a 10 8 colony forming unit of the probiotic HII01, 10% prebiotic XOS, and synbiotics for 12 wk. The metabolic parameters, serum lipopolysaccharide levels, fecal Firmicutes/Bacteroidetes ratios, levels of Enterobacteriaceae, Bifidobacteria, and gut proinflammatory cytokine gene expression were quantified. The consumption of probiotic L. paracasei HII01, prebiotic XOS, and synbiotics for 12 wk led to a decrease in metabolic endotoxemia, gut dysbiosis (a reduction in the Firmicutes/Bacteroidetes ratio and Enterobacteriaceae), and gut inflammation in obese-insulin resistant rats. Pro-, pre-, and synbiotics reduced gut dysbiosis and gut inflammation, which lead to improvements in metabolic dysfunction in obese-insulin resistant rats. Copyright © 2018 Elsevier Inc. All rights reserved.

Rifaximin, but not growth factor 1, reduces brain edema in cirrhotic rats

PubMed Central

Òdena, Gemma; Miquel, Mireia; Serafín, Anna; Galan, Amparo; Morillas, Rosa; Planas, Ramon; Bartolí, Ramon

2012-01-01

AIM: To compare rifaximin and insulin-like growth factor (IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion. METHODS: Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups: Cirrhosis; Cirrhosis + IGF-1; Cirrhosis + rifaximin; Controls; Controls + IGF-1; and Controls + rifaximin. An oral glutamine-challenge test was performed, and plasma and cerebral ammonia, glucose, bilirubin, transaminases, endotoxemia, brain water content and ileocecal cultures were measured and liver histology was assessed. RESULTS: Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups, and improved some liver function parameters (bilirubin, alanine aminotransferase and aspartate aminotransferase). These effects were associated with a significant reduction in cerebral water content. Blood and cerebral ammonia levels, and area-under-the-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals. By contrast, IGF-1 administration failed to improve most alterations observed in cirrhosis. CONCLUSION: By reducing gut bacterial overgrowth, only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema, alterations associated with hepatic encephalopathy. PMID:22563196

Oral methylphenidate alleviates the fine motor dysfunction caused by chronic postnatal manganese exposure in adult rats.

PubMed

Beaudin, Stéphane A; Strupp, Barbara J; Lasley, Stephen M; Fornal, Casimir A; Mandal, Shyamali; Smith, Donald R

2015-04-01

Developmental manganese (Mn) exposure is associated with motor dysfunction in children and animal models, but little is known about the underlying neurochemical mechanisms or the potential for amelioration by pharmacotherapy. We investigated whether methylphenidate (MPH) alleviates fine motor dysfunction due to chronic postnatal Mn exposure, and whether Mn exposure impairs brain extracellular dopamine (DA) and norepinephrine (NE) in the prefrontal cortex (PFC) and striatum in adult animals. Rats were orally exposed to 0 or 50 mg Mn/kg/day from postnatal day 1 until the end of the study (PND 145). The staircase test was used to assess skilled forelimb function. Oral MPH (2.5 mg/kg/day) was administered daily 1 h before staircase testing for 16 days. DA and NE levels were measured by dual probe microdialysis. Results show that Mn exposure impaired reaching and grasping skills and the evoked release of DA and NE in the PFC and striatum of adult rats. Importantly, oral MPH treatment fully alleviated the fine motor deficits in the Mn-exposed animals, but did not affect forelimb skills of control rats not exposed to Mn. These results suggest that catecholaminergic hypofunctioning in the PFC and striatum may underlie the Mn-induced fine motor dysfunction, and that oral MPH pharmacotherapy is an effective treatment approach for alleviating this dysfunction in adult animals. The therapeutic potential of MPH for the treatment of motor dysfunction in Mn-exposed children and adults appears promising pending further characterization of MPH efficacy in other functional areas (eg, attention) believed to be affected by developmental Mn exposure. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Exercise reduces inflammation and cell proliferation in rat colon carcinogenesis.

PubMed

Demarzo, Marcelo Marcos Piva; Martins, Lisandra Vanessa; Fernandes, Cleverson Rodrigues; Herrero, Fábio Augusto; Perez, Sérgio Eduardo de Andrade; Turatti, Aline; Garcia, Sérgio Britto

2008-04-01

There is evidence that the risk of colon cancer is reduced by appropriate levels of physical exercise. Nevertheless, the mechanisms involved in this protective effect of exercise remain largely unknown. Inflammation is emerging as a unifying link between a range of environment exposures and neoplastic risk. The carcinogen dimethyl-hydrazine (DMH) induces an increase in epithelial cell proliferation and in the expression of the inflammation-related enzyme cyclooxigenase-2 (COX-2) in the colon of rats. Our aim was to verify whether these events could be attenuated by exercise. Four groups of eight Wistar rats were used in the experiment. The groups G1 and G3 were sedentary (controls), and the groups G2 and G4 were submitted to 8 wk of swimming training, 5 d.wk. The groups G3 and G4 were given subcutaneous injections of DMH immediately after the exercise protocols. Fifteen days after the neoplasic induction, the rats were sacrificed and the colon was processed for histological examination and immunohistochemistry staining of proliferating cell nuclear antigen (PCNA) and COX-2. We found a significant increase in the PCNA-labeling index in both DMH-treated groups of rats. However, this increase was significantly attenuated in the training group G4 (P < 0.01). Similar results were observed in relation to the COX-2 expression. From our findings, we conclude that exercise training exerts remarkable antiproliferative and antiinflammatory effects in the rat colonic mucosa, suggesting that this may be an important mechanism to explain how exercise protects against colonic cancer.

Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats.

PubMed

Úbeda, María; Lario, Margaret; Muñoz, Leticia; Borrero, María-José; Rodríguez-Serrano, Macarena; Sánchez-Díaz, Ana-María; Del Campo, Rosa; Lledó, Lourdes; Pastor, Óscar; García-Bermejo, Laura; Díaz, David; Álvarez-Mon, Melchor; Albillos, Agustín

2016-05-01

In advanced cirrhosis, gut bacterial translocation is the consequence of intestinal barrier disruption and leads to bacterial infection. Bile acid abnormalities in cirrhosis could play a role in the integrity of the intestinal barrier and the control of microbiota, mainly through the farnesoid X receptor. We investigated the long-term effects of the farnesoid X receptor agonist, obeticholic acid, on gut bacterial translocation, intestinal microbiota composition, barrier integrity and inflammation in rats with CCl4-induced cirrhosis with ascites. Cirrhotic rats received a 2-week course of obeticholic acid or vehicle starting once ascites developed. We then determined: bacterial translocation by mesenteric lymph node culture, ileum expression of antimicrobial peptides and tight junction proteins by qPCR, fecal albumin loss, enteric bacterial load and microbiota composition by qPCR and pyrosequencing of ileum mucosa-attached contents, and intestinal inflammation by cytometry of the inflammatory infiltrate. Obeticholic acid reduced bacterial translocation from 78.3% to 33.3% (p<0.01) and upregulated the expression of the farnesoid X receptor-associated gene small heterodimer partner. Treatment improved ileum expression of antimicrobial peptides, angiogenin-1 and alpha-5-defensin, tight junction proteins zonulin-1 and occludin, and reduced fecal albumin loss and liver fibrosis. Enteric bacterial load normalized, and the distinctive mucosal microbiota of cirrhosis was reduced. Gut immune cell infiltration was reduced and inflammatory cytokine and Toll-like receptor 4 expression normalized. In ascitic cirrhotic rats, obeticholic acid reduces gut bacterial translocation via several complementary mechanisms at the intestinal level. This agent could be used as an alternative to antibiotics to prevent bacterial infection in cirrhosis. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Lifelong Aerobic Exercise Reduces the Stress Response in Rats.

PubMed

Pietrelli, A; Di Nardo, M; Masucci, A; Brusco, A; Basso, N; Matkovic, L

2018-04-15

The aim of this study was to analyze the effects of lifelong aerobic exercise (AE) on the adaptive response of the stress system in rats. It is well known that hypothalamic-pituitary-adrenal axis (HPA) activity differs when triggered by voluntary or forced exercise models. Male Wistar rats belonging to exercise (E) or control (C) groups were subjected to chronic AE, and two cutoff points were established at 8 (middle age) and 18 months (old age). Behavioral, biochemical and histopathological studies were performed on the main components/targets of the stress system. AE increased adrenal sensitivity (AS), brain corticosterone (CORT) and corticotropin-releasing factor (CRF), but had no effect on the thymus, adrenal glands (AGs) weight or plasma CORT. In addition, AE exerted no effect on the sympathetic tone, but significantly reduced anxiety-related behavior and emotionality. Aging decreased AS and deregulated neuroendocrine feedback, leading to an anxiogenic state which was mitigated by AE. Histopathological and morphometric analysis of AGs showed no alterations in middle-aged rats but adrenal vacuolization in approximately 20% old rats. In conclusion, lifelong AE did not produce adverse effects related to a chronic stress state. On the contrary, while AE upregulated some components of the HPA axis, it generated an adaptive response to cumulative changes, possibly through different compensatory and/or super compensatory mechanisms, modulated by age. The long-term practice of AE had a strong positive impact on stress resilience so that it could be recommended as a complementary therapy in stress and depression disease. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Noribogaine reduces nicotine self-administration in rats

PubMed Central

Chang, Qing; Hanania, Taleen; Mash, Deborah C

2015-01-01

Noribogaine, a polypharmacological drug with activities at opioid receptors, ionotropic nicotinic receptors, and serotonin reuptake transporters, has been investigated for treatment of substance abuse-related disorders. Smoking cessation has major benefits for both individuals and society, therefore the aim of this study was to evaluate the potential of noribogaine for use as a treatment for nicotine dependence. Adult male Sprague-Dawley rats were trained to self-administer nicotine intravenous. After initial food pellet training, followed by 26 sessions of nicotine self-administration training, the rats were administered noribogaine (12.5, 25 or 50 mg/kg orally), noribogaine vehicle, varenicline or saline using a within-subject design with a Latin square test schedule. Noribogaine dose-dependently decreased nicotine self-administration by up to 64% of saline-treated rats’ levels and was equi-effective to 1.7 mg/kg intraperitoneal varenicline. Noribogaine was less efficient at reducing food pellets self-administration than at nicotine self-administration, inhibiting the nondrug reinforcing effects of palatable pellets by 23% at the highest dose. These results suggest that noribogaine dose-dependently attenuates drug-taking behavior for nicotine, attenuates the reinforcing effects of nicotine and is comparable to varenicline power in that regard. The findings from the present study hold promise for a new therapy to aid smoking cessation. PMID:25995321

Halofuginone reduces the occurrence of renal fibrosis in 5/6 nephrectomized rats.

PubMed

Benchetrit, Sydney; Yarkoni, Shy; Rathaus, Mauro; Pines, Marc; Rashid, Gloria; Bernheim, Joelle; Bernheim, Jacques

2007-01-01

Halofuginone is a novel antifibrotic agent that can reverse the fibrotic process by specific inhibition of collagen type I synthesis. To evaluate the effect of Halo on the development of glomerulosclerosis and interstitial fibrosis in the 5/6 nephrectomy rat model Male Wistar rats were assigned to undergo 5/6 NX or sham operation, and then divided into three groups: 5/6 NX rats (NX-Halo and NX-Control) and sham. Systolic blood pressure, proteinuria and body weight were determined every 2 weeks. At sacrifice (10 weeks) creatinine clearance was evaluated and remnant kidneys removed for histologic examination, sirius red staining and in situ hybridization Systolic blood pressure increased progressively in both 5/6 NX groups. Halo slowed the increase in proteinuria in 5/6 NX rats. As expected, creatinine clearance was lower in 5/6 NX groups when compared to sham rats. Creatinine clearance was significantly higher in the NX-Halo group at the end of the study period. Histologic examination by light microscopy showed significantly less severe interstitial fibrosis and glomerulosclerosis in Halo-treated rats. The increase in collagen alpha1 (I) gene expression and collagen staining after nephrectomy was almost completely abolished by Halo. Halofuginone reduced proteinuria as well as the severity of interstitial fibrosis and glomerulosclerosis in 5/6 NX rats. The renal beneficial effect of Halo was also demonstrated by the blunted decrease in creatinine clearance observed in the treated animals.

Efficacy of FDA-Approved Hemostatic Drugs to Improve Survival and Reduce Bleeding in Rat Models of Uncontrolled Hemorrhage

DTIC Science & Technology

2005-07-01

drugs are used to reduce surgical bleeding. This series of studies tested whether these drugs (aprotinin, desmopressin, tranexamic acid , e- aminocaproic ...desmopressin, tranexamic acid , 8- aminocaproic acid ) could reduce bleeding due to traumatic injuries in two models of uncontrolled hemorrhage in rats... acid ) could reduce bleeding due to traumatic injuries in two models of uncontrolled hemorrhage in rats. In the first phase of each study, a lethal

Repeated administration of amitriptyline reduces oxaliplatin-induced mechanical allodynia in rats.

PubMed

Sada, Hikaru; Egashira, Nobuaki; Ushio, Soichiro; Kawashiri, Takehiro; Shirahama, Masafumi; Oishi, Ryozo

2012-01-01

Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Amitriptyline has widely been used in patients with painful neuropathy. In this study, we investigated the effect of amitriptyline on the oxaliplatin-induced neuropathy in rats. Repeated administration of amitriptyline (5 and 10 mg/kg, p.o., once a day) reduced the oxaliplatin-induced mechanical allodynia but not cold hyperalgesia and reversed the oxaliplatin-induced increase in the expression of NR2B protein and mRNA in rat spinal cord. These results suggest that amitriptyline is useful for the treatment of oxaliplatin-induced neuropathy clinically.

Energetics of swimming by the ferret: consequences of forelimb paddling.

PubMed

Fish, Frank E; Baudinette, Russell V

2008-06-01

The domestic ferret (Mustela putorius furo) swims by alternate strokes of the forelimbs. This pectoral paddling is rare among semi-aquatic mammals. The energetic implications of swimming by pectoral paddling were examined by kinematic analysis and measurement of oxygen consumption. Ferrets maintained a constant stroke frequency, but increased swimming speed by increasing stroke amplitude. The ratio of swimming velocity to foot stroke velocity was low, indicating a low propulsive efficiency. Metabolic rate increased linearly with increasing speed. The cost of transport decreased with increasing swimming speed to a minimum of 3.59+/-0.28 J N(-1) m(-1) at U=0.44 m s(-1). The minimum cost of transport for the ferret was greater than values for semi-aquatic mammals using hind limb paddling, but lower than the minimum cost of transport for the closely related quadrupedally paddling mink. Differences in energetic performance may be due to the amount of muscle recruited for propulsion and the interrelationship hydrodynamic drag and interference between flow over the body surface and flow induced by propulsive appendages.

Oral Administration of Interferon Tau Enhances Oxidation of Energy Substrates and Reduces Adiposity in Zucker Diabetic Fatty Rats

PubMed Central

Tekwe, Carmen D.; Lei, Jian; Yao, Kang; Rezaei, Reza; Li, Xilong; Dahanayaka, Sudath; Carroll, Raymond J.; Meininger, Cynthia J.; Bazer, Fuller W.; Wu, Guoyao

2013-01-01

Male Zucker diabetic fatty (ZDF) rats were used to study effects of oral administration of interferon tau (IFNT) in reducing obesity. Eighteen ZDF rats (28 days of age) were assigned randomly to receive 0, 4 or 8 μg IFNT/kg body weight (BW) per day (n=6/group) for 8 weeks. Water consumption was measured every two days. Food intake and BW were recorded weekly. Energy expenditure in 4-, 6-, 8-, and 10-week-old rats was determined using indirect calorimetry. Starting at 7 weeks of age, urinary glucose and ketone bodies were tested daily. Rates of glucose and oleate oxidation in liver, brown adipose tissue, and abdominal adipose tissue, leucine catabolism in skeletal muscle, and lipolysis in white and brown adipose tissues were greater for rats treated with 8 μg IFNT/kg BW/day in comparison with control rats. Treatment with 8 μg IFNT/kg BW/day increased heat production, reduced BW gain and adiposity, ameliorated fatty liver syndrome, delayed the onset of diabetes, and decreased concentrations of glucose, free fatty acids, triacylglycerol, cholesterol, and branched-chain amino acids in plasma, compared to control rats. Oral administration of 8 μg IFNT/kg BW/day ameliorated oxidative stress in skeletal muscle, liver and adipose tissue, as indicated by decreased ratios of oxidized glutathione to reduced glutathione and increased concentrations of the antioxidant tetrahydrobiopterin. These results indicate that IFNT stimulates oxidation of energy substrates and reduces obesity in ZDF rats and may have broad important implications for preventing and treating obesity-related diseases in mammals. PMID:23804503

Mineralocorticoid Receptor Antagonism Prevents Obesity-Induced Cerebral Artery Remodeling and Reduces White Matter Injury in rats.

PubMed

Pires, Paulo Wagner; McClain, Jonathon Lee; Hayoz, Sebastian F; Dorrance, Anne McLaren

2018-05-14

Midlife obesity is a risk factor for dementia development. Obesity has also been linked to hyperaldosteronism, and this can be modeled in rats by high fat (HF) feeding from weaning. Aldosterone, or activation of the mineralocorticoid receptor (MR) causes cerebrovascular injury in lean hypertensive rats. We hypothesized that rats fed a HF diet would show inward middle cerebral artery (MCA) remodeling that could be prevented by MR antagonism. We further proposed that the cerebral artery remodeling would be associated with white mater injury. Three-week-old male Sprague-Dawley rats were fed a HF diet ± the MR antagonist canrenoic acid (Canr) for 17 weeks. Control rats received normal chow (Control NC). MCA structure was assessed by pressure myography. The MCAs from HF fed rats had smaller lumens and thicker walls when compared to arteries from Control NC rats; Canr prevented the MCA remodeling associated with HF feeding. HF feeding increased the mRNA expression of markers of cell proliferation and vascular inflammation in cerebral arteries and Canr treatment prevented this. White mater injury was increased in the rats fed the HF diet and this was reduced by Canr treatment. The expression of doublecortin, a marker of new and immature neurons was reduced in HF fed rats, and MR antagonism normalized this. These data suggest that HF feeding leads to MR dependent remodeling of the MCA and this is associated with markers of dementia development. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Social instability stress in adolescent male rats reduces social interaction and social recognition performance and increases oxytocin receptor binding.

PubMed

Hodges, Travis E; Baumbach, Jennet L; Marcolin, Marina L; Bredewold, Remco; Veenema, Alexa H; McCormick, Cheryl M

2017-09-17

Social experiences in adolescence are essential for displaying context-appropriate social behaviors in adulthood. We previously found that adult male rats that underwent social instability stress (SS) in adolescence had reduced social interactions with unfamiliar peers compared with non-stressed controls (CTL). Here we determined whether SS altered social recognition and social reward and brain oxytocin and vasopressin receptor density in adolescence. We confirmed that SS rats spent less time interacting with unfamiliar peers than did CTL rats (p=0.006). Furthermore, CTL rats showed a preference for novel over familiar conspecifics in a social recognition test whereas SS rats did not, which may reflect reduced recognition, impaired memory, or reduced preference for novelty in SS rats. The reward value of social interactions was not affected by SS based on conditioned place preference tests and based on the greater time SS rats spent investigating stimulus rats than did CTL rats when the stimulus rat was behind wire mesh (p=0.03). Finally, oxytocin receptor binding density was higher in the dorsal lateral septum and nucleus accumbens shell in SS rats compared with CTL rats (p=0.02, p=0.01, respectively). No effect of SS was found for vasopressin 1a receptor binding density in any of the brain regions analyzed. We discuss the extent to which the differences in social behavior exhibited after social instability in adolescence involve changes in social salience and social competency, and the possibility that changes in oxytocin signaling in the brain underlie the differences in social behavior. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Reduced-calorie avocado paste attenuates metabolic factors associated with a hypercholesterolemic-high fructose diet in rats.

PubMed

Pahua-Ramos, María Elena; Garduño-Siciliano, Leticia; Dorantes-Alvarez, Lidia; Chamorro-Cevallos, German; Herrera-Martínez, Julieta; Osorio-Esquivel, Obed; Ortiz-Moreno, Alicia

2014-03-01

The objective of this study was to evaluate the effect of reduced-calorie avocado paste on lipid serum profile, insulin sensitivity, and hepatic steatosis in rats fed a hypercholesterolemic-high fructose diet. Thirty five male Wistar rats were randomly separated in five groups: Control group (ground commercial diet); hypercholesterolemic diet plus 60% fructose solution (HHF group); hypercholesterolemic diet plus 60% fructose solution supplemented with avocado pulp (HHF+A group); hypercholesterolemic diet plus 60% fructose solution supplemented with reduced-calorie avocado paste (HHF+P group); and hypercholesterolemic diet plus 60% fructose solution supplemented with a reduced-calorie avocado paste plus fiber (HHF+FP group). The A, P, and FP were supplemented at 2 g/kg/d. The study was carried out for seven weeks. Rats belonging to the HHF group exhibited significantly (P ≤ 0.05) higher total cholesterol, triglycerides, and insulin levels in serum as well as lower insulin sensitivity than the control group. Supplementation with reduced-calorie avocado paste showed a significant (P ≤ 0.05) decrease in total cholesterol (43.1%), low-density lipoprotein (45.4%), and triglycerides (32.8%) in plasma as well as elevated insulin sensitivity compared to the HHF group. Additionally, the liver enzymes alanine aminotransferase and aspartate aminotransferase decreased significantly in the HHF-P group (39.8 and 35.1%, respectively). These results are likely due to biocompounds present in the reduced-calorie avocado paste, such as polyphenols, carotenoids, chlorophylls, and dietary fibre, which are capable of reducing oxidative stress. Therefore, reduced-calorie avocado paste attenuates the effects of a hypercholesterolemic-high fructose diet in rats.

Tungstate Reduces the Expression of Gluconeogenic Enzymes in STZ Rats

PubMed Central

Calbó, Joaquim; Domínguez, Jorge; Guinovart, Joan J.

2012-01-01

Aims Oral administration of sodium tungstate has shown hyperglycemia-reducing activity in several animal models of diabetes. We present new insights into the mechanism of action of tungstate. Methods We studied protein expression and phosphorylation in the liver of STZ rats, a type I diabetes model, treated with sodium tungstate in the drinking water (2 mg/ml) and in primary cultured-hepatocytes, through Western blot and Real Time PCR analysis. Results Tungstate treatment reduces the expression of gluconeogenic enzymes (PEPCK, G6Pase, and FBPase) and also regulates transcription factors accountable for the control of hepatic metabolism (c-jun, c-fos and PGC1α). Moreover, ERK, p90rsk and GSK3, upstream kinases regulating the expression of c-jun and c-fos, are phosphorylated in response to tungstate. Interestingly, PKB/Akt phosphorylation is not altered by the treatment. Several of these observations were reproduced in isolated rat hepatocytes cultured in the absence of insulin, thereby indicating that those effects of tungstate are insulin-independent. Conclusions Here we show that treatment with tungstate restores the phosphorylation state of various signaling proteins and changes the expression pattern of metabolic enzymes. PMID:22905122

Tungstate reduces the expression of gluconeogenic enzymes in STZ rats.

PubMed

Nocito, Laura; Zafra, Delia; Calbó, Joaquim; Domínguez, Jorge; Guinovart, Joan J

2012-01-01

Oral administration of sodium tungstate has shown hyperglycemia-reducing activity in several animal models of diabetes. We present new insights into the mechanism of action of tungstate. We studied protein expression and phosphorylation in the liver of STZ rats, a type I diabetes model, treated with sodium tungstate in the drinking water (2 mg/ml) and in primary cultured-hepatocytes, through Western blot and Real Time PCR analysis. Tungstate treatment reduces the expression of gluconeogenic enzymes (PEPCK, G6Pase, and FBPase) and also regulates transcription factors accountable for the control of hepatic metabolism (c-jun, c-fos and PGC1α). Moreover, ERK, p90rsk and GSK3, upstream kinases regulating the expression of c-jun and c-fos, are phosphorylated in response to tungstate. Interestingly, PKB/Akt phosphorylation is not altered by the treatment. Several of these observations were reproduced in isolated rat hepatocytes cultured in the absence of insulin, thereby indicating that those effects of tungstate are insulin-independent. Here we show that treatment with tungstate restores the phosphorylation state of various signaling proteins and changes the expression pattern of metabolic enzymes.

Growth and formation of the foreleg skeleton inbred mice and rats under conditions of hypo-, normo- and hyperdynamia

NASA Technical Reports Server (NTRS)

Kogan, B. I.; Antipov, Y. S.

1980-01-01

Inbred 1 month old males of C57B 1/6, CBA, CC57Br/Mw interlinear hybrid mice of the first generation and rats of the August and Wistar lines were subjected to conditions of hypo-, normo- and hyperdynamia for 2 months. The statistically reliable dependence is shown between mechanical underloadings and overloadings and macro microscopic changes in the hind limb skeleton of animals. Genetic determination of growth and formation of the forelimb skeleton is established. Hereditary susceptibility and the phenomenon of heterosis are preserved under all motor conditions.

Acute elevations in salt intake and reduced renal mass hypertension compromise arteriolar dilation in rat cremaster muscle.

PubMed

Frisbee, J C; Lombard, J H

1999-05-01

Alterations in arteriolar reactivity to dilator agonists were assessed in the skeletal muscle microcirculation of normotensive male Sprague-Dawley rats fed either high- (4% NaCl; HS) or low- (0. 4% NaCl; LS) salt diets and in reduced renal mass hypertensive rats (RRM-HT) on a high-salt diet for 3 days. An in situ cremaster muscle preparation was superfused with physiological salt solution, transilluminated, and viewed via television microscopy. A videomicrometer was used to measure changes in diameter of distal arterioles in response to increasing concentrations of acetylcholine (ACH), iloprost (ILO), cholera toxin (CT), forskolin (FOR), and sodium nitroprusside (SNP). Arteriolar dilation in response to ACH, ILO, and CT was significantly reduced in both HS and RRM-HT rats, while responses to FOR and SNP were decreased in RRM-HT rats only. The maximum dilation of the arterioles (determined during superfusion of the muscle with Ca2+-free solution containing 10(-4) M adenosine) was similar in the normotensive control animals on LS and HS diets, but was reduced in the RRM-HT rats, suggesting that early anatomic remodeling of the vessel wall may be occurring with RRM-HT. We conclude that arteriolar reactivity to endothelium-dependent and -independent vasodilator agonists is impaired as early as 3 days after the development of RRM hypertension or commencement of a high-salt diet in normotensive rats. Structural remodeling of the arteriolar wall, although becoming evident in the hypertensive rats, takes longer to develop than the impaired vasodilator reactivity. Copyright 1999 Academic Press.

Dietary resistant starch dose-dependently reduces adiposity in obesity-prone and obesity-resistant male rats.

PubMed

Belobrajdic, Damien P; King, Roger A; Christophersen, Claus T; Bird, Anthony R

2012-10-25

Animal studies show that diets containing resistant starch (RS) at levels not achievable in the human diet result in lower body weight and/or adiposity in rodents. We aimed to determine whether RS dose-dependently reduces adiposity in obesity-prone (OP) and obesity-resistant (OR) rats. Male Sprague-Dawley rats (n=120) were fed a moderate-fat, high-energy diet for 4 wk. Rats that gained the most weight (40%) were classified as obesity-prone (OP) and obesity-resistant (OR) rats were the 40% that gained the least weight. OP and OR rats were randomly allocated to one of six groups (n=8 for each phenotype). One group was killed for baseline measurements, the other five groups were allocated to AIN-93 based diets that contained 0, 4, 8, 12 and 16% RS (as high amylose maize starch) for 4 wk. These diets were matched for total carbohydrate content. At 0, 4 and 7 wk from the start of the study insulin sensitivity was calculated by homeostasis model assessment of insulin resistance (HOMA-IR) and adiposity was determined by dual-energy X-ray absorptiometry (DXA). At 8 wk, rats were euthanized and fat pad weights, intestinal digesta short chain fatty acid (SCFA) pools and plasma gut hormone levels were determined. Obesity prone rats gained less weight with 4, 12 and 16% RS compared to 0% RS, but the effect in OR animals was significant only at 16% RS. Irrespective of phenotype, diets containing ≥8% RS reduced adiposity compared to 0% RS. Energy intake decreased by 9.8 kJ/d for every 4% increase in RS. All diets containing RS increased total SCFA pools in the caecum and lowered plasma GIP concentrations compared to the 0% RS, whereas plasma GLP-1 and PYY were increased when the diet contained at least 8% RS. Insulin sensitivity was not affected by RS. RS in amounts that could be potentially consumed by humans were effective in reducing adiposity and weight gain in OP and OR rats, due in part to a reduction in energy intake, and changes in gut hormones and large bowel

COMBINED ALISKIREN AND AMLODIPINE REDUCE ALBUMINURIA VIA REDUCTION IN RENAL INFLAMMATION IN DIABETIC RATS

PubMed Central

Matavelli, Luis C.; Huang, Jiqian; Siragy, Helmy M.

2011-01-01

SUMMARY We hypothesized that compared to hydrochlorothiazide (HCTZ), the renin inhibitor aliskiren (ALISK) or amlodipine (AMLO) and their combination reduce albuminuria via reduction in renal inflammation, independent of BP changes. We studied normal and streptozotocin induced diabetic (DM) Sprague-Dawley rats treated for 6 weeks with vehicle, ALISK, HCTZ or AMLO individually and combined and evaluated effects of treatments on BP, urine albumin to creatinine ratio (UACR), renal interstitial fluid (RIF) levels of angiotensin II (Ang II), tumor necrosis factor-alpha (TNFα) and interleukin-6 (IL-6), and renal expression of TNFα, IL-6, transforming growth factor-beta1 (TGF-β1) and nuclear factor-kappa B (NF-κB). There were no differences in BP between treatments. Only ALISK and its combinations reduced RIF Ang II. UACR increased in DM rats and decreased with ALISK alone or combined with HCTZ or AMLO. HCTZ or AMLO individually and combined did not influence UACR. RIF TNFα and IL-6, and the renal expression of TNFα, IL-6, TGF-β1 and NF-κB were increased in DM rats. These renal inflammatory markers were reduced only with ALISK or AMLO individually or combined with other treatments. We conclude that ALISK alone and combined with HCTZ or AMLO reduced albuminuria in diabetes via reduction in renal inflammation, independent of BP changes. PMID:22075749

Combined aliskiren and amlodipine reduce albuminuria via reduction in renal inflammation in diabetic rats.

PubMed

Matavelli, Luis C; Huang, Jiqian; Siragy, Helmy M

2012-03-01

We hypothesized that compared with hydrochlorothiazide (HCTZ), the renin inhibitor aliskiren (ALISK) or amlodipine (AMLO) and their combination reduce albuminuria via reduction in renal inflammation, independent of blood pressure (BP) changes. We studied normal and streptozotocin-induced diabetic (DM) Sprague-Dawley rats treated for 6 weeks with vehicle, ALISK, HCTZ, or AMLO individually and combined and evaluated the effects of treatments on BP, urine albumin to creatinine ratio, renal interstitial fluid levels of angiotensin II, tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) and renal expression of TNF-α, IL-6, transforming growth factor beta 1, and nuclear factor kappa B. There were no differences in BP between treatments. Only ALISK and its combinations reduced renal interstitial fluid angiotensin II. Urine albumin to creatinine ratio increased in DM rats and decreased with ALISK alone or combined with HCTZ or AMLO. HCTZ or AMLO individually and combined did not influence urine albumin to creatinine ratio. Renal interstitial fluid TNF-α and IL-6, and the renal expression of TNF-α, IL-6, transforming growth factor beta 1, and nuclear factor kappa B were increased in DM rats. These renal inflammatory markers were reduced only with ALISK or AMLO individually or combined with other treatments. We conclude that ALISK alone and combined with HCTZ or AMLO reduced albuminuria in diabetes via reduction in renal inflammation, independent of BP changes.

Effect of short-term hyperinsulinemia on the localization and expression of endothelin receptors A and B in lamellar tissue of the forelimbs of horses

PubMed Central

Gauff, Felicia C.; Patan-Zugaj, Bianca; Licka, Theresia F.

2014-01-01

Objective To determine the effect of short-term hyperinsulinemia on the localization and expression of endothelin receptor (ETR)-A and ETR-B in lamellar tissue of the forelimbs of horses. Samples Distal portion of 15 cadaveric forelimbs from healthy adult horses (1 limb/horse) obtained immediately after slaughter at an abattoir. Procedures Each forelimb was assigned to 1 of 3 treatment groups (perfused with autologous blood for 10 hours [control perfusion; n = 5], perfused with an insulin [142 ± 81 μU/mL] perfusate for 10 hours [insulinemic perfusion; 5], or not perfused [unperfused control; 5]). Immunohistochemical evaluation of lamellar tissue was performed to assess localization of ETR-A and ETR-B. Expression of ETR-A and ETR-B was measured semiquantitatively on a scale of 0 to 3 (0 = none, 1 = mild, 2 = moderate, and 3 = high-intensity staining) and quantitatively by means of gray value analysis with imaging software. Results In all specimens, ETR-A and ETR-B were localized in endothelium, smooth muscle cells, axons, and keratinocytes. Quantitative expression of ETR-A in the midportion of the primary epidermal lamellae for the insulinemic perfusion group (149 ± 16) was lower than that for the control perfusion group (158 ± 15). Expression of ETR-B in the primary epidermal lamellae tips for the insulinemic perfusion group (140 ± 29) was higher than that for the control perfusion group (114 ± 8). Conclusions and Clinical Relevance Hyperinsulinemia caused significant changes in endothelin receptor expression, which suggested that ETR antagonists might be beneficial for treatment of laminitis in horses. PMID:24669922

Inhalation toxicity of methanol/gasoline in rats: effects of 13-week exposure.

PubMed

Poon, R; Park, G; Viau, C; Chu, I; Potvin, M; Vincent, R; Valli, V

1998-01-01

The subchronic inhalation toxicity of a methanol/gasoline blend (85% methanol, 15% gasoline, v/v) was studied in rats. Sprague Dawley rats (10 animals per group) of both sexes were exposed to vapours of methanol/gasoline at 50/3, 500/30 and 5000/300ppm for 6 hours per day, 5 days per week, for 13 weeks. Control animals inhaled filtered room air only. Control recovery and high dose recovery groups were also included which inhaled room air for an extra 4 weeks following the treatment period. No clinical signs of toxicity were observed in the treatment group and their growth curves were not significantly different from the control. Except for decreased forelimb grip strength in high dose females, no treatment-related neurobehavioural effects (4-6 hours post inhalation) were observed using screening tests which included cage-side observations, righting reflex, open field activities, and forelimb and hindlimb grip strength. At necropsy, the organ to body weight ratios for the liver, spleen, testes, thymus and lungs were not significantly different from the control group. There were no treatment-related effects in the hematological endpoints and no elevation in serum formate levels. Minimal serum biochemical changes were observed with the only treatment-related change being the decreased creatinine in the females. A dose-related increase in urinary ascorbic acid was detected in males after 2, 4 and 8 weeks of exposure, but not after the 12th week, and in females only at week-2. Increased urinary albumin was observed in treated males starting at the lowest dose and at all exposure periods, but not in females. A treatment-related increase in urinary beta 2-microglobulin was detected in males at week-2 only. Except for mild to moderate mucous cell metaplasia in nasal septum B, which occurred more often and with a slightly higher degree of severity in the low dose groups of both sexes, and presence of a minimal degree of interstitial lymphocyte infiltration in the prostate

Functional associations between support use and forelimb shape in strepsirrhines and their relevance to inferring locomotor behavior in early primates.

PubMed

Fabre, Anne-Claire; Marigó, Judit; Granatosky, Michael C; Schmitt, Daniel

2017-07-01

The evolution of primates is intimately linked to their initial invasion of an arboreal environment. However, moving and foraging in this milieu creates significant mechanical challenges related to the presence of substrates differing in their size and orientation. It is widely assumed that primates are behaviorally and anatomically adapted to movement on specific substrates, but few explicit tests of this relationship in an evolutionary context have been conducted. Without direct tests of form-function relationships in living primates it is impossible to reliably infer behavior in fossil taxa. In this study, we test a hypothesis of co-variation between forelimb morphology and the type of substrates used by strepsirrhines. If associations between anatomy and substrate use exist, these can then be applied to better understand limb anatomy of extinct primates. The co-variation between each forelimb long bone and the type of substrate used was studied in a phylogenetic context. Our results show that despite the presence of significant phylogenetic signal for each long bone of the forelimb, clear support use associations are present. A strong co-variation was found between the type of substrate used and the shape of the radius, with and without taking phylogeny into account, whereas co-variation was significant for the ulna only when taking phylogeny into account. Species that use a thin branch milieu show radii that are gracile and straight and have a distal articular shape that allows for a wide range of movements. In contrast, extant species that commonly use large supports show a relatively robust and curved radius with an increased surface area available for forearm and hand muscles in pronated posture. These results, especially for the radius, support the idea that strepsirrhine primates exhibit specific skeletal adaptations associated with the supports that they habitually move on. With these robust associations in hand it will be possible to explore the same

Targeted ablation of cardiac sympathetic neurons reduces resting, reflex and exercise-induced sympathetic activation in conscious rats.

PubMed

Lujan, Heidi L; Palani, Gurunanthan; Chen, Ying; Peduzzi, Jean D; Dicarlo, Stephen E

2009-05-01

Cholera toxin B subunit conjugated to saporin (SAP, a ribosomal inactivating protein that binds to and inactivates ribosomes) was injected in both stellate ganglia to evaluate the physiological response to targeted ablation of cardiac sympathetic neurons. Resting cardiac sympathetic activity (cardiac sympathetic tonus), exercise-induced sympathetic activity (heart rate responses to graded exercise), and reflex sympathetic activity (heart rate responses to graded doses of sodium nitroprusside, SNP) were determined in 18 adult conscious Sprague-Dawley male rats. Rats were randomly divided into the following three groups (n = 6/group): 1) control (no injection), 2) bilateral stellate ganglia injection of unconjugated cholera toxin B (CTB), and 3) bilateral stellate ganglia injection of cholera toxin B conjugated to SAP (CTB-SAP). CTB-SAP rats, compared with control and CTB rats, had reduced cardiac sympathetic tonus and reduced heart rate responses to graded exercise and graded doses of SNP. Furthermore, the number of stained neurons in the stellate ganglia and spinal cord (segments T(1)-T(4)) was reduced in CTB-SAP rats. Thus CTB-SAP retrogradely transported from the stellate ganglia is effective at ablating cardiac sympathetic neurons and reducing resting, exercise, and reflex sympathetic activity. Additional studies are required to further characterize the physiological responses to this procedure as well as determine if this new approach is safe and efficacious for the treatment of conditions associated with excess sympathetic activity (e.g., autonomic dysreflexia, hypertension, heart failure, and ventricular arrhythmias).

Administration of dried Aloe vera gel powder reduced body fat mass in diet-induced obesity (DIO) rats.

PubMed

Misawa, Eriko; Tanaka, Miyuki; Nabeshima, Kazumi; Nomaguchi, Kouji; Yamada, Muneo; Toida, Tomohiro; Iwatsuki, Keiji

2012-01-01

The aim of the present study was to investigate the anti-obesity effects of Aloe vera gel administration in male Sprague-Dawley (SD) rats with diet-induced obesity (DIO). SD rats at 7 wk of age were fed either a standard diet (10 kcal% fat) (StdD) or high-fat (60 kcal% fat) diet (HFD) during the experimental period. Four weeks after of HFD-feeding, DIO rats (11 wk of age) were orally administered with two doses of Aloe vera gel powder (20 and 200 mg/kg/d) for 90 d. Body weights (g) and body fat (%) of HFD fed rats were significantly higher than those of StdD-fed rats. Although a modest decrease of body weight (g) was observed with the administration of dried Aloe vera gel powder, both subcutaneous and visceral fat weight (g) and body fat (%) were reduced significantly in Aloe vera gel-treated rats. Serum lipid parameters elevated by HFD were also improved by the Aloe vera gel treatment. The oxygen consumption (VO(2)), an index of energy expenditure, was decreased in HFD-fed rats compared with that in StdD-fed rats. Administration of Aloe vera gel reversed the change in VO(2) in the HFD-fed rats. These results suggest that intake of Aloe vera gel reduced body fat accumulation, in part, by stimulation of energy expenditure. Aloe vera gel might be beneficial for the prevention and improvement of diet-induced obesity.

Developmental toxicity evaluation of Bendectin in CD rats.

PubMed

Tyl, R W; Price, C J; Marr, M C; Kimmel, C A

1988-06-01

Bendectin, composed of doxylamine succinate and pyridoxine HCl (1:1), is an antinauseant previously prescribed for nausea and vomiting during pregnancy. The present study examined the maternal and developmental effects of Bendectin (0, 200, 500, or 800 mg/kg/day, po) administered to timed-pregnant CD rats (36-41/group) during organogenesis (gestational days [gd] 6-15). At death (gd 20), all live fetuses were examined for external, visceral, and skeletal abnormalities. At 500 and 800 mg/kg/day, maternal toxicity included reduced food consumption during treatment and for the gestation period, increased water consumption in the posttreatment period, reduced weight gain during treatment, and sedation; water consumption was reduced during treatment and for the gestation period, and maternal mortality (17.1%) was observed only at the high dose. Developmental toxicity included reduced prenatal viability (800 mg/kg/day) and reduced fetal body weight/litter (500 and 800 mg/kg/day). In addition, reduced ossification of metacarpals (800 mg/kg/day), phalanges of the forelimbs (500 and 800 mg/kg/day), and of caudal vertebral centra (all doses) was observed. No increase in percent malformed live fetuses/litter was observed. The proportion of litters with one or more malformed fetuses was higher than vehicle controls only at 800 mg/kg/day, with short 13th rib (to which the test species is predisposed) as the predominant observation. By contrast, a positive control agent (nitrofen, 50 mg/kg/day, po, 14 dams) produced 85% malformed fetuses/litter with the predominant malformation being diaphragmatic hernia. In conclusion, the incidence of litters with one or more malformed fetuses was increased only at a dose of Bendectin which produced maternal mortality (17.1%) and other indices of maternal and developmental toxicity (see Discussion).

A Phaseolus vulgaris Extract Reduces Cue-Induced Reinstatement of Chocolate Seeking in Rats

PubMed Central

Lorrai, Irene; Piga, Valentina; Carai, Mauro A. M.; Riva, Antonella; Morazzoni, Paolo; Gessa, Gian Luigi; Colombo, Giancarlo; Maccioni, Paola

2016-01-01

Previous evidence has suggested that treatment with a standardized dry extract of Phaseolus vulgaris reduced intake and operant self-administration of highly palatable foods and fluids in rats and mice. The present study was designed to assess whether such extract was also effective in reducing seeking behavior for a highly hedonic chocolate-flavored beverage, using a “reinstatement” procedure adopted from the drug addiction research field and modeling relapse behavior. Rats were initially trained to lever-respond for the chocolate-flavored beverage under the Fixed Ratio (FR) 10 schedule of reinforcement. Subsequently, rats were exposed to an extinction responding phase, during which lever-responding – being unreinforced – diminished progressively up to extinction. Lever-responding was then powerfully reinstated by the non-contingent presentation of a complex of gustatory, olfactory, auditory, and visual stimuli previously associated to the availability of the chocolate-flavored beverage. Acute, intragastric administration of P. vulgaris dry extract (100 and 500 mg/kg) reduced lever-responding by 40–45%, in comparison to vehicle condition. These results indicate the ability of P. vulgaris dry extract to reduce seeking behavior for a highly palatable nourishment in an experimental model of relapse into disordered eating of palatable foods. The unavailability of the chocolate-flavored beverage in the reinstatement session tends to exclude that the observed effect of the P. vulgaris dry extract was secondary to any inhibition of carbohydrate metabolism; conversely, it is the likely consequence on a central action on the rewarding and hedonic properties of food. PMID:27199752

EEG patterns from acute to chronic stroke phases in focal cerebral ischemic rats: correlations with functional recovery.

PubMed

Zhang, Shao-jie; Ke, Zheng; Li, Le; Yip, Shea-ping; Tong, Kai-yu

2013-04-01

Monitoring the neural activities from the ischemic penumbra provides critical information on neurological recovery after stroke. The purpose of this study is to evaluate the temporal alterations of neural activities using electroencephalography (EEG) from the acute phase to the chronic phase, and to compare EEG with the degree of post-stroke motor function recovery in a rat model of focal ischemic stroke. Male Sprague-Dawley rats were subjected to 90 min transient middle cerebral artery occlusion surgery followed by reperfusion for seven days (n = 58). The EEG signals were recorded at the pre-stroke phase (0 h), acute phase (3, 6 h), subacute phase (12, 24, 48, 72 h) and chronic phase (96, 120, 144, 168 h) (n = 8). This study analyzed post-stroke seizures and polymorphic delta activities (PDAs) and calculated quantitative EEG parameters such as the alpha-to-delta ratio (ADR). The ADR represented the ratio between alpha power and delta power, which indicated how fast the EEG activities were. Forelimb and hindlimb motor functions were measured by De Ryck's test and the beam walking test, respectively. In the acute phase, delta power increased fourfold with the occurrence of PDAs, and the histological staining showed that the infarct was limited to the striatum and secondary sensory cortex. In the subacute phase, the alpha power reduced to 50% of the baseline, and the infarct progressed to the forelimb cortical region. ADRs reduced from 0.23 ± 0.09 to 0.04 ± 0.01 at 3 h in the acute phase and gradually recovered to 0.22 ± 0.08 at 168 h in the chronic phase. In the comparison of correlations between the EEG parameters and the limb motor function from the acute phase to the chronic phase, ADRs were found to have the highest correlation coefficients with the beam walking test (r = 0.9524, p < 0.05) and De Ryck's test (r = 0.8077, p < 0.05). This study measured EEG activities after focal cerebral ischemia and showed that functional recovery was closely

Reduced motor neuron excitability is an important contributor to weakness in a rat model of sepsis.

PubMed

Nardelli, Paul; Vincent, Jacob A; Powers, Randall; Cope, Tim C; Rich, Mark M

2016-08-01

The mechanisms by which sepsis triggers intensive care unit acquired weakness (ICUAW) remain unclear. We previously identified difficulty with motor unit recruitment in patients as a novel contributor to ICUAW. To study the mechanism underlying poor recruitment of motor units we used the rat cecal ligation and puncture model of sepsis. We identified striking dysfunction of alpha motor neurons during repetitive firing. Firing was more erratic, and often intermittent. Our data raised the possibility that reduced excitability of motor neurons was a significant contributor to weakness induced by sepsis. In this study we quantified the contribution of reduced motor neuron excitability and compared its magnitude to the contributions of myopathy, neuropathy and failure of neuromuscular transmission. We injected constant depolarizing current pulses (5s) into the soma of alpha motor neurons in the lumbosacral spinal cord of anesthetized rats to trigger repetitive firing. In response to constant depolarization, motor neurons in untreated control rats fired at steady and continuous firing rates and generated smooth and sustained tetanic motor unit force as expected. In contrast, following induction of sepsis, motor neurons were often unable to sustain firing throughout the 5s current injection such that force production was reduced. Even when firing, motor neurons from septic rats fired erratically and discontinuously, leading to irregular production of motor unit force. Both fast and slow type motor neurons had similar disruption of excitability. We followed rats after recovery from sepsis to determine the time course of resolution of the defect in motor neuron excitability. By one week, rats appeared to have recovered from sepsis as they had no piloerection and appeared to be in no distress. The defects in motor neuron repetitive firing were still striking at 2weeks and, although improved, were present at one month. We infer that rats suffered from weakness due to reduced

Reduced cholesterol levels in renal membranes of undernourished rats may account for urinary Na⁺ loss.

PubMed

Oliveira, Fabiana S T; Vieira-Filho, Leucio D; Cabral, Edjair V; Sampaio, Luzia S; Silva, Paulo A; Carvalho, Vera C O; Vieyra, Adalberto; Einicker-Lamas, Marcelo; Lima, Vera L M; Paixão, Ana D O

2013-04-01

It has been demonstrated that reabsorption of Na⁺ in the thick ascending limb is reduced and the ability to concentrate urine can be compromised in undernourished individuals. Alterations in phospholipid and cholesterol content in renal membranes, leading to Na⁺ loss and the inability to concentrate urine, were investigated in undernourished rats. Sixty-day-old male Wistar rats were utilized to evaluate (1) phospholipid and cholesterol content in the membrane fraction of whole kidneys, (2) cholesterol content and the levels of active Na⁺ transporters, (Na⁺ + K⁺)ATPase and Na⁺-ATPase, in basolateral membranes of kidney proximal tubules, and (3) functional indicators of medullary urine concentration. Body weight in the undernourished group was 73 % lower than in control. Undernourishment did not affect the levels of cholesterol in serum or in renal homogenates. However, membranes of whole kidneys revealed 56 and 66 % reduction in the levels of total phospholipids and cholesterol, respectively. Furthermore, cholesterol and (Na⁺ + K⁺)ATPase activity in proximal tubule membranes were reduced by 55 and 68 %, respectively. Oxidative stress remained unaltered in the kidneys of undernourished rats. In contrast, Na⁺-ATPase activity, an enzyme with all regulatory components in membrane, was increased in the proximal tubules of undernourished rats. Free water clearance and fractional Na⁺ excretion were increased by 86 and 24 %, respectively, and urinary osmolal concentration was 21 % lower in undernourished rats than controls. Life-long undernutrition reduces the levels of total phospholipids and cholesterol in membranes of renal tubular cells. This alteration in membrane integrity could diminish (Na⁺ + K⁺)ATPase activity resulting in reduced Na⁺ reabsorption and urinary concentrating ability.

Swimming reduces the severity of physical and psychological dependence and voluntary morphine consumption in morphine dependent rats.

PubMed

Fadaei, Atefeh; Gorji, Hossein Miladi; Hosseini, Shahrokh Makvand

2015-01-15

Previous studies have indicated that voluntary exercise decreases the severity of the anxiogenic-like behaviors in both morphine-dependent and withdrawn rats. This study examined the effects of regular swimming exercise during the development of dependency and spontaneous morphine withdrawal on the anxiety-depression profile and voluntary morphine consumption in morphine dependent rats. The rats were chronically treated with bi-daily doses (10 mg/kg, at 12h intervals) of morphine over a period of 14 days. The exercising rats were allowed to swim (45 min/d, five days per a week, for 14 or 21 days) during the development of morphine dependence and withdrawal. Then, rats were tested for the severity of morphine dependence, the elevated plus-maze (EPM), sucrose preference test (SPT) and voluntary morphine consumption using a two-bottle choice paradigm in animal models of craving. The results showed that withdrawal signs were decreased in swimmer morphine dependent rats than sedentary rats (P<0.05). Also, the swimmer morphine-dependent and withdrawn rats exhibited an increase in EPM open arm time and entries (P<0.05), higher levels of sucrose preference (P<0.001) than sedentary rats. Voluntary consumption of oral morphine was less in the swimmer morphine-withdrawn rats than the sedentary groups during four periods of the intake of drug (P<0.01). We conclude that regular swimming exercise reduces the severity of morphine dependence and voluntary morphine consumption with reducing anxiety and depression in morphine-dependent and withdrawn rats. Thus, swimming exercise may be a potential method to ameliorate some of the deleterious behavioral consequences of morphine dependence. Copyright © 2014 Elsevier B.V. All rights reserved.

The effects of Kinesio Taping on the trajectory of the forelimb and the muscle activity of the Musculus brachiocephalicus and the Musculus extensor carpi radialis in horses

PubMed Central

Zellner, Antonia; Bockstahler, Barbara; Peham, Christian

2017-01-01

Background information The present study aimed to investigate the effects of Kinesio Taping on the trajectory of the forelimb and the muscle activity of the M. brachiocephalicus and the M. extensor carpi radialis in horses. 19 horses and ponies of different breeds (body weight: 496±117 kg), gender (8 mares, 10 geldings and 3 stallions) and ages (14.9±6.9 years old) were analysed without Kinesio Tape (“no tape”), with Kinesio Tape (muscle facilitation application on both muscles of both sides, “with tape”) and immediately after Kinesio Taping (“post tape”) through kinematic motion analysis and surface electromyography on a treadmill at the walk (speed: 1.5±0.1 m/s) and trot (speed: 3.1±0.3 m/s). Results The results of the surface electromyography (maximum muscle activity at the walk and trot) and the kinematic motion analysis (maximum stride length and maximum height of the forelimbs flight arc at the walk and trot) showed that there were no significant differences between "no tape", "with tape" and "post tape". Conclusion To sum up, Kinesio Taping on the M. brachiocephalicus and the M. extensor carpi radialis does not affect (in a positive or negative manner) the trajectory of the forelimb or the muscle activity of the M. brachiocephalicus and the M. extensor carpi radialis in horses. PMID:29166657

Prenatal zinc reduces stress response in adult rat offspring exposed to lipopolysaccharide during gestation.

PubMed

Galvão, Marcella C; Chaves-Kirsten, Gabriela P; Queiroz-Hazarbassanov, Nicolle; Carvalho, Virgínia M; Bernardi, Maria M; Kirsten, Thiago B

2015-01-01

Previous investigations by our group have shown that prenatal treatment with lipopolysaccharide (LPS; 100 μg/kg, intraperitoneally) on gestation day (GD) 9.5 in rats, which mimics infections by Gram-negative bacteria, induces short- and long-term behavioral and neuroimmune changes in the offspring. Because LPS induces hypozincemia, dams were treated with zinc after LPS in an attempt to prevent or ameliorate the impairments induced by prenatal LPS exposure. LPS can also interfere with hypothalamic-pituitary-adrenal (HPA) axis development; thus, behavioral and neuroendocrine parameters linked to HPA axis were evaluated in adult offspring after a restraint stress session. We prenatally exposed Wistar rats to LPS (100 μg/kg, intraperitoneally, on GD 9.5). One hour later they received zinc (ZnSO4, 2 mg/kg, subcutaneously). Adult female offspring that were in metestrus/diestrus were submitted to a 2 h restraint stress session. Immediately after the stressor, 22 kHz ultrasonic vocalizations, open field behavior, serum corticosterone and brain-derived neurotrophic factor (BDNF) levels, and striatal and hypothalamic neurotransmitter and metabolite levels were assessed. Offspring that received prenatal zinc after LPS presented longer periods in silence, increased locomotion, and reduced serum corticosterone and striatal norepinephrine turnover compared with rats treated with LPS and saline. Prenatal zinc reduced acute restraint stress response in adult rats prenatally exposed to LPS. Our findings suggest a potential beneficial effect of prenatal zinc, in which the stress response was reduced in offspring that were stricken with infectious/inflammatory processes during gestation. Copyright © 2014 Elsevier Inc. All rights reserved.

Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats

PubMed Central

McBride, Devin W.; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H.

2015-01-01

Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected to either sham surgery or surgical brain injury via partial frontal lobectomy. All animals were tested for neurological deficits 24 post-SBI and fourteen were also tested 72 hours after surgery using seven common behavior tests: modified Garcia neuroscore (Neuroscore), beam walking, corner turn test, forelimb placement test, adhesive removal test, beam balance test, and foot fault test. After assessing the functional outcome, animals were euthanized for brain water content measurement. Surgical brain injury resulted in a significantly elevated frontal lobe brain water content 24 and 72 hours after surgery compared to that of sham animals. In all behavior tests, significance was observed between sham and SBI animals. However, a correlation between brain water content and functional outcome was observed for all tests except Neuroscore. The selection of behavior tests is critical to determine the effectiveness of therapeutics. Based on this study’s results, we recommend using beam walking, the corner turn test, the beam balance test, and the foot fault test since correlations with brain water content were observed at both 24 and 72 hours post-SBI. PMID:25975171

Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats.

PubMed

McBride, Devin W; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H

2015-09-01

Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected to either sham surgery or surgical brain injury via partial frontal lobectomy. All animals were tested for neurological deficits 24 post-SBI and fourteen were also tested 72 h after surgery using seven common behavior tests: modified Garcia neuroscore (Neuroscore), beam walking, corner turn test, forelimb placement test, adhesive removal test, beam balance test, and foot fault test. After assessing the functional outcome, animals were euthanized for brain water content measurement. Surgical brain injury resulted in significantly elevated frontal lobe brain water content 24 and 72 h after surgery compared to that of sham animals. In all behavior tests, significance was observed between sham and SBI animals. However, a correlation between brain water content and functional outcome was observed for all tests except Neuroscore. The selection of behavior tests is critical to determine the effectiveness of therapeutics. Based on this study's results, we recommend using beam walking, the corner turn test, the beam balance test, and the foot fault test since correlations with brain water content were observed at both 24 and 72 h post-SBI. Copyright © 2015 Elsevier B.V. All rights reserved.

Aerobic Exercise Training Attenuates Tumor Growth and Reduces Insulin Secretion in Walker 256 Tumor-Bearing Rats

PubMed Central

Moreira, Veridiana Mota; da Silva Franco, Claudinéia Conationi; Prates, Kelly Valério; Gomes, Rodrigo Mello; de Moraes, Ana Maria Praxedes; Ribeiro, Tatiane Aparecida; Martins, Isabela Peixoto; Previate, Carina; Pavanello, Audrei; Matiusso, Camila Cristina Ianoni; Almeida, Douglas Lopes; Francisco, Flávio Andrade; Malta, Ananda; Tófolo, Laize Peron; da Silva Silveira, Sandra; Saavedra, Lucas Paulo Jacinto; Machado, Katia; da Silva, Paulo Henrique Olivieri; Fabrício, Gabriel S.; Palma-Rigo, Kesia; de Souza, Helenir Medri; de Fátima Silva, Flaviane; Biazi, Giuliana Regina; Pereira, Taís Susane; Vieira, Elaine; Miranda, Rosiane Aparecida; de Oliveira, Júlio Cezar; da Costa Lima, Luiz Delmar; Rinaldi, Wilson; Ravanelli, Maria Ida; de Freitas Mathias, Paulo Cezar

2018-01-01

Aerobic exercise training can improve insulin sensitivity in many tissues; however, the relationship among exercise, insulin, and cancer cell growth is unclear. We tested the hypothesis that aerobic exercise training begun during adolescence can attenuate Walker 256 tumor growth in adult rats and alter insulin secretion. Thirty-day-old male Wistar rats engaged in treadmill running for 8 weeks, 3 days/week, 44 min/day, at 55–65% VO2max until they were 90 days old (TC, Trained Control). An equivalently aged group was kept inactive during the same period (SC, Sedentary Control). Then, half the animals of the SC and TC groups were reserved as the control condition and the other half were inoculated with Walker 256 cancer cells, yielding two additional groups (Sedentary Walker and Trained Walker). Zero mortalities were observed in tumor-bearing rats. Body weight (BW), food intake, plasma glucose, insulin levels, and peripheral insulin sensitivity were analyzed before and after tumor cell inoculation. We also evaluated tumor growth, metastasis and cachexia. Isolated pancreatic islets secretory activity was analyzed. In addition, we evaluated mechanic sensibility. Our results showed improved physical performance according to the final workload and VO2max and reduced BW in trained rats at the end of the running protocol. Chronic adaptation to the aerobic exercise training decreased tumor weight, cachexia and metastasis and were associated with low glucose and insulin levels and high insulin sensitivity before and after tumor cell inoculation. Aerobic exercise started at young age also reduced pancreatic islet insulin content and insulin secretion in response to a glucose stimulus, without impairing islet morphology in trained rats. Walker 256 tumor-bearing sedentary rats also presented reduced pancreatic islet insulin content, without changing insulin secretion through isolated pancreatic islets. The mechanical sensitivity test indicated that aerobic exercise training

Aerobic Exercise Training Attenuates Tumor Growth and Reduces Insulin Secretion in Walker 256 Tumor-Bearing Rats.

PubMed

Moreira, Veridiana Mota; da Silva Franco, Claudinéia Conationi; Prates, Kelly Valério; Gomes, Rodrigo Mello; de Moraes, Ana Maria Praxedes; Ribeiro, Tatiane Aparecida; Martins, Isabela Peixoto; Previate, Carina; Pavanello, Audrei; Matiusso, Camila Cristina Ianoni; Almeida, Douglas Lopes; Francisco, Flávio Andrade; Malta, Ananda; Tófolo, Laize Peron; da Silva Silveira, Sandra; Saavedra, Lucas Paulo Jacinto; Machado, Katia; da Silva, Paulo Henrique Olivieri; Fabrício, Gabriel S; Palma-Rigo, Kesia; de Souza, Helenir Medri; de Fátima Silva, Flaviane; Biazi, Giuliana Regina; Pereira, Taís Susane; Vieira, Elaine; Miranda, Rosiane Aparecida; de Oliveira, Júlio Cezar; da Costa Lima, Luiz Delmar; Rinaldi, Wilson; Ravanelli, Maria Ida; de Freitas Mathias, Paulo Cezar

2018-01-01

Aerobic exercise training can improve insulin sensitivity in many tissues; however, the relationship among exercise, insulin, and cancer cell growth is unclear. We tested the hypothesis that aerobic exercise training begun during adolescence can attenuate Walker 256 tumor growth in adult rats and alter insulin secretion. Thirty-day-old male Wistar rats engaged in treadmill running for 8 weeks, 3 days/week, 44 min/day, at 55-65% VO 2max until they were 90 days old (TC, Trained Control). An equivalently aged group was kept inactive during the same period (SC, Sedentary Control). Then, half the animals of the SC and TC groups were reserved as the control condition and the other half were inoculated with Walker 256 cancer cells, yielding two additional groups (Sedentary Walker and Trained Walker). Zero mortalities were observed in tumor-bearing rats. Body weight (BW), food intake, plasma glucose, insulin levels, and peripheral insulin sensitivity were analyzed before and after tumor cell inoculation. We also evaluated tumor growth, metastasis and cachexia. Isolated pancreatic islets secretory activity was analyzed. In addition, we evaluated mechanic sensibility. Our results showed improved physical performance according to the final workload and VO 2max and reduced BW in trained rats at the end of the running protocol. Chronic adaptation to the aerobic exercise training decreased tumor weight, cachexia and metastasis and were associated with low glucose and insulin levels and high insulin sensitivity before and after tumor cell inoculation. Aerobic exercise started at young age also reduced pancreatic islet insulin content and insulin secretion in response to a glucose stimulus, without impairing islet morphology in trained rats. Walker 256 tumor-bearing sedentary rats also presented reduced pancreatic islet insulin content, without changing insulin secretion through isolated pancreatic islets. The mechanical sensitivity test indicated that aerobic exercise training

Antibiotics Suppress Activation of Intestinal Mucosal Mast Cells and Reduce Dietary Lipid Absorption in Sprague-Dawley Rats.

PubMed

Sato, Hirokazu; Zhang, Linda S; Martinez, Kristina; Chang, Eugene B; Yang, Qing; Wang, Fei; Howles, Philip N; Hokari, Ryota; Miura, Soichiro; Tso, Patrick

2016-11-01

The gut microbiota affects intestinal permeability and mucosal mast cells (MMCs) responses. Activation of MMCs has been associated with absorption of dietary fat. We investigated whether the gut microbiota contributes to the fat-induced activation of MMCs in rats, and how antibiotics might affect this process. Adult male Sprague-Dawley rats were given streptomycin and penicillin for 4 days (n = 6-8) to reduce the abundance of their gut flora, or normal drinking water (controls, n = 6-8). They underwent lymph fistula surgery and after an overnight recovery were given an intraduodenal bolus of intralipid. We collected intestinal tissues and lymph fluid and assessed activation of MMCs, intestinal permeability, and fat transport parameters. Compared with controls, intestinal lymph from rats given antibiotics had reduced levels of mucosal mast cell protease II (produced by MMCs) and decreased activity of diamine oxidase (produced by enterocytes) (P < .05). Rats given antibiotics had reduced intestinal permeability in response to dietary lipid compared with controls (P < .01). Unexpectedly, antibiotics also reduced lymphatic transport of triacylglycerol and phospholipid (P < .01), concomitant with decreased levels of mucosal apolipoproteins B, A-I, and A-IV (P < .01). No differences were found in intestinal motility or luminal pancreatic lipase activity between rats given antibiotics and controls. These effects were not seen with an acute dose of antibiotics or 4 weeks after the antibiotic regimen ended. The intestinal microbiota appears to activate MMCs after the ingestion of fat in rats; this contributes to fat-induced intestinal permeability. We found that the gut microbiome promotes absorption of lipid, probably by intestinal production of apolipoproteins and secretion of chylomicrons. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk Rats

PubMed Central

Ari, Csilla; Kovács, Zsolt; Juhasz, Gabor; Murdun, Cem; Goldhagen, Craig R.; Koutnik, Andrew P.; Poff, Angela M.; Kesl, Shannon L.; D’Agostino, Dominic P.

2016-01-01

Nutritional ketosis has been proven effective for seizure disorders and other neurological disorders. The focus of this study was to determine the effects of ketone supplementation on anxiety-related behavior in Sprague-Dawley (SPD) and Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. We tested exogenous ketone supplements added to food and fed chronically for 83 days in SPD rats and administered sub-chronically for 7 days in both rat models by daily intragastric gavage bolus followed by assessment of anxiety measures on elevated plus maze (EPM). The groups included standard diet (SD) or SD + ketone supplementation. Low-dose ketone ester (LKE; 1,3-butanediol-acetoacetate diester, ~10 g/kg/day, LKE), high dose ketone ester (HKE; ~25 g/kg/day, HKE), beta-hydroxybutyrate-mineral salt (βHB-S; ~25 g/kg/day, KS) and βHB-S + medium chain triglyceride (MCT; ~25 g/kg/day, KSMCT) were used as ketone supplementation for chronic administration. To extend our results, exogenous ketone supplements were also tested sub-chronically on SPD rats (KE, KS and KSMCT; 5 g/kg/day) and on WAG/Rij rats (KE, KS and KSMCT; 2.5 g/kg/day). At the end of treatments behavioral data collection was conducted manually by a blinded observer and with a video-tracking system, after which blood βHB and glucose levels were measured. Ketone supplementation reduced anxiety on EPM as measured by less entries to closed arms (sub-chronic KE and KS: SPD rats and KSMCT: WAG/Rij rats), more time spent in open arms (sub-chronic KE: SPD and KSMCT: WAG/Rij rats; chronic KSMCT: SPD rats), more distance traveled in open arms (chronic KS and KSMCT: SPD rats) and by delayed latency to entrance to closed arms (chronic KSMCT: SPD rats), when compared to control. Our data indicates that chronic and sub-chronic ketone supplementation not only elevated blood βHB levels in both animal models, but reduced anxiety-related behavior. We conclude that ketone supplementation may represent a promising anxiolytic strategy through a

Muscle synergies obtained from comprehensive mapping of the primary motor cortex forelimb representation using high-frequency, long-duration ICMS.

PubMed

Amundsen Huffmaster, Sommer L; Van Acker, Gustaf M; Luchies, Carl W; Cheney, Paul D

2017-07-01

Simplifying neuromuscular control for movement has previously been explored by extracting muscle synergies from voluntary movement electromyography (EMG) patterns. The purpose of this study was to investigate muscle synergies represented in EMG recordings associated with direct electrical stimulation of single sites in primary motor cortex (M1). We applied single-electrode high-frequency, long-duration intracortical microstimulation (HFLD-ICMS) to the forelimb region of M1 in two rhesus macaques using parameters previously found to produce forelimb movements to stable spatial end points (90-150 Hz, 90-150 μA, 1,000-ms stimulus train lengths). To develop a comprehensive representation of cortical output, stimulation was applied systematically across the full extent of M1. We recorded EMG activity from 24 forelimb muscles together with movement kinematics. Nonnegative matrix factorization (NMF) was applied to the mean stimulus-evoked EMG, and the weighting coefficients associated with each synergy were mapped to the cortical location of the stimulating electrode. Synergies were found for three data sets including 1 ) all stimulated sites in the cortex, 2 ) a subset of sites that produced stable movement end points, and 3 ) EMG activity associated with voluntary reaching. Two or three synergies accounted for 90% of the overall variation in voluntary movement EMG whereas four or five synergies were needed for HFLD-ICMS-evoked EMG data sets. Maps of the weighting coefficients from the full HFLD-ICMS data set show limited regional areas of higher activation for particular synergies. Our results demonstrate fundamental NMF-based muscle synergies in the collective M1 output, but whether and how the central nervous system might coordinate movements using these synergies remains unclear. NEW & NOTEWORTHY While muscle synergies have been investigated in various muscle activity sets, it is unclear whether and how synergies may be organized in the cortex. We have investigated

High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats

PubMed Central

Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R.

2013-01-01

Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P < 0.05). Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (−9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity. PMID:23883680

Lipopolysaccharide treatment reduces rat platelet aggregation independent of intracellular reactive-oxygen species generation.

PubMed

Lopes-Pires, M Elisa; Casarin, André L; Pereira-Cunha, Fernanda G; Lorand-Metze, Irene; Antunes, Edson; Marcondes, Sisi

2012-01-01

High production of reactive-oxygen species (ROS) by blood cells is involved in damage of the vascular endothelium and multiple organ dysfunction in sepsis. However, little is known about the intraplatelet ROS production in sepsis and its consequences on platelet reactivity. In this study, we evaluated whether the treatment of rats with lipopolysaccharide (LPS) affects platelet aggregation through intraplatelet ROS generation. Rats were injected with LPS (1 mg/kg, i.p.), and at 2 to 72 h thereafter, adenosine diphosphate (ADP) (3-10 µM) induced platelet aggregation was evaluated. Production of ROS in platelets was measured by flow cytometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA). Treatment of rats with LPS time-dependently inhibited ADP-induced platelet aggregation within 72 h. The inhibitory effect of LPS on platelet aggregation was further increased when the platelets were incubated with polyethylene glycol-superoxide dismutase (PEG-SOD; 30 U/mL), polyethylene glycol-catalase (PEG-CAT; 1000 U/mL) or the NADPH oxidase inhibitor diphenyleneiodonium (DPI; 10 µM). The ROS production in non-stimulated platelets did not differ between control and LPS-treated rats. However, in ADP-activated platelets, generation of ROS was increased by 3.0- and 7.0-fold, as evaluated at 8 and 48 h after LPS injection, respectively. This increased ROS production was significantly reduced when platelets were incubated in vitro with DPI, PEG-SOD or PEG-CAT. In contrast, treatment of rats with N-acetylcysteine (150 mg/kg, i.p.) significantly reduced the inhibitory effect of LPS on platelet aggregation, and prevented the increased ROS production by in vivo LPS. Our results indicate that the increased intraplatelet ROS production does not contribute to the inhibitory effect of LPS on platelet aggregation; however, the maintenance of redox balance in LPS-treated rats is fundamental to restore the normal platelet response in these animals.

Pulmonary arterial hypertension reduces energy efficiency of right, but not left, rat ventricular trabeculae.

PubMed

Pham, Toan; Nisbet, Linley; Taberner, Andrew; Loiselle, Denis; Han, June-Chiew

2018-04-01

Pulmonary arterial hypertension (PAH) triggers right ventricle (RV) hypertrophy and left ventricle (LV) atrophy, which progressively leads to heart failure. We designed experiments under conditions mimicking those encountered by the heart in vivo that allowed us to investigate whether consequent structural and functional remodelling of the ventricles affects their respective energy efficiencies. We found that peak work output was lower in RV trabeculae from PAH rats due to reduced extent and velocity of shortening. However, their suprabasal enthalpy was unaffected due to increased activation heat, resulting in reduced suprabasal efficiency. There was no effect of PAH on LV suprabasal efficiency. We conclude that the mechanism underlying the reduced energy efficiency of hypertrophied RV tissues is attributable to the increased energy cost of Ca 2+ cycling, whereas atrophied LV tissues still maintain normal mechano-energetic performance. Pulmonary arterial hypertension (PAH) greatly increases the afterload on the right ventricle (RV), triggering RV hypertrophy, which progressively leads to RV failure. In contrast, the disease reduces the passive filling pressure of the left ventricle (LV), resulting in LV atrophy. We investigated whether these distinct structural and functional consequences to the ventricles affect their respective energy efficiencies. We studied trabeculae isolated from both ventricles of Wistar rats with monocrotaline-induced PAH and their respective Control groups. Trabeculae were mounted in a calorimeter at 37°C. While contracting at 5 Hz, they were subjected to stress-length work-loops over a wide range of afterloads. They were subsequently required to undergo a series of isometric contractions at various muscle lengths. In both protocols, stress production, length change and suprabasal heat output were simultaneously measured. We found that RV trabeculae from PAH rats generated higher activation heat, but developed normal active stress. Their

Interleukin 1 alpha-induced expression of manganous superoxide dismutase reduces myocardial reperfusion injury in the rat.

PubMed

Nogae, C; Makino, N; Hata, T; Nogae, I; Takahashi, S; Suzuki, K; Taniguchi, N; Yanaga, T

1995-10-01

We investigated the effects of pretreatment with interleukin (IL)-1 alpha on the expression of manganous (Mn) superoxide dismutase (SOD) mRNA and reperfusion-induced arrhythmias and the size of myocardial infarct in rats. Male Wistar rats received 10 mg intraperitoneal injections of human recombinant IL-1 alpha. Their hearts were thereafter isolated at 6, 12, 24, 36 h. A Northern analysis showed that Mn-SOD mRNA was mainly expressed in the heart and slightly in kidney, but not in any other organs. The expression of Mn-SOD mRNA peaked at 6 h after the injection of IL-1 alpha. The Mn-SOD protein content was most increased 12 h after injection. In the isolated heart model, the rats were pretreated with IL-1 alpha 24 h earlier and their hearts were perfused by the Langendorff method. After 20 min of ischemia which was induced by a ligation of a coronary artery, reperfusion-induced arrhythmias were observed. There were no significant differences in the incidence of ventricular arrhythmias between the IL-1 alpha pretreated and the untreated hearts. IL-1 alpha pretreatment significantly reduced the mean duration of the ventricular arrhythmias and also delayed the onset of arrhythmias. The effect of IL-1 alpha pretreatment was also investigated in a 30-min model of ischemia followed by a 3-min reperfusion in anesthetized rats. The infarct size expressed as a percentage of the area at risk was significantly reduced in the IL-1 alpha pretreated hearts compared with the untreated hearts. The left ventricular systolic pressure increased significantly in rat hearts pretreated with IL-1 alpha. Our results therefore showed that the pretreatment with IL-1 alpha induced the overexpression of Mn-SOD mRNA in the rat hearts and also suggested that pretreatment with IL-1 alpha 24 h before ischemia reduced the risk of ischemia-reperfusion injury.

Antrodia Cinnamomea Reduces Carbon Tetrachloride-induced Hepatotoxicity In Male Wister Rats.

PubMed

Shih, Yung-Luen; Wu, Ming-Fang; Lee, Ching-Hsiao; Yeh, Ming-Yang; Chou, Jason; Liu, Jia-You; Lu, Hsu-Feng; Huang, Yi-Ping; Liao, Nien-Chieh; Chung, Jing-Gung

2017-01-01

Antrodia cinnamomea is found with polysaccharides, lipids, vitamins, fibers and ash (minerals) and is well known in Taiwan as a traditional Chinese medicine. Its biological activities have been reported to have anti-inflammatory, anti-fatigue, anti-tumor and immunomodulatory effects, but its protective effects on liver function are still unclear. We determined if Antrodia cinnamomea was hepatoprotective against carbon tetrachloride (CCl 4 ) toxicity in Wistar rats. Six groups were used in the study: 1) control (no induction by CCl 4 ); 2) negative control (CCl 4 -induction and no treatment); 3) positive control (silymarin treatment); 4) groups 4-6 were treated with CC1 4 and different concentrations (350 mg/kg, 1,400 mg/kg, 3,150 mg/kg) of Antrodia cinnamomea. Blood and liver samples of rats were harvested and then detected by biochemical and tissue histochemical analysis. Activity of the antioxidative enzymes glutathione peroxidase, superoxide dismutase and catalase in the liver were also monitored. Only the high-dose treatment was able to decrease serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels and improve liver function. High and medium doses increased total liver protein and reduced hydroxyproline. It was also observed that the high dose treatment reduced lipid peroxidation. Liver sections of CC1 4 treated animals receiving Antrodia cinnamomea showed less fibrosis compared to the CCl 4 control group. This finding suggested that Antrodia cinnamomea can either enhance liver recovering from CCl 4 damage or attenuate CCl 4 toxicity in rats. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Resistance exercise reduces memory impairment induced by monosodium glutamate in male and female rats.

PubMed

Araujo, Paulo Cesar Oliveira; Quines, Caroline Brandão; Jardim, Natália Silva; Leite, Marlon Regis; Nogueira, Cristina Wayne

2017-07-01

What is the central question of this study? Monosodium glutamate causes cognitive impairment. Does resistance exercise improve the performance of rats treated with monosodium glutamate? What is the main finding and its importance? Resistance exercise is effective against monosodium glutamate-induced memory impairment in male and female rats. Monosodium glutamate (MSG), a flavour enhancer in diets, causes cognitive impairment in rodents. Exercise has been reported to protect against impairment of memory in humans. In this study, we investigated whether resistance exercise improves the performance of male and female rats treated with MSG in tests of memory and motor co-ordination. Wistar rats received MSG [4 g (kg body weight) -1  day -1 , s.c.] from postnatal day 1 to 10. At postnatal day 60, the animals started a resistance exercise protocol in an 80 deg inclined vertical ladder apparatus and performed it during 7 weeks. Rats performed object recognition and location memory tests. Resistance exercise reduced impairment in motor co-ordination of male and female rats treated with MSG. Resistance exercise was effective against the decrease in exploratory preference in the long-term recognition memory for novel objects of male rats treated with MSG. In MSG-treated female rats, resistance exercise was effective against the decrease in exploratory preference in the novel object location test. The exploratory preference of female rats in the long-term recognition memory test was similar in all groups. The short-term memory was not altered by MSG or resistance exercise in male and female rats. This study demonstrates that MSG affected the memory of male and female rats in different ways. Resistance exercise was effective against the decrease in recognition for male rats and in location memory for female rats treated with MSG. This report demonstrates the beneficial effects of resistance exercise against the prejudice of motor condition and impairment of memory induced

The soluble fiber complex PolyGlycopleX lowers serum triglycerides and reduces hepatic steatosis in high-sucrose-fed rats.

PubMed

Reimer, Raylene A; Grover, Gary J; Koetzner, Lee; Gahler, Roland J; Lyon, Michael R; Wood, Simon

2011-04-01

Viscous soluble fibers have been shown to reduce risk factors associated with type 2 diabetes and cardiovascular disease. The novel functional fiber, PolyGlycopleX (PGX) (InovoBiologic Inc, Calgary, Alberta, Canada) displays greater viscosity than other currently identified soluble fibers. The objective of this study was to determine if PGX lowers serum and hepatic triglycerides (TGs) in a high-sucrose-fed rat model. In this rodent model, feeding a high-sucrose diet consistently increases serum TGs. We hypothesized that consumption of PGX would attenuate hypertriglyceridemia and reduce hepatic steatosis compared with cellulose in rats fed a high-sucrose background diet. Male Sprague-Dawley rats were fed diets containing 65% sucrose and supplemented with either 5% cellulose (control) or 5% PGX (wt/wt) for 43 weeks. At study termination, serum insulin and TGs, hepatic steatosis, and hepatocellular injury were assessed. Body weight increased over time in both groups, but weight gain was attenuated in rats fed PGX vs cellulose in weeks 2 through 22 (P < .05). Serum TGs did not differ from baseline for the first half of the study but consistently increased in the cellulose group thereafter. PolyGlycopleX significantly reduced serum TG to near-baseline levels. At study termination, rats fed PGX had significantly lower hepatic steatosis scores (measured by Sudan black staining) compared with rats fed cellulose. Hepatocellular injury scores did not differ between the groups. In conclusion, PGX reduced serum TG and lipid accumulation in the liver of sucrose-fed rats. Further examination of its potential as a fiber supplement aimed at lessening the burden of hepatic steatosis is warranted. Copyright © 2011 Elsevier Inc. All rights reserved.

Female Wistar rats tested during late proestrus or during pregnancy and ovariectomized rats tested after receiving progesterone or allopregnanolone displayed reduced conflict behavior.

PubMed

Molina-Hernandez, Miguel; Perez, Julian Garcia; Olivera Lopez, Jorge Ivan

2002-06-01

In a conflict test based on the rat's choice between an immediate punished reinforcer or a delayed nonpunished reinforcer, anxiolytic drugs increase the number of immediate punished reinforcers. In this study, two hypotheses were tested: first, during late proestrus or during midpregnancy, female rats will display an elevated amount of immediate punished reinforcers; second, ovariectomized rats will display an elevated amount of immediate punished reinforcers when they receive anxiolytic doses of neurosteroids. Thus, female rats (n = 15) were tested repeatedly during late proestrus, diestrus, and pregnancy in the aforementioned conflict task. They displayed an elevated amount of immediate punished reinforcers during late proestrus (P < .05) and during the 14th (P < .05) and 17th (P < .05) days of pregnancy compared to diestrus or 3rd, 7th, or 20th days of pregnancy. Likewise, ovariectomized rats (n = 90) displayed an elevated amount of immediate punished reinforcers compared to control rats only when they received anxiolytic doses of progesterone (1.0-2.0 mg/kg, P < .05) or allopregnanolone (1.0-2.0 mg/kg, P < .05). In conclusion, female rats displayed reduced conflict behavior during late proestrus and pregnancy, or after received anxiolytic doses of neurosteroids.

Methylphenidate disrupts cytoskeletal homeostasis and reduces membrane-associated lipid content in juvenile rat hippocampus.

PubMed

Schmitz, Felipe; Pierozan, Paula; Biasibetti-Brendler, Helena; Ferreira, Fernanda Silva; Dos Santos Petry, Fernanda; Trindade, Vera Maria Treis; Pessoa-Pureur, Regina; Wyse, Angela T S

2017-12-29

Although methylphenidate (MPH) is ubiquitously prescribed to children and adolescents, the consequences of chronic utilization of this psychostimulant are poorly understood. In this study, we investigated the effects of MPH on cytoskeletal homeostasis and lipid content in rat hippocampus. Wistar rats received intraperitoneal injections of MPH (2.0 mg/kg) or saline solution (controls), once a day, from the 15th to the 44th day of age. Results showed that MPH provoked hypophosphorylation of glial fibrillary acidic protein (GFAP) and reduced its immunocontent. Middle and high molecular weight neurofilament subunits (NF-M, NF-H) were hypophosphorylated by MPH on KSP repeat tail domains, while NFL, NFM and NFH immunocontents were not altered. MPH increased protein phosphatase 1 (PP1) and 2A (PP2A) immunocontents. MPH also decreased the total content of ganglioside and phospholipid, as well as the main brain gangliosides (GM1, GD1a, and GD1b) and the major brain phospholipids (sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine). Total cholesterol content was also reduced in the hippocampi of juvenile rats treated with MPH. These results provide evidence that disruptions of cytoskeletal and lipid homeostasis in hippocampus of juvenile rats are triggers by chronic MPH treatment and present a new basis for understanding the effects and consequences associated with chronic use of this psychostimulant during the development of the central nervous system.

Esmolol reduces apoptosis and inflammation in early sepsis rats with abdominal infection.

PubMed

Lu, Yang; Yang, Yang; He, Xin; Dong, Shangwen; Wang, Wanhua; Wang, Donghao; Zhang, Peng

2017-10-01

Esmolol is a highly selective beta 1 receptor blocker with various effects such as slowing heart rate, lowering blood pressure and reducing myocardial oxygen consumption. However, few studies have reported the use of beta blockers in sepsis with multiple organ dysfunctions. This study aimed to investigate the effects of esmolol on reducing apoptosis and inflammation in early sepsis rats with abdominal infection. Rats were randomly divided into sham operation group, sepsis group, antibiotic group, Esmolol + antibiotic group with low, median and high dose Esmolol (L group, M group and H group). Values between two or more groups were compared by independent t-tests. In the liver and kidney, we found inflammatory infiltration in sepsis group while pathological aspects reduced in L, M and H groups. Bcl-2 mRNA and protein levels increased while Bax mRNA and protein levels decreased in the liver and kidney of L, M and H groups. Serum IL-6, HMGB-1 and TNF-α levels decreased but IL-10 level increased in L, M and H groups, compared to sepsis group. Compared to sepsis and antibiotic groups, the levels of myocardial enzymes were lower in L, M and H groups. The administration of esmolol in early sepsis may reduce inflammation, inhibit apoptosis and protect key organs. Copyright © 2017 Elsevier Inc. All rights reserved.

Progranulin Reduced Neuronal Cell Death by Activation of Sortilin 1 Signaling Pathways After Subarachnoid Hemorrhage in Rats.

PubMed

Li, Bo; He, Yue; Xu, Liang; Hu, Qin; Tang, Junjia; Chen, Yujie; Tang, Jiping; Feng, Hua; Zhang, John H

2015-08-01

Progranulin has been reported to have neuroprotective actions in cultured neurons. This study investigated the effect of recombinant rat progranulin on early brain injury after subarachnoid hemorrhage. Controlled in vivo laboratory study. Animal research laboratory. Two hundred thirty adult male Sprague-Dawley rats weighing 280-320 g. Subarachnoid hemorrhage was induced in rats by endovascular perforation. Rat recombinant progranulin (1 and 3 ng) was administrated intracerebroventricularly at 1.5 hours after subarachnoid hemorrhage. Progranulin small interfering RNA was administrated by intracerebroventricularly at 1 day before subarachnoid hemorrhage induction. Subarachnoid hemorrhage grade, neurologic score, and brain water content were measured at 24 and 72 hours after subarachnoid hemorrhage. Neural apoptosis was evaluated by double immunofluorescence staining using terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick-end labeling and neuronal nuclei. For mechanistic study, the expression of progranulin, phosphorylated Akt, Akt, p-Erk, Erk, Bcl-2, and cleaved caspase-3 were analyzed by Western blot at 24 hours after subarachnoid hemorrhage. siRNA for sortilin 1 (a progranulin receptor) was used to intervene the downstream pathway. The expression of progranulin decreased and reached the lowest point at 24 hours after subarachnoid hemorrhage. Administration of rat recombinant progranulin decreased brain water content and improved neurologic functions at both 24 and 72 hours after subarachnoid hemorrhage, while knockdown of endogenous progranulin aggravated neurologic deficits after subarachnoid hemorrhage. Rat recombinant progranulin treatment reduced neuronal apoptosis, while progranulin deficiency promoted neuronal apoptosis at 24 hours after subarachnoid hemorrhage. Rat recombinant progranulin promoted Akt activation, increased Bcl-2 level, but reduced caspase-3 level. Knockdown of progranulin binding factor sortilin 1

Green tea polyphenols reduce body weight in rats by modulating obesity-related genes.

PubMed

Lu, Chuanwen; Zhu, Wenbin; Shen, Chwan-Li; Gao, Weimin

2012-01-01

Beneficial effects of green tea polyphenols (GTP) against obesity have been reported, however, the mechanism of this protection is not clear. Therefore, the objective of this study was to identify GTP-targeted genes in obesity using the high-fat-diet-induced obese rat model. A total of three groups (n = 12/group) of Sprague Dawley (SD) female rats were tested, including the control group (rats fed with low-fat diet), the HF group (rats fed with high-fat diet), and the HF+GTP group (rats fed with high-fat diet and GTP in drinking water). The HF group increased body weight as compared to the control group. Supplementation of GTP in the drinking water in the HF+GTP group reduced body weight as compared to the HF group. RNA from liver samples was extracted for gene expression analysis. A total of eighty-four genes related to obesity were analyzed using PCR array. Compared to the rats in the control group, the rats in the HF group had the expression levels of 12 genes with significant changes, including 3 orexigenic genes (Agrp, Ghrl, and Nr3c1); 7 anorectic genes (Apoa4, Cntf, Ghr, IL-1β, Ins1, Lepr, and Sort); and 2 genes that relate to energy expenditure (Adcyap1r1 and Adrb1). Intriguingly, the HF+GTP group restored the expression levels of these genes in the high-fat-induced obese rats. The protein expression levels of IL-1β and IL-6 in the serum samples from the control, HF, and HF+GTP groups confirmed the results of gene expression. Furthermore, the protein expression levels of superoxide dismutase-1 (SOD1) and catechol-O-methyltransferase (COMT) also showed GTP-regulated protective changes in this obese rat model. Collectively, this study revealed the beneficial effects of GTP on body weight via regulating obesity-related genes, anti-inflammation, anti-oxidant capacity, and estrogen-related actions in high-fat-induced obese rats.

Green Tea Polyphenols Reduce Body Weight in Rats by Modulating Obesity-Related Genes

PubMed Central

Lu, Chuanwen; Zhu, Wenbin; Shen, Chwan-Li; Gao, Weimin

2012-01-01

Beneficial effects of green tea polyphenols (GTP) against obesity have been reported, however, the mechanism of this protection is not clear. Therefore, the objective of this study was to identify GTP-targeted genes in obesity using the high-fat-diet-induced obese rat model. A total of three groups (n = 12/group) of Sprague Dawley (SD) female rats were tested, including the control group (rats fed with low-fat diet), the HF group (rats fed with high-fat diet), and the HF+GTP group (rats fed with high-fat diet and GTP in drinking water). The HF group increased body weight as compared to the control group. Supplementation of GTP in the drinking water in the HF+GTP group reduced body weight as compared to the HF group. RNA from liver samples was extracted for gene expression analysis. A total of eighty-four genes related to obesity were analyzed using PCR array. Compared to the rats in the control group, the rats in the HF group had the expression levels of 12 genes with significant changes, including 3 orexigenic genes (Agrp, Ghrl, and Nr3c1); 7 anorectic genes (Apoa4, Cntf, Ghr, IL-1β, Ins1, Lepr, and Sort); and 2 genes that relate to energy expenditure (Adcyap1r1 and Adrb1). Intriguingly, the HF+GTP group restored the expression levels of these genes in the high-fat-induced obese rats. The protein expression levels of IL-1β and IL-6 in the serum samples from the control, HF, and HF+GTP groups confirmed the results of gene expression. Furthermore, the protein expression levels of superoxide dismutase-1 (SOD1) and catechol-O-methyltransferase (COMT) also showed GTP-regulated protective changes in this obese rat model. Collectively, this study revealed the beneficial effects of GTP on body weight via regulating obesity-related genes, anti-inflammation, anti-oxidant capacity, and estrogen-related actions in high-fat-induced obese rats. PMID:22715380

Swimming exercise demonstrates advantages over running exercise in reducing proteinuria and glomerulosclerosis in spontaneously hypertensive rats.

PubMed

Totou, N L; Moura, S S; Coelho, D B; Oliveira, E C; Becker, L K; Lima, W G

2018-03-01

Experimental studies in animal models have described the benefits of physical exercise (PE) to kidney diseases associated with hypertension. Land- and water-based exercises induce different responses in renal function. Our aim was to evaluate the renal alterations induced by different environments of PE in spontaneously hypertensive rats (SHRs). The SHRs were divided into sedentary (S), swimming exercise (SE), and running exercise (RE) groups, and were trained for 8 weeks under similar intensities (60 min/day). Arterial pressure (AP) and heart rate (HR) were recorded. The renal function was evaluated through urinary volume at each week of training; sodium and potassium excretions, plasma and urinary osmolarities, glomerular filtration rate (GFR), levels of proteinuria, and renal damage were determined. SE and RE rats presented reduced mean AP, systolic blood pressure, and HR in comparison with S group. SE and RE rats showed higher urine osmolarity compared with S. SE rats showed higher free water clearance (P < 0.01), lower urinary density (P < 0.0001), and increased weekly urine volume (P < 0.05) in comparison with RE and S groups. GFR was increased in both SE and RE rats. The proteinuria of SE (7.0 ± 0.8 mg/24 h) rats was decreased at the 8th week of the PE in comparison with RE (9.6 ± 0.8 mg/24 h) and S (9.8 ± 0.5 mg/24 h) groups. The glomerulosclerosis was reduced in SE rats (P < 0.02). SE produced different response in renal function in comparison with RE, in which only swimming-trained rats had better profile for proteinuria and glomerulosclerosis.

Myenteric denervation differentially reduces enteroendocrine serotonin cell population in rats during postnatal development.

PubMed

Hernandes, Luzmarina; Fernandes, Marilda da Cruz; Pereira, Lucieni Cristina Marques da Silva; Freitas, Priscila de; Gama, Patrícia; Alvares, Eliana Parisi

2006-05-01

The enteric nervous and enteroendocrine systems regulate different processes in the small intestine. Ablation of myenteric plexus with benzalkonium chloride (BAC) stimulates epithelial cell proliferation, whereas endocrine serotonin cells may inhibit the process. To evaluate the connection between the systems and the influence of myenteric plexus on serotoninergic cells in rats during postnatal development, the ileal plexus was partially removed with BAC. Rats were treated at 13 or 21 days and sacrificed after 15 days. The cell bodies of myenteric neurons were stained by beta NADH-diaphorase to detect the extension of denervation. The number of enteroendocrine cells in the ileum was estimated in crypts and villi in paraffin sections immunostained for serotonin. The number of neurons was reduced by 27.6 and 45% in rats treated on the 13th and 21st days, respectively. We tried to establish a correlation of denervation and the serotonin population according to the age of treatment. We observed a reduction of immunolabelled cells in the crypts of rats treated at 13 days, whereas this effect was seen in the villi of rats denervated at 21 days. These results suggest that the enteric nervous system might control the enteroendocrine cell population and this complex mechanism could be correlated to changes in cell proliferation.

Decoding bipedal locomotion from the rat sensorimotor cortex

NASA Astrophysics Data System (ADS)

Rigosa, J.; Panarese, A.; Dominici, N.; Friedli, L.; van den Brand, R.; Carpaneto, J.; DiGiovanna, J.; Courtine, G.; Micera, S.

2015-10-01

Objective. Decoding forelimb movements from the firing activity of cortical neurons has been interfaced with robotic and prosthetic systems to replace lost upper limb functions in humans. Despite the potential of this approach to improve locomotion and facilitate gait rehabilitation, decoding lower limb movement from the motor cortex has received comparatively little attention. Here, we performed experiments to identify the type and amount of information that can be decoded from neuronal ensemble activity in the hindlimb area of the rat motor cortex during bipedal locomotor tasks. Approach. Rats were trained to stand, step on a treadmill, walk overground and climb staircases in a bipedal posture. To impose this gait, the rats were secured in a robotic interface that provided support against the direction of gravity and in the mediolateral direction, but behaved transparently in the forward direction. After completion of training, rats were chronically implanted with a micro-wire array spanning the left hindlimb motor cortex to record single and multi-unit activity, and bipolar electrodes into 10 muscles of the right hindlimb to monitor electromyographic signals. Whole-body kinematics, muscle activity, and neural signals were simultaneously recorded during execution of the trained tasks over multiple days of testing. Hindlimb kinematics, muscle activity, gait phases, and locomotor tasks were decoded using offline classification algorithms. Main results. We found that the stance and swing phases of gait and the locomotor tasks were detected with accuracies as robust as 90% in all rats. Decoded hindlimb kinematics and muscle activity exhibited a larger variability across rats and tasks. Significance. Our study shows that the rodent motor cortex contains useful information for lower limb neuroprosthetic development. However, brain-machine interfaces estimating gait phases or locomotor behaviors, instead of continuous variables such as limb joint positions or speeds

Decoding bipedal locomotion from the rat sensorimotor cortex.

PubMed

Rigosa, J; Panarese, A; Dominici, N; Friedli, L; van den Brand, R; Carpaneto, J; DiGiovanna, J; Courtine, G; Micera, S

2015-10-01

Decoding forelimb movements from the firing activity of cortical neurons has been interfaced with robotic and prosthetic systems to replace lost upper limb functions in humans. Despite the potential of this approach to improve locomotion and facilitate gait rehabilitation, decoding lower limb movement from the motor cortex has received comparatively little attention. Here, we performed experiments to identify the type and amount of information that can be decoded from neuronal ensemble activity in the hindlimb area of the rat motor cortex during bipedal locomotor tasks. Rats were trained to stand, step on a treadmill, walk overground and climb staircases in a bipedal posture. To impose this gait, the rats were secured in a robotic interface that provided support against the direction of gravity and in the mediolateral direction, but behaved transparently in the forward direction. After completion of training, rats were chronically implanted with a micro-wire array spanning the left hindlimb motor cortex to record single and multi-unit activity, and bipolar electrodes into 10 muscles of the right hindlimb to monitor electromyographic signals. Whole-body kinematics, muscle activity, and neural signals were simultaneously recorded during execution of the trained tasks over multiple days of testing. Hindlimb kinematics, muscle activity, gait phases, and locomotor tasks were decoded using offline classification algorithms. We found that the stance and swing phases of gait and the locomotor tasks were detected with accuracies as robust as 90% in all rats. Decoded hindlimb kinematics and muscle activity exhibited a larger variability across rats and tasks. Our study shows that the rodent motor cortex contains useful information for lower limb neuroprosthetic development. However, brain-machine interfaces estimating gait phases or locomotor behaviors, instead of continuous variables such as limb joint positions or speeds, are likely to provide more robust control

(-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine self-administration in rats.

PubMed

Manuszak, M; Harding, W; Gadhiya, S; Ranaldi, R

2018-05-31

Dopamine receptors are implicated in cocaine reward and seeking. We hypothesize that (-)-stepholidine, a dopamine D1/D2/D3 multi-receptor agent, would be effective in reducing cocaine reward and seeking in an animal model. We investigated the effects of (-)-stepholidine in cue-induced reinstatement of cocaine seeking and cocaine self-administration (reward). Cue-induced reinstatement experiment: Rats were trained to press a lever reinforced by cocaine (1 mg/kg/injection) for 15 consecutive daily sessions, after which the response was extinguished by withholding cocaine and cocaine-paired cues (light and pump activation). This was followed by a cue-induced reinstatement test where subjects were exposed to two cocaine cue presentations and presses on the active lever produced cues. Subjects were treated with one of four (-)-stepholidine doses prior to the reinstatement test. Cocaine self-administration (reward) experiment: Rats were trained to self-administer cocaine under a progressive ratio schedule of reinforcement. After stable breakpoints were established, rats were injected with four doses of (-)-stepholidine prior to testing; each dose was injected prior to a separate test session with no-treatment sessions intervening to re-establish break points. (-)-Stepholidine significantly reduced cue-induced reinstatement of cocaine seeking in a dose-related manner. Additionally, (-)-stepholidine significantly reduced break points for cocaine reward. (-)-Stepholidine did not significantly affect locomotor activity. (-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine reward, suggesting that it may be useful in treating relapse in cocaine addiction. Copyright © 2018 Elsevier B.V. All rights reserved.

Transient voltage-dependent potassium currents are reduced in NTS neurons isolated from renal wrap hypertensive rats.

PubMed

Belugin, Sergei; Mifflin, Steve

2005-12-01

Whole cell patch-clamp measurements were made in neurons enzymatically dispersed from the nucleus of the solitary tract (NTS) to determine if alterations occur in voltage-dependent potassium channels from rats made hypertensive (HT) by unilateral nephrectomy/renal wrap for 4 wk. Some rats had the fluorescent tracer DiA applied to the aortic nerve before the experiment to identify NTS neurons receiving monosynaptic baroreceptor afferent inputs. Mean arterial pressure (MAP) was greater in 4-wk HT (165 +/- 5 mmHg, n = 26, P < 0.001) rats compared with normotensive (NT) rats (109 +/- 3 mmHg measured in 10 of 69 rats). Transient outward currents (TOCs) were observed in 67-82% of NTS neurons from NT and HT rats. At activation voltages from -10 to +10 mV, TOCs were significantly less in HT neurons compared with those observed in NT neurons (P < 0.001). There were no differences in the voltage-dependent activation kinetics, the voltage dependence of steady-state inactivation, and the rise and decay time constants of the TOCs comparing neurons isolated from NT and HT rats. The 4-aminopyridine-sensitive component of the TOC was significantly less in neurons from HT compared with NT rats (P < 0.001), whereas steady-state outward currents, whether or not sensitive to 4-aminopyridine or tetraethylammonium, were not different. Delayed excitation, studied under current clamp, was observed in 60-80% of NTS neurons from NT and HT rats and was not different comparing neurons from NT and HT rats. However, examination of the subset of NTS neurons exhibiting somatic DiA fluorescence revealed that DiA-labeled neurons from HT rats had a significantly shorter duration delayed excitation (n = 8 cells, P = 0.022) than DiA-labeled neurons from NT rats (n = 7 cells). Neurons with delayed excitation from HT rats had a significantly broader first action potential (AP) and a slower maximal downstroke velocity of repolarization compared with NT neurons with delayed excitation (P = 0.016 and P = 0

Rosiglitazone reduces body wasting and improves survival in a rat model of cancer cachexia.

PubMed

Trobec, Katja; Palus, Sandra; Tschirner, Anika; von Haehling, Stephan; Doehner, Wolfram; Lainscak, Mitja; Anker, Stefan D; Springer, Jochen

2014-09-01

Rosiglitazone improves insulin sensitivity and promotes weight gain in patients with type 2 diabetes mellitus, which could be useful in wasting and cachexia. However, its effects on cardiac function are controversial. The aim of this study was to investigate the effects of rosiglitazone on body wasting, body composition, cardiac function, and survival in a rat model of cancer cachexia. Rats were injected with Yoshida AH-130 hepatoma tumor cells and randomized to receive placebo or rosiglitazone 4 mg/kg daily. Treatment started 1 d after tumor inoculation and the rats were sacrificed 14 d thereafter. Body weight and body composition was measured at baseline and after removal of tumor. Echocardiography was performed at baseline and on day 11. At the end of the study, organs were weighed and the proteasome activity in gastrocnemius muscle was measured. Survival analysis showed a significant benefit from treatment with rosiglitazone (hazard ratio = 0.38, 95% confidence interval: 0.15-0.86). Rosiglitazone reduced average daily weight loss (2.33 g/d rosiglitazone versus 3.93 g/d placebo; P < 0.05) as a result of both fat and lean mass preservation. It decelerated white and brown tissue wasting, but had no effect on skeletal muscle mass and heart mass. However, peptidyl-glutamyl-protein-hydrolysing and trypsin-like activity in gastrocnemius muscle was significantly reduced by rosiglitazone. Finally, it increased left ventricular ejection fraction, fractional shortening, and systolic volume and improved cardiac output in cachectic cancer rats. Rosiglitazone prevents weight loss and improves survival in a rat model of cancer cachexia. It exerts beneficial effects on cardiac function. Copyright © 2014 Elsevier Inc. All rights reserved.

Exposure to sucrose during periods of withdrawal does not reduce cocaine-seeking behavior in rats.

PubMed

Nicolas, Céline; Lafay-Chebassier, Claire; Solinas, Marcello

2016-03-21

Concomitant access to drugs of abuse and alternative rewards such as sucrose has been shown to decrease addiction-related behaviors in animals. Here we investigated whether access to sucrose during abstinence in contexts that are temporally and physically distinct from drug-related contexts could reduce subsequent drug seeking. In addition, we investigated whether a history of cocaine self-administration would alter the rewarding effects of sucrose. Rats self-administered cocaine for ten sessions, while yoked-saline rats received only saline injections, and then we subjected them to a 30-day withdrawal period during which they had access to water and sucrose continuously or intermittently according to a schedule that induces binge-drinking behavior. At the end of the withdrawal period, rats were tested for cocaine seeking behavior during a single 6 h session. We found that exposure to cocaine increased sucrose consumption only when rats had intermittent access to sucrose, but exposure to sucrose did not alter drug seeking regardless of the schedule of access. These results suggest that exposure to cocaine cross-sensitizes to the rewarding effects of sucrose, but exposure to sucrose during abstinence, temporally and physically distinct from drug-related environments, does not to reduce drug seeking.

Effect of streptozotocin-induced diabetes on motor representations in the motor cortex and corticospinal tract in rats.

PubMed

Muramatsu, Ken; Ikutomo, Masako; Tamaki, Toru; Shimo, Satoshi; Niwa, Masatoshi

2018-02-01

Motor disorders in patients with diabetes are associated with diabetic peripheral neuropathy, which can lead to symptoms such as lower extremity weakness. However, it is unclear whether central motor system disorders can disrupt motor function in patients with diabetes. In a streptozotocin-induced rat model of type 1 diabetes, we used intracortical microstimulation to evaluate motor representations in the motor cortex, recorded antidromic motor cortex responses to spinal cord stimulation to evaluate the function of corticospinal tract (CST) axons, and used retrograde labeling to evaluate morphological alterations of CST neurons. The diabetic rats exhibited size reductions in the hindlimb area at 4 weeks and in trunk and forelimb areas after 13 weeks, with the hindlimb and trunk area reductions being the most severe. Other areas were unaffected. Additionally, we observed reduced antidromic responses in CST neurons with axons projecting to lumbar spinal segments (CST-L) but not in those with axons projecting to cervical segments (CST-C). This was consistent with the observation that retrograde-labeled CST-L neurons were decreased in number following tracer injection into the spinal cord in diabetic animals but that CST-C neurons were preserved. These results show that diabetes disrupts the CST system components controlling hindlimb and trunk movement. This disruption may contribute to lower extremity weakness in patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Human recombinant erythropoietin reduces sensorimotor dysfunction and cognitive impairment in rat models of chronic kidney disease.

PubMed

Reza-Zaldívar, E E; Sandoval-Avila, S; Gutiérrez-Mercado, Y K; Vázquez-Méndez, E; Canales-Aguirre, A A; Esquivel-Solís, H; Gómez-Pinedo, U; Márquez-Aguirre, A L

2017-11-10

Chronic kidney disease (CKD) can cause anaemia and neurological disorders. Recombinant human erythropoietin (rHuEPO) is used to manage anaemia in CKD. However, there is little evidence on the effects of rHuEPO on behaviour and cognitive function in CKD. This study aimed to evaluate the impact of rHuEPO in sensorimotor and cognitive functions in a CKD model. Male Wistar rats were randomly assigned to 4 groups: control and CKD, with and without rHuEPO treatment (1050 IU per kg body weight, once weekly for 4 weeks). The Morris water maze, open field, and adhesive removal tests were performed simultaneously to kidney damage induction and treatment. Markers of anaemia and renal function were measured at the end of the study. Treatment with rHuEPO reduced kidney damage and corrected anaemia in rats with CKD. We observed reduced sensorimotor dysfunction in animals with CKD and treated with rHuEPO. These rats also completed the water maze test in a shorter time than the control groups. rHuEPO reduces kidney damage, corrects anemia, and reduces sensorimotor and cognitive dysfunction in animals with CKD. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

A Vegetable, Launaea taraxacifolia, Mitigated Mercuric Chloride Alteration of the Microanatomy of Rat Brain.

PubMed

Owoeye, Olatunde; Arinola, Ganiyu O

2017-11-02

Mercuric chloride is an environmental pollutant that affects the nervous systems of mammals. Oxidative damage is one of the mechanisms of its toxicity, and antioxidants should mitigate this effect. A vegetable with antioxidant activity is Launaea taraxacifolia, whose ethanolic extract (EELT) was investigated in this experiment to determine its effect against mercuric chloride (MC) intoxication in rat brain. Thirty male Wistar rats were randomly assigned into five groups (n = 6) as follows: control; propylene glycol; EELT (400 mg/kg bwt) for 19 days; MC (HgCl 2 ) (4 mg/bwt) for 5 days from day 15 of the experiment; EELT+ MC, EELT (400 mg/kg bwt) for 14 days + MC (4 mg/bwt) for 5 days from day 15 of the experiment. All treatments were administered orally by gastric gavage. Behavioral tests were conducted on the 20th day, and rats were euthanized the same day. Blood and brain tissue were examined with regard to microanatomical parameters. Data were analyzed using analysis of variance with statistical significance set at p < .05. MC induced significant (19%) reduction of thrombocytes, which was ameliorated by 57% (p < .05) by pretreatment with EELT when compared with the MC group. Behavioral results showed that MC elicited significant reduction in transitions, rearings, forelimb grip strength, and latency of geotaxis. Histologically, MC induced alterations in the microanatomy of cerebral cortex, dentate gyrus, cornu ammonis 3, and cerebellum of rats. Treatment with EELT prior to MC administration significantly reduced the effect of MC on the hematological, behavioral, and ameliorated histological alterations of the brain. These findings may be attributed partially to the antioxidant property of EELT, which demonstrated protective effects against MC-induced behavioral parameters and alteration of microanatomy of rats' cerebral cortex, hippocampus, and cerebellum. In conclusion, EELT may be a valuable agent for further investigation in the prevention of acute

Trichloroethylene Metabolism in the Rat Ovary Reduces Oocyte Fertilizability

PubMed Central

Wu, Katherine Lily; Berger, Trish

2007-01-01

Exposure to trichloroethylene (TCE, an environmental toxicant) reduced oocyte fertilizability in the rat. In vivo, TCE may be metabolized by cytochrome P450 dependent oxidation or glutathione conjugation in the liver or kidneys, respectively. Cytochrome P450 dependent oxidation is the higher affinity pathway. The primary isoform of cytochrome P450 to metabolize TCE in the liver, cytochrome P450 2E1, is present in the rodent ovary. Ovarian metabolism of TCE by the oxidative pathway and the production of reactive oxygen species may occur given the presence of the metabolizing enzyme. The objectives of this study were to define the sensitive interval of oocyte growth to TCE exposure, and to determine if TCE exposure resulted in the formation of ovarian protein carbonyls, an indicator of oxidative damage. Rats were exposed to TCE in drinking water (0.45% TCE (v/v) in 3% Tween) or 3% Tween (vehicle-control) during three 4–5 day intervals of oocyte development preceding ovulation. Oocytes from TCE-exposed females were less fertilizable compared with vehicle-control oocytes. Immunohistochemical labeling of ovaries and Western blotting of ovarian proteins demonstrated TCE treatment induced a greater incidence of protein carbonyls compared with vehicle controls. Protein carbonyl formation in the ovary is consistent with TCE metabolism by the cytochrome P450 pathway. Oxidative damage following ovarian TCE metabolism or the presence of TCE metabolites may contribute to reduced oocyte fertilizability. In summary, these results indicate maturing oocytes are susceptible to very short in vivo exposures to TCE. PMID:17673192

Use of quadrupedal step training to re-engage spinal interneuronal networks and improve locomotor function after spinal cord injury.

PubMed

Shah, Prithvi K; Garcia-Alias, Guillermo; Choe, Jaehoon; Gad, Parag; Gerasimenko, Yury; Tillakaratne, Niranjala; Zhong, Hui; Roy, Roland R; Edgerton, V Reggie

2013-11-01

Can lower limb motor function be improved after a spinal cord lesion by re-engaging functional activity of the upper limbs? We addressed this issue by training the forelimbs in conjunction with the hindlimbs after a thoracic spinal cord hemisection in adult rats. The spinal circuitries were more excitable, and behavioural and electrophysiological analyses showed improved hindlimb function when the forelimbs were engaged simultaneously with the hindlimbs during treadmill step-training as opposed to training only the hindlimbs. Neuronal retrograde labelling demonstrated a greater number of propriospinal labelled neurons above and below the thoracic lesion site in quadrupedally versus bipedally trained rats. The results provide strong evidence that actively engaging the forelimbs improves hindlimb function and that one likely mechanism underlying these effects is the reorganization and re-engagement of rostrocaudal spinal interneuronal networks. For the first time, we provide evidence that the spinal interneuronal networks linking the forelimbs and hindlimbs are amenable to a rehabilitation training paradigm. Identification of this phenomenon provides a strong rationale for proceeding toward preclinical studies for determining whether training paradigms involving upper arm training in concert with lower extremity training can enhance locomotor recovery after neurological damage.

Calpain inhibition reduces NMDA receptor rundown in rat substantia nigra dopamine neurons.

PubMed

Zhao, Jerry; Baudry, Michel; Jones, Susan

2018-05-04

Repeated activation of N-Methyl-d-aspartate receptors (NMDARs) causes a Ca 2+ -dependent reduction in NMDAR-mediated current in dopamine (DA) neurons of the substantia nigra pars compacta (SNc) in one week old rats; however, a Ca 2+ -dependent regulatory protein has not been identified. The role of the Ca 2+ -dependent cysteine protease, calpain, in mediating NMDAR current rundown was investigated. In brain slices from rats aged postnatal day 7-9 ('P7'), bath application of either of the membrane permeable calpain inhibitors, N-Acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN, 20 μM) or MDL-28170 (30 μM) significantly reduced whole-cell NMDAR current rundown. To investigate the role of the calpain-2 isoform, the membrane permeable calpain-2 inhibitor, Z-Leu-Abu-CONH-CH2-C6H3 (3, 5-(OMe)2 (C2I, 200 nM), was applied; C2I application significantly reduced whole cell NMDAR current rundown. Interestingly, ALLN but not C2I significantly reduced rundown of NMDA-EPSCs. These results suggest the calpain-2 isoform mediates Ca 2+ -dependent regulation of extrasynaptic NMDAR current in the first postnatal week, while calpain-1 might mediate rundown of synaptic NMDAR currents. One week later in postnatal development, at P12-P16 ('P14'), there was significantly less rundown in SNc-DA neurons, and no significant effect on rundown of either Ca 2+ chelation or treatment with the calpain inhibitor, ALLN, suggesting that the rundown observed in SNc-DA neurons from two week-old rats might be Ca 2+ -independent. In conclusion, Ca 2+ -dependent rundown of extrasynaptic NMDAR currents in SNc DA neurons involves calpain-2 activation, but Ca 2+ - and calpain-2-dependent NMDAR current rundown is developmentally regulated. Copyright © 2018 Elsevier Ltd. All rights reserved.

D-Serine and D-Cycloserine Reduce Compulsive Alcohol Intake in Rats

PubMed Central

Seif, Taban; Simms, Jeffrey A; Lei, Kelly; Wegner, Scott; Bonci, Antonello; Messing, Robert O; Hopf, F Woodward

2015-01-01

There is considerable interest in NMDAR modulators to enhance memory and treat neuropsychiatric disorders such as addiction, depression, and schizophrenia. D-serine and D-cycloserine, the NMDAR activators at the glycine site, are of particular interest because they have been used in humans without serious adverse effects. Interestingly, D-serine also inhibits some NMDARs active at hyperpolarized potentials (HA-NMDARs), and we previously found that HA-NMDARs within the nucleus accumbens core (NAcore) are critical for promoting compulsion-like alcohol drinking, where rats consume alcohol despite pairing with an aversive stimulus such as quinine, a paradigm considered to model compulsive aspects of human alcohol use disorders (AUDs). Here, we examined the impact of D-serine and D-cycloserine on this aversion-resistant alcohol intake (that persists despite adulteration with quinine) and consumption of quinine-free alcohol. Systemic D-serine reduced aversion-resistant alcohol drinking, without altering consumption of quinine-free alcohol or saccharin with or without quinine. Importantly, D-serine within the NAcore but not the dorsolateral striatum also selectively reduced aversion-resistant alcohol drinking. In addition, D-serine inhibited EPSCs evoked at −70 mV in vitro by optogenetic stimulation of mPFC–NAcore terminals in alcohol-drinking rats, similar to reported effects of the NMDAR blocker AP5. Further, D-serine preexposure occluded AP5 inhibition of mPFC-evoked EPSCs, suggesting that D-serine reduced EPSCs by inhibiting HA-NMDARs. Systemic D-cycloserine also selectively reduced intake of quinine-adulterated alcohol, and D-cycloserine inhibited NAcore HA-NMDARs in vitro. Our results indicate that HA-NMDAR modulators can reduce aversion-resistant alcohol drinking, and support testing of D-serine and D-cycloserine as immediately accessible, FDA-approved drugs to treat AUDs. PMID:25801502

The incentive amplifying effects of nicotine are reduced by selective and non-selective dopamine antagonists in rats.

PubMed

Palmatier, Matthew I; Kellicut, Marissa R; Brianna Sheppard, A; Brown, Russell W; Robinson, Donita L

2014-11-01

Nicotine is a psychomotor stimulant with 'reinforcement enhancing' effects--the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate groups of rats were injected with nicotine (0.4mg/kg base) or saline prior to Pavlovian conditioning sessions in which a CS (30s illumination of a light or presentation of a lever) was immediately followed by a sweet reward delivered in an adjacent location. Both saline and nicotine pretreated rats exhibited similar levels of conditioned approach to the reward location (goal tracking), but nicotine pretreatment significantly increased approach to the CS (sign tracking), regardless of type (lever or light). The DAD1 antagonist SCH-23390 and the DAD2/3 antagonist eticlopride reduced conditioned approach in all rats, but specifically reduced goal tracking in the saline pretreated rats and sign tracking in the nicotine pretreated rats. The non-selective DA antagonist flupenthixol reduced sign-tracking in nicotine rats at all doses tested; however, only the highest dose of flupenthixol reduced goal tracking in both nicotine and saline groups. The reductions in conditioned approach behavior, especially those by SCH-23390, were dissociated from simple motor suppressant effects of the antagonists. These experiments are the first to investigate the effects of dopaminergic drugs on the facilitation of sign-tracking engendered by

Cyclosporine A at reperfusion fails to reduce infarct size in the in vivo rat heart.

PubMed

De Paulis, Damien; Chiari, Pascal; Teixeira, Geoffrey; Couture-Lepetit, Elisabeth; Abrial, Maryline; Argaud, Laurent; Gharib, Abdallah; Ovize, Michel

2013-09-01

We examined the effects on infarct size and mitochondrial function of ischemic (Isch), cyclosporine A (CsA) and isoflurane (Iso) preconditioning and postconditioning in the in vivo rat model. Anesthetized open-chest rats underwent 30 min of ischemia followed by either 120 min (protocol 1: infarct size assessment) or 15 min of reperfusion (protocol 2: assessment of mitochondrial function). All treatments administered before the 30-min ischemia (Pre-Isch, Pre-CsA, Pre-Iso) significantly reduced infarct as compared to control. In contrast, only Post-Iso significantly reduced infarct size, while Post-Isch and Post-CsA had no significant protective effect. As for the postconditioning-like interventions, the mitochondrial calcium retention capacity significantly increased only in the Post-Iso group (+58 % vs control) after succinate activation. Only Post-Iso increased state 3 (+177 and +62 %, for G/M and succinate, respectively) when compared to control. Also, Post-Iso reduced the hydrogen peroxide (H2O2) production (-46 % vs control) after complex I activation. This study suggests that isoflurane, but not cyclosporine A, can prevent lethal reperfusion injury in this in vivo rat model. This might be related to the need for a combined effect on cyclophilin D and complex I during the first minutes of reperfusion.

Intestinal ischemic preconditioning reduces liver ischemia reperfusion injury in rats

PubMed Central

XUE, TONG-MIN; TAO, LI-DE; ZHANG, JIE; ZHANG, PEI-JIAN; LIU, XIA; CHEN, GUO-FENG; ZHU, YI-JIA

2016-01-01

The aim of the current study was to investigate whether intestinal ischemic preconditioning (IP) reduces damage to the liver during hepatic ischemia reperfusion (IR). Sprague Dawley rats were used to model liver IR injury, and were divided into the sham operation group (SO), IR group and IP group. The results indicated that IR significantly increased Bax, caspase 3 and NF-κBp65 expression levels, with reduced expression of Bcl-2 compared with the IP group. Compared with the IR group, the levels of AST, ALT, MPO, MDA, TNF-α and IL-1 were significantly reduced in the IP group. Immunohistochemistry for Bcl-2 and Bax indicated that Bcl-2 expression in the IP group was significantly increased compared with the IR group. In addition, IP reduced Bax expression compared with the IR group. The average liver injury was worsened in the IR group and improved in the IP group, as indicated by the morphological evaluation of liver tissues. The present study suggested that IP may alleviates apoptosis, reduce the release of pro-inflammatory cytokines, ameloriate reductions in liver function and reduce liver tissue injury. To conclude, IP provided protection against hepatic IR injury. PMID:26821057

Early and late changes in the distal forelimb representation of the supplementary motor area after injury to frontal motor areas in the squirrel monkey.

PubMed

Eisner-Janowicz, Ines; Barbay, Scott; Hoover, Erica; Stowe, Ann M; Frost, Shawn B; Plautz, Erik J; Nudo, Randolph J

2008-09-01

Neuroimaging studies in stroke survivors have suggested that adaptive plasticity occurs following stroke. However, the complex temporal dynamics of neural reorganization after injury make the interpretation of functional imaging studies equivocal. In the present study in adult squirrel monkeys, intracortical microstimulation (ICMS) techniques were used to monitor changes in representational maps of the distal forelimb in the supplementary motor area (SMA) after a unilateral ischemic infarct of primary motor (M1) and premotor distal forelimb representations (DFLs). In each animal, ICMS maps were derived at early (3 wk) and late (13 wk) postinfarct stages. Lesions resulted in severe deficits in motor abilities on a reach and retrieval task. Limited behavioral recovery occurred and plateaued at 3 wk postinfarct. At both early and late postinfarct stages, distal forelimb movements could still be evoked by ICMS in SMA at low current levels. However, the size of the SMA DFL changed after the infarct. In particular, wrist-forearm representations enlarged significantly between early and late stages, attaining a size substantially larger than the preinfarct area. At the late postinfarct stage, the expansion in the SMA DFL area was directly proportional to the absolute size of the lesion. The motor performance scores were positively correlated to the absolute size of the SMA DFL at the late postinfarct stage. Together, these data suggest that, at least in squirrel monkeys, descending output from M1 and dorsal and ventral premotor cortices is not necessary for SMA representations to be maintained and that SMA motor output maps undergo delayed increases in representational area after damage to other motor areas. Finally, the role of SMA in recovery of function after such lesions remains unclear because behavioral recovery appears to precede neurophysiological map changes.

Evidence for reduced cancellous bone mass in the spontaneously hypertensive rat

NASA Technical Reports Server (NTRS)

Wang, T. M.; Hsu, J. F.; Jee, W. S.; Matthews, J. L.

1993-01-01

The histomorphometric changes in the proximal tibial metaphysis and epiphyseal growth plate and midtibial shaft of 26-week-old spontaneously hypertensive rats (SHR) compared with those of the corresponding normotensive Wistar-Kyoto (WKY) rats were studied. A decrease in body weight, growth plate thickness, and longitudinal growth rate of the proximal tibial epiphysis, trabecular bone volume, trabecular thickness and number, the number of osteoblasts and osteoprogenitor cells per millimeter square surface of the proximal tibial metaphysis, periosteal and endocortical apposition rate and bone formation rate of the tibial diaphysis were observed in the SHR. Additionally, systolic blood pressure, the number of osteoclasts per millimeter square surface and average number of nuclei per osteoclast of the proximal tibial metaphysis were significantly increased. Thus, osteoclastic activity is dominant over osteoblastic and chondroblastic activity in the SHR that results in a cancellous bone deficit in the skeleton. It will require additional work to ascertain the underlying cause for this condition as several factors in the SHR with a potential for causing this change are present, including elevated parathyroid hormone (PTH), depressed 1,25-(OH)2D3, low calcium absorption, reduced body weight (reduced loading) elevated blood pressure and possibly other direct cell differences in the mutant strain. At present elevated PTH and adaptation to underloading from reduced weight are postulated to be a likely cause, but additional studies are required to test this interpretation.

Pre-pubertal diet restriction reduces reactive oxygen species and restores fertility in male WNIN/Obese rat.

PubMed

Dinesh Yadav, D M; Muralidhar, M N; Prasad, S M V K; Rajender Rao, K

2018-03-01

Obesity is a multifactorial disorder associated with increased body adiposity, chronic oxidative stress which contributes to impaired fertility in males. Diet restriction and anti-oxidant supplementations are known to protect obese subjects from oxidative stress and improves fertility. However, the role of oxidative stress and the age of intervention in restoring male fertility are poorly understood. This study was aimed to assess the effect of diet restriction on fertility with respect to the age of intervention, body composition and oxidative stress using WNIN/Ob obese mutant rat strain. Unlike lean and carrier phenotypes, obese rats are hyperphagic, hyperlipaemic and infertile. Male obese rats aged for 35, 60 and 90 days were fed either ad libitum or diet restricted for 6 weeks. Upon diet restriction mean body weight, total body fat percentage, circulatory lipids and oxidative stress markers were significantly reduced and it follows the order as 35 < 60 < 90 days. Diet-restricted males of the three age groups were allowed to mate with female carrier rats, and fertility was restored only in 35-day group. Diet restriction in male obese WNIN/Ob rats lowered the rate of body weight gain, with reduced oxidative stress overall and fertility restoration in groups intervened at pre-pubertal stages. © 2017 Blackwell Verlag GmbH.

Argan oil reduces, in rats, the high fat diet-induced metabolic effects of obesity.

PubMed

Sour, S; Belarbi, M; Sari, N; Benammar, C H; Baghdad, C H; Visioli, F

2015-04-01

Obesity is a multi-factorial disorder which is of worldwide concern. In addition to calorie control, some specific dietary components might help resolving some of the complication of obesity, by providing antioxidant and anti-inflammatory activities. We investigated the effect of argan oil supplementation on plasma lipid profile and oxidant-antioxidant status of rats with high-fat diet (HFD)-induced obesity compared with rats fed a normal diet (ND). We used an animal model of high fat diet-induced obesity to study the metabolic effects of argan oil and we measured several markers lipid and redox statuses. Consumption of a high-fat diet led to an increase in serum total cholesterol (TC), LDL-cholesterol (LDL-C), and triacylglycerols (TAG) concentrations; however, argan oil blunted the increases of TC, LDL-C and TG, glucose, and insulin. Plasma total antioxidant capacity, erythrocyte catalase and superoxide dismutase activities were lower, whereas plasma hydroperoxide, thiobarbituric acid-reacting substances, and susceptibility of LDL to copper-induced oxidation were higher in obese rats compared with normal rats. Administration of argan oil ameliorated all these indices of redox status. Proper diet and lifestyle should be foremost implemented to reduce the lipoprotein metabolism and oxidant/antioxidant status alterations brought about by obesity. In addition, argan oil reduces the metabolic effects of obesity and its use might be promoted within the context of a balanced diet. Copyright © 2015 Elsevier B.V. All rights reserved.

Different functional reorganization of motor cortex after transfer of the contralateral C7 to different recipient nerves in young rats with total brachial plexus root avulsion.

PubMed

Pan, Feng; Wei, Hai-feng; Chen, Liang; Gu, Yu-dong

2012-12-07

Clinically, contralateral C7 transfer is used for nerve reconstruction in brachial plexus injuries. Postoperatively, synchronous motions at the donor limb are noteworthy. This study studied if different recipient nerves influenced transhemispheric functional reorganization of motor cortex after this procedure. 90 young rats with total root avulsion of the brachial plexus were divided into groups 1-3 of contralateral C7 transfer to anterior division of the upper trunk, to both the musculocutaneous and median nerves, and to the median nerve, respectively. After reinnervation of target muscles, number of sites for forelimb representations in bilateral motor cortices was determined by intracortical microstimulation at 1.5, 3, 6, 9, and 12 months postoperatively. At nine months, transhemispheric reorganization of nerves neurotized by contralateral C7 was fulfilled in four of six rats in group 1, one of six in group 2 and none in group 3, respectively; at 12 months, that was fulfilled in five of six in group 1, four of six in groups 2 and 3, respectively. Logistic regression analysis showed that rate of fulfilled transhemispheric reorganization in group 1 was 12.19 times that in group 3 (95% CI 0.006-0.651, p=0.032). At 12 months, number of sites for hindlimb representations which had encroached upon original forelimb representations on the uninjured side was statistically more in group 3 than in group 2 (t=9.5, p<0.0001). It is concluded that contralateral C7 transfer to upper trunk or to both the musculocutaneous and median nerves induces faster transhemispheric functional reorganization of motor cortex than that to median nerve alone in rats. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Effects of ventrolateral thalamic nucleus cooling on initiation of forelimb ballistic flexion movements by conditioned cats.

PubMed

Bénita, M; Condé, H; Dormont, J F; Schmied, A

1979-02-15

Five cats were trained to perform a forelimb ballistic flexion on a reaction time paradigm including an upper limit of about 400 ms for reinforcement (food pellets). They were implanted with a cyrogenic probe thermically insulated, except at the tip, by a vacuum jacket (outer diameter, 1.1 mm). Four cats had the probe inserted into the ventrolateral thalamic nucleus (VL), contralateral to the moving limb. During cooling they showed increased reaction times, which remained constant throughout daily sessions performed during many weeks, independent of the foreperiod but varying from 25 to 100 ms according to the subject. The temperatures used to upset the reaction times varied from +10 decrees C to -8 degrees C, depending on the localisation of the probe and on the insulation of the silver tip used to prevent nervous tissue reaction, but for each subject the reaction times always increased when the temperature was lowered. The fifth cat, with a probe inserted between VL and the Centre Median, showed a decrease of reaction times on cooling to 0 degrees C and an increase of the reaction times for a cooling at -10 degrees C. For one of the four cats with a probe properly inserted into the VL, strain-gauges were stuck on the lever to measure the latency of the decrease of the pressure exerted by the subject when the subject initiated the forelimb flexion in response to the CS. Reaction times and latencies of pressure changes were closely correlated with the movement onset, and they were equally delayed during cooling. This result demonstrates that it is not by slowing down movement velocity that reaction times are upset during VL cooling but by delaying the movement onset.

Mitochondria-targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats.

PubMed

Vilaseca, Marina; García-Calderó, Héctor; Lafoz, Erica; Ruart, Maria; López-Sanjurjo, Cristina Isabel; Murphy, Michael P; Deulofeu, Ramon; Bosch, Jaume; Hernández-Gea, Virginia; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos

2017-07-01

In cirrhosis, activated hepatic stellate cells (HSC) play a major role in increasing intrahepatic vascular resistance and developing portal hypertension. We have shown that cirrhotic livers have increased reactive oxygen species (ROS), and that antioxidant therapy decreases portal pressure. Considering that mitochondria produce many of these ROS, our aim was to assess the effects of the oral mitochondria-targeted antioxidant mitoquinone on hepatic oxidative stress, HSC phenotype, liver fibrosis and portal hypertension. Ex vivo: Hepatic stellate cells phenotype was analysed in human precision-cut liver slices in response to mitoquinone or vehicle. In vitro: Mitochondrial oxidative stress was analysed in different cell type of livers from control and cirrhotic rats. HSC phenotype, proliferation and viability were assessed in LX2, and in primary human and rat HSC treated with mitoquinone or vehicle. In vivo: CCl 4 - and thioacetamide-cirrhotic rats were treated with mitoquinone (5 mg/kg/day) or the vehicle compound, DecylTPP, for 2 weeks, followed by measurement of oxidative stress, systemic and hepatic haemodynamic, liver fibrosis, HSC phenotype and liver inflammation. Mitoquinone deactivated human and rat HSC, decreased their proliferation but with no effects on viability. In CCl 4 -cirrhotic rats, mitoquinone decreased hepatic oxidative stress, improved HSC phenotype, reduced intrahepatic vascular resistance and diminished liver fibrosis. These effects were associated with a significant reduction in portal pressure without changes in arterial pressure. These results were further confirmed in the thioacetamide-cirrhotic model. We propose mitochondria-targeted antioxidants as a novel treatment approach against portal hypertension and cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Varenicline Reduces Alcohol Intake During Repeated Cycles of Alcohol Reaccess Following Deprivation in Alcohol-Preferring (P) Rats.

PubMed

Froehlich, Janice C; Nicholson, Emily R; Dilley, Julian E; Filosa, Nick J; Rademacher, Logan C; Smith, Teal N

2017-08-01

Most alcoholics experience periods of voluntary alcohol abstinence or imposed alcohol deprivation followed by a return to alcohol drinking. This study examined whether varenicline (VAR) reduces alcohol intake during a return to drinking after periods of alcohol deprivation in rats selectively bred for high alcohol drinking (the alcohol preferring or "P" rats). Alcohol-experienced P rats were given 24-hour access to food and water and scheduled access to alcohol (15% and 30% v/v) for 2 h/d. After 4 weeks, rats were deprived of alcohol for 2 weeks, followed by reaccess to alcohol for 2 weeks, and this pattern was repeated for a total of 3 cycles. Rats were fed either vehicle (VEH) or VAR, in doses of 0.5, 1.0, or 2.0 mg/kg BW, at 1 hour prior to onset of the daily alcohol reaccess period for the first 5 days of each of the 3 alcohol reaccess cycles. Low-dose VAR (0.5 mg/kg BW) reduced alcohol intake during the 5 days of drug treatment in alcohol reaccess cycles 1 and 2. Higher doses of VAR (1.0 mg/kg BW and 2.0 mg/kg BW) reduced alcohol intake during the 5 days of treatment in all 3 alcohol reaccess cycles. The decrease in alcohol intake disappeared with termination of VAR treatment in all alcohol reaccess cycles. The results demonstrate that VAR decreases alcohol intake during multiple cycles of alcohol reaccess following alcohol deprivation in rats and suggests that it may prevent a return to heavy alcohol drinking during a lapse from alcohol abstinence in humans with alcohol use disorder. Copyright © 2017 by the Research Society on Alcoholism.

Talampanel improves the functional deficit after transient focal cerebral ischemia in rats. A 30-day follow up study.

PubMed

Erdo, Franciska; Berzsenyi, Pál; Német, László; Andrási, Ferenc

2006-01-15

The neuroprotective effect of talampanel, a negative allosteric modulator of alpha-amino-3-hydroxy-methyl-4-isoxazolyl-propionic acid (AMPA) receptors has been described previously. However, in these studies the histological changes and not the functional consequences of the brain damage were evaluated. The aim of present investigation was to analyze the sensorimotor function after stroke and to test the influence of talampanel (GYKI-53773, LY-300164) by 30-day monitoring in rats. After 1h middle cerebral artery occlusion (MCAO) general 'well-being', neurological status, spontaneous motor activity, rotation, motor coordination, balancing, muscle strength and reaction time were followed for 1 month. Talampanel (6 x 10 mg/kg i.p. given on the day of stroke) improved the motor coordination in rotarod (p < 0.01) and beam walking (p < 0.01) tests, reduced the number of stroke-induced rotations (p < 0.05), shortened the reflex time on the forelimb contralateral to brain ischemia and improved the survival rate comparing with vehicle treated control. After stroke, serious sensorimotor deficits appeared in rats but they showed partial spontaneous recovery after 30 days. Talampanel treatment enhanced the rate of functional improvement without changing the morphology at the end of the experiment. Our results indicate that modulation of AMPA receptors by talampanel can be a promising therapeutic approach to the treatment of stroke.

Broccoli (Brassica oleracea) Reduces Oxidative Damage to Pancreatic Tissue and Combats Hyperglycaemia in Diabetic Rats

PubMed Central

Suresh, Sithara; Waly, Mostafa Ibrahim; Rahman, Mohammad Shafiur; Guizani, Nejib; Al-Kindi, Mohamed Abdullah Badar; Al-Issaei, Halima Khalfan Ahmed; Al-Maskari, Sultan Nasser Mohd; Al-Ruqaishi, Bader Rashid Said; Al-Salami, Ahmed

2017-01-01

Oxidative stress plays a pivotal role in the development of diabetes and hyperglycaemia. The protective effects of natural extracts against diabetes are mainly dependent on their antioxidant and hypoglycaemic properties. Broccoli (Brassica oleracea) exerts beneficial health effects in several diseases including diabetes; however, the mechanism has not been elucidated yet. The present study was carried out to evaluate the potential hypoglycaemic and antioxidant properties of aqueous broccoli extracts (BEs) in diabetic rats. Streptozotocin (STZ) drug was used as a diabetogenic agent in a single intraperitoneal injection dose of 50 mg/kg body weight. The blood glucose level for each rat was measured twice a week. After 8 weeks, all animals were fasted overnight and sacrificed; pancreatic tissues were homogenized and used for measuring oxidative DNA damage, biochemical assessment of glutathione (GSH), and total antioxidant capacity (TAC) as well as histopathological examination for pancreatic tissues was examined. Diabetic rats showed significantly higher levels of DNA damage, GSH depletion, and impaired TAC levels in comparison to non-diabetics (P<0.05). The treatment of diabetic rats with BE significantly reduced DNA damage and conserved GSH and TAC values (P<0.01). BE attenuated pancreatic histopathological changes in diabetic rats. The results of this study indicated that BE reduced the STZ mediated hyperglycaemia and the STZ-induced oxidative injury to pancreas tissue. The used in vivo model confirmed the efficacy of BE as an anti-diabetic herbal medicine and provided insights into the capacity of BE to be used for phytoremediation purposes for human type 2 diabetes. PMID:29333379

Broccoli (Brassica oleracea) Reduces Oxidative Damage to Pancreatic Tissue and Combats Hyperglycaemia in Diabetic Rats.

PubMed

Suresh, Sithara; Waly, Mostafa Ibrahim; Rahman, Mohammad Shafiur; Guizani, Nejib; Al-Kindi, Mohamed Abdullah Badar; Al-Issaei, Halima Khalfan Ahmed; Al-Maskari, Sultan Nasser Mohd; Al-Ruqaishi, Bader Rashid Said; Al-Salami, Ahmed

2017-12-01

Oxidative stress plays a pivotal role in the development of diabetes and hyperglycaemia. The protective effects of natural extracts against diabetes are mainly dependent on their antioxidant and hypoglycaemic properties. Broccoli ( Brassica oleracea ) exerts beneficial health effects in several diseases including diabetes; however, the mechanism has not been elucidated yet. The present study was carried out to evaluate the potential hypoglycaemic and antioxidant properties of aqueous broccoli extracts (BEs) in diabetic rats. Streptozotocin (STZ) drug was used as a diabetogenic agent in a single intraperitoneal injection dose of 50 mg/kg body weight. The blood glucose level for each rat was measured twice a week. After 8 weeks, all animals were fasted overnight and sacrificed; pancreatic tissues were homogenized and used for measuring oxidative DNA damage, biochemical assessment of glutathione (GSH), and total antioxidant capacity (TAC) as well as histopathological examination for pancreatic tissues was examined. Diabetic rats showed significantly higher levels of DNA damage, GSH depletion, and impaired TAC levels in comparison to non-diabetics ( P <0.05). The treatment of diabetic rats with BE significantly reduced DNA damage and conserved GSH and TAC values ( P <0.01). BE attenuated pancreatic histopathological changes in diabetic rats. The results of this study indicated that BE reduced the STZ mediated hyperglycaemia and the STZ-induced oxidative injury to pancreas tissue. The used in vivo model confirmed the efficacy of BE as an anti-diabetic herbal medicine and provided insights into the capacity of BE to be used for phytoremediation purposes for human type 2 diabetes.

Valnoctamide, which reduces rat brain arachidonic acid turnover, is a potential non-teratogenic valproate substitute to treat bipolar disorder.

PubMed

Modi, Hiren R; Ma, Kaizong; Chang, Lisa; Chen, Mei; Rapoport, Stanley I

2017-08-01

Valproic acid (VPA), used for treating bipolar disorder (BD), is teratogenic by inhibiting histone deacetylase. In unanaesthetized rats, chronic VPA, like other mood stabilizers, reduces arachidonic acid (AA) turnover in brain phospholipids, and inhibits AA activation to AA-CoA by recombinant acyl-CoA synthetase-4 (Acsl-4) in vitro. Valnoctamide (VCD), a non-teratogenic constitutional isomer of VPA amide, reported effective in BD, also inhibits recombinant Acsl-4 in vitro. VCD like VPA will reduce brain AA turnover in unanaesthetized rats. A therapeutically relevant (50mg/kg i.p.) dose of VCD or vehicle was administered daily for 30 days to male rats. AA turnover and related parameters were determined using our kinetic model, following intravenous [1- 14 C]AA in unanaesthetized rats for 10min, and measuring labeled and unlabeled lipids in plasma and high-energy microwaved brain. VCD, compared with vehicle, increased λ, the ratio of brain AA-CoA to unesterified plasma AA specific activities; and decreased turnover of AA in individual and total brain phospholipids. VCD's ability like VPA to reduce rat brain AA turnover and inhibit recombinant Acsl-4, and its efficacy in BD, suggest that VCD be further considered as a non-teratogenic VPA substitute for treating BD. Published by Elsevier B.V.

Helichrysum and Grapefruit Extracts Boost Weight Loss in Overweight Rats Reducing Inflammation.

PubMed

de la Garza, Ana Laura; Etxeberria, Usune; Haslberger, Alexander; Aumueller, Eva; Martínez, J Alfredo; Milagro, Fermín I

2015-08-01

Obesity is characterized by an increased production of inflammatory markers. High levels of circulating free fatty acids and chronic inflammation lead to increased oxidative stress, contributing to the development of insulin resistance (IR). Recent studies have focused on the potential use of flavonoids for obesity management due to their antioxidant and anti-inflammatory properties. This study was designed to investigate the antioxidant and anti-inflammatory effects of helichrysum and grapefruit extracts in overweight insulin-resistant rats. Thirty-eight male Wistar rats were randomly distributed in two groups: control group (n=8) and high-fat sucrose (HFS) group (n=30). After 22 days of ad libitum water and food access, the rats fed HFS diet changed to standard diet and were reassigned into three groups (n=10 each group): nonsupplemented, helichrysum extract (2 g/kg bw), and grapefruit extract (1 g/kg bw) administered for 5 weeks. Rats supplemented with both extracts gained less body weight during the 5-week period of treatment, showed lower serum insulin levels and liver TBARS levels. Leptin/adiponectin ratio, as an indicator of IR, was lower in both extract-administered groups. These results were accompanied by a reduction in TNFα gene expression in epididymal adipose tissue and intestinal mucosa, and TLR2 expression in intestinal mucosa. Helichrysum and grapefruit extracts might be used as complement hypocaloric diets in weight loss treatment. Both extracts helped to reduce weight gain, hyperinsulinemia, and IR, improved inflammation markers, and decreased the HFS diet-induced oxidative stress in insulin-resistant rats.

Azithromycin reduces inflammation in a rat model of acute conjunctivitis

PubMed Central

Fernandez-Robredo, Patricia; Recalde, Sergio; Moreno-Orduña, Maite; García-García, Laura; Zarranz-Ventura, Javier; García-Layana, Alfredo

2013-01-01

Purpose Macrolide antibiotics are known to have various anti-inflammatory effects in addition to their antimicrobial activity, but the mechanisms are still unclear. The effect of azithromycin on inflammatory molecules in the lipopolysaccharide-induced rat conjunctivitis model was investigated. Methods Twenty-four Wistar rats were divided into two groups receiving topical ocular azithromycin (15 mg/g) or vehicle. In total, six doses (25 µl) were administered as one dose twice a day for three days before subconjunctival lipopolysaccharide injection (3 mg/ml). Before the rats were euthanized, mucus secretion, conjunctival and palpebral edema and redness were evaluated. Real-time polymerase chain reaction was used to determine gene expression for interleukin-6, cyclooxygenase-2, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, and MMP-9. Interleukin-6 was determined with enzyme-linked immunosorbent assay, nuclear factor-kappa B with western blot, and MMP-2 activity with gelatin zymogram. Four eyes per group were processed for histology and subsequent periodic acid-Schiff staining and CD68 for immunofluorescence. The Student t test or the Wilcoxon test for independent samples was applied (SPSS v.15.0). Results Azithromycin-treated animals showed a significant reduction in all clinical signs (p<0.05) compared to controls. Interleukin-6 (p<0.05), nuclear factor-kappa B protein expression (p<0.01), and MMP-2 activity (p<0.05) in conjunctival homogenates were significantly reduced compared with the control animals. MMP-2 gene expression showed a tendency to decrease in the azithromycin group (p=0.063). Mucus secretion by goblet cells and the macrophage count in conjunctival tissue were also decreased in the azithromycin group (p<0.05). Conclusions These results suggest that azithromycin administration ameliorates induced inflammation effects in a rat model of acute conjunctivitis. PMID:23378729

Forelimb muscle function in pig-nosed turtles, Carettochelys insculpta: testing neuromotor conservation between rowing and flapping in swimming turtles

PubMed Central

Rivera, Angela R. V.; Blob, Richard W.

2013-01-01

Changes in muscle activation patterns can lead to new locomotor modes; however, neuromotor conservation—the evolution of new forms of locomotion through changes in structure without concurrent changes to underlying motor patterns—has been documented across diverse styles of locomotion. Animals that swim using appendages do so via rowing (anteroposterior oscilations) or flapping (dorsoventral oscilations). Yet few studies have compared motor patterns between these swimming modes. In swimming turtles, propulsion is generated exclusively by limbs. Kinematically, turtles swim using multiple styles of rowing (freshwater species), flapping (sea turtles) and a unique hybrid style with superficial similarity to flapping by sea turtles and characterized by increased dorsoventral motions of synchronously oscillated forelimbs that have been modified into flippers (Carettochelys insculpta). We compared forelimb motor patterns in four species of turtle (two rowers, Apalone ferox and Trachemys scripta; one flapper, Caretta caretta; and Carettochelys) and found that, despite kinematic differences, motor patterns were generally similar among species with a few notable exceptions: specifically, presence of variable bursts for pectoralis and triceps in Trachemys (though timing of the non-variable pectoralis burst was similar), and the timing of deltoideus activity in Carettochelys and Caretta compared with other taxa. The similarities in motor patterns we find for several muscles provide partial support for neuromotor conservation among turtles using diverse locomotor styles, but the differences implicate deltoideus as a prime contributor to flapping limb motions. PMID:23966596

Effect of feeding graded doses of Citrinin on clinical and teratology in female Wistar rats.

PubMed

Singh, N D; Sharma, A K; Patil, R D; Rahman, S; Leishangthem, G D; Kumar, M

2014-02-01

Citrinin is the one of the well-known mycotoxins, which is possibly spread all over the world. The graded doses of citrinin (1, 3 and 5 ppm CIT in feed) in female Wistar rats 10 weeks prior to mating, during mating and during organogenesis resulted in resorptions and post implantation losses, decreased fetal body weights and crown-rump lengths in fetuses of all groups. Various developmental anomalies recorded in fetuses of treated rats included gross (wrist drop, curled tail, stretched forelimb, subcutaneous haematoma), skeletal (incomplete ossification of skull bones, incomplete fusion of vertebral bodies, complete and partial agenesis of sternaebrae, metacarpals, metatarsals and phalanges, fused ribs and swing out ribs) and visceral (internal and external hydrocephalus, cerebellar hypoplasia, microphthalmia, roundening of heart, contracted kidneys, dilated renal pelvis and cryptorchid testes). The results suggest that CIT has adverse effects on fetal development which may be due to the longer bioavailability of citrinin in the animals.

Reduced Cerebrovascular Reactivity and Increased Resting Cerebral Perfusion in Rats Exposed to a Cafeteria Diet.

PubMed

Gomez-Smith, Mariana; Janik, Rafal; Adams, Conner; Lake, Evelyn M; Thomason, Lynsie A M; Jeffers, Matthew S; Stefanovic, Bojana; Corbett, Dale

2018-02-10

To better understand the effects of a diet high in fat, sugar, and sodium on cerebrovascular function, Sprague Dawley rats were chronically exposed to a Cafeteria diet. Resting cerebral perfusion and cerebrovascular reactivity was quantified using continuous arterial spin labeling (CASL) magnetic resonance imaging (MRI). In addition, structural changes to the cerebrovasculature and susceptibility to ischemic lesion were examined. Compared to control animals fed standard chow (SD), Cafeteria diet (CAF) rats exhibited increased resting brain perfusion in the hippocampus and reduced cerebrovascular reactivity in response to 10% inspired CO 2 challenges in both the hippocampus and the neocortex. CAF rats switched to chow for one month (SWT) exhibited improved resting perfusion in the hippocampus as well as improved cerebrovascular reactivity in the neocortex. However, the diet switch did not correct cerebrovascular reactivity in the hippocampus. These changes were not accompanied by alterations in the structural integrity of the cerebral microvasculature, examined using rat endothelial cell antigen-1 (RECA-1) and immunoglobulin G (IgG) immunostaining. Also, the extent of tissue damage induced by endothelin-1 injection into sensorimotor cortex was not affected by the Cafeteria diet. These results demonstrate that short-term consumption of an ultra-processed diet reduces cerebrovascular reactivity. This effect persists after dietary normalization despite recovery of peripheral symptomatology. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Dynamic weight bearing analysis is effective for evaluation of tendinopathy using a customized corridor with multi-directional force sensors in a rat model.

PubMed

Wu, Po-Ting; Hsu, Chieh-Hsiang; Su, Fong-Chin; Jou, I-Ming; Chen, Shih-Yao; Wu, Chao-Liang; Su, Wei-Ren; Kuo, Li-Chieh

2017-08-18

Few studies discuss kinetic changes in tendinopathy models. We propose a customized corridor to evaluate dynamic weight bearing (DWB) and shearing forces. Sixty rats were randomly given ultrasound-assisted collagenase injections (Collagenase rats) or needle punctures (Control rats) in their left Achilles tendons, and then evaluated 1, 4, and 8 weeks later. The Collagenase rats always had significantly (p < 0.001) higher histopathological and ultrasound feature scores than did the Controls, significantly lower DWB values in the injured than in the right hindlimbs, and compensatorily higher (p < 0.05) DWB values in the contralateral than in the left forelimbs. The injured hindlimbs had lower outward shearing force 1 and 4 weeks later, and higher (p < 0.05) push-off shearing force 8 weeks later, than did the contralateral hindlimbs. Injured Control rat hindlimbs had lower DWB values than did the contralateral only at week 1. The Collagenase rats had only lower static weight bearing ratios (SWBRs) values than did the Controls at week 1 (p < 0.05). Our customized corridor showed changes in DWB compatible with histopathological and ultrasound feature changes in the rat tendinopathy model. The hindlimb SWBRs did not correspond with any tendinopathic changes.

Targeted, activity-dependent spinal stimulation produces long-lasting motor recovery in chronic cervical spinal cord injury

PubMed Central

McPherson, Jacob G.; Miller, Robert R.; Perlmutter, Steve I.

2015-01-01

Use-dependent movement therapies can lead to partial recovery of motor function after neurological injury. We attempted to improve recovery by developing a neuroprosthetic intervention that enhances movement therapy by directing spike timing-dependent plasticity in spared motor pathways. Using a recurrent neural–computer interface in rats with a cervical contusion of the spinal cord, we synchronized intraspinal microstimulation below the injury with the arrival of functionally related volitional motor commands signaled by muscle activity in the impaired forelimb. Stimulation was delivered during physical retraining of a forelimb behavior and throughout the day for 3 mo. Rats receiving this targeted, activity-dependent spinal stimulation (TADSS) exhibited markedly enhanced recovery compared with animals receiving targeted but open-loop spinal stimulation and rats receiving physical retraining alone. On a forelimb reach and grasp task, TADSS animals recovered 63% of their preinjury ability, more than two times the performance level achieved by the other therapy groups. Therapeutic gains were maintained for 3 additional wk without stimulation. The results suggest that activity-dependent spinal stimulation can induce neural plasticity that improves behavioral recovery after spinal cord injury. PMID:26371306

Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis

PubMed Central

Lowes, D. A.; Webster, N. R.; Murphy, M. P.; Galley, H. F.

2013-01-01

Background Sepsis-induced organ failure is the major cause of death in critical care units, and is characterized by a massive dysregulated inflammatory response and oxidative stress. We investigated the effects of treatment with antioxidants that protect mitochondria (MitoQ, MitoE, or melatonin) in a rat model of lipopolysaccharide (LPS) plus peptidoglycan (PepG)-induced acute sepsis, characterized by inflammation, mitochondrial dysfunction and early organ damage. Methods Anaesthetized and ventilated rats received an i.v. bolus of LPS and PepG followed by an i.v. infusion of MitoQ, MitoE, melatonin, or saline for 5 h. Organs and blood were then removed for determination of mitochondrial and organ function, oxidative stress, and key cytokines. Results MitoQ, MitoE, or melatonin had broadly similar protective effects with improved mitochondrial respiration (P<0.002), reduced oxidative stress (P<0.02), and decreased interleukin-6 levels (P=0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P=0.02) and creatinine concentrations (P<0.0001). Conclusions Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis. PMID:23381720

Secondhand Smoke Exposure Reduced the Compensatory Effects of IGF-I Growth Signaling in the Aging Rat Hearts

PubMed Central

Wu, Jia-Ping; Hsieh, Dennis Jine-Yuan; Kuo, Wei-Wen; Han, Chien-Kuo; Pai, Peiying; Yeh, Yu-Lan; Lin, Chien-Chung; Padma, V. Vijaya; Day, Cecilia Hsuan; Huang, Chih-Yang

2015-01-01

Background: Secondhand smoke (SHS) exposure is associated with increased risk of cardiovascular disease. Aging is a physiological process that involves progressive impairment of normal heart functions due to increased vulnerability to damage. This study examines secondhand smoke exposure in aging rats to determine the age-related death-survival balance. Methods: Rats were placed into a SHS exposure chamber and exposed to smog. Old age male Sprague-Dawley rats were exposed to 10 cigarettes for 30 min, day and night, continuing for one week. After 4 weeks the rats underwent morphological and functional studies. Left ventricular sections were stained with hematoxylin-eosin for histopathological examination. TUNEL detected apoptosis cells and protein expression related death and survival pathway were analyzed using western blot. Results: Death receptor-dependent apoptosis upregulation pathways and the mitochondria apoptosis proteins were apparent in young SHS exposure and old age rats. These biological markers were enhanced in aging SHS-exposed rats. The survival pathway was found to exhibit compensation only in young SHS-exposed rats, but not in the aging rats. Further decrease in the activity of this pathway was observed in aging SHS-exposed rats. TUNEL apoptotic positive cells were increased in young SHS-exposed rats, and in aging rats with or without SHS-exposure. Conclusions: Aging reduces IGF-I compensated signaling with accelerated cardiac apoptotic effects from second-hand smoke. PMID:26392808

Long-Term Dexamethasone Exposure Down-Regulates Hepatic TFR1 and Reduces Liver Iron Concentration in Rats

PubMed Central

Li, Huifang; Jiang, Shuxia; Yang, Chun; Yang, Shu; He, Bin; Ma, Wenqiang; Zhao, Ruqian

2017-01-01

Exposure to stress is known to cause hepatic iron dysregulation, but the relationship between prolonged stress and liver iron metabolism is not yet fully understood. Thirty 13-week-old female Sprague–Dawley rats were randomly divided into two groups, as follows: the control group (saline-injection) and the dexamethasone group (Dexamethasone (Dex)-injection 0.1 mg/kg/day). After the 21-day stress trial, the results showed that chronic Dex administration not only impaired serum corticosterone (p = 0.00) and interleukin-6 (IL-6) (p = 0.01) levels, but also decreased white blood cell counts (p = 0.00), and reduced blood lymphocyte counts (p = 0.00). The daily Dex-injection also significantly reduced body weight (p < 0.01) by inhibiting food intake. Consecutive Dex administration resulted in decreased iron intake (p = 0.00), enhanced serum iron levels (p = 0.01), and increased the serum souble transferrin receptor (sTfR) content (p = 0.00) in rats. Meanwhile, long-term Dex exposure down-regulated duodenal cytochrome b (DCYTB) (p = 0.00) and the divalent metal transporter 1 (DMT1) (p = 0.04) protein expression, but up-regulated ferroportin (FPN) protein expression (p = 0.04). Chronic Dex administration reduced liver iron concentration (p = 0.02) in rats. Hepatic transferrin receptor 1 (TFR1) expression was lowered at the protein level (p = 0.03), yet with uncoupled mRNA abundance in Dex-treated rats. Enhanced iron-regulatory protein (IRP)/iron-responsive element (IRE) binding activity was observed, but did not line up with lowered hepatic TFR1 protein expression. This study indicates that long-term Dex exposure reduces liver iron content, which is closely associated with down-regulated hepatic TFR1 protein expression. PMID:28629118

Resistance Exercise Reduces Seizure Occurrence, Attenuates Memory Deficits and Restores BDNF Signaling in Rats with Chronic Epilepsy.

PubMed

de Almeida, Alexandre Aparecido; Gomes da Silva, Sérgio; Lopim, Glauber Menezes; Vannucci Campos, Diego; Fernandes, Jansen; Cabral, Francisco Romero; Arida, Ricardo Mario

2017-04-01

Epilepsy is a disease characterized by recurrent, unprovoked seizures. Cognitive impairment is an important comorbidity of chronic epilepsy. Human and animal model studies of epilepsy have shown that aerobic exercise induces beneficial structural and functional changes and reduces the number of seizures. However, little is yet understood about the effects of resistance exercise on epilepsy. We evaluated the effects of a resistance exercise program on the number of seizures, long-term memory and expression/activation of signaling proteins in rats with epilepsy. The number of seizures was quantified by video-monitoring and long-term memory was assessed by an inhibitory avoidance test. Using western blotting, multiplex and enzyme-linked immunosorbent assays, we determined the effects of a 4-week resistance exercise program on IGF-1 and BDNF levels and ERK, CREB, mTOR activation in the hippocampus of rats with epilepsy. Rats with epilepsy submitted to resistance exercise showed a decrease in the number of seizures compared to non-exercised epileptic rats. Memory deficits were attenuated by resistance exercise. Rats with epilepsy showed an increase in IGF-1 levels which were restored to control levels by resistance exercise. BDNF levels and ERK and mTOR activation were decreased in rats with epilepsy and resistance exercise restored these to control levels. In conclusion, resistance exercise reduced seizure occurrence and mitigated memory deficits in rats with epilepsy. These resistance exercise-induced beneficial effects can be related to changes in IGF-1 and BDNF levels and its signaling protein activation. Our findings indicate that the resistance exercise might be included as complementary therapeutic strategy for epilepsy treatment.

Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome.

PubMed

Kusaka, Hiroaki; Koibuchi, Nobutaka; Hasegawa, Yu; Ogawa, Hisao; Kim-Mitsuyama, Shokei

2016-11-11

The potential benefit of SGLT2 inhibitors in metabolic syndrome is with prediabetic stage unclear. This work was undertaken to investigate the non-glycemic effect of empagliflozin on metabolic syndrome rats with prediabetes. SHR/NDmcr-cp(+/+) rats (SHRcp), a model of metabolic syndrome with prediabetes, were given empagliflozin for 10 weeks to examine the effects on urinary sodium and water balance, visceral and subcutaneous adipocyte, and cardiac injury. Further, the effect of empagliflozin on blood pressure and autonomic nervous system was continuously investigated by using radiotelemetry system. Empagliflozin significantly reduced urinary sodium and water balance of SHRcp only within 1 week of the treatment, but later than 1 week did not alter them throughout the treatment. Empagliflozin significantly reduced body weight of SHRcp, which was mainly attributed to the significant reduction of subcutaneous fat mass. Empagliflozin significantly reduced the size of visceral adipocytes and increased the number of smaller size of adipocytes, which was associated with the attenuation of oxidative stress. Empagliflozin ameliorated cardiac hypertrophy and fibrosis of SHRcp, in association with the attenuation of cardiac oxidative stress and inflammation. However, empagliflozin did not significantly change blood pressure, heart rate, sympathetic activity, or baroreceptor function, as evidenced by radiotelemetry analysis. Our present work provided the evidence that SGLT2 inhibition reduced visceral adipocytes hypertrophy and ameliorated cardiac injury in prediabetic metabolic syndrome rat, independently of diuretic effect or blood pressure lowering effect. Thus, SGLT2 inhibition seems to be a promising therapeutic strategy for prediabetic metabolic syndrome.

Oral Lactobacillus reuteri GMN-32 treatment reduces blood glucose concentrations and promotes cardiac function in rats with streptozotocin-induced diabetes mellitus.

PubMed

Lin, Chih-Hsueh; Lin, Cheng-Chieh; Shibu, Marthandam Asokan; Liu, Chiu-Shong; Kuo, Chia-Hua; Tsai, Fuu-Jen; Tsai, Chang-Hai; Hsieh, Cheng-Hong; Chen, Yi-Hsing; Huang, Chih-Yang

2014-02-01

Impaired regulation of blood glucose levels in diabetes mellitus (DM) patients and the associated elevation of blood glucose levels are known to increase the risk of diabetic cardiomyopathy (DC). In the present study, a probiotic bacterium, Lactobacillus reuteri GMN-32, was evaluated for its potential to reduce blood glucose levels and to provide protection against DC risks in streptozotocin (STZ)-induced DM rats. The blood glucose levels of the STZ-induced DM rats when treated with L. reuteri GMN-32 decreased from 4480 to 3620 mg/l (with 10⁷ colony-forming units (cfu)/d) and 3040 mg/l (with 10⁹ cfu/d). Probiotic treatment also reduced the changes in the heart caused by the effects of DM. Furthermore, the Fas/Fas-associated protein with death domain pathway-induced caspase 8-mediated apoptosis that was observed in the cardiomyocytes of the STZ-induced DM rats was also found to be controlled in the probiotic-treated rats. The results highlight that L. reuteri GMN-32 treatment reduces blood glucose levels, inhibits caspase 8-mediated apoptosis and promotes cardiac function in DM rats as observed from their ejection fraction and fractional shortening values. In conclusion, the administration of L. reuteri GMN-32 probiotics can regulate blood glucose levels, protect cardiomyocytes and prevent DC in DM rats.

Atorvastatin reduces cardiac and adipose tissue inflammation in rats with metabolic syndrome.

PubMed

Yamada, Yuichiro; Takeuchi, Shino; Yoneda, Mamoru; Ito, Shogo; Sano, Yusuke; Nagasawa, Kai; Matsuura, Natsumi; Uchinaka, Ayako; Murohara, Toyoaki; Nagata, Kohzo

2017-08-01

Statins are strong inhibitors of cholesterol biosynthesis and help to prevent cardiovascular disease. They also exert additional pleiotropic effects that include an anti-inflammatory action and are independent of cholesterol, but the molecular mechanisms underlying these additional effects have remained unclear. We have now examined the effects of atorvastatin on cardiac and adipose tissue inflammation in DahlS.Z-Lepr fa /Lepr fa (DS/obese) rats, which we previously established as a model of metabolic syndrome (MetS). DS/obese rats were treated with atorvastatin (6 or 20mgkg -1 day -1 ) from 9 to 13weeks of age. Atorvastatin ameliorated cardiac fibrosis, diastolic dysfunction, oxidative stress, and inflammation as well as adipose tissue inflammation in these animals at both doses. The high dose of atorvastatin reduced adipocyte hypertrophy to a greater extent than did the low dose. Atorvastatin inhibited the up-regulation of peroxisome proliferator-activated receptor γ gene expression in adipose tissue as well as decreased the serum adiponectin concentration in DS/obese rats. It also activated AMP-activated protein kinase (AMPK) as well as inactivated nuclear factor-κB (NF-κB) in the heart of these animals. The down-regulation of AMPK and NF-κB activities in adipose tissue of DS/obese rats was attenuated and further enhanced, respectively, by atorvastatin treatment. The present results suggest that the anti-inflammatory effects of atorvastatin on the heart and adipose tissue are attributable at least partly to increased AMPK activity and decreased NF-κB activity in this rat model of MetS. Copyright © 2017 Elsevier B.V. All rights reserved.

Fenofibrate--a lipid-lowering drug--reduces voluntary alcohol drinking in rats.

PubMed

Karahanian, Eduardo; Quintanilla, Maria Elena; Fernandez, Katia; Israel, Yedy

2014-11-01

The administration of disulfiram raises blood acetaldehyde levels when ethanol is ingested, leading to an aversion to alcohol. This study was aimed at assessing the effect of fenofibrate on voluntary ethanol ingestion in rats. Fenofibrate reduces blood triglyceride levels by increasing fatty acid oxidation by liver peroxisomes, along with an increase in the activity of catalase, which can oxidize ethanol to acetaldehyde. UChB drinker rats were allowed to consume alcohol 10% v/v freely for 60 days, until consumption stabilized at around 7 g ethanol/kg/24 h. About 1-1.2 g ethanol/kg of this intake is consumed in the first 2 h of darkness of the circadian cycle. Fenofibrate subsequently administered (50 mg/kg/day by mouth [p.o.]) for 14 days led to a 60-70% (p < 0.001) reduction of 24-h ethanol consumption. When ethanol intake was determined within the first 2 h of darkness, the reduction was 85-90% (p < 0.001). We determined whether animals chronically allowed access to ethanol and subsequently treated with fenofibrate, would a) increase liver catalase activity, and b) increase blood acetaldehyde levels after a 24-h ethanol deprivation and the subsequent administration of 1 g ethanol/kg. The oral administration of 1 g ethanol/kg produced a rapid increase in blood (arterial) acetaldehyde in fenofibrate-treated animals versus controls also administered 1 g/kg ethanol (70 μM vs. 7 μM; p < 0.001). Liver catalase activity following fenofibrate treatment was increased 3-fold (p < 0.01). Other hepatic enzymes responsible for the metabolism of ethanol (alcohol dehydrogenase and aldehyde dehydrogenase) remained unchanged. No liver damage was induced, as measured by serum glutamic-pyruvic transaminase (GPT) activity. The effect of fenofibrate in reducing alcohol intake was fully reversible. Overall, in rats allowed chronic ethanol intake, by mouth (p.o.), fenofibrate administration increased liver catalase activity and reduced voluntary ethanol intake. The administration of

Inhibited osteoclastic bone resorption through alendronate treatment in rats reduces severe osteoarthritis progression.

PubMed

Siebelt, M; Waarsing, J H; Groen, H C; Müller, C; Koelewijn, S J; de Blois, E; Verhaar, J A N; de Jong, M; Weinans, H

2014-09-01

Osteoarthritis (OA) is a non-rheumatoid joint disease characterized by progressive degeneration of extra-cellular cartilage matrix (ECM), enhanced subchondral bone remodeling, osteophyte formation and synovial thickening. Alendronate (ALN) is a potent inhibitor of osteoclastic bone resorption and results in reduced bone remodeling. This study investigated the effects of pre-emptive use of ALN on OA related osteoclastic subchondral bone resorption in an in vivo rat model for severe OA. Using multi-modality imaging we measured effects of ALN treatment within cartilage and synovium. Severe osteoarthritis was induced in left rat knees using papain injections in combination with a moderate running protocol. Twenty rats were treated with subcutaneous ALN injections and compared to twenty untreated controls. Animals were longitudinally monitored for 12weeks with in vivo μCT to measure subchondral bone changes and SPECT/CT to determine synovial macrophage activation using a folate-based radiotracer. Articular cartilage was analyzed at 6 and 12weeks with ex vivo contrast enhanced μCT and histology to measure sulfated-glycosaminoglycan (sGAG) content and cartilage thickness. ALN treatment successfully inhibited subchondral bone remodeling. As a result we found less subchondral plate porosity and reduced osteophytosis. ALN treatment did not reduce subchondral sclerosis. However, after the OA induction phase, ALN treatment protected cartilage ECM from degradation and reduced synovial macrophage activation. Surprisingly, ALN treatment also improved sGAG content of tibia cartilage in healthy joints. Our data was consistent with the hypothesis that osteoclastic bone resorption might play an important role in OA and may be a driving force for progression of the disease. However, our study suggest that this effect might not solely be effects on osteoclastic activity, since ALN treatment also influenced macrophage functioning. Additionally, ALN treatment and physical activity

Soyo-san reduces depressive-like behavior and proinflammatory cytokines in ovariectomized female rats

PubMed Central

2014-01-01

Background Soyo-san is a traditional oriental medicinal formula, a mixture of 9 crude drugs, and it has been clinically used for treating mild depressive disorders. The role of pro- and anti-inflammatory cytokines in psychiatric disorders has been the focus of great research attention in recent years. In the present study, we detected the antidepressant effect of soyo-san in the ovariectomized and repeated stressed female rats. Methods This study was designed to evaluate the antidepressant-like effect of soyo-san on the forced swimming test (FST). The rats were randomly divided into the following groups: the nonoperated and nonstressed group (non-op), the nonoperated and stressed group (non-op + ST), the ovariectomized and stress group (OVX) and sham operated and stressed group (sham), the ovariectomized and stressed group (OVX + ST), the ovariectomized, stressed and soyo-san 100 mg/kg treated group (SOY100) and the ovariectomized, stressed and soyo-san 400 mg/kg treated group (SOY400). The rats were exposed to immobilization stress (IMO) for 14day (2 h/14day), and soyo-san (100 mg/kg and 400 mg/kg) was administrated during the same time. In the same animals, the levels of corticosterone and interleukin-1-beta (IL-1β) were examined in the serum. Also, the change of IL-1β expression in brain regions was examined after behavior test. Results In the FST, the lower dose (100 mg/kg) of extract was effective in reducing immobility, along with an increase in swimming time. The serum levels of corticosterone and IL-1β in the SOY groups were significantly lower than those in the control group. In the brain, the expression of IL-1β positive neurons in the control group were significantly increased in the paraventricular nucleus (PVN) and hippocampus compared to the non-op. However, soyo-san groups significantly reduced the IL-1β-ir neurons in the PVN and hippocampal regions compared to the control. Conclusion The present results demonstrated that soyo

Prehypertensive treatment with losartan, however not amlodipine, leads to long-term effects on blood pressure and reduces the risk of stroke in spontaneously hypertensive stroke-prone rats.

PubMed

Zhang, Liangmin; He, Dehua; Lin, Jinxiu

2016-02-01

The current study investigated the efficacy of losartan and amlodipine in protecting spontaneously hypertensive stroke-prone (SHRSP) rats against the risk of stroke. SHRSP rats were administered losartan, amlodipine or the vehicle for 6 weeks. There were no significant differences in systolic blood pressure (SBP) in rats treated with losartan or amlodipine, however, following drug withdrawal, rats treated with losartan maintained reduced SBP for a longer time compared with rats treated with amlodipine. In addition, rats treated with losartan exhibited thinner vascular walls and improved systolic and diastolic function. Clinical stroke scores in the losartan group were significantly reduced compared with those in the amlodipine and vehicle groups. However, rats treated with losartan exhibited higher levels of angiotensin II and lower levels of aldosterone in the serum and brain cortex compared with the vehicle and amlodipine-treated rats. Furthermore, losartan significantly reduced the abnormal expression of angiotensin II receptors type 1 and 2 in SHRSP rats, whilst amlodipine did not. These results suggest that losartan may be more efficacious than amlodipine in ameliorating blood pressure deterioration and reducing stroke risk in SHRSP rats via regulation of the renin angiotensin system.

High-fat feeding reduces endothelium-dependent vasodilation in rats: differential mechanisms for saturated and unsaturated fatty acids?

PubMed

Song, Guang-Yao; Gao, Yu; Di, Yu-Wei; Pan, Li-Li; Zhou, Yu; Ye, Ji-Ming

2006-08-01

1. Chronic feeding with a high-fat diet can cause metabolic syndrome in rodents similar to humans, but the role of saturated versus unsaturated fats in vascular tension remains unclear. 2. The present study shows that rats on a diet rich in either saturated or unsaturated fat had higher blood pressure compared with chow-fed rats (approximately 130 vs 100 mmHg, respectively), along with hyperlipidaemia and insulin resistance. Compared with responses of phenylephrine-preconstricted artery segments from chow-fed rats, vasorelaxation of isolated renal arteries from high-fat fed rats was reduced substantially (> 50%) in response to acetylcholine (0.01-10 micromol/L) and moderately to nitroprusside (>or=1 micromol/L) at low concentrations. Acetylcholine-induced vasorelaxation of arteries from high-fat fed rats was also more sensitive to inhibition by the nitric oxide (NO) synthase inhibitors NG-nitro-L-arginine and methylene blue. 3. In human umbilical vein endothelial cells, the production of NO and endothelin-1 was significantly inhibited by unsaturated fatty acids. In comparison, saturated fatty acids stimulated endothelin-1 production without altering NO production. 4. The data indicate that both saturated and unsaturated high-fat feeding may result in an increase in blood pressure owing to reduced endothelium-dependent vasorelaxation in the arterial system. The impaired endothelium-dependent vasorelaxation induced by saturated and unsaturated fatty acids may involve different mechanisms.

Phenobarbital reduces blood glucose and gluconeogenesis through down-regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression in rats.

PubMed

Oda, Hiroaki; Okuda, Yuji; Yoshida, Yukiko; Kimura, Noriko; Kakinuma, Atsushi

2015-10-23

The regulatory mechanism of phosphoenolpyruvate carboykinase (GTP) (EC 4.1.1.32) (PEPCK) gene expression and gluconeogenesis by phenobarbital (PB), which is known to induce drug-metabolizing enzymes, was investigated. Higher level of PEPCK mRNA was observed in spherical rat primary hepatocytes on EHS-gel than monolayer hepatocytes on TIC (type I collagen). We found that PB directly suppressed PEPCK gene expression in spherical hepatocytes on EHS-gel, but not in those on TIC. PB strongly suppressed cAMP-dependent induction of PEPCK gene expression. Tyrosine aminotransferase (TAT), another gluconeogenic enzyme, was induced by cAMP, but not suppressed by PB. Chronic administration of PB reduced hepatic PEPCK mRNA in streptozotocin-induced diabetic and nondiabetic rats, and PB reduced blood glucose level in diabetic rats. Increased TAT mRNA in diabetic rats was not suppressed by PB. These results indicated that PB-dependent reduction is specific to PEPCK. From pyrvate challenge test, PB suppressed the increased gluconeogenesis in diabetic rats. PEPCK gene promoter activity was suppressed by PB in HepG2 cells. In conclusion, we found that spherical hepatocytes cultured on EHS-gel are capable to respond to PB to suppress PEPCK gene expression. Moreover, our results indicate that hypoglycemic action of PB result from transcriptional repression of PEPCK gene and subsequent suppression of gluconeogenesis. Copyright © 2015. Published by Elsevier Inc.

Evidence of reduced oral bioavailability of paracetamol in rats following multiple ingestion of grapefruit juice.

PubMed

Qinna, Nidal A; Ismail, Obbei A; Alhussainy, Tawfiq M; Idkaidek, Nasir M; Arafat, Tawfiq A

2016-04-01

The aim of the current investigation was to assess the ability GFJ to modulate the pharmacokinetic profile of paracetamol following single or repeated administrations of GFJ in Sprague-Dawley rats. Diclofenac and carbamazepine were both used as positive controls. Rats received single GFJ or single distilled water doses or pretreated with three doses of GFJ prior to test drug administration. Blood samples were collected, processed and analyzed using validated HPLC methods, and pharmacokinetic data were constructed for each group. Increase in the bioavailability of both diclofenac and carbamazepine following multiple GFJ ingestion was revealed. Conversely, the bioavailability of paracetamol was significantly reduced following multiple GFJ administration. The percentage of reduction in the C max and AUC of paracetamol were calculated as 31 and 51 %, respectively, compared to none-GFJ-treated control (P < 0.05). The T(max) was not essentially changed. In conclusion, frequent administration of GFJ was confirmed to modulate the pharmacokinetics of paracetamol in rats by reducing its bioavailability. Meanwhile, it may be advisable not to ingest large amounts of GFJ along with paracetamol to avoid a possible potential loss of the efficacy.

Electrolyzed-reduced water inhibits acute ethanol-induced hangovers in Sprague-Dawley rats.

PubMed

Park, Seung-Kyu; Qi, Xu-Feng; Song, Soon-Bong; Kim, Dong-Heui; Teng, Yung-Chien; Yoon, Yang-Suk; Kim, Kwang-Yong; Li, Jian-Hong; Jin, Dan; Lee, Kyu-Jae

2009-10-01

Ethanol consumption disturbs the balance between the pro- and anti-oxidant systems of the organism, leading to oxidative stress. Electrolyzed-reduced water (ERW) is widely used by people in East Asia for drinking purposes because of its therapeutic properties including scavenging effect of reactive oxygen species. This study was performed to investigate the effect of ERW on acute ethanol-induced hangovers in Sprague-Dawley rats. Alcohol concentration in serum of ERW-treated rats showed significant difference at 1 h, 3 h and 5 h respectively as compared with the rats treated with distilled water. Both alcohol dehydrogenase type 1 and acetaldehyde dehydrogenase related with oxidation of alcohol were significantly increased in liver tissue while the level of aspartate aminotransferase and alanine aminotransferase in serum was markedly decreased 24 h after pre-oral administration of ERW. Moreover, oral administration of ERW significantly activated non-ezymatic (glutathione) and enzymatic (glutathione peroxidase, glutathione-S-transferase, Cu/Zn-superoxide dismutase and catalase) antioxidants in liver tissues compared with the control group. These results suggest that drinking ERW has an effect of alcohol detoxification by antioxidant mechanism and has potentiality for relief of ethanol-induced hangover symptoms.

Poloxamer-188 reduces muscular edema after tourniquet-induced ischemia-reperfusion injury in rats.

PubMed

Walters, Thomas J; Mase, Vincent J; Roe, Janet L; Dubick, Michael A; Christy, Robert J

2011-05-01

Skeletal muscle injury can result in significant edema, which can in turn lead to the development of acute extremity compartment syndrome (CS). Poloxamer-188 (P-188), a multiblock copolymer surfactant, has been shown to decrease edema by sealing damaged membranes in a number of tissues after a variety of injury modalities. The objective is to determine whether the administration of P-188 significantly reduces skeletal muscle edema associated with ischemia/reperfusion injury (I-R). Male Sprague-Dawley rats underwent 180 minutes of tourniquet-induced ischemia. Five minutes before tourniquet release, rats received either a bolus of (1) P-188 (150 mg/kg; P-188 group) or (2) vehicle (Vehicle group) via a jugular catheter (n=10 per group). After 240 minutes reperfusion, both groups received a second bolus of either P-188 (P-188) or vehicle (Vehicle) via a tail vein catheter. Sixteen hours later, rats were killed; muscle weights were determined, infarct size (2,3,5-triphenyltetrazolium chloride method), and blinded histologic analysis (hematoxylin and eosin) were performed on the gastrocnemius and tibialis anterior muscles, as well as indices of antioxidant status. P-188 resulted in significantly less edema (wet weight) and reduced an index of lipid peroxidation compared with Vehicle (p<0.05). Wet:dry weight ratios were less in the P-188 group (indicating less edema). Muscle viability as indicated by 2,3,5-triphenyltetrazolium chloride staining or routine histology did not reveal statistically significant differences between groups. P-188 significantly reduced ischemia-reperfusion-related muscle edema and lipid peroxidation but did not impact muscle viability. Excess edema can lead to acute extremity CS, which is associated with significant morbidity and mortality. P-188 may provide a potential adjunctive treatment for the reduction of CS.

Neural and Hemodynamic Responses Elicited by Forelimb- and Photo-stimulation in Channelrhodopsin-2 Mice: Insights into the Hemodynamic Point Spread Function

PubMed Central

Vazquez, Alberto L.; Fukuda, Mitsuhiro; Crowley, Justin C.; Kim, Seong-Gi

2014-01-01

Hemodynamic responses are commonly used to map brain activity; however, their spatial limits have remained unclear because of the lack of a well-defined and malleable spatial stimulus. To examine the properties of neural activity and hemodynamic responses, multiunit activity, local field potential, cerebral blood volume (CBV)-sensitive optical imaging, and laser Doppler flowmetry were measured from the somatosensory cortex of transgenic mice expressing Channelrhodopsin-2 in cortex Layer 5 pyramidal neurons. The magnitude and extent of neural and hemodynamic responses were modulated using different photo-stimulation parameters and compared with those induced by somatosensory stimulation. Photo-stimulation-evoked spiking activity across cortical layers was similar to forelimb stimulation, although their activity originated in different layers. Hemodynamic responses induced by forelimb- and photo-stimulation were similar in magnitude and shape, although the former were slightly larger in amplitude and wider in extent. Altogether, the neurovascular relationship differed between these 2 stimulation pathways, but photo-stimulation-evoked changes in neural and hemodynamic activities were linearly correlated. Hemodynamic point spread functions were estimated from the photo-stimulation data and its full-width at half-maximum ranged between 103 and 175 µm. Therefore, submillimeter functional structures separated by a few hundred micrometers may be resolved using hemodynamic methods, such as optical imaging and functional magnetic resonance imaging. PMID:23761666

Biobreeding rat islets exhibit reduced antioxidative defense and N-acetyl cysteine treatment delays type 1 diabetes

PubMed Central

Bogdani, Marika; Henschel, Angela M.; Kansra, Sanjay; Fuller, Jessica M.; Geoffrey, Rhonda; Jia, Shuang; Kaldunski, Mary L.; Pavletich, Scott; Prosser, Simon; Chen, Yi-Guang; Lernmark, Åke; Hessner, Martin J.

2014-01-01

Islet-level oxidative stress has been proposed as a trigger for type 1 diabetes (T1D), and release of cytokines by infiltrating immune cells further elevates reactive oxygen species (ROS), exacerbating β cell duress. To identify genes/mechanisms involved with diabeto-genesis at the β cell level, gene expression profiling and targeted follow-up studies were used to investigate islet activity in the biobreeding (BB) rat. Forty-day-old spontaneously diabetic lymphopenic BB DRlyp/lyp rats (before T cell insulitis) as well as nondiabetic BB DR+/+ rats, nondiabetic but lymphopenic F344lyp/lyp rats, and healthy Fischer (F344) rats were examined. Gene expression profiles of BB rat islets were highly distinct from F344 islets and under-expressed numerous genes involved in ROS metabolism, including glutathione S-transferase (GST) family members (Gstm2, Gstm4, Gstm7, Gstt1, Gstp1, and Gstk1), superoxide dismutases (Sod2 and Sod3), peroxidases, and peroxiredoxins. This pattern of under-expression was not observed in brain, liver, or muscle. Compared with F344 rats, BB rat pancreata exhibited lower GST protein levels, while plasma GST activity was found significantly lower in BB rats. Systemic administration of the antioxidant N-acetyl cysteine to DRlyp/lyp rats altered abundances of peripheral eosinophils, reduced severity of insulitis, and significantly delayed but did not prevent diabetes onset. We find evidence of β cell dysfunction in BB rats independent of T1D progression, which includes lower expression of genes related to antioxidative defense mechanisms during the pre-onset period that may contribute to overall T1D susceptibility. PMID:23111281

Rimonabant reduces the essential value of food in the genetically obese Zucker rat: an exponential demand analysis.

PubMed

Rasmussen, Erin B; Reilly, William; Buckley, Jessica; Boomhower, Steven R

2012-02-01

Research on free-food intake suggests that cannabinoids are implicated in the regulation of feeding. Few studies, however, have characterized how environmental factors that affect food procurement interact with cannabinoid drugs that reduce food intake. Demand analysis provides a framework to understand how cannabinoid blockers, such as rimonabant, interact with effort in reducing demand for food. The present study examined the effects rimonabant had on demand for sucrose in obese Zucker rats when effort to obtain food varied and characterized the data using the exponential ("essential value") model of demand. Twenty-nine male (15 lean, 14 obese) Zucker rats lever-pressed under eight fixed ratio (FR) schedules of sucrose reinforcement, in which the number of lever-presses to gain access to a single sucrose pellet varied between 1 and 300. After behavior stabilized under each FR schedule, acute doses of rimonabant (1-10mg/kg) were administered prior to some sessions. The number of food reinforcers and responses in each condition was averaged and the exponential and linear demand equations were fit to the data. These demand equations quantify the value of a reinforcer by its sensitivity to price (FR) increases. Under vehicle conditions, obese Zucker rats consumed more sucrose pellets than leans at smaller fixed ratios; however, they were equally sensitive to price increases with both models of demand. Rimonabant dose-dependently reduced reinforcers and responses for lean and obese rats across all FR schedules. Data from the exponential analysis suggest that rimonabant dose-dependently increased elasticity, i.e., reduced the essential value of sucrose, a finding that is consistent with graphical depictions of normalized demand curves. Copyright © 2011 Elsevier Inc. All rights reserved.

Sulphonylurea drugs reduce hypoxic damage in the isolated perfused rat kidney.

PubMed

Engbersen, R; Moons, M M; Wouterse, A C; Dijkman, H B; Kramers, C; Smits, P; Russel, F G

2000-08-01

Sulphonylurea drugs have been shown to protect against hypoxic damage in isolated proximal tubules of the kidney. In the present study we investigated whether these drugs can protect against hypoxic damage in a whole kidney preparation. Tolbutamide (200 microM) and glibenclamide (10 microM) were applied to the isolated perfused rat kidney prior to changing the gassing from oxygen to nitrogen for 30 min. Hypoxic perfusions resulted in an increased fractional excretion of glucose (FE % glucose 14.3+/-1.5 for hypoxic perfusions vs 4.9+/-1.6 for normoxic perfusions, mean +/- s.e. mean, P<0.05), which could be completely restored by 200 microM tolbutamide (5.7+/-0.4 for tolbutamide vs 14.3+/-1.5 for untreated hypoxic kidneys, P<0.01). Furthermore, tolbutamide reduced the total amount of LDH excreted in the urine (220+/-100 mU for tolbutamide vs. 1220+/-160 mU for untreated hypoxic kidneys, P<0.01). Comparable results were obtained with glibenclamide (10 microM). In agreement with the effect on functional parameters, ultrastructural analysis of proximal tubules showed increased brush border preservation in tolbutamide treated kidneys compared to untreated hypoxic kidneys. We conclude that glibenclamide and tolbutamide are both able to reduce hypoxic damage to proximal tubules in the isolated perfused rat kidney when applied in the appropriate concentrations.

Dexterity: A MATLAB-based analysis software suite for processing and visualizing data from tasks that measure arm or forelimb function.

PubMed

Butensky, Samuel D; Sloan, Andrew P; Meyers, Eric; Carmel, Jason B

2017-07-15

Hand function is critical for independence, and neurological injury often impairs dexterity. To measure hand function in people or forelimb function in animals, sensors are employed to quantify manipulation. These sensors make assessment easier and more quantitative and allow automation of these tasks. While automated tasks improve objectivity and throughput, they also produce large amounts of data that can be burdensome to analyze. We created software called Dexterity that simplifies data analysis of automated reaching tasks. Dexterity is MATLAB software that enables quick analysis of data from forelimb tasks. Through a graphical user interface, files are loaded and data are identified and analyzed. These data can be annotated or graphed directly. Analysis is saved, and the graph and corresponding data can be exported. For additional analysis, Dexterity provides access to custom scripts created by other users. To determine the utility of Dexterity, we performed a study to evaluate the effects of task difficulty on the degree of impairment after injury. Dexterity analyzed two months of data and allowed new users to annotate the experiment, visualize results, and save and export data easily. Previous analysis of tasks was performed with custom data analysis, requiring expertise with analysis software. Dexterity made the tools required to analyze, visualize and annotate data easy to use by investigators without data science experience. Dexterity increases accessibility to automated tasks that measure dexterity by making analysis of large data intuitive, robust, and efficient. Copyright © 2017 Elsevier B.V. All rights reserved.

Cyanidin-3-glucoside extracted from mulberry fruit can reduce N-methyl-N-nitrosourea-induced retinal degeneration in rats.

PubMed

Lee, Seung Hee; Jeong, Eojin; Paik, Sun-Sook; Jeon, Ji Hyun; Jung, Sung Won; Kim, Hyun-Bok; Kim, Muyan; Chun, Myung-Hoon; Kim, In-Beom

2014-01-01

To investigate the effect of cyanidin-3-O-glucoside (C3G) on a rat retinal degeneration (RD) model. Experimental RD was induced in rats by the intraperitoneal injection of N-methyl-N-nitrosourea (MNU) at 50 mg/kg. C3G extracted from mulberry (Morus alba L.) fruit (50 mg/kg) was orally administered, daily for 1, 2 and 4 weeks after MNU injection. The effects of C3G administration on MNU-induced RD retinas were histologically and functionally assessed by hematoxylin and eosin staining and electroretinography (ERG), respectively. The degree of retinal injury in C3G-administered RD rats was evaluated by immunohistochemistry with an antibody against glial fibrillary acidic protein (GFAP). The preferential protective effect of C3G on scotopic vision was examined by western blot analysis. Marked loss of photoreceptors in the outer nuclear layer (ONL) was observed in RD rats at 2 and 4 weeks after MNU injection, while the ONL in the MNU-induced RD rats given C3G was relatively well preserved. Immunohistochemistry with anti-GFAP showed that retinal injury was also reduced in the retinas of the rats given C3G. Functional assessment by using ERG recordings showed that scotopic ERG responses were significantly increased in RD rats given C3G for 4 weeks (p < 0.01) compared with that of untreated RD rats. In the RD rats given short-term C3G (for 1 and 2 weeks), the increase in ERG responses was not significant. In addition, western blot analysis showed that rhodopsin level in the C3G-administered RD retinas significantly increased compared to that in the non-administered RD retinas (p < 0.05), whereas red/green opsin level did not show any significant difference. Long-term administration of C3G extracted from mulberry fruit could structurally reduce photoreceptor damage and functionally improve scotopic visual functions in the RD rat model induced by MNU.

Injectable caltrop fruit saponin protects against ischemia-reperfusion injury in rat brain.

PubMed

Yan, Ling-Geng; Lu, Yin; Zheng, Shi-Zhong; Wang, Ai-Yun; Li, Meng-Qiu; Ruan, Jun-Shan; Zhang, Lei

2011-01-01

The present study aimed to investigate the protective effects of injectable caltrop fruit saponin preparation (ICFSP) on ischemia-reperfusion injury in rat brain. Rats were injected with ICFSP and then subjected to cerebral ischemia-reperfusion injury induced by middle cerebral artery occlusion. Then the neurological deficit score was evaluated by Bederson's method. The infarct size was assessed by TTC staining. The content of malondialdehyde (MDA) and nitric oxide (NO), and the activity of superoxide dismutase (SOD) in rat cerebrum were measured with kits, and the content of 6 K prostaglandin F1α (6-K-PGF 1α), thromboxane B2 (TXB2) and endothelin (ET) in blood plasma was measured by radioimmunoassay. The results demonstrated that ICFSP led to a decrease in infarct size (p < 0.01), neurological deficit score (p < 0.05) and plasma content of TXB2 and ET (p < 0.05), and an increase of the plasma level of 6-K-PGF 1α (p < 0.05) and SOD activity in cerebrum, where the MDA and NO content were decreased. The treatment improved forelimb function. ICFSP showed a similar potency compared to that of Ligustrazine hydrochloride parenteral solution (LHPS) and nimodipine (Nim). We concluded that ICFSP protects the brain damage caused by ischemia-reperfusion injury in rats, and this may be closely related to the regulation of reactive oxygen species (MDA and SOD activity) and NO levels in the rat cerebrum, as well as vasoactive factors in the plasma (6-K-PGF 1α, TXB2 and ET).

Pre-Treatment with Metformin in Comparison with Post-Treatment Reduces Cerebral Ischemia Reperfusion Induced Injuries in Rats.

PubMed

Karimipour, Mojtaba; Shojaei Zarghani, Sara; Mohajer Milani, Majid; Soraya, Hamid

2018-04-01

To explore the effects of pre versus post ischemic treatment with metformin after global cerebral ischemia in rats. Male Wister rats underwent forebrain ischemia by bilateral common carotid artery occlusion for 17 min. Metformin (200 mg/kg) or vehicle was given orally by gavage for 7-14 days. Rats were divided into: control, metformin pre-treatment, metformin post-treatment and metformin pre and post continuous treatment groups. Cerebral infarct size, histopathology, myeloperoxidase and serum malondialdehyde were measured 7 days after ischemia. Histopathological analysis showed that metformin pre-treatment significantly decreased leukocyte infiltration, myeloperoxidase activity and also malondialdehyde level. Metformin pre-treatment and metformin post-treatment reduced infarct size compared with the control group, but it was not significant in the pre and post continuous treatment group. Our findings suggest that pre-treatment with metformin in comparison with post-treatment in experimental stroke can reduce the extent of brain damage and is more neuroprotective at least in part by inhibiting oxidative stress and inflammation.

Ingestion of Lactobacillus strain reduces anxiety and improves cognitive function in the hyperammonemia rat.

PubMed

Luo, Jia; Wang, Tao; Liang, Shan; Hu, Xu; Li, Wei; Jin, Feng

2014-03-01

Evidence suggests that the hyperammonemia (HA)-induced neuroinflammation and alterations in the serotonin (5-HT) system may contribute to cognitive decline and anxiety disorder during hepatic encephalopathy (HE). Probiotics that maintain immune system homeostasis and regulate the 5-HT system may be potential treatment for HA-mediated neurological disorders in HE. In this study, we tested the efficacy of probiotic Lactobacillus helveticus strain NS8 in preventing cognitive decline and anxiety-like behavior in HA rats. Chronic HA was induced by intraperitoneal injection of ammonium acetate for four weeks in male Sprague-Dawley rats. HA rats were then given Lactobacillus helveticus strain NS8 (10(9) CFU mL(-1)) in drinking water as a daily supplementation. The Morris water maze task assessed cognitive function, and the elevated plus maze test evaluated anxiety-like behavior. Neuroinflammation was assessed by measuring the inflammatory markers: inducible nitric oxide synthase, prostaglandin E2, and interleukin-1 β in the brain. 5-HT system activity was evaluated by measuring 5-HT and its metabolite, 5-HIAA, and the 5-HT precursor, tryptophan. Probiotic treatment of HA rats significantly reduced the level of inflammatory markers, decreased 5-HT metabolism, restored cognitive function and improved anxiety-like behavior. These results indicate that probiotic L. helveticus strain NS8 is beneficial for the treatment of cognitive decline and anxiety-like behavior in HA rats.

A magnesium based phosphate binder reduces vascular calcification without affecting bone in chronic renal failure rats.

PubMed

Neven, Ellen; De Schutter, Tineke M; Dams, Geert; Gundlach, Kristina; Steppan, Sonja; Büchel, Janine; Passlick-Deetjen, Jutta; D'Haese, Patrick C; Behets, Geert J

2014-01-01

The alternative phosphate binder calcium acetate/magnesium carbonate (CaMg) effectively reduces hyperphosphatemia, the most important inducer of vascular calcification, in chronic renal failure (CRF). In this study, the effect of low dose CaMg on vascular calcification and possible effects of CaMg on bone turnover, a persistent clinical controversy, were evaluated in chronic renal failure rats. Adenine-induced CRF rats were treated daily with 185 mg/kg CaMg or vehicle for 5 weeks. The aortic calcium content and area% calcification were measured to evaluate the effect of CaMg. To study the effect of CaMg on bone remodeling, rats underwent 5/6th nephrectomy combined with either a normal phosphorus diet or a high phosphorus diet to differentiate between possible bone effects resulting from either CaMg-induced phosphate deficiency or a direct effect of Mg. Vehicle or CaMg was administered at doses of 185 and 375 mg/kg/day for 8 weeks. Bone histomorphometry was performed. Aortic calcium content was significantly reduced by 185 mg/kg/day CaMg. CaMg ameliorated features of hyperparathyroid bone disease. In CRF rats on a normal phosphorus diet, the highest CaMg dose caused an increase in osteoid area due to phosphate depletion. The high phosphorus diet combined with the highest CaMg dose prevented the phosphate depletion and thus the rise in osteoid area. CaMg had no effect on osteoblast/osteoclast or dynamic bone parameters, and did not alter bone Mg levels. CaMg at doses that reduce vascular calcification did not show any harmful effect on bone turnover.

N-Acetylcysteine and deferoxamine reduce pulmonary oxidative stress and inflammation in rats after coal dust exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinho, R.A.; Silveira, P.C.L.; Silva, L.A.

2005-11-01

Coal dust inhalation induces oxidative damage and inflammatory infiltration on lung parenchyma. Thus, the aim of this study was to determine whether N-acetylcysteine (NAC) administered alone or in combination with deferoxamine (DFX), significantly reduced the inflammatory infiltration and oxidative damage in the lungs of rats exposed to coal dust. Forty-two male Wistar rats (200-250 g) were exposed to the coal dust (3 mg/0.5 mL saline, 3 days/week, for 3 weeks) by intratracheal instillation. The animals were randomly divided into three groups: saline 0.9% (n = 8), supplemented with NAC (20 mg/kg of body weight/day, intraperitoneal injection (i.p.)) (n = 8),more » and supplemented with NAC (20 mg/kg of body weight/day, i.p.) plus DFX (20 mg/kg of body weight/week) (n = 8). Control animals received only saline solution (0.5 mL). Lactate dehydrogenase activity and total cell number were determined in the bronchoalveolar lavage fluid. We determined lipid peroxidation and oxidative protein damage parameters and catalase and superoxide dismutase activities in the lungs of animals. Intratracheal instillation of coal dust in the lungs of rats led to an inflammatory response and induced significant oxidative damage. The administration of NAC alone or in association with DFX reduced the inflammatory response and the oxidative stress parameters in rats exposed to coal dust.« less

N-Acetylcysteine and Allopurinol Synergistically Enhance Cardiac Adiponectin Content and Reduce Myocardial Reperfusion Injury in Diabetic Rats

PubMed Central

Wang, Tingting; Qiao, Shigang; Lei, Shaoqing; Liu, Yanan; Ng, Kwok F. J.; Xu, Aimin; Lam, Karen S. L.; Irwin, Michael G.; Xia, Zhengyuan

2011-01-01

Background Hyperglycemia-induced oxidative stress plays a central role in the development of diabetic myocardial complications. Adiponectin (APN), an adipokine with anti-diabetic and anti-ischemic effects, is decreased in diabetes. It is unknown whether or not antioxidant treatment with N-acetylcysteine (NAC) and/or allopurinol (ALP) can attenuate APN deficiency and myocardial ischemia reperfusion (MI/R) injury in the early stage of diabetes. Methodology/Principal Findings Control or streptozotocin (STZ)-induced diabetic rats were either untreated (C, D) or treated with NAC (1.5 g/kg/day) or ALP (100 mg/kg/day) or their combination for four weeks starting one week after STZ injection. Plasma and cardiac biochemical parameters were measured after the completion of treatment, and the rats were subjected to MI/R by occluding the left anterior descending artery for 30 min followed by 2 h reperfusion. Plasma and cardiac APN levels were decreased in diabetic rats accompanied by decreased cardiac APN receptor 2 (AdipoR2), reduced phosphorylation of Akt, signal transducer and activator of transcription 3 (STAT3) and endothelial nitric oxide synthase (eNOS) but increased IL-6 and TNF-α (all P<0.05 vs. C). NAC but not ALP increased cardiac APN concentrations and AdipoR2 expression in diabetic rats. ALP enhanced the effects of NAC in restoring cardiac AdipoR2 and phosphorylation of Akt, STAT3 and eNOS in diabetic rats. Further, NAC and ALP, respectively, decreased postischemic myocardial infarct size and creatinine kinase-MB (CK-MB) release in diabetic rats, while their combination conferred synergistic protective effects. In addition, exposure of cultured rat cardiomyocytes to high glucose resulted in significant reduction of cardiomyocyte APN concentration and AdipoR2 protein expression. APN supplementation restored high glucose induced AdipoR2 reduction in cardiomyocytes. Conclusions/Significance NAC and ALP synergistically restore myocardial APN and AdipoR2 mediated e

Developmental treatment with difluoromethylornithine has few effects on behavior or body weight in Sprague-Dawley rats.

PubMed

Ferguson, Sherry A; Cada, Amy M

2004-01-01

Developmental difluoromethylornithine (DFMO) treatment reduces cerebellar weight [Neuroscience 17 (1986) 399, Neurotoxicol. Teratol. 22 (2000) 415, Behav. Brain Res. 126 (2001) 135], but the functional alterations resulting from this have been little investigated. Here, Sprague-Dawley rats were subcutaneously injected with 500 mg/kg DFMO on postnatal days (PNDs) 5-12 and a comprehensive set of behavioral assessments measured early developmental behaviors (righting reflex, negative geotaxis), motor coordination, acoustic startle, short- and long-term activity, social behaviors, anxiety, and spatial learning and memory. DFMO treatment appeared to cause a decreased latency to perform the negative geotaxis behavior on PNDs 8-10 and increased latency to hang by the forelimbs on PNDs 12-14. Our previous study did not indicate similar effects, but age at testing differed between the two studies. DFMO treatment caused a decreased latency to maximum acoustic startle response in both the acoustic startle paradigm and in the pulse-alone trials of the prepulse inhibition test. This DFMO treatment paradigm induced a 10% decrease in adult cerebellar weight [Behav. Brain Res. 126 (2001) 135], but the results here imply that such developmental stunting has few functional alterations.

Large‐scale analysis reveals populational contributions of cortical spike rate and synchrony to behavioural functions

PubMed Central

Saiki, Akiko; Fujiwara‐Tsukamoto, Yoko; Sakai, Yutaka; Isomura, Yoshikazu

2016-01-01

Key points There have been few systematic population‐wide analyses of relationships between spike synchrony within a period of several milliseconds and behavioural functions.In this study, we obtained a large amount of spike data from > 23,000 neuron pairs by multiple single‐unit recording from deep layer neurons in motor cortical areas in rats performing a forelimb movement task.The temporal changes of spike synchrony in the whole neuron pairs were statistically independent of behavioural changes during the task performance, although some neuron pairs exhibited correlated changes in spike synchrony.Mutual information analyses revealed that spike synchrony made a smaller contribution than spike rate to behavioural functions.The strength of spike synchrony between two neurons was statistically independent of the spike rate‐based preferences of the pair for behavioural functions. Abstract Spike synchrony within a period of several milliseconds in presynaptic neurons enables effective integration of functional information in the postsynaptic neuron. However, few studies have systematically analysed the population‐wide relationships between spike synchrony and behavioural functions. Here we obtained a sufficiently large amount of spike data among regular‐spiking (putatively excitatory) and fast‐spiking (putatively inhibitory) neuron subtypes (> 23,000 pairs) by multiple single‐unit recording from deep layers in motor cortical areas (caudal forelimb area, rostral forelimb area) in rats performing a forelimb movement task. After holding a lever, rats pulled the lever either in response to a cue tone (external‐trigger trials) or spontaneously without any cue (internal‐trigger trials). Many neurons exhibited functional spike activity in association with forelimb movements, and the preference of regular‐spiking neurons in the rostral forelimb area was more biased toward externally triggered movement than that in the caudal forelimb area. We found that

Large-scale analysis reveals populational contributions of cortical spike rate and synchrony to behavioural functions.

PubMed

Kimura, Rie; Saiki, Akiko; Fujiwara-Tsukamoto, Yoko; Sakai, Yutaka; Isomura, Yoshikazu

2017-01-01

There have been few systematic population-wide analyses of relationships between spike synchrony within a period of several milliseconds and behavioural functions. In this study, we obtained a large amount of spike data from > 23,000 neuron pairs by multiple single-unit recording from deep layer neurons in motor cortical areas in rats performing a forelimb movement task. The temporal changes of spike synchrony in the whole neuron pairs were statistically independent of behavioural changes during the task performance, although some neuron pairs exhibited correlated changes in spike synchrony. Mutual information analyses revealed that spike synchrony made a smaller contribution than spike rate to behavioural functions. The strength of spike synchrony between two neurons was statistically independent of the spike rate-based preferences of the pair for behavioural functions. Spike synchrony within a period of several milliseconds in presynaptic neurons enables effective integration of functional information in the postsynaptic neuron. However, few studies have systematically analysed the population-wide relationships between spike synchrony and behavioural functions. Here we obtained a sufficiently large amount of spike data among regular-spiking (putatively excitatory) and fast-spiking (putatively inhibitory) neuron subtypes (> 23,000 pairs) by multiple single-unit recording from deep layers in motor cortical areas (caudal forelimb area, rostral forelimb area) in rats performing a forelimb movement task. After holding a lever, rats pulled the lever either in response to a cue tone (external-trigger trials) or spontaneously without any cue (internal-trigger trials). Many neurons exhibited functional spike activity in association with forelimb movements, and the preference of regular-spiking neurons in the rostral forelimb area was more biased toward externally triggered movement than that in the caudal forelimb area. We found that a population of neuron pairs with

Metformin reduces the Walker-256 tumor development in obese-MSG rats via AMPK and FOXO3a.

PubMed

de Queiroz, Eveline A I F; Akamine, Eliana H; de Carvalho, Maria Helena C; Sampaio, Sandra C; Fortes, Zuleica B

2015-01-15

Studies have associated obesity with a wide variety of cancers. Metformin, an anti-diabetic drug, has recently received attention as a potentially useful therapeutic agent for treating cancer. Therefore, the objective of this study was to analyze the mechanisms involved in the increase in tumor development and the reduction of it by metformin in obesity using an experimental breast tumor model. Newborn male Wistar rats were subcutaneously injected with 400mg/kg monosodium glutamate (MSG) (obese) or saline (control) at 2, 3, 4, 5 and 6 days of age. After 16 weeks, 1 × 10(7) Walker-256 tumor cells were subcutaneously injected in the right flank of the rats and concomitantly the treatment with metformin 300 mg/kg/15 days, via gavage, started. The rats were divided into 4 groups: control tumor (CT), control tumor metformin (CTM), obese-MSG tumor (OT) and obese-MSG tumor metformin (OTM). On the 18th week the tumor development and metformin effect were analyzed. Tumor development was higher in OT rats compared with CT rats. Activation of insulin-IR-ERK1/2 pathway and an anti-apoptotic effect might be the mechanisms involved in the higher development of tumor in obesity. The effect of metformin reducing the tumor development in obese rats might involve increased mRNA expression of pRb and p27, increased activity of AMPK and FOXO3a and decreased expression of p-ERK1/2 (Thr202/Tyr204) in Walker-256 tumor. Our data allow us to suggest that metformin, reducing the stimulatory effect of obesity on tumor development, has a potential role in the management of cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

High fiber probiotic fermented mare's milk reduces the toxic effects of mercury in rats

PubMed Central

Abdel-Salam, Ahmed M.; Al-Dekheil, Ali; Babkr, Ali; Farahna, Mohammed; Mousa, Hassan M.

2010-01-01

Background: Since the advent of the Industrial Revolution in the late 19th century, we have all been unfortunately exposed to an increasingly toxic and polluted world. Among the most dangerous of these pollutants is mercury, which is considered to be the most toxic non-radioactive heavy metal. Fermented foods may help cleanse the body of heavy metals. Fermentation breaks down the nutrients in foods by the action of beneficial microorganisms and creates natural chelators that are available to bind toxins and remove them from the body. Aims: The current study was designed to determine the impact of feeding a high fiber probiotic fermented mare's milk on the biological effects of mercury toxicity in rat model. Methods and Materials: The high fiber fermented mare's milk containing probiotics was prepared and its sensory properties, chemical composition, and antioxidant activity were determined. A rat model of mercury toxicity was used. The effect of feeding the high fiber probiotic fermented mare's milk to rats, along with mercury ingestion, was determined by the analysis of several biochemical markers in serum and histopathological examinations of brain and kidney. Results: The high fiber fermented mare's milk containing probiotics was found to be acceptable by all test panels and volunteers. Mercury ingestion was found to cause biochemical and histopathological alterations in rat serum and tissues. The mercury-treated rats showed a decrease in body weight and an increase in kidney weight. Sera of the mercury treated rats showed alterations in biochemical parameters, and histopathological changes in brain and kidney. However, the rats fed high fiber fermented mare`s milk along with mercury ingestion showed improved histopathology of kidney and brain, and there was restoration of the biochemical parameters in serum to almost normal values. Conclusions: Feeding high fiber fermented mare`s milk may reduce the toxic effects of mercury. PMID:22558569

Infusions of muscimol into the lateral septum do not reduce rats' defensive behaviors toward a cat odor stimulus.

PubMed

Chee, San-San A; Patel, Ronak; Menard, Janet L

2015-01-01

The lateral septum (LS) is implicated in behavioral defense. We tested whether bilateral infusions of the GABAA receptor agonist muscimol into the LS suppress rats' defensive responses to cat odor. Rats received intra-LS infusions of either saline or muscimol (40 ng/rat) and were exposed to either a piece of a cat collar that had been previously worn by a cat or to a control (cat odor free) collar. Rats exposed to the cat odor collar displayed more head-out postures, while intra-LS application of muscimol reduced the number of head-out postures. However, this reduction was also present in rats exposed to a control (cat odor free) collar. This latter finding suggests that despite its involvement in other defensive behaviors (e.g., open arm avoidance in the elevated plus maze), the LS does not selectively regulate rats' receptor defensive responding to the olfactory cues present in our cat odor stimulus. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Green tea, phytic acid, and inositol in combination reduced the incidence of azoxymethane-induced colon tumors in Fisher 344 male rats.

PubMed

Khatiwada, Janak; Verghese, Martha; Davis, Shurrita; Williams, Leonard L

2011-11-01

Experimental as well as epidemiologic studies in human populations provide evidence that consumption of phytochemicals reduces the incidence of degenerative diseases. Green tea (GT) catechins are known for their antioxidative potential. Phytic acid (PA) also acts as a natural antioxidant and may have numerous health benefits. This experiment was designed to investigate the inhibitory effects of combinations of 1% and 2% GT, PA, and inositol (I) in reducing the incidence of azoxymethane-induced colon tumors in Fisher 344 male rats. After an acclimatization period of 1 week, nine groups of rats (15 rats per group) were initially assigned to consume AIN 93 G diet and later AIN 93 M diet after 20 weeks of age. Treatments were given in drinking water. All rats received azoxymethane injections (16 mg/kg of body weight) subcutaneously at 7 and 8 weeks of age. Rats were killed at 45 weeks of age by CO(2) euthanasia. Tumor incidence (93.76%) and the number of tumors per tumor-bearing rat ratio (2.25) were significantly (P<.05) higher in the control group compared with treatment groups. Glutathione S-transferase activity was significantly (P<.05) higher in rats fed combinations of 2% GT+PA+I and GT+PA (33.25 ± 1.23 and 29.83 ± 1.10 μmol/mL, respectively) compared with other groups. These findings suggest that the synergistic effect of the 2% level of GT, PA, and I may reduce the incidence of colon tumors and therefore have potential as a chemopreventive agent.

Observation of a system of linear loops formed by re-growing hairs on rat skin.

PubMed

Liu, Li-Yuan; Guo, Dong-Sheng; Xin, Xiu-Yu; Fang, Jin

2008-07-01

This paper details linear hair re-growth patterns observed in rats. Adult rats were shaved and observed. The first wave of hair re-growth did not distribute everywhere, but along specific craniocaudally-oriented lines. The hair-lines were 2-15 mm wide and ran from the head, through the torso to the limbs, and were symmetrical along the left and right sides of the body. The symmetric hair-lines from both sides of the body converged around the mouth, nose, and at the pubic region or ventral midline to form a system of hair-loop-lines (HLLs). The loops can be differentiated into four main patterns. The Dorsal Loop and the Lateral Dorsal Loop run along the dorsum and hindlimb. The Ventral Loop and Lateral Ventral Loop travel along the thorax, abdomen, and forelimb. These hair-lines coincide with our previously observed sympathetic-substance lines (SSLs) in the rat's skin. Histological observation indicates that rat hair follicles along the hair-lines were at anagen phase. The catecholamine histofluorescent check showed abundant sympathetic nerve fibers beneath the hair-lines. After the rats' hairs were dyed, and selected portions shaved, re-growth was only observed on the shaved portions, indicating that the linear hair growth closely correlated with the shaving. Lastly we examine the cause of the preferential re-growth and briefly discuss the purpose and physiological role of the HLL. (c) 2008 Wiley-Liss, Inc.

Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats

NASA Technical Reports Server (NTRS)

Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.

1998-01-01

Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that

Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts

PubMed Central

2014-01-01

Background Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. Methods Eighty Sprague–Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. Results Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. Conclusions The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities. PMID:24533833

Sargassum polycystum reduces hyperglycaemia, dyslipidaemia and oxidative stress via increasing insulin sensitivity in a rat model of type 2 diabetes.

PubMed

Motshakeri, Mahsa; Ebrahimi, Mahdi; Goh, Yong Meng; Matanjun, Patricia; Mohamed, Suhaila

2013-05-01

Sargassum polycystum, a brown seaweed, contains various nutrients and bioactive compounds that have antioxidant and healing properties. The research hypothesises that antioxidants and pigments in dietary S. polycystum extracts can improve insulin sensitivity, blood sugar levels and blood lipid levels in a rat model of type 2 diabetes. The diabetes was induced by a high-sugar, high-fat diet for 16 weeks to enhance insulin resistance, followed by a low-dose intraperitoneal injection of streptozotocin (35 mg kg(-1) body weight). The doses of S. polycystum tested on diabetic rats were 150 and 300 mg kg(-1) body weight for the ethanolic extract or 150 and 300 mg kg(-1) for the water extract. Normal rats, untreated diabetic and metformin-treated diabetic rats (n = 6) were used as control. Both doses of the alcohol extract of S. polycystum and the 300 mg kg(-1) water extract, significantly reduced blood glucose and glycosylated haemoglobin (HbA1C ) levels. Serum total cholesterol, triglyceride levels and plasma atherogenic index were significantly decreased after 22 days treatment in all seaweed groups. Unlike metformin, S. polycystum did not significantly change plasma insulin in the rats, but increased the response to insulin. The consumption of either ethanolic or water extracts of S. polycystum dose dependently reduced dyslipidaemia in type 2 diabetic rats. S. polycystum is a potential insulin sensitiser, for a comestible complementary therapy in the management of type 2 diabetes which can help reduce atherogenic risk. © 2012 Society of Chemical Industry.

A model for hypokinesia: Effects on muscle atrophy in the rat

NASA Technical Reports Server (NTRS)

Musacchia, X. J.; Deavers, D. R.; Meininger, G. A.; Davis, T. P.

1980-01-01

Hypokinesia in the hindlimbs of rats was induced by suspension; a newly developed harness system was used. The animal was able to use its forelimbs to maneuver, within a 140 deg arc, to obtain food and water and to permit limited grooming of the forequarters. The hindlimbs were nonload bearing for 7 days; following a 7-day period of hypodynamia, selected animals were placed in metabolic cages for 7 days to study recovery from hypokinesia. During the 7-day period of hypokinesia there was evidence of muscle atrophy. Gastrocnemius weight decreased, renal papillary urea content increased, and daily urinary losses of NH3 and 3-methylhistidine increased. During the 7-day recovery period muscle mass and excretion rate of urea, NH3 and 3-methylhistidine returned to control levels. Calcium balance was positive throughout the 7-day period of hypokinesia. Hypertrophy of the adrenals suggested the occurrence of some level of stress despite the apparent behavioral adjustment to the suspension harness. It was concluded that significant muscle atrophy and parallel changes in nitrogen metabolism occur in suspended rats and these changes are readily reversible.

Sexual interactions with unfamiliar females reduce hippocampal neurogenesis among adult male rats.

PubMed

Spritzer, M D; Curtis, M G; DeLoach, J P; Maher, J; Shulman, L M

2016-03-24

Recent experiments have shown that sexual interactions prior to cell proliferation cause an increase in neurogenesis in adult male rats. Because adult neurogenesis is critical for some forms of memory, we hypothesized that sexually induced changes in neurogenesis may be involved in mate recognition. Sexually naive adult male rats were either exposed repeatedly to the same sexual partner (familiar group) or to a series of novel sexual partners (unfamiliar group), while control males never engaged in sexual interactions. Ovariectomized female rats were induced into estrus every four days. Males were given two injections of 5-bromo-2'-deoxyuridine (BrdU) (200mg/kg) to label proliferating cells, and the first sexual interactions occurred three days later. Males in the familiar and unfamiliar groups engaged in four, 30-min sexual interactions at four-day intervals, and brain tissue was collected the day after the last sexual interaction. Immunohistochemistry followed by microscopy was used to quantify BrdU-labeled cells. Sexual interactions with unfamiliar females caused a significant reduction in neurogenesis in the dentate gyrus compared to males that interacted with familiar females and compared to the control group. The familiar group showed no difference in neurogenesis compared to the control group. Males in the familiar group engaged in significantly more sexual behavior (ejaculations and intromissions) than did males in the unfamiliar group, suggesting that level of sexual activity may influence neurogenesis levels. In a second experiment, we tested whether this effect was unique to sexual interactions by replicating the entire procedure using anestrus females. We found that interactions with unfamiliar anestrus females reduced neurogenesis relative to the other groups, but this effect was not statistically significant. In combination, these results indicate that interactions with unfamiliar females reduce adult neurogenesis and the effect is stronger for sexual

Reduced sensitivity to MDMA-induced facilitation of social behaviour in MDMA pre-exposed rats.

PubMed

Thompson, Murray R; Callaghan, Paul D; Hunt, Glenn E; McGregor, Iain S

2008-05-15

The acute effects of the party drug 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") in humans include feelings of love, closeness towards other people and an increased acceptance of others views and feelings. Some evidence suggests that regular MDMA users develop a subsensitivity to the positive effects of the drug and escalate their intake of the drug over time as a result. The current study investigated whether brief exposure to relatively high doses of MDMA in rats produces a subsequent attenuation in the ability of MDMA to enhance social interaction. Male Wistar rats were exposed to either MDMA (4 x 5 mg/kg over 4 h) or vehicle on two consecutive days. Twelve weeks later, MDMA pre-exposed rats displayed a significantly shorter period of time spent in social interaction than controls when tested in the drug-free state. MDMA pre-exposed rats also showed a blunted prosocial response to MDMA (2.5 mg/kg) relative to controls. This difference was overcome by increasing the MDMA dose to 5 mg/kg. The 5-HT(1A) agonist 8-OH-DPAT (250 microg/kg but not 125 microg/kg) increased social interaction and this effect did not differ in MDMA and vehicle pre-exposed rats. HPLC analysis showed a small but significant depletion of prefrontal 5-HT and 5-HIAA in MDMA pre-exposed rats. Prefrontal 5-HIAA concentrations were also reduced in the subset of vehicle and MDMA pre-exposed rats that received additional testing with MDMA. These results indicate that treatment with MDMA not only causes lasting reductions in social interaction in rats but causes an attenuation of the prosocial effects of subsequent MDMA administration. The lack of a differential response to 8-OH-DPAT agrees with other findings that the 5-HT(1A) receptor system remains functionally intact following MDMA pre-exposure and suggests that other neuroadaptations may underlie the lasting social deficits caused by MDMA.

Repeated rat-forced swim test: reducing the number of animals to evaluate gradual effects of antidepressants.

PubMed

Mezadri, T J; Batista, G M; Portes, A C; Marino-Neto, J; Lino-de-Oliveira, C

2011-02-15

The forced swim test (FST) is a pre-clinical test to short and long term treatment with antidepressant drugs (ADT), which requires between-subject designs. Herein a modified protocol of the FST using within-subject design (repeated rat-FST) was evaluated. Male Wistar rats were submitted to 15 min of swimming (Day 1: pretest) followed by three subsequent 5 min-swimming tests one week apart (Day 2: test, Day 7: retest 1, Day 14: retest 2). To determine the temporal and factorial characteristics of the variables scored in the repeated rat-FST, the protocol was carried out in untreated animals (E1). To validate the method, daily injections of Fluoxetine (FLX, 2.5mg/kg, i.p.) or saline were given over a 2-week period (E2). Tests and retests have been videotaped for further register of the latency, frequency and duration of behaviors. Over retesting the latency to immobility decreased whereas duration of immobility tended to increase. Factorial analysis revealed that the test, the retest 1 as well as the retest 2 have variables suitable to detection of antidepressant-like effects of ADT. Compared to saline, FLX chronically administrated reduced duration of immobility whereas increased duration of swimming in retest 2. The data suggest that repeated rat-FST detected the gradual increase in the efficacy of low doses of FLX over time. Therefore, repeated rat-FST seemed suitable to detect short and long term effects of selective serotonin reuptake inhibitors, or other ADT, thus reducing the number of animals used in the screenings of this type of compounds. © 2010 Elsevier B.V. All rights reserved.

Haptoglobin Reduces Inflammatory Cytokine INF-γ and Facilitates Clot Formation in Acute Severe Burn Rat Model.

PubMed

Koami, Hiroyuki; Sakamoto, Yuichiro; Miyasho, Taku; Noguchi, Ryo; Sato, Norio; Kai, Keita; Chris Yamada, Kosuke; Inoue, Satoshi

2017-01-01

Haptoglobin exerts renal protective function by scavenging free hemoglobin from the urine and blood stream in patients with hemolytic disorders. Recent studies elucidate the relationships between haptoglobin and inflammation. In addition, coagulopathy is often induced by systemic inflammation characterized by the presence of vascular endothelial damage. We hypothesize that haptoglobin might have an anti-inflammatory effect and affect hypercoagulability using rat burn model. Thirty anesthetized rats of six-weeks of age received over 30% full-thickness scald burn on the dorsal skin surface. All rats were injected with either haptoglobin (Hpt) or normal saline (NS) intraperitoneally. The rats were divided into three groups: 1) control group (NS 20 mL/kg); 2) low concentration of Hpt group, L-Hpt, (Hpt 4 mL (80 U) /kg+NS 16 mL/kg); and 3) high concentration of Hpt group, H-Hpt, (Hpt 20 mL (400 U) /kg). While under anesthesia, all rats were euthanized by exsanguination at 6 hours (N=5) and 24 hours (N=5). Inflammatory and anti-inflammatory cytokines were measured and whole-blood viscoelastic tests were performed by thromboelastometry (ROTEM). Haptoglobin significantly reduced free hemoglobin 24 hours after the injury. Improvement of hematuria was confirmed in the H-Hpt group. There were no differences in thrombin-antithrombin complex and plasmin-α2 plasmin inhibitor complex. The haptoglobin tended to decrease interferon-gamma (IFN-γ) in H-Hpt group. ROTEM findings of the L-Hpt group showed significantly higher clot firmness and shorter time to maximum clot formation velocity than the control group. Haptoglobin reduced INF-γ, and accelerated speed of clot formation in acute phase of severe burn.

Investigation of Implantable Multi-Channel Electrode Array in Rat Cerebral Cortex Used for Recording

NASA Astrophysics Data System (ADS)

Taniguchi, Noriyuki; Fukayama, Osamu; Suzuki, Takafumi; Mabuchi, Kunihiko

There have recently been many studies concerning the control of robot movements using neural signals recorded from the brain (usually called the Brain-Machine interface (BMI)). We fabricated implantable multi-electrode arrays to obtain neural signals from the rat cerebral cortex. As any multi-electrode array should have electrode alignment that minimizes invasion, it is necessary to customize the recording site. We designed three types of 22-channel multi-electrode arrays, i.e., 1) wide, 2) three-layered, and 3) separate. The first extensively covers the cerebral cortex. The second has a length of 2 mm, which can cover the area of the primary motor cortex. The third array has a separate structure, which corresponds to the position of the forelimb and hindlimb areas of the primary motor cortex. These arrays were implanted into the cerebral cortex of a rat. We estimated the walking speed from neural signals using our fabricated three-layered array to investigate its feasibility for BMI research. The neural signal of the rat and its walking speed were simultaneously recorded. The results revealed that evaluation using either the anterior electrode group or posterior group provided accurate estimates. However, two electrode groups around the center yielded poor estimates although it was possible to record neural signals.

Jinlida reduces insulin resistance and ameliorates liver oxidative stress in high-fat fed rats.

PubMed

Liu, Yixuan; Song, An; Zang, Shasha; Wang, Chao; Song, Guangyao; Li, Xiaoling; Zhu, Yajun; Yu, Xian; Li, Ling; Wang, Yun; Duan, Liyuan

2015-03-13

Jinlida (JLD) is a compound preparation formulated on the basis of traditional Chinese medicine and is officially approved for the treatment of type 2 diabetes (T2DM) in China. We aimed to elucidate the mechanism of JLD treatment, in comparison to metformin treatment, on ameliorating insulin sensitivity in insulin resistant rats and to reveal its anti-oxidant properties. Rats were fed with standard or high-fat diet for 6 weeks. After 6 weeks, the high-fat fed rats were subdivided into five groups and orally fed with JLD or metformin for 8 weeks. Fasting blood glucose (FBG), fasting blood insulin, blood lipid and antioxidant enzymes were measured. Intraperitoneal glucose tolerance test (IPGTT) and hyperinsulinemic euglycemic clamp technique were carried out to measure insulin sensitivity. Gene expression of the major signaling pathway molecules that regulate glucose uptake, including insulin receptor (INSR), insulin receptor substrate-1 (IRS-1), phosphoinositide-3-kinase (PI3K), protein kinase beta (AKT), and glucose transporter type 2 (GLUT2), were assessed by quantitative RT-PCR. The totle and phosphorylation expression of IRS-1, AKT, JNK and p38MAPK were determined by Western blot. Treatment with JLD effectively ameliorated the high-fat induced hyperglycemia, hyperinsulinemia and hyperlipidemia. Similar to metformin, the high insulin resistance in high-fat fed rats was significantly decreased by JLD treatment. JLD displayed anti-oxidant effects, coupled with up-regulation of the insulin signaling pathway. The attenuation of hepatic oxidative stress by JLD treatment was associated with reduced phosphorylation protein levels of JNK and p38MAPK. Treatment with JLD could moderate glucose and lipid metabolism as well as reduce hepatic oxidative stress, most likely through the JNK and p38MAPK pathways. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Ontogeny of cocaine-induced behaviors and cocaine pharmacokinetics in male and female neonatal, preweanling, and adult rats.

PubMed

McDougall, Sanders A; Apodaca, Matthew G; Mohd-Yusof, Alena; Mendez, Adrian D; Katz, Caitlin G; Teran, Angie; Garcia-Carachure, Israel; Quiroz, Anthony T; Crawford, Cynthia A

2018-04-18

Ontogenetic differences in the behavioral responsiveness to cocaine have often been attributed to the maturation of dopaminergic elements (e.g., dopamine transporters, D2 High receptors, receptor coupling, etc.). The purpose of this study was to determine whether ontogenetic changes in cocaine pharmacokinetics might contribute to age-dependent differences in behavioral responsiveness. Male and female neonatal (PD 5), preweanling (PD 10 and PD 20), and adult (PD 70) rats were injected (IP) with cocaine or saline and various behaviors (e.g., locomotor activity, forelimb paddle, vertical activity, head-down sniffing, etc.) were measured for 90 min. In a separate experiment, the dorsal striata of young and adult rats were removed at 10 time points (0-210 min) after IP cocaine administration. Peak cocaine values, cocaine half-life, and dopamine levels were determined using HPLC. When converted to percent of saline controls, PD 5 and PD 10 rats were generally more sensitive to cocaine than older rats, but this effect varied according to the behavior being assessed. Peak cocaine values did not differ according to age or sex, but cocaine half-life in brain was approximately 2 times longer in PD 5 and PD 10 rats than adults. Cocaine pharmacokinetics did not differ between PD 20 and PD 70 rats. Differences in the cocaine-induced behavioral responsiveness of very young rats (PD 5 and PD 10) and adults may be attributable, at least in part, to pharmacokinetic factors; whereas, age-dependent behavioral differences between the late preweanling period and adulthood cannot readily be ascribed to cocaine pharmacokinetics.

Sulphonylurea drugs reduce hypoxic damage in the isolated perfused rat kidney

PubMed Central

Engbersen, Richard; Moons, Miek M; Wouterse, Alfons C; Dijkman, Henry B; Kramers, Cees; Smits, Paul; Russel, Frans G M

2000-01-01

Sulphonylurea drugs have been shown to protect against hypoxic damage in isolated proximal tubules of the kidney. In the present study we investigated whether these drugs can protect against hypoxic damage in a whole kidney preparation. Tolbutamide (200 μM) and glibenclamide (10 μM) were applied to the isolated perfused rat kidney prior to changing the gassing from oxygen to nitrogen for 30 min. Hypoxic perfusions resulted in an increased fractional excretion of glucose (FE % glucose 14.3±1.5 for hypoxic perfusions vs 4.9±1.6 for normoxic perfusions, mean±s.e.mean, P<0.05), which could be completely restored by 200 μM tolbutamide (5.7±0.4 for tolbutamide vs 14.3±1.5 for untreated hypoxic kidneys, P<0.01). Furthermore, tolbutamide reduced the total amount of LDH excreted in the urine (220±100 mU for tolbutamide vs 1220±160 mU for untreated hypoxic kidneys, P<0.01). Comparable results were obtained with glibenclamide (10 μM). In agreement with the effect on functional parameters, ultrastructural analysis of proximal tubules showed increased brush border preservation in tolbutamide treated kidneys compared to untreated hypoxic kidneys. We conclude that glibenclamide and tolbutamide are both able to reduce hypoxic damage to proximal tubules in the isolated perfused rat kidney when applied in the appropriate concentrations. PMID:10928974

The Effect of Lesion Size on the Organization of the Ipsilesional and Contralesional Motor Cortex.

PubMed

Touvykine, Boris; Mansoori, Babak K; Jean-Charles, Loyda; Deffeyes, Joan; Quessy, Stephan; Dancause, Numa

2016-03-01

Recovery of hand function following lesions in the primary motor cortex (M1) is associated with a reorganization of premotor areas in the ipsilesional hemisphere, and this reorganization depends on the size of the lesion. It is not clear how lesion size affects motor representations in the contralesional hemisphere and how the effects in the 2 hemispheres compare. Our goal was to study how lesion size affects motor representations in the ipsilesional and contralesional hemispheres. In rats, we induced lesions of different sizes in the caudal forelimb area (CFA), the equivalent of M1. The effective lesion volume in each animal was quantified histologically. Behavioral recovery was evaluated with the Montoya Staircase task for 28 days after the lesion. Then, the organization of the CFA and the rostral forelimb area (RFA)--the putative premotor area in rats--in the 2 cerebral hemispheres was studied with intracortical microstimulation mapping techniques. The distal forelimb representation in the RFA of both the ipsilesional and contralesional hemispheres was positively correlated with the size of the lesion. In contrast, lesion size had no effect on the contralesional CFA, and there was no relationship between movement representations in the 2 hemispheres. Finally, only the contralesional RFA was negatively correlated with chronic motor deficits of the paretic forelimb. Our data show that lesion size has comparable effects on motor representations in premotor areas of both hemispheres and suggest that the contralesional premotor cortex may play a greater role in the recovery of the paretic forelimb following large lesions. © The Author(s) 2015.

Motor tics evoked by striatal disinhibition in the rat

PubMed Central

Bronfeld, Maya; Yael, Dorin; Belelovsky, Katya; Bar-Gad, Izhar

2013-01-01

Motor tics are sudden, brief, repetitive movements that constitute the main symptom of Tourette syndrome (TS). Multiple lines of evidence suggest the involvement of the cortico-basal ganglia system, and in particular the basal ganglia input structure—the striatum in tic formation. The striatum receives somatotopically organized cortical projections and contains an internal GABAergic network of interneurons and projection neurons' collaterals. Disruption of local striatal GABAergic connectivity has been associated with TS and was found to induce abnormal movements in model animals. We have previously described the behavioral and neurophysiological characteristics of motor tics induced in monkeys by local striatal microinjections of the GABAA antagonist bicuculline. In the current study we explored the abnormal movements induced by a similar manipulation in freely moving rats. We targeted microinjections to different parts of the dorsal striatum, and examined the effects of this manipulation on the induced tic properties, such as latency, duration, and somatic localization. Tics induced by striatal disinhibition in monkeys and rats shared multiple properties: tics began within several minutes after microinjection, were expressed solely in the contralateral side, and waxed and waned around a mean inter-tic interval of 1–4 s. A clear somatotopic organization was observed only in rats, where injections to the anterior or posterior striatum led to tics in the forelimb or hindlimb areas, respectively. These results suggest that striatal disinhibition in the rat may be used to model motor tics such as observed in TS. Establishing this reliable and accessible animal model could facilitate the study of the neural mechanisms underlying motor tics, and the testing of potential therapies for tic disorders. PMID:24065893

Glutamine reduces myocardial cell apoptosis in a rat model of sepsis by promoting expression of heat shock protein 90.

PubMed

Li, Wanxia; Tao, Shaoyu; Wu, Qinghua; Wu, Tao; Tao, Ran; Fan, Jun

2017-12-01

Myocardial cell injury and cardiac myocyte apoptosis are associated with sepsis. Glutamine (Gln) has been reported to repair myocardial cell injury. The aim of this study was to explore the role of Gln on cardiac myocytes in a cecal ligation and puncture (CLP) model of sepsis in Wistar rats. Following induction of sepsis in a CLP rat model, viral encoding heat shock protein 90 (Hsp90) gene and Hsp90dsDNA were designed to express and knockdown Hsp90, respectively. Rat cardiac tissues were examined histologically, and apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, Hsp90, p53 upregulated modulator of apoptosis, and p53 was measured by western blotting and real-time polymerase chain reaction. Caspase-3, caspase-8, and caspase-9 were detected by enzyme-linked immunosorbent assay. Rat cardiac myocyte damage induced by CLP was reduced by Gln treatment and Hsp90 overexpression, and these changes were reversed by Hsp90 knockdown. Bcl-2 expression, Bcl-2-associated X protein, p53, p53 upregulated modulator of apoptosis, caspase-8, caspase-9, and caspase-3 activities were significantly upregulated in the CLP model, which were reduced by Gln treatment and Hsp90 overexpression. Gln reduced apoptosis of cardiac myocytes in a rat model of sepsis, by promoting Hsp90 expression. Further studies are needed to determine the possible therapeutic action of Gln in sepsis in human tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

β-Glucans (Saccharomyces cereviseae) Reduce Glucose Levels and Attenuate Alveolar Bone Loss in Diabetic Rats with Periodontal Disease

PubMed Central

2015-01-01

The objective of this study was to assess the effects of oral ingestion of β-glucans isolated from Saccharomyces cereviseae on the metabolic profile, expression of gingival inflammatory markers and amount of alveolar bone loss in diabetic rats with periodontal disease. Diabetes mellitus was induced in 48 Wistar rats by intraperitoneal injection of streptozotocin (80 mg/kg). After confirming the diabetes diagnosis, the animals were treated with β-glucans (by gavage) for 28 days. On the 14th day of this period, periodontal disease was induced using a ligature protocol. β-glucans reduced the amount of alveolar bone loss in animals with periodontal disease in both the diabetic and non-diabetic groups (p < 0.05). β-glucans reduced blood glucose, cholesterol and triacylglycerol levels in diabetic animals, both with and without periodontal disease (p < 0.05). Furthermore, treatment with β-glucans reduced the expression of cyclooxygenase-2 and receptor activator of nuclear factor kappa-B ligand and increased osteoprotegerin expression in animals with diabetes and periodontal disease (p < 0.05). It was concluded that treatment with β-glucans has beneficial metabolic and periodontal effects in diabetic rats with periodontal disease. PMID:26291983

Reduced carotid baroreceptor distensibility-induced baroreflex resetting contributes to impairment of sodium regulation in rats fed a high-fat diet.

PubMed

Abe, Chikara; Nagai, Yuko; Yamaguchi, Aoi; Aoki, Hitomi; Shimizu, Shuji; Akiyama, Tsuyoshi; Kawada, Toru; Sugimachi, Masaru; Morita, Hironobu

2015-04-15

Decreased carotid arterial compliance has been reported in obese subjects and animals. Carotid baroreceptors are located at the bifurcation of the common carotid artery, and respond to distension of the arterial wall, suggesting that higher pressure is required to obtain the same distension in obese subjects and animals. A hyperosmotic NaCl solution induces circulatory volume expansion and arterial pressure (AP) increase, which reflexively augment renal excretion. Thus, we hypothesized that sodium regulation via the baroreflex might be impaired in response to chronic hyperosmotic NaCl infusion in rats fed a high-fat diet. To examine this hypothesis, we used rats fed a high-fat (Fat) or normal (NFD) diet, and measured mean AP, water and sodium balance, and renal function in response to chronic infusion of hyperosmotic NaCl solution via a venous catheter. Furthermore, we examined arterial baroreflex characteristics with static open-loop analysis and distensibility of the common carotid artery. Significant positive water and sodium balance was observed on the 1st day of 9% NaCl infusion; however, this disappeared by the 2nd day in Fat rats. Mean AP was significantly higher during 9% NaCl infusion in Fat rats compared with NFD rats. In the open-loop analysis of carotid sinus baroreflex, a rightward shift of the neural arc was observed in Fat rats compared with NFD rats. Furthermore, distensibility of the common carotid artery was significantly reduced in Fat rats. These results indicate that a reduced baroreceptor distensibility-induced rightward shift of the neural arc might contribute to impairment of sodium regulation in Fat rats. Copyright © 2015 the American Physiological Society.

Exercise to reduce the escalation of cocaine self-administration in adolescent and adult rats.

PubMed

Zlebnik, Natalie E; Anker, Justin J; Carroll, Marilyn E

2012-12-01

Concurrent access to an exercise wheel decreases cocaine self-administration under short access (5 h/day for 5 days) conditions and suppresses cocaine-primed reinstatement in adult rats. The effect of exercise (wheel running) on the escalation of cocaine intake during long access (LgA, 6 h/day for 26 days) conditions was evaluated. Adolescent and adult female rats acquired wheel running, and behavior was allowed to stabilize for 3 days. They were then implanted with an iv catheter and allowed to self-administer cocaine (0.4 mg/kg, iv) during 6-h daily sessions for 16 days with concurrent access to either an unlocked or a locked running wheel. Subsequently, for ten additional sessions, wheel access conditions during cocaine self-administration sessions were reversed (i.e., locked wheels became unlocked and vice versa). In the adolescents, concurrent access to the unlocked exercise wheel decreased responding for cocaine and attenuated escalation of cocaine intake irrespective of whether the locked or unlocked condition came first. However, cocaine intake increased when the wheel was subsequently locked for the adolescents that had initial access to an unlocked wheel. Concurrent wheel access either before or after the locked wheel access did not reduce cocaine intake in adults. Wheel running reduced cocaine intake during LgA conditions in adolescent but not adult rats, and concurrent access to the running wheel was necessary. These results suggest that exercise prevents cocaine seeking and that this effect is more pronounced in adolescents than adults.

Activation of N-methyl-d-aspartate receptors reduces heart rate variability and facilitates atrial fibrillation in rats.

PubMed

Shi, Shaobo; Liu, Tao; Wang, Dandan; Zhang, Yan; Liang, Jinjun; Yang, Bo; Hu, Dan

2017-07-01

The goal of this study was to assess the effects of N-methyl-d-aspartate (NMDA) receptors activation on heart rate variability (HRV) and susceptibility to atrial fibrillation (AF). Rats were randomized for treatment with saline, NMDA (agonist of NMDA receptors), or NMDA plus MK-801 (antagonist of NMDA receptors) for 2 weeks. Heart rate variability was evaluated by using implantable electrocardiogram telemeters. Atrial fibrillation susceptibility was assessed with programmed stimulation in isolated hearts. Compared with the controls, the NMDA-treated rats displayed a decrease in the standard deviation of normal RR intervals, the standard deviation of the average RR intervals, the mean of the 5-min standard deviations of RR intervals, the root mean square of successive differences, and high frequency (HF); and an increase in low frequency (LF) and LF/HF (all P< 0.01). Additionally, the NMDA-treated rats showed prolonged activation latency and reduced effective refractory period (all P< 0.01). Importantly, AF was induced in all NMDA-treated rats. While atrial fibrosis developed, connexin40 downgraded and metalloproteinase 9 upgraded in the NMDA-treated rats (all P< 0.01). Most of the above alterations were mitigated by co-administering with MK-801. These results indicate that NMDA receptors activation reduces HRV and enhances AF inducibility, with cardiac autonomic imbalance, atrial fibrosis, and degradation of gap junction protein identified as potential mechanistic contributors. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Piper sarmentosum is comparable to glycyrrhizic acid in reducing visceral fat deposition in adrenalectomised rats given dexamethasone.

PubMed

Fairus, A; Ima Nirwana, S; Elvy Suhana, M R; Tan, M H; Santhana, R; Farihah, H S

2013-01-01

Visceral obesity may be due to the dysregulation of cortisol production or metabolism that lead to metabolic disease. In adipose tissue, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 regulates cortisol metabolism (11beta-HSD1). A previous study showed an increase in the visceral fat deposition in adrenalectomised rats given intramuscular dexamethasone. Glycyrrhizic acid (GCA) has been shown to reduce fat deposition because it is a known potent inhibitor of the 11beta-HSD1 enzyme. Piper sarmentosum (PS) is an edible medicinal plant commonly used in Asia as traditional medicine for treating diabetes, hypertension and joint pains. In this study, we determined the effects of PS extract on the disposition and morphology of perirenal adipocytes of adrenalectomised rats given intramuscular dexamethasone. A total of 21 male Spraque Dawley rats were adrenalectomised and given intramuscular dexamethasone, 120 μg/kg/day. These rats were further divided into three groups: adrenalectomised control (ADR+Dexa; n=7), GCA-treated (ADR+Dexa+GCA; dose=240 mg/kg/day; n=7) and PS-treated (ADR+Dexa+PS; dose=125 mg/kg/day; n=7) groups. The various treatments were given via gastric gavage following 2 weeks of adrenalectomy. Treatment with PS extract for 8 weeks showed decreased deposition of perirenal adipocytes which was similar to the GCA-treated group. However, PS-treated rats had thinner adipocyte membrane compared with that of the GCA-treated group. In conclusion, PS extract decreased perirenal fat deposition and reduced the diameter of the adipocyte membrane. However, the mechanisms of action needed further study.

Exercise reward induces appetitive 50-kHz calls in rats.

PubMed

Heyse, Natalie C; Brenes, Juan C; Schwarting, Rainer K W

2015-08-01

Rats express affective states by visible behaviors (like approach or flight) and through different kinds of ultrasonic vocalizations (USV). 50-kHz calls are thought to reflect positive affective states since they occur during rewarding situations like social play or palatable food. However, the effects of voluntary exercise on USV have not been investigated yet, although such exercise can serve as reward. To this aim, we gave young adult rats restricted daily access to a runway maze, where they could interact with either a movable (experimental group) or locked wheel (sedentary group) for 14days and we tested USV in anticipation of and during subsequent running. We also studied inter-individual differences in running, and relationships with USV, and rat-typical trait measures. The results showed that the experimental rats had to be separated into "runners" and "pseudorunners" since only runners performed true running, whereas pseudorunners hardly entered the wheel and turned it only with their forelimbs. This outcome seems to be related to subject-dependent differences in responding to novelty and in reward sensitivity, as indicated by pertinent screening tests, which we had performed prior to the 14days of wheel access. In the runway, our experimental and control groups did not differ in visible anticipatory behavior, like approach. Yet, only runners and sedentary rats displayed an increasing but similar amount of anticipatory USV, which is suggestive of a state of incentive anticipation of the coming wheel access. During exercise, only runners increased USV, probably indicating a highly positive emotional state. To conclude, voluntary exercise provides a promising tool to induce 50-kHz USV during and in anticipation of exercise. When performing such studies, possible individual differences between subjects have to be taken into account, and the actual wheel performance should carefully be controlled. Copyright © 2015 Elsevier Inc. All rights reserved.

Clopidogrel (Plavix) reduces the rate of thrombosis in the rat tuck model for microvenous anastomosis.

PubMed

Moore, Michael G; Deschler, Daniel G

2007-04-01

To evaluate the effect of clopidogrel on the rate of thrombosis in a rat model for venous microvascular failure. Forty rats were treated with clopidogrel or saline control via gastric gavage in a randomized, blinded fashion. After allowing for absorption and activation, each femoral vein was isolated and a venous "tuck" procedure was performed. The bleeding time and vessel patency were subsequently evaluated. The rate of vessel thrombosis was decreased in the clopidogrel-treated group compared to controls (7.9% vs 31.4%, P < 0.025). The bleeding time was longer in the clopidogrel-treated group compared to controls (250 +/- 100 seconds vs 173 +/- 59 seconds, P < 0.015). Clopidogrel decreased the rate of thrombosis in the rat model for venous microvascular failure. The use of clopidogrel may reduce the rate of venous thrombosis after free tissue transfer and may be indicated in select patients.

Ursodeoxycholic acid pretreatment reduces oral bioavailability of the multiple drug resistance-associated protein 2 substrate baicalin in rats.

PubMed

Wu, Tao; Li, Xi-Ping; Xu, Yan-Jiao; Du, Guang; Liu, Dong

2013-11-01

Baicalin is a major bioactive component of Scutellaria baicalensis and a substrate of multiple drug resistance-associated protein 2. Expression of multiple drug resistance-associated protein 2 is regulated by NF-E2-related factor 2. The aim of this study was to explore whether ursodeoxycholic acid, an NF-E2-related factor 2 activator, could influence the oral bioavailability of baicalin. A single dose of baicalin (200 mg/kg) was given orally to rats pretreated with ursodeoxycholic acid (75 mg/kg and 150 mg/kg, per day, intragastrically) or normal saline (per day, intragastrically) for six consecutive days. The plasma concentration of baicalin was measured with the HPLC method. The result indicated that the oral bioavailability of baicalin was significantly and dose-dependently reduced in rats pretreated with ursodeoxycholic acid. Compared with control rats, the mean area under concentration-time curve of baicalin was reduced from 13.25 ± 0.24 mg/L h to 7.62 ± 0.15 mg/L h and 4.97 ± 0.21 mg/L h, and the C(max) value was decreased from 1.31 ± 0.03 mg/L to 0.62 ± 0.05 mg/L and 0.36 ± 0.04 mg/L in rats pretreated with ursodeoxycholic acid at doses of 75 mg/kg and 150 mg/kg, respectively, for six consecutive days. Hence, ursodeoxycholic acid treatment reduced the oral bioavailability of baicalin in rats, probably due to the enhanced efflux of baicalin from the intestine and liver by multiple drug resistance-associated protein 2. Georg Thieme Verlag KG Stuttgart · New York.

Bepridil decreases Aβ and calcium levels in the thalamus after middle cerebral artery occlusion in rats

PubMed Central

Sarajärvi, Timo; Lipsanen, Anu; Mäkinen, Petra; Peräniemi, Sirpa; Soininen, Hilkka; Haapasalo, Annakaisa; Jolkkonen, Jukka; Hiltunen, Mikko

2012-01-01

Alzheimer's disease (AD) and cerebral ischaemia share similar features in terms of altered amyloid precursor protein (APP) processing and β-amyloid (Aβ) accumulation. We have previously shown that Aβ and calcium deposition, and β-secretase activity, are robustly increased in the ipsilateral thalamus after transient middle cerebral artery occlusion (MCAO) in rats. Here, we investigated whether the non-selective calcium channel blocker bepridil, which also inhibits β-secretase cleavage of APP, affects thalamic accumulation of Aβ and calcium and in turn influences functional recovery in rats subjected to MCAO. A 27-day bepridil treatment (50 mg/kg, p.o.) initiated 2 days after MCAO significantly decreased the levels of soluble Aβ40, Aβ42 and calcium in the ipsilateral thalamus, as compared with vehicle-treated MCAO rats. Expression of seladin-1/DHCR24 protein, which is a potential protective factor against neuronal damage, was decreased at both mRNA and protein levels in the ipsilateral thalamus of MCAO rats. Conversely, bepridil treatment restored seladin-1/DHCR24 expression in the ipsilateral thalamus. Bepridil treatment did not significantly affect heme oxygenase-1- or NAD(P)H quinone oxidoreductase-1-mediated oxidative stress or inflammatory responses in the ipsilateral thalamus of MCAO rats. Finally, bepridil treatment mitigated MCAO-induced alterations in APP processing in the ipsilateral thalamus and improved contralateral forelimb use in MCAO rats. These findings suggest that bepridil is a plausible therapeutic candidate in AD or stroke owing to its multifunctional role in key cellular events that are relevant for the pathogenesis of these diseases. PMID:22805236

Long-term treatment with nebivolol improves arterial reactivity and reduces ventricular hypertrophy in spontaneously hypertensive rats.

PubMed

Guerrero, Estela; Voces, Felipe; Ardanaz, Noelia; Montero, María José; Arévalo, Miguel; Sevilla, María Angeles

2003-09-01

The aim of this study was to assess the effects of long-term nebivolol therapy on high blood pressure, impaired endothelial function in aorta, and damage observed in heart and conductance arteries in spontaneously hypertensive rats (SHR). For this purpose, SHR were treated for 9 weeks with nebivolol (8 mg/kg per day). Untreated SHR and Wistar Kyoto rats were used as hypertensive and normotensive controls, respectively. The left ventricle/body weight ratio was used as an index of cardiac hypertrophy, and to evaluate vascular function, responses induced by potassium chloride, noradrenaline, acetylcholine, and sodium nitroprusside were tested on aortic rings. Aortic morphometry and fibrosis were determined in parallel by a quantitative technique. Systolic blood pressure, measured by the tail-cuff method, was lower in treated SHR than in the untreated group (194 +/- 3 versus 150 +/- 4 mm Hg). The cardiac hypertrophy index was significantly reduced by the treatment. In aortic rings, treatment with nebivolol significantly reduced the maximal response to both KCl and NA in SHR. In vessels precontracted with phenylephrine relaxant, activity due to acetylcholine was higher in normotensive rats than in SHR and the treatment significantly improved this response. The effect of sodium nitroprusside on aortic rings was similar in all groups. Medial thickness and collagen content were significantly reduced in comparison with SHR. In conclusion, the chronic antihypertensive effect of nebivolol in SHR was accompanied by an improvement in vascular structure and function and in the cardiac hypertrophy index.

Silymarin ameliorates fructose induced insulin resistance syndrome by reducing de novo hepatic lipogenesis in the rat.

PubMed

Prakash, Prem; Singh, Vishal; Jain, Manish; Rana, Minakshi; Khanna, Vivek; Barthwal, Manoj Kumar; Dikshit, Madhu

2014-03-15

High dietary fructose causes insulin resistance syndrome (IRS), primarily due to simultaneous induction of genes involved in glucose, lipid and mitochondrial oxidative metabolism. The present study evaluates effect of a hepatoprotective agent, silymarin (SYM) on fructose-induced metabolic abnormalities in the rat and also assessed the associated thrombotic complications. Wistar rats were kept on high fructose (HFr) diet throughout the 12-week study duration (9 weeks of HFr feeding and subsequently 3 weeks of HFr plus SYM oral administration [once daily]). SYM treatment significantly reduced the HFr diet-induced increase expression of peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α/β, peroxisome proliferator-activated receptor (PPAR)-α, forkhead box protein O1 (FOXO1), sterol regulatory element binding protein (SREBP)-1c, liver X receptor (LXR)-β, fatty acid synthase (FAS) and PPARγ genes in rat liver. SYM also reduced HFr diet mediated increase in plasma triglycerides (TG), non-esterified fatty acids (NEFA), uric acid, malondialdehyde (MDA), total nitrite and pro-inflammatory cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-gamma [IFN-γ] and tumor necrosis factor [TNF]) levels. Moreover, SYM ameliorated HFr diet induced reduction in glucose utilization and endothelial dysfunction. Additionally, SYM significantly reduced platelet activation (adhesion and aggregation), prolonged ferric chloride-induced blood vessel occlusion time and protected against exacerbated myocardial ischemia reperfusion (MI-RP) injury. SYM treatment prevented HFr induced mRNA expression of hepatic PGC-1α/β and also its target transcription factors which was accompanied with recovery in insulin sensitivity and reduced propensity towards thrombotic complications and aggravated MI-RP injury. Copyright © 2014 Elsevier B.V. All rights reserved.

Reliability in the location of hindlimb motor representations in Fischer-344 rats: laboratory investigation.

PubMed

Frost, Shawn B; Iliakova, Maria; Dunham, Caleb; Barbay, Scott; Arnold, Paul; Nudo, Randolph J

2013-08-01

The purpose of the present study was to determine the feasibility of using a common laboratory rat strain for reliably locating cortical motor representations of the hindlimb. Intracortical microstimulation techniques were used to derive detailed maps of the hindlimb motor representations in 6 adult Fischer-344 rats. The organization of the hindlimb movement representation, while variable across individual rats in topographic detail, displayed several commonalities. The hindlimb representation was positioned posterior to the forelimb motor representation and posterolateral to the motor trunk representation. The areal extent of the hindlimb representation across the cortical surface averaged 2.00 ± 0.50 mm(2). Superimposing individual maps revealed an overlapping area measuring 0.35 mm(2), indicating that the location of the hindlimb representation can be predicted reliably based on stereotactic coordinates. Across the sample of rats, the hindlimb representation was found 1.25-3.75 mm posterior to the bregma, with an average center location approximately 2.6 mm posterior to the bregma. Likewise, the hindlimb representation was found 1-3.25 mm lateral to the midline, with an average center location approximately 2 mm lateral to the midline. The location of the cortical hindlimb motor representation in Fischer-344 rats can be reliably located based on its stereotactic position posterior to the bregma and lateral to the longitudinal skull suture at midline. The ability to accurately predict the cortical localization of functional hindlimb territories in a rodent model is important, as such animal models are being increasingly used in the development of brain-computer interfaces for restoration of function after spinal cord injury.

Secondary damage in the spinal cord after motor cortex injury in rats.

PubMed

Weishaupt, Nina; Silasi, Gergely; Colbourne, Frederick; Fouad, Karim

2010-08-01

When neurons within the motor cortex are fatally injured, their axons, many of which project into the spinal cord, undergo wallerian degeneration. Pathological processes occurring downstream of the cortical damage have not been extensively studied. We created a focal forelimb motor cortex injury in rats and found that axons from cell bodies located in the hindlimb motor cortex (spared by the cortical injury) become secondarily damaged in the spinal cord. To assess axonal degeneration in the spinal cord, we quantified silver staining in the corticospinal tract (CST) at 1 week and 4 weeks after the injury. We found a significant increase in silver deposition at the thoracic spinal cord level at 4 weeks compared to 1 week post-injury. At both time points, no degenerating neurons could be found in the hindlimb motor cortex. In a separate experiment, we showed that direct injury of neurons within the hindlimb motor cortex caused marked silver deposition in the thoracic CST at 1 week post-injury, and declined thereafter. Therefore, delayed axonal degeneration in the thoracic spinal cord after a focal forelimb motor cortex injury is indicative of secondary damage at the spinal cord level. Furthermore, immunolabeling of spinal cord sections showed that a local inflammatory response dominated by partially activated Iba-1-positive microglia is mounted in the CST, a viable mechanism to cause the observed secondary degeneration of fibers. In conclusion, we demonstrate that following motor cortex injury, wallerian degeneration of axons in the spinal cord leads to secondary damage, which is likely mediated by inflammatory processes.

The sensorimotor and cognitive deficits in rats following 90- and 120-min transient occlusion of the middle cerebral artery.

PubMed

Zvejniece, Liga; Svalbe, Baiba; Liepinsh, Edgars; Pulks, Eduards; Dambrova, Maija

2012-07-15

Middle cerebral artery occlusion (MCAO) is the most commonly used method to study the neurological and histological outcomes and the pathological mechanisms of ischaemic stroke. The current work compares sensorimotor and cognitive deficits and the infarct volume in rats following a transient 90- or 120-min MCAO, which allows the appropriate behavioural tests to be chosen based on the goal and design of the experiment. In the beam-walking test, we found significant differences between the 90- and 120-min MCAO groups in the number of foot faults made with the impaired hindlimb on post-stroke days 3, 7 and 14. In the cylinder test, a difference between the 90- and 120-min groups was observed on post-operation day 14. The responses to tactile and proprioceptive stimulation were impaired to a similar extent after 90- and 120-min MCAO in the vibrissae-evoked forelimb-placing and limb-placing tests. Moreover, we found significant memory impairment in the 120-min MCAO group 6 days after the acquisition trial. The brain tissue damage was significantly higher after 120-min occlusion of the MCA compared with 90-min occlusion; the infarct volumes were 13% and 25% of the contralateral hemispheres, respectively. In conclusion, both the 90- and 120-min occlusion models result in a significant impairment of sensorimotor, tactile and proprioceptive function, but memory impairment is only observed in the 120-min MCAO group. The beam-walking and cylinder tests detected neurological dysfunction after the 120-min MCAO, whereas the limb-placing and vibrissae-evoked forelimb-placing tests were able to evaluate the neurological dysfunction in rats after 90- and 120-min MCAO. Copyright © 2012 Elsevier B.V. All rights reserved.

Halothane reduces the early lipopolysaccharide-induced lung inflammation in mechanically ventilated rats.

PubMed

Giraud, O; Seince, P F; Rolland, C; Leçon-Malas, V; Desmonts, J M; Aubier, M; Dehoux, M

2000-12-01

Several studies suggest that anesthetics modulate the immune response. The aim of this study was to investigate the effect of halothane and thiopental on the lung inflammatory response. Rats submitted or not to intratracheal (IT) instillation of lipopolysaccharides (LPS) were anesthetized with either halothane (0. 5, 1, or 1.5%) or thiopental (60 mg. kg(-1)) and mechanically ventilated for 4 h. Control rats were treated or not by LPS without anesthesia. Lung inflammation was assessed by total and differential cell counts in bronchoalveolar lavage fluids (BALF) and by cytokine measurements (tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6], macrophage inflammatory protein-2 [MIP-2], and monocyte chemoattractant protein-1 [MCP-1]) in BALF and lung homogenates. In the absence of LPS treatment, neither halothane nor thiopental modified the moderate inflammatory response induced by tracheotomy or mechanical ventilation. Cell recruitment and cytokine concentrations were increased in all groups receiving IT LPS. However, in halothane-anesthetized rats (halothane > or = 1%), but not in thiopental-anesthetized rats, the LPS-induced lung inflammation was altered in a dose-dependent manner. Indeed, when using 1% halothane, polymorphonuclear leukocyte (PMN) recruitment was decreased by 55% (p < 0.001) and TNF-alpha, IL-6, and MIP-2 concentrations in BALF and lung homogenates were decreased by more than 60% (p < 0.001) whereas total protein and MCP-1 concentrations remained unchanged. The decrease of MIP-2 (observed at the protein and messenger RNA [mRNA] level) was strongly correlated to the decrease of PMN recruitment (r = 0.73, p < 0.05). This halothane-reduced lung inflammatory response was transient and was reversed 20 h after the end of the anesthesia. Our study shows that halothane > or = 1%, delivered during 4 h by mechanical ventilation, but not mechanical ventilation per se, alters the early LPS-induced lung inflammation in the rat, suggesting a specific

Red algae (Gelidium amansii) reduces adiposity via activation of lipolysis in rats with diabetes induced by streptozotocin-nicotinamide.

PubMed

Yang, Tsung-Han; Yao, Hsien-Tsung; Chiang, Meng-Tsan

2015-12-01

Gelidium amansii (GA) is an edible red algae that is distributed mainly in northeastern Taiwan. This study was designed to investigate the effects of GA on plasma glucose, lipids, and adipocytokines in rats with streptozotocin-nicotinamide-induced diabetes. Rats were divided into four groups: (1) rats without diabetes fed a high-fat diet (control group); (2) rats with diabetes fed a high-fat diet; (3) rats with diabetes fed a high-fat diet with thiazolidinedione in the diet; and (4) rats with diabetes fed a high-fat diet and GA. The experimental diet and drinking water were available ad libitum for 11 weeks. After the 11-week feeding study, plasma glucose, triglyceride, and cholesterol concentrations were lower in rats with diabetes fed the GA diet than in animals with diabetes fed the control diet. In addition, cholesterol and triglyceride excretion were significantly higher in rats with diabetes fed the GA diet. Moreover, GA feeding induced lipolysis in both paraepididymal and perirenal adipose tissues. Adipose tissue (paraepididymal and perirenal) weight and triglyceride contents were lower after GA treatment. Plasma adipocytokines including tumor necrosis factor-alpha, interleukin-6, and plasminogen activator inhibitor-1 were reduced by GA feeding in rats with diabetes. The results of the current study suggest that GA feeding may regulate plasma glucose and lipid levels and prevent adipose tissue accumulation in rats with diabetes. Copyright © 2015. Published by Elsevier B.V.

Scalp acupuncture attenuates neurological deficits in a rat model of hemorrhagic stroke.

PubMed

Liu, Hao; Sun, Xiaowei; Zou, Wei; Leng, Mengtong; Zhang, Beng; Kang, Xiaoyu; He, Tao; Wang, Hui

2017-06-01

Hemorrhagic stroke accounts for approximately 15% of all stroke cases, and is associated with high morbidity and mortality. Limited human studies suggested that scalp acupuncture could facilitate functional recovery after cerebral hemorrhage. In the current study, we used an animal model of cerebral hemorrhage to examine the potential effects of scalp acupuncture. Adult male Sprague-Dawley rats received autologous blood (50μL) into the right caudate nucleus on the right side under pentobarbital anesthesia, and then received scalp acupuncture (DU20 through GB7 on the lesion side) or sham acupuncture (1cm to the right side of the acupoints) (n=10 per group). A group of rats receiving autologous blood into the caudate nucleus but no other intervention, as well as a group of rats receiving anesthesia but no blood injection to the brain (n=10 per group) were included as additional controls. Composite neuroscore, corner turn test, forelimb placing test, wire hang task and beam walking were used to evaluate the behavior of rats. Hematoxylin and Eosin (HE) staining was used to observe the histopathological changes. Western blot was used to detect the content of tumor necrosis factor alpha (TNF-α) and nuclear factor-KappaB (NFκB) protein expression. Scalp acupuncture attenuated neurological deficits (p<0.01 or <0.05 vs. sham acupuncture using a variety of behavioral tests) at 1-7days after the treatment. The brain content of TNF-α and NFκB was decreased (p<0.01 for both). Scalp acupuncture could improve neurological deficits in a rat model of hemorrhagic stroke. Copyright © 2017 Elsevier Ltd. All rights reserved.

Repeated intermittent MDMA binges reduce DAT density in mice and SERT density in rats in reward regions of the adolescent brain.

PubMed

Kindlundh-Högberg, Anna M S; Schiöth, Helgi B; Svenningsson, Per

2007-11-01

The popular recreational drug, 3,4-methylenedioxymethamphetamine (MDMA) is often taken as intermittent binges by adolescents at dance clubs. The neurobiological mechanisms that underlie MDMA-induced psychiatric conditions are still poorly understood. In the present study, mimicking adolescent patterns of administration, repeated intermittent MDMA binges (3x5 mg/(kg day) given 3h apart, every 7th day for 4 weeks) were given to adolescent mice and rats. Behavioral responses in the open-field and autoradiographic ligand-binding to dopamine (DAT) and serotonin (SERT) transporters in reward regions of the brain were measured. In the open-field, total horizontal activity (HA) was significantly increased in both mice and rats following the first and third weekly administered MDMA binge. However, rats, but not mice, exhibited an enhanced activity in the centre of the open-field arena, indicating on reduced anxiety or enhanced impulsivity, which is known to be associated with altered serotonin activity. Specific binding of DAT, but not SERT, was significantly reduced in the mouse AcbSh and CPU using in vitro autoradiography. On the contrary, SERT, but not DAT density was significantly reduced in the AcbSh of rats. Taken together, our data provide evidence for differential regulation of DAT and SERT densities in reward-related brain regions of rats and mice after long-term intermittent administration of MDMA.

Agmatine Reduces Ultrasonic Vocalization Deficits in Female Rat Pups Exposed Neonatally to Ethanol

PubMed Central

Wellmann, Kristen; Lewis, Ben; Barron, Susan

2010-01-01

Rat pups, in isolation, produce ultrasonic vocalizations (USVs). These USVs have been used as a diagnostic tool for developmental toxicity. We have shown that neonatal ethanol (ETOH) exposure produces deficits in this behavior. The current study was designed to examine whether agmatine (AG), which binds to imidazoline receptors and modulates n-methyl-d-aspartate receptors (NMDAR), could reduce these deficits. In addition, this study examined critical periods for ETOH’s effects on USVs by administering ETOH during either the 1st or 2nd postnatal week. Neonatal rats received intragastric intubations of either ETOH (6g/kg/day), ETOH and AG (6g/kg/day and 20 mg/kg/day), AG (20mg/kg/day), or maltose on postnatal days (PND) 1–7 or 8–14. A non-intubated control was also included. Subjects were tested on PND 15. Neonatal ETOH exposure significantly increased the latency to vocalize for females and reduced the rate of USVs in both males and females exposed to ETOH on PND 1–7. Agmatine reduced these deficits, in female but not male pups. Subjects exposed to ETOH on PND 8–14 showed no evidence of abnormal USVs. These findings suggest that there may be gender differences in response to AG following neonatal ETOH exposure and also provide further support that the first neonatal week is a particularly sensitive time for the developmentally toxic effects of ETOH in rodents. PMID:19945529

Reduced incidence of stress ulcer in germ-free Sprague Dawley rats.

PubMed

Paré, W P; Burken, M I; Allen, E D; Kluczynski, J M

1993-01-01

Recent findings with respect to the role of spiral gram-negative bacteria in peptic ulcer disease have stimulated interest in discerning the role of these agents in stress ulcer disease. We tested the hypothesis that a standard restraint-cold ulcerogenic procedure would fail to produce ulcers in axenic rats. Axenic, as well as normal Sprague Dawley rats, were exposed to a cold-restraint procedure. The germ-free condition was maintained throughout the study in the axenic rats. Axenic rats had significantly fewer ulcers as compared to normal rats exposed to the standard cold-restraint procedure, as well as handling control rats. The data represent the first report suggesting a microbiologic component in the development of stress ulcer using the rat model.

Long-term exposure to a ‘safe’ dose of bisphenol A reduced protein acetylation in adult rat testes

NASA Astrophysics Data System (ADS)

Chen, Zhuo; Zuo, Xuezhi; He, Dongliang; Ding, Shibin; Xu, Fangyi; Yang, Huiqin; Jin, Xin; Fan, Ying; Ying, Li; Tian, Chong; Ying, Chenjiang

2017-01-01

Bisphenol A (BPA), a typical environmental endocrine-disrupting chemical, induces epigenetic inheritance. Whether histone acetylation plays a role in these effects of BPA is largely unknown. Here, we investigated histone acetylation in male rats after long-term exposure to a ‘safe’ dose of BPA. Twenty adult male rats received either BPA (50 μg/kg·bw/day) or a vehicle diet for 35 weeks. Decreased protein lysine-acetylation levels at approximately ~17 kDa and ~25 kDa, as well as decreased histone acetylation of H3K9, H3K27 and H4K12, were detected by Western blot analysis of testes from the treated rats compared with controls. Additionally, increased protein expression of deacetylase Sirt1 and reduced binding of Sirt1, together with increased binding of estrogen receptor β (ERβ) to caveolin-1 (Cav-1), a structural protein component of caveolar membranes, were detected in treated rats compared with controls. Moreover, decreased acetylation of Cav-1 was observed in the treated rats for the first time. Our study showed that long-term exposure to a ‘safe’ dose of BPA reduces histone acetylation in the male reproductive system, which may be related to the phenotypic paternal-to-offspring transmission observed in our previous study. The evidence also suggested that these epigenetic effects may be meditated by Sirt1 via competition with ERβ for binding to Cav-1.

Long-term exposure to a ‘safe’ dose of bisphenol A reduced protein acetylation in adult rat testes

PubMed Central

Chen, Zhuo; Zuo, Xuezhi; He, Dongliang; Ding, Shibin; Xu, Fangyi; Yang, Huiqin; Jin, Xin; Fan, Ying; Ying, Li; Tian, Chong; Ying, Chenjiang

2017-01-01

Bisphenol A (BPA), a typical environmental endocrine-disrupting chemical, induces epigenetic inheritance. Whether histone acetylation plays a role in these effects of BPA is largely unknown. Here, we investigated histone acetylation in male rats after long-term exposure to a ‘safe’ dose of BPA. Twenty adult male rats received either BPA (50 μg/kg·bw/day) or a vehicle diet for 35 weeks. Decreased protein lysine-acetylation levels at approximately ~17 kDa and ~25 kDa, as well as decreased histone acetylation of H3K9, H3K27 and H4K12, were detected by Western blot analysis of testes from the treated rats compared with controls. Additionally, increased protein expression of deacetylase Sirt1 and reduced binding of Sirt1, together with increased binding of estrogen receptor β (ERβ) to caveolin-1 (Cav-1), a structural protein component of caveolar membranes, were detected in treated rats compared with controls. Moreover, decreased acetylation of Cav-1 was observed in the treated rats for the first time. Our study showed that long-term exposure to a ‘safe’ dose of BPA reduces histone acetylation in the male reproductive system, which may be related to the phenotypic paternal-to-offspring transmission observed in our previous study. The evidence also suggested that these epigenetic effects may be meditated by Sirt1 via competition with ERβ for binding to Cav-1. PMID:28067316

Lisdexamfetamine reduces the compulsive and perseverative behaviour of binge-eating rats in a novel food reward/punished responding conflict model.

PubMed

Heal, David J; Goddard, Simon; Brammer, Richard J; Hutson, Peter H; Vickers, Steven P

2016-07-01

Compulsive and perseverative behaviour in binge-eating, female, Wistar rats was investigated in a novel food reward/punished responding conflict model. Rats were trained to perform the conditioned avoidance response task. When proficient, the paradigm was altered to a food-associated conflict test by placing a chocolate-filled jar (empty jar for controls) in one compartment of the shuttle box. Entry into the compartment with the jar triggered the conditioning stimulus after a variable interval, and foot-shock 10 seconds later if the rat did not leave. Residence in the 'safe' compartment with no jar did not initiate trials or foot-shocks. By frequently entering the chocolate-paired compartment, binge-eating rats completed their 10 trials more quickly than non-binge controls. Binge-eating rats spent a greater percentage of the session in the chocolate-paired compartment, received foot-shocks more frequently, and tolerated foot-shocks for longer periods; all consistent with compulsive and perseverative behaviour. The d-amphetamine prodrug, lisdexamfetamine, has recently received US approval for the treatment of moderate to severe binge-eating disorder in adults. Lisdexamfetamine (0.8 mg/kg po [d-amphetamine base]) decreased chocolate consumption by binge-eating rats by 55% and markedly reduced compulsive and perseverative responding in the model. These findings complement clinical results showing lisdexamfetamine reduced compulsiveness scores in subjects with binge-eating disorder. © The Author(s) 2016.

Effects of leptin replacement alone and with exendin-4 on food intake and weight regain in weight-reduced diet-induced obese rats

PubMed Central

Haver, Alvin; Chelikani, Prasanth K.; Apenteng, Bettye; Perriotte-Olson, Curtis; Anders, Krista; Steenson, Sharalyn; Blevins, James E.

2012-01-01

Weight loss in obese humans produces a relative leptin deficiency, which is postulated to activate potent orexigenic and energy conservation mechanisms to restrict weight loss and promote weight regain. Here we determined whether leptin replacement alone or with GLP-1 receptor agonist exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced diet-induced obese (DIO) rats. Forty percent restriction in daily intake of a high-fat diet in DIO rats for 4 wk reduced body weight by 12%, body fat by 29%, and plasma leptin by 67% and normalized leptin sensitivity. When food restriction ended, body weight, body fat, and plasma leptin increased rapidly. Daily administration of leptin [3-h intraperitoneal (ip) infusions (4 nmol·kg−1·h−1)] at onset and end of dark period for 3 wk did not attenuate hyperphagia and weight regain, nor did it affect mean daily meal sizes or meal numbers. Exendin-4 (50 pmol·kg−1·h−1) infusions during the same intervals prevented postrestriction hyperphagia and weight regain by normalizing meal size. Coadministration of leptin and exendin-4 did not reduce body weight more than exendin-4 alone. Instead, leptin began to attenuate the inhibitory effects of exendin-4 on food intake, meal size, and weight regain by the end of the second week of administration. Plasma leptin in rats receiving leptin was sevenfold greater than in rats receiving vehicle and 17-fold greater than in rats receiving exendin-4. Together, these results do not support the hypothesis that leptin replacement alone or with exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced DIO rats. PMID:22510712

Kenaf seed supercritical fluid extract reduces aberrant crypt foci formation in azoxymethane-induced rats.

PubMed

Ghafar, Siti Aisyah Abd; Yazan, Latifah Saiful; Tahir, Paridah Md; Ismail, Maznah

2012-03-01

Kenaf (Hibiscus cannabinus) a plant of the family Malvaceae, is a valuable fiber plant native to India and Africa. Kenaf seeds contain alpha-linolenic acid, phytosterol such as β-sitosterol, vitamin E and other antioxidants with chemopreventive properties. In the present study we examined the hypothesis that kenaf seed 'supercritical fluid extract' (SFE) extract could suppress the early colon carcinogenesis in vivo by virtue of its bioactive compounds. To accomplish this goal, 60 male rats were randomly assigned to 5 groups which were (1) negative control group [not induced with azoxymethane (AOM)]; (2) positive control group (induced with AOM but received no treatment); (3) group treated with 500 mg/kg kenaf seed SFE extract; (4) group treated with 1000 mg/kg kenaf seed SFE extract; (5) group treated with 1500 mg/kg kenaf seed SFE extract. At 7 weeks of age, all rats except the negative control group received 15 mg/kg of AOM injection subcutaneously once a week for 2 weeks. Rats were euthanized at 13 weeks of the experiment. Number of ACF (mean±SD) ranged from 84.4±4.43 to 179.5±12.78 in group 2, 3, 4, 5. ACF reductions compared with the untreated group were 45.3, 51.4 and 53.1% in rats fed with 500, 1000 and 1500 mg/kg body weight, respectively. There were no significant differences in weight gain among groups. Our finding indicates that kenaf seed SFE extract reduced AOM-induced ACF in Sprague-Dawley male rats. Copyright © 2010 Elsevier GmbH. All rights reserved.

A novel mode-of-action mediated by the fetal muscle nicotinic acetylcholine receptor resulting in developmental toxicity in rats.

PubMed

Rasoulpour, Reza J; Ellis-Hutchings, Robert G; Terry, Claire; Millar, Neil S; Zablotny, Carol L; Gibb, Alasdair; Marshall, Valerie; Collins, Toby; Carney, Edward W; Billington, Richard

2012-06-01

Sulfoxaflor (X11422208), a novel agricultural molecule, induced fetal effects (forelimb flexure, hindlimb rotation, and bent clavicle) and neonatal death in rats at high doses (≥ 400 ppm in diet); however, no such effects occurred in rabbit dietary studies despite achieving similar maternal and fetal plasma exposure levels. Mode-of-action (MoA) studies were conducted to test the hypothesis that the effects in rats had a single MoA induced by sulfoxaflor agonism on the fetal rat muscle nicotinic acetylcholine receptor (nAChR). The studies included cross-fostering and critical windows of exposure studies in rats, fetal ((α1)(2)β1γδ) and adult ((α1)(2)β1δε) rat and human muscle nAChR in vitro agonism experiments, and neonatal rat phrenic nerve-hemidiaphragm contracture studies. The weight of evidence from these studies supported a novel MoA where sulfoxaflor is an agonist to the fetal, but not adult, rat muscle nAChR and that prolonged agonism on this receptor in fetal/neonatal rats causes sustained striated muscle contracture resulting in concomitant reduction in muscle responsiveness to physiological nerve stimulation. Fetal effects were inducible with as little as 1 day of exposure at the end of gestation, but were rapidly reversible after birth, consistent with a pharmacological MoA. With respect to human relevance, sulfoxaflor was shown to have no agonism on human fetal or adult muscle nAChRs. Taken together, the data support the hypothesis that the developmental effects of sulfoxaflor in rats are mediated via sustained agonism on the fetal muscle nAChR during late fetal development and are considered not relevant to humans.

A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics.

PubMed

Marmarou, A; Foda, M A; van den Brink, W; Campbell, J; Kita, H; Demetriadou, K

1994-02-01

This report describes the development of an experimental head injury model capable of producing diffuse brain injury in the rodent. A total of 161 anesthetized adult rats were injured utilizing a simple weight-drop device consisting of a segmented brass weight free-falling through a Plexiglas guide tube. Skull fracture was prevented by cementing a small stainless-steel disc on the calvaria. Two groups of rats were tested: Group 1, consisting of 54 rats, to establish fracture threshold; and Group 2, consisting of 107 animals, to determine the primary cause of death at severe injury levels. Data from Group 1 animals showed that a 450-gm weight falling from a 2-m height (0.9 kg-m) resulted in a mortality rate of 44% with a low incidence (12.5%) of skull fracture. Impact was followed by apnea, convulsions, and moderate hypertension. The surviving rats developed decortication flexion deformity of the forelimbs, with behavioral depression and loss of muscle tone. Data from Group 2 animals suggested that the cause of death was due to central respiratory depression; the mortality rate decreased markedly in animals mechanically ventilated during the impact. Analysis of mathematical models showed that this mass-height combination resulted in a brain acceleration of 900 G and a brain compression gradient of 0.28 mm. It is concluded that this simple model is capable of producing a graded brain injury in the rodent without a massive hypertensive surge or excessive brain-stem damage.

l-tetrahydropalmatine reduces nicotine self-administration and reinstatement in rats.

PubMed

Faison, Shamia L; Schindler, Charles W; Goldberg, Steven R; Wang, Jia Bei

2016-11-07

The negative consequences of nicotine use are well known and documented, however, abstaining from nicotine use and achieving abstinence poses a major challenge for the majority of nicotine users trying to quit. l-Tetrahydropalmatine (l-THP), a compound extracted from the Chinese herb Corydalis, displayed utility in the treatment of cocaine and heroin addiction via reduction of drug-intake and relapse. The present study examined the effects of l-THP on abuse-related effects of nicotine. Self-administration and reinstatement testing was conducted. Rats trained to self-administer nicotine (0.03 mg/kg/injection) under a fixed-ratio 5 schedule (FR5) of reinforcement were pretreated with l-THP (3 or 5 mg/kg), varenicline (1 mg/kg), bupropion (40 mg/kg), or saline before daily 2-h sessions. Locomotor, food, and microdialysis assays were also conducted in separate rats. l-THP significantly reduced nicotine self-administration (SA). l-THP's effect was more pronounced than the effect of varenicline and similar to the effect of bupropion. In reinstatement testing, animals were pretreated with the same compounds, challenged with nicotine (0.3 mg/kg, s.c.), and reintroduced to pre-extinction conditions. l-THP blocked reinstatement of nicotine seeking more effectively than either varenicline or bupropion. Locomotor data revealed that therapeutic doses of l-THP had no inhibitory effects on ambulatory ability and that l-THP (3 and 5 mg/kg) significantly blocked nicotine induced hyperactivity when administered before nicotine. In in-vivo microdialysis experiments, l-THP, varenicline, and bupropion alone elevated extracellular dopamine (DA) levels in the nucleus accumbens shell (nAcb). Since l-THP reduces nicotine taking and blocks relapse it could be a useful alternative to varenicline and bupropion as a treatment for nicotine addiction.

Periconceptional Folic Acid Supplementation Benefit to Development of Early Sensory-Motor Function through Increase DNA Methylation in Rat Offspring

PubMed Central

Li, Wen; Li, Zhenshu; Li, Shou; Wang, Xinyan; Wilson, John X.; Huang, Guowei

2018-01-01

Periconceptional maternal folate levels may alter DNA methylation patterns and health outcomes in offspring. We hypothesized that maternal folic acid supplementation alters fetal neural development through DNA methylation in the fetal brain. Twenty-eight rats were randomly assigned to four groups: three groups of the female rats were fed folate-normal, folate-deficient or folate-supplemented diets from seven days before mating to delivery. In another group, folic acid supplementation diet short-period group was fed a folate-normal diet, except for 10 days (begin mating) when this group was fed a folate-supplemented diet. After delivery, the diets were changed to folate-normal diet for all four groups. The cliff avoidance and forelimb grip tests were used to assess sensory motor function of rat offspring. The results indicate that maternal folic acid supplementation improved the early development of sensory-motor function in offspring. Maternal folic acid supplementation increased the methylation potential, global DNA methylation (5-mC) and DNA methyltransferase expression and activity in the brains of the offspring. In conclusion, maternal folic acid supplementation increases DNA methylation pattern in offspring brain and improves the early development of sensory-motor function. PMID:29494536

Tributyltin contributes in reducing the vascular reactivity to phenylephrine in isolated aortic rings from female rats.

PubMed

Rodrigues, Samya Mere L; Ximenes, Carolina F; de Batista, Priscila R; Simões, Fabiana V; Coser, Pedro Henrique P; Sena, Gabriela C; Podratz, Priscila L; de Souza, Leticia N G; Vassallo, Dalton V; Graceli, Jones B; Stefanon, Ivanita

2014-03-21

Organotin compounds such as tributyltin (TBT) are used as antifouling paints by shipping companies. TBT inhibits the aromatase responsible for the transformation of testosterone into estrogen. Our hypothesis is that TBT modulates the vascular reactivity of female rats. Female Wistar rats were treated daily (Control; CONT) or TBT (100 ng/kg) for 15 days. Rings from thoracic aortas were incubated with phenylephrine (PHE, 10(-10)-10(-4) M) in the presence and absence of endothelium, and in the presence of N(G)-Nitro-L-Arginine Methyl Ester (L-NAME), tetraethylammonium (TEA) and apocynin. TBT decreased plasma levels of estrogen and the vascular response to PHE. In the TBT group, the vascular reactivity was increased in the absence of endothelium, L-NAME and TEA. The decrease in PHE reactivity during incubation with apocynin was more evident in the TBT group. The sensitivity to acetylcholine (ACh) and sodium nitroprusside (SNP) was reduced in the TBT group. TBT increased collagen, reduced α1-smooth muscle actin. Female rats treated with TBT for 15 days showed morphology alteration of the aorta and decreased their vascular reactivity, probably due to mechanisms dependent on nitric oxide (NO) bioavailability, K(+) channels and an increase in oxidative stress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Comparative anatomy, homologies and evolution of the pectoral and forelimb musculature of tetrapods with special attention to extant limbed amphibians and reptiles

PubMed Central

Abdala, Virginia; Diogo, Rui

2010-01-01

The main aim of the present work is to synthesize the information obtained from our dissections of the pectoral and forelimb muscles of representative members of the major extant taxa of limbed amphibians and reptiles and from our review of the literature, in order to provide an account of the comparative anatomy, homologies and evolution of these muscles in the Tetrapoda. The pectoral and forelimb musculature of all these major taxa conform to a general pattern that seems to have been acquired very early in the evolutionary history of tetrapods. Although some muscles are missing in certain taxa, and a clear departure from this general pattern is obviously present in derived groups such as birds, the same overall configuration is easily distinguishable in these taxa. Among the most notable anatomical differences between the groups, one that seems to have relevant evolutionary and functional implications, concerns the distal insertion points of the forearm musculature. In tetrapods, the muscles of the radial and ulnar complexes of the forearm are pleisomorphically mainly inserted onto the radius/ulna or onto the more proximal carpal bones, but in mammals some of these muscles insert more distally onto bones such as the metacarpals. Interestingly, a similar trend towards a more distal insertion of these muscles is also found in some non-mammalian tetrapod taxa, such as some anurans (e.g. Phyllomedusa). This may be correlated with the acquisition of more subtle digital movement abilities in these latter taxa. PMID:20807270

Environmental enrichment reduces the impact of novelty and motivational properties of ethanol in spontaneously hypertensive rats.

PubMed

de Carvalho, Cristiane Ribeiro; Pandolfo, Pablo; Pamplona, Fabrício Alano; Takahashi, Reinaldo Naoto

2010-03-17

The present study investigated the consequences of environmental enrichment on the impact of novelty and motivational properties of ethanol in spontaneously hypertensive rats (SHR), a validated model of attention deficit hyperactivity disorder (ADHD). This rat strain displays increased sensitivity to distinct classes of abused drugs, which makes it an interesting model for the study of the association between ADHD and drug abuse. Female SHR reared from weaning to adulthood in standard (SE) or enriched (EE) environment were tested on novelty-induced locomotion, saccharin consumption, ethanol consumption (forced and free-choice schedules) and ethanol-induced conditioned place preference (CPP). SHR reared in an EE showed reduced novelty-induced locomotion, consumed less saccharin and ethanol in a forced schedule and showed less ethanol preference in a free-choice schedule compared to SE rats. Moreover, EE rats did not develop CPP, whereas SE rats developed preference for ethanol (1.2g/kg). These results show that exposure to stimuli mimicking positive life experiences (environmental enrichment) induces persistent changes in the reward/motivational system of female SHR, suggesting an important role of the familiar environment during early stages of the neurodevelopment on the co-morbidity of ADHD and drug abuse. Copyright 2009 Elsevier B.V. All rights reserved.

High doses of nandrolone decanoate reduce volume of testis and length of seminiferous tubules in rats.

PubMed

Noorafshan, Ali; Karbalay-Doust, Saied; Ardekani, Fakhrodin Mesbah

2005-02-01

Anabolic-androgenic steroid (AAS) compounds rank among the drugs most widely abused with the goal of improving athletic ability, appearance, or muscle mass. It has been shown that these compounds have adverse effects on human and animal physiology and sperm quality, but quantitative structural changes of the testis have received less attention. The present study was conducted to evaluate the effects of nandrolone decanoate, which is one of the AAS compounds, on testis weight and volume, diameter and length of seminiferous tubules in rats by unbiased stereological methods. Adult rats were divided into three groups. The first comprised control rats; the second and third groups received low and high doses of nandrolone decanoate for 14 weeks. The rats were then left untreated for 14 weeks. After removal of the testis, stereological study of these tissues showed that the mean volume of testis and length of the seminiferous tubules in the animals that received high doses of nandrolone decanoate were reduced approximately 32% (p<0.01) and approximately 31% (p<0.04), respectively, in comparison with the control group. It can be concluded that the high doses of nandrolone decanoate produce structural changes in the rat testis that remain 14 weeks after stopping injection of the drug.

Resveratrol Reduces the Incidence of Portal Vein System Thrombosis after Splenectomy in a Rat Fibrosis Model

PubMed Central

Xu, Meng; Xue, Wanli; Ma, Zhenhua; Bai, Jigang

2016-01-01

Purpose. To investigate the preventive effect of resveratrol (RES) on the formation of portal vein system thrombosis (PVST) in a rat fibrosis model. Methods. A total of 64 male SD rats, weighing 200–300 g, were divided into five groups: Sham operation, Splenectomy I, Splenectomy II, RES, and low molecular weight heparin (LMWH), with the former two groups as nonfibrosis controls. Blood samples were subjected to biochemical assays. Platelet apoptosis was measured by flow cytometry. All rats were euthanized for PVST detection one week after operation. Results. No PVST occurred in nonfibrosis controls. Compared to Splenectomy II, the incidences of PVST in RES and LMWH groups were significantly decreased (both p < 0.05). Two rats in LMWH group died before euthanasia due to intra-abdominal hemorrhage. In RES group, significant decreases in platelet aggregation, platelet radical oxygen species (ROS) production, and increase in platelet nitric oxide (NO) synthesis and platelet apoptosis were observed when compared with Splenectomy II (all p < 0.001), while in LMWH group only significant decrease in platelet aggregation was observed. Conclusion. Prophylactic application of RES could safely reduce the incidence of PVST after splenectomy in cirrhotic rat. Regulation of platelet function and induction of platelet apoptosis might be the underlying mechanisms. PMID:27433290

A preliminary study on the effect of manuka honey on second-intention healing of contaminated wounds on the distal aspect of the forelimbs of horses.

PubMed

Bischofberger, Andrea S; Dart, Christina M; Perkins, Nigel R; Dart, Andrew J

2011-10-01

To determine the effect of manuka honey on second-intention healing of contaminated, full-thickness skin wounds in horses. Experimental. Adult Standardbred horses (n = 8). One wound was created on the dorsomedial aspect of the third metacarpus in both forelimbs, contaminated with feces, and bandaged for 24 hours. Bandages were removed and wounds rinsed with isotonic saline solution. Wounds on 1 limb had manuka honey applied daily (n = 8) whereas wounds on the contralateral limb received no treatment (n = 8). Bandages were replaced and changed daily for 12 days, after which treatment stopped, bandages were removed, leaving wounds open to heal. Wound area was measured 24 hours after wound creation (day 1), then weekly for 8 weeks. Overall time for healing was recorded. Wound area and rate of healing of treated and control wounds were compared statistically. Treatment with manuka honey decreased wound retraction and treated wounds remained significantly smaller than control wounds until day 42; however, there was no difference in overall healing time between treatment and control wounds. Treatment with manuka honey reduced wound area by reducing retraction but did not affect overall healing time of full-thickness distal limb wounds using this wound-healing model. © Copyright 2011 by The American College of Veterinary Surgeons.

Co-Administration of Low-Dose Naltrexone and Bupropion Reduces Alcohol Drinking in Alcohol-Preferring (P) Rats.

PubMed

Nicholson, Emily R; Dilley, Julian E; Froehlich, Janice C

2018-03-01

This study examined whether combining naltrexone (NTX) with bupropion (BUP) is more effective in reducing alcohol drinking in alcohol-preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake than either drug alone. Alcohol-experienced, adult, male, P rats were fed NTX alone in a dose of 10.0 mg/kg BW, BUP alone in a dose of 10.0 mg/kg BW, BUP alone in a dose of 20.0 mg/kg BW, NTX (10.0 mg/kg BW) + BUP (10.0 mg/kg BW), or vehicle (VEH) at 1 hour prior to onset of a daily 2-hour alcohol access period for 5 consecutive days. When administered alone, neither NTX (10.0 mg/kg BW) nor BUP, in either of 2 doses (10.0 mg/kg BW or 20.0 mg/kg BW), reduced voluntary alcohol intake in P rats. However, NTX combined with BUP (10.0 mg/kg NTX + 10.0 mg/kg BUP) and given as a single medication significantly reduced alcohol consumption throughout prolonged treatment. Combining low doses of NTX and BUP, each of which is ineffective when given alone, increases the efficacy of the medication. Low drug doses circumvent the problem of negative side effects that can occur with higher doses of either drug. A reduction in side effects can facilitate patient compliance and improve clinical outcomes for alcoholics and heavy drinkers who want to reduce their alcohol intake. The results, together with those from our prior studies, demonstrate the strength of a combinatorial pharmacotherapeutic approach to the treatment of alcohol use disorder. Copyright © 2017 by the Research Society on Alcoholism.

Endotoxin-induced mortality in rats is reduced by nitrones

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamburger, S.A.; McCay, P.B.

The goal of these investigations was to determine if nitrone spin-trapping agents can alter mortality associated with endotoxemia in the rat. Reactive free radicals attack nitrone spin-trapping agents forming relatively reactive, persistent free radical spin adducts. We administered 85 mM (10 ml/kg) of alpha-phenyl N-tert-butyl nitrone (PBN), alpha-4-pyridyl-N-oxide N-tert-butyl nitrone (4-POBN), 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), or vehicle (saline i.p.) 30 min before endotoxin (25 mg/kg i.p.) or vehicle to Sprague-Dawley (SD) or Holtzman virus-free (HVF) rats (n = 10-17/group). All vehicle-treated rats receiving endotoxin were dead by 1 day. At 7 days, 83% of PBN-treated SD, 42% of PBN- or POBN-treated HVF,more » and 25% of DMPO-treated HVF rats were alive. The difference in survival of PBN-treated animals between strains may reflect the higher susceptibility of HVF rats to endotoxin. The observed reduction in mortality may be related to the well-established capacity of spin-trapping agents to capture reactive free radicals that may be generated in target tissues in response to endotoxin, and that would otherwise react with cell components and produce tissue injury.« less

Regenerative effects of peptide nanofibers in an experimental model of Parkinson's disease.

PubMed

Sever, Melike; Turkyilmaz, Mesut; Sevinc, Cansu; Cakir, Aysen; Ocalan, Busra; Cansev, Mehmet; Guler, Mustafa O; Tekinay, Ayse B

2016-12-01

Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic nigrostriatal neurons and reduction in striatal dopamine levels. Although there are few treatment options for PD such as Levodopa, they are used just to relieve and modify the symptoms. There are no therapies available for PD to slow down the degeneration process in the brain and recover the lost function. In this study, we used extracellular matrix (ECM) mimetic peptide amphiphile (PA) nanofibers as a potential therapeutic approach in a PD rat model. We demonstrated the effect of heparan sulfate mimetic and laminin mimetic PA nanofibers on reducing striatal injury and enhancing functional recovery after unilateral striatal injection of 6-hydroxydopamine (6-OHDA). The bioactive self-assembled PA nanofibers significantly reduced forelimb asymmetry, contralateral forelimb akinesia and d-amphetamine-induced rotational behavior in cylinder, stepping and rotation tests, respectively, in 6-OHDA-lesioned rats after 6 weeks. The behavioral improvement with PA nanofiber administration was associated with enhanced striatal dopamine and tyrosine hydroxylase content as well as reduced cleaved-Caspase-3 levels. Histological assessment also showed that PA nanofiber injection to the striatum resulted in better tissue integrity compared to control groups. In addition, PA nanofibers reduced the progressive cell loss in SH-SY5Y cells caused by 6-OHDA treatment. These data showed that the bioactive peptide nanofibers improve neurochemical and behavioral consequences of Parkinsonism in rats and provide a promising new strategy for treatment of PD. Biomimetic nanomaterials bearing natural bioactive signals which are derived from extracellular matrix components like laminin and heparan sulfates provide promising therapeutic strategies for regeneration of the nervous system. However, no research has been reported exploring the use of biomimetic materials against degeneration in Parkinson's disease. In

Mosapride Stabilizes Intestinal Microbiota to Reduce Bacterial Translocation and Endotoxemia in CCl4-Induced Cirrhotic Rats.

PubMed

Xu, Hong; Xiong, Jingfang; Xu, Jianjun; Li, Shuiming; Zhou, Yang; Chen, Dongya; Cai, Xinjun; Ping, Jian; Deng, Min; Chen, Jianyong

2017-10-01

Impaired intestinal motility may lead to the disruption of gut microbiota equilibrium, which in turn facilitates bacterial translocation (BT) and endotoxemia in cirrhosis. We evaluated the influence of mosapride, a prokinetic agent, on BT and DNA fingerprints of gut microbiota in cirrhotic rats. A rat model of cirrhosis was set up via subcutaneous injection of carbon tetrachloride (CCl 4 ). The portal pressure, liver and intestinal damage, plasma endotoxin, BT, and intestinal transit rate (ITR) of cirrhotic rats were determined. Fecal DNA fingerprints were obtained by ERIC-PCR. The expressions of tight junction proteins were evaluated by western blotting. Mosapride treatment to cirrhotic rats significantly reduced the plasma endotoxin level and incidence of BT, accompanied by increased ITR. Cirrhotic rats (including those treated with mosapride) suffered from BT exhibited significantly lower ITR than those who are free of BT. Pearson coefficient indicated a significant and negative correlation between the plasma endotoxin level and ITR. The genomic fingerprints of intestinal microbiota from the three groups fell into three distinctive clusters. In the mosapride-treated group, Shannon's index was remarkably increased compared to the model group. Significantly positive correlation was detected between Shannon's index and ITR. Mosapride did not improve hepatic and intestinal damages and ileal expressions of occludin and ZO-1. Mosapride significantly increases intestinal motility in cirrhotic rats, thus to recover the disordered intestinal microbiota, finally resulting in decreased plasma endotoxin and BT.

Fish oil supplementation reduces cachexia and tumor growth while improving renal function in tumor-bearing rats.

PubMed

Coelho, Isabela; Casare, Fernando; Pequito, Danielle C T; Borghetti, Gina; Yamazaki, Ricardo K; Brito, Gleisson A P; Kryczyk, Marcelo; Fernandes, Luiz Claudio; Coimbra, Terezila M; Fernandez, Ricardo

2012-11-01

The objective of the present work was to study the renal function of healthy and tumor-bearing rats chronically supplemented with fish oil (FO), a source of n-3 polyunsaturated fatty acids. Weanling male rats were divided in two groups, one control (C) and another orally supplemented for 70 days with FO (1 g/kg body weight). After this time, half the animals of each group were injected in the right flank with a suspension of Walker 256 tumor cells (W and WFO). The W group had less proteinemia reflecting cachectic proteolysis, FO reversed this fact. Tumor weight gain was also reduced in WFO. Glomerular filtration rate (GFR) was not different in FO or W compared to C, but was higher in WFO. Renal plasma flow (RPF) was higher in the FO supplemented groups. The W group had lower plasma osmolality than the C group, but FO supplementation resulted in normalization of this parameter. Fractional sodium excretion (FE(Na+)) of FO rats was similar to C. Proximal Na(+) reabsorption, evaluated by lithium clearance, was similar among the groups. Urinary thromboxane B(2) (TXB(2)) excretion was lower in the supplemented groups. The number of macrophages in renal tissue was higher in W compared to C rats, but was lower in WFO rats compared to W rats. In conclusion, FO supplementation resulted in less tumor growth and cachexia, and appeared to be renoprotective, as suggested by higher RPF and GFR.

Normobaric Hyperoxia Reduces Blood Occludin Fragments in Rats and Patients With Acute Ischemic Stroke.

PubMed

Shi, Shuhai; Qi, Zhifeng; Ma, Qingfeng; Pan, Rong; Timmins, Graham S; Zhao, Yongmei; Shi, Wenjuan; Zhang, Yunzhou; Ji, Xunming; Liu, Ke Jian

2017-10-01

Damage of the blood-brain barrier (BBB) increases the incidence of neurovascular complications, especially for cerebral hemorrhage after tPA (tissue-type plasminogen activator) therapy. Currently, there is no effective method to evaluate the extent of BBB damage to guide tPA use. Herein, we investigated whether blood levels of tight junction proteins could serve as biomarker of BBB damages in acute ischemic stroke (AIS) in both rats and patients. We examined whether this biomarker could reflect the extent of BBB permeability during cerebral ischemia/reperfusion and the effects of normobaric hyperoxia (NBO) on BBB damage. Rats were exposed to NBO (100% O 2 ) or normoxia (21% O 2 ) during middle cerebral artery occlusion. BBB permeability was determined. Occludin and claudin-5 in blood and cerebromicrovessels were measured. Patients with AIS were assigned to oxygen therapy or room air for 4 hours, and blood occludin and claudin-5 were measured at different time points after stroke. Cerebral ischemia/reperfusion resulted in the degradation of occludin and claudin-5 in microvessels, leading to increased BBB permeability in rats. In blood samples, occludin increased with 4-hour ischemia and remained elevated during reperfusion, correlating well with its loss from ischemic cerebral microvessels. NBO treatment both prevented occludin degradation in microvessels and reduced occludin levels in blood, leading to improved neurological functions in rats. In patients with AIS receiving intravenous tPA thrombolysis, the blood occludin was already elevated when patients arrived at hospital (within 4.5 hours since symptoms appeared) and remained at a high level for 72 hours. NBO significantly lowered the level of blood occludin and improved neurological functions in patients with AIS. Blood occludin may be a clinically viable biomarker for evaluating BBB damage during ischemia/reperfusion. NBO therapy has the potential to reduce blood occludin, protect BBB, and improve outcome in

Effects of NADPH oxidase inhibitor on diabetic nephropathy in OLETF rats: the role of reducing oxidative stress in its protective property.

PubMed

Nam, Soo Min; Lee, Mi Young; Koh, Jang Hyun; Park, Jun Ho; Shin, Jang Yel; Shin, Young Goo; Koh, Sang Baek; Lee, Eun Young; Chung, Choon Hee

2009-02-01

Diabetic nephropathy is the most serious complication in diabetes mellitus. Oxidative stress via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and vascular endothelial growth factor (VEGF) pathway play critical roles in the development of diabetic nephropathy. We evaluated the effects of apocynin, NADPH oxidase inhibitor on diabetic nephropathy in a type 2 diabetic rat model. Sixteen Otsuka Long Evans Tokushima Fatty (OLETF) rats and 9 Long Evans Tokushima Otsuka (LETO) were divided into the following three groups: LETO rats (n=9), control OLETF rats (n=7) and apocynin-treated OLETF rats (n=9). We examined body weights, plasma glucose levels, urinary albumin-creatinine ratio (ACR) and protein-creatinine ratio (PCR). At 50 weeks, experimental rats were sacrificed and their kidneys were extracted for hematoxylin eosin stain, immunohistochemical VEGF stain and VEGF mRNA real-time RT-PCR. To examine oxidative stress, we checked 24h urinary 8-OHdG (8-hydroxy-2'-deoxyguanosine) and MDA (malondialdehyde). Urinary protein and albumin excretions were reduced after apocynin treatment, though apocynin could not significantly decrease serum glucose levels. There were improvements of glomerular and mesangial expansion in the apocynin-treated OLETF rats. Apocynin significantly decreased optical density of glomerular VEGF expression in immunohistochemical stain and reduced the concentration of 24h urinary 8-OHdG and MDA. From these results, it was suggested that apocynin may have the potential to protect against diabetic nephropathy via amelioration of oxidative stress.

Vildagliptin reduces cardiac ischemic-reperfusion injury in obese orchiectomized rats.

PubMed

Pongkan, Wanpitak; Pintana, Hiranya; Jaiwongkam, Thidarat; Kredphoo, Sasiwan; Sivasinprasasn, Sivaporn; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2016-10-01

Obesity and testosterone deprivation are associated with coronary artery disease. Testosterone and vildagliptin (dipeptidyl peptidase-4 inhibitors) exert cardioprotection during ischemic-reperfusion (I/R) injury. However, the effect of these drugs on I/R heart in a testosterone-deprived, obese, insulin-resistant model is unclear. This study investigated the effects of testosterone and vildagliptin on cardiac function, arrhythmias and the infarct size in I/R heart of testosterone-deprived rats with obese insulin resistance. Orchiectomized (O) or sham operated (S) male Wistar rats were divided into 2 groups to receive normal diet (ND) or high-fat diet (HFD) for 12 weeks. Orchiectomized rats in each diet were divided to receive testosterone (2 mg/kg), vildagliptin (3 mg/kg) or the vehicle daily for 4 weeks. Then, I/R was performed by a 30-min left anterior descending coronary artery ligation, followed by a 120-min reperfusion. LV function, arrhythmia scores, infarct size and cardiac mitochondrial function were determined. HFD groups developed insulin resistance at week 12. At week 16, cardiac function was impaired in NDO, HFO and HFS rats, but was restored in all testosterone- and vildagliptin-treated rats. During I/R injury, arrhythmia scores, infarct size and cardiac mitochondrial dysfunction were prominently increased in NDO, HFO and HFS rats, compared with those in NDS rats. Treatment with either testosterone or vildagliptin similarly attenuated these impairments during I/R injury. These finding suggest that both testosterone replacement and vildagliptin share similar efficacy for cardioprotection during I/R injury by decreasing the infarct size and attenuating cardiac mitochondrial dysfunction caused by I/R injury in testosterone-deprived rats with obese insulin resistance. © 2016 Society for Endocrinology.

Noopept reduces the postischemic functional and metabolic disorders in the brain of rats with different sensitivity to hypoxia.

PubMed

Zarubina, I V; Shabanov, P D

2009-03-01

Chronic cerebral ischemia was induced by ligation of both common carotid arteries in Wistar rats, divided by sensitivity to hypoxia into highly sensitive and low-sensitive. Noopept (peptide preparation), injected (0.5 mg/kg) during 7 days after occlusion of the carotid arteries, reduced the neurological disorders in rats with high and low sensitivity to hypoxia and improved their survival during the postischemic period. Noopept normalized behavior disordered by cerebral ischemia (according to the open field and elevated plus maze tests), prevented accumulation of LPO products and inhibition of antioxidant systems in the brain of rats with high and low sensitivity to hypoxia. Hence, noopept exhibited a neuroprotective effect in cerebral ischemia.

Numb rats walk - a behavioural and fMRI comparison of mild and moderate spinal cord injury.

PubMed

Hofstetter, Christoph P; Schweinhardt, Petra; Klason, Tomas; Olson, Lars; Spenger, Christian

2003-12-01

Assessment of sensory function serves as a sensitive measure for predicting the functional outcome following spinal cord injury in patients. However, little is known about loss and recovery of sensory function in rodent spinal cord injury models as most tests of sensory functions rely on behaviour and thus motor function. We used functional magnetic resonance imaging (fMRI) to investigate cortical and thalamic BOLD-signal changes in response to limb stimulation following mild or moderate thoracic spinal cord weight drop injury in Sprague-Dawley rats. While there was recovery of close to normal hindlimb motor function as determined by open field locomotor testing following both degrees of injury, recovery of hindlimb sensory function as determined by fMRI and hot plate testing was only seen following mild injury and not following moderate injury. Thus, moderate injury can lead to near normal hindlimb motor function in animals with major sensory deficits. Recovered fMRI signals following mild injury had a partly altered cortical distribution engaging also ipsilateral somatosensory cortex and the cingulate gyrus. Importantly, thoracic spinal cord injury also affected sensory representation of the upper nonaffected limbs. Thus, cortical and thalamic activation in response to forelimb stimulation was significantly increased 16 weeks after spinal cord injury compared to control animals. We conclude that both forelimb and hindlimb cortical sensory representation is altered following thoracic spinal cord injury. Furthermore tests of sensory function that are independent of motor behaviour are needed in rodent spinal cord injury research.

CM352 Reduces Brain Damage and Improves Functional Recovery in a Rat Model of Intracerebral Hemorrhage.

PubMed

Rodríguez, José A; Sobrino, Tomás; López-Arias, Esteban; Ugarte, Ana; Sánchez-Arias, Juan A; Vieites-Prado, Alba; de Miguel, Irene; Oyarzabal, Julen; Páramo, José A; Campos, Francisco; Orbe, Josune; Castillo, José

2017-06-01

Intracerebral hemorrhage (ICH) is an acute neurological disorder with high mortality and no effective treatment. In addition to the initial bleeding event, rebleeding and hematoma expansion are associated with poor outcome in these patients. We studied the effectiveness of the new antifibrinolytic agent CM352, a short-half-life matrix metalloproteinase inhibitor, for achieving early hemostasis and improving functional recovery in a rat model of collagenase-induced ICH. ICH was induced by striatal injection of collagenase, and 1 hour later, rats received an intravenous injection of saline (n=6) or CM352 (1 mg/kg, n=6). Hematoma (basal and after 3 and 24 hours) and lesion (14 days) volumes were quantified on T2-weighted (T2) magnetic resonance images. Neurological and functional recovery was evaluated by using Bederson score and a cylinder test (basal, 24 hours, and 14 days). Early treatment (1 hour) with CM352 was efficient reducing hematoma expansion at 3 hours ( P <0.01) and, more markedly, at 24 hours ( P <0.01). Decreased bleeding after antifibrinolytic treatment was accompanied by reduced interleukin-6 levels at 3 hours ( P <0.05) and smaller lesion volume at 14 days ( P <0.01). CM352 drastically reduced sensorimotor impairment (cylinder test) after ICH in rats at 24 hours ( P <0.01) and 14 days ( P <0.01). Similarly, it also attenuated neurological deficit (Bederson scale) at 24 hours ( P <0.01) and 14 days ( P <0.01). Interestingly, late (3 hours) CM352 administration also resulted in reduced lesion size and better functional outcome. CM352, a new antifibrinolytic agent and matrix metalloproteinase inhibitor, effectively prevented hematoma growth and reduced lesion size in ICH in association with improved functional and neurological recovery. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Slow Physical Growth, Delayed Reflex Ontogeny, and Permanent Behavioral as Well as Cognitive Impairments in Rats Following Intra-generational Protein Malnutrition

PubMed Central

Naik, Aijaz A.; Patro, Ishan K.; Patro, Nisha

2015-01-01

Environmental stressors including protein malnutrition (PMN) during pre-, neo- and post-natal age have been documented to affect cognitive development and cause increased susceptibility to neuropsychiatric disorders. Most studies have addressed either of the three windows and that does not emulate the clinical conditions of intra-uterine growth restriction (IUGR). Such data fail to provide a complete picture of the behavioral alterations in the F1 generation. The present study thus addresses the larger window from gestation to F1 generation, a new model of intra-generational PMN. Naive Sprague Dawley (SD) dams pre-gestationally switched to LP (8% protein) or HP (20% protein) diets for 45 days were bred and maintained throughout gestation on same diets. Pups born (HP/LP dams) were maintained on the respective diets post-weaningly. The present study aimed to show the sex specific differences in the neurobehavioral evolution and behavioral phenotype of the HP/LP F1 generation pups. A battery of neurodevelopmental reflex tests, behavioral (Open field and forelimb gripstrength test), and cognitive [Elevated plus maze (EPM) and Morris water maze (MWM)] assays were performed. A decelerated growth curve with significantly restricted body and brain weight, delays in apparition of neuro-reflexes and poor performance in the LP group rats was recorded. Intra-generational PMN induced poor habituation-with-time in novel environment exploration, low anxiety and hyperactive like profile in open field test in young and adult rats. The study revealed poor forelimb neuromuscular strength in LP F1 pups till adulthood. Group occupancy plots in MWM test revealed hyperactivity with poor learning, impaired memory retention and integration, thus modeling the signs of early onset Alzehemier phenotype. In addition, a gender specific effect of LP diet with severity in males and favoring female sex was also noticed. PMID:26696810

Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles.

PubMed Central

Tawa, N E; Odessey, R; Goldberg, A L

1997-01-01

Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlysosomal protein breakdown by up to 50% (P < 0.01), and this effect was rapidly reversed upon removal of the inhibitor. The peptide aldehydes did not alter protein synthesis or amino acid pools, but improved overall protein balance in the muscle. Upon treatment with MG132, ubiquitin-conjugated proteins accumulated in the muscle. The inhibition of muscle proteolysis correlated with efficacy against the proteasome, although these agents could also inhibit calpain-dependent proteolysis induced with Ca2+. These inhibitors had much larger effects on proteolysis in atrophying muscles than in controls. In the denervated soleus undergoing atrophy, the increase in ATP-dependent proteolysis was reduced 70% by MG132 (P < 0.001). Similarly, the rise in muscle proteolysis induced by administering thyroid hormones was reduced 40-70% by the inhibitors. Finally, in rats made septic by cecal puncture, the increase in muscle proteolysis was completely blocked by MG132. Thus, the enhanced proteolysis in many catabolic states (including denervation, hyperthyroidism, and sepsis) is due to a proteasome-dependent pathway, and inhibition of proteasome function may be a useful approach to reduce muscle wasting. PMID:9202072

Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles.

PubMed

Tawa, N E; Odessey, R; Goldberg, A L

1997-07-01

Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlysosomal protein breakdown by up to 50% (P < 0.01), and this effect was rapidly reversed upon removal of the inhibitor. The peptide aldehydes did not alter protein synthesis or amino acid pools, but improved overall protein balance in the muscle. Upon treatment with MG132, ubiquitin-conjugated proteins accumulated in the muscle. The inhibition of muscle proteolysis correlated with efficacy against the proteasome, although these agents could also inhibit calpain-dependent proteolysis induced with Ca2+. These inhibitors had much larger effects on proteolysis in atrophying muscles than in controls. In the denervated soleus undergoing atrophy, the increase in ATP-dependent proteolysis was reduced 70% by MG132 (P < 0.001). Similarly, the rise in muscle proteolysis induced by administering thyroid hormones was reduced 40-70% by the inhibitors. Finally, in rats made septic by cecal puncture, the increase in muscle proteolysis was completely blocked by MG132. Thus, the enhanced proteolysis in many catabolic states (including denervation, hyperthyroidism, and sepsis) is due to a proteasome-dependent pathway, and inhibition of proteasome function may be a useful approach to reduce muscle wasting.

Successful Transplantation of Reduced Sized Rat Alcoholic Fatty Livers Made Possible by Mobilization of Host Stem Cells

PubMed Central

Hisada, Masayuki; Ota, Yoshihiro; Zhang, Xiuying; Cameron, Andrew M; Gao, Bin; Montgomery, Robert A; Williams, George Melville; Sun, Zhaoli

2015-01-01

Livers from Lewis rats fed with 7% alcohol for 5 weeks were used for transplantation. Reduced sized (50%) livers or whole livers were transplanted into normal DA recipients, which, in this strain combination, survive indefinitely when the donor has not been fed alcohol. However, none of the rats survived a whole fatty liver transplant while six of seven recipients of reduced sized alcoholic liver grafts survived long term. SDF-1 and HGF were significantly increased in reduced size liver grafts compared to whole liver grafts. Lineage-negative Thy-1+CXCR4+CD133+ stem cells were significantly increased in the peripheral blood and in allografts after reduced size fatty liver transplantation. In contrast, there were meager increases in cells reactive with anti Thy-1, CXCR4 and CD133 in peripheral blood and allografts in whole alcoholic liver recipients. The provision of plerixafor, a stem cell mobilizer, salvaged 5 of 10 whole fatty liver grafts. Conversely, blocking SDF-1 activity with neutralizing antibodies diminished stem cell recruitment and four of five reduced sized fatty liver recipients died. Thus chemokine insuficiency was associated with transplant failure of whole grafts which was overcome by the increased regenerative requirements promoted by the small grafts and mediated by SDF-1 resulting in stem cell influx. PMID:22994609

Diazepam reduces excitability of amygdala and further influences auditory cortex following sodium salicylate treatment in rats.

PubMed

Song, Yu; Liu, Junxiu; Ma, Furong; Mao, Lanqun

2016-12-01

Diazepam can reduce the excitability of lateral amygdala and eventually suppress the excitability of the auditory cortex in rats following salicylate treatment, indicating the regulating effect of lateral amygdala to the auditory cortex in the tinnitus procedure. To study the spontaneous firing rates (SFR) of the auditory cortex and lateral amygdala regulated by diazepam in the tinnitus rat model induced by sodium salicylate. This study first created a tinnitus rat modal induced by sodium salicylate, and recorded SFR of both auditory cortex and lateral amygdala. Then diazepam was intraperitoneally injected and the SFR changes of lateral amygdala recorded. Finally, diazepam was microinjected on lateral amygdala and the SFR changes of the auditory cortex recorded. Both SFRs of the auditory cortex and lateral amygdala increased after salicylate treatment. SFR of lateral amygdala decreased after intraperitoneal injection of diazepam. Microinjecting diazepam to lateral amygdala decreased SFR of the auditory cortex ipsilaterally and contralaterally.

Ebselen alters mitochondrial physiology and reduces viability of rat hippocampal astrocytes.

PubMed

Santofimia-Castaño, Patricia; Salido, Ginés M; González, Antonio

2013-04-01

The seleno-organic compound and radical scavenger ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) have been extensively employed as an anti-inflammatory and neuroprotective compound. However, its glutathione peroxidase activity at the expense of cellular thiols groups could underlie certain deleterious actions of the compound on cell physiology. In this study, we have analyzed the effect of ebselen on rat hippocampal astrocytes in culture. Cellular viability, the intracellular free-Ca(2+) concentration ([Ca(2+)]c), the mitochondrial free-Ca(2+) concentration ([Ca(2+)]m), and mitochondrial membrane potential (ψm) were analyzed. The caspase-3 activity was also assayed. Our results show that cell viability was reduced by treatment of cells with ebselen, depending on the concentration employed. In the presence of ebselen, we observed an initial transient increase in [Ca(2+)]c that was then followed by a progressive increase to an elevated plateau. We also observed a transient increase in [Ca(2+)]m in the presence of ebselen that returned toward a value over the prestimulation level. The compound induced depolarization of ψm and altered the permeability of the mitochondrial membrane. Additionally, a disruption of the mitochondrial network was observed. Finally, we did not detect changes in caspase-3 activation in response to ebselen treatment. Collectively, these data support the likelihood of ebselen, depending on the concentration employed, reduces viability of rat hippocampal astrocytes via its action on the mitochondrial activity. These may be early effects that do not involve caspase-3 activation. We conclude that, depending on the concentration used, ebselen might exert deleterious actions on astrocyte physiology that could compromise cell function.

Pentadecapeptide BPC 157 reduces bleeding time and thrombocytopenia after amputation in rats treated with heparin, warfarin or aspirin.

PubMed

Stupnisek, Mirjana; Franjic, Sandra; Drmic, Domagoj; Hrelec, Masa; Kolenc, Danijela; Radic, Bozo; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

2012-05-01

Recently, in rat abdominal aorta terminoterminal-anastomosis the stable gastric pentadecapeptide BPC 157 prevents obstructive thrombus formation and rapidly destroys already formed obstructive thrombus. Also, BPC 157 wound healing may signify the clot as conductive matrix or "scaffold" to speed up wound healing process, and decrease bleeding. Here, in rats, BPC 157 (10 μg/kg, 10 ng/kg) improved always reduced bleeding time and amount of bleeding after (tail) amputation only, heparin (250 mg/kg, 25mg/kg, 10mg/kg i.v.), warfarin (1.5mg/kg i.g. once daily for 3 consecutive days), aspirin (0.1g/kg i.g. (once daily/3 consecutive days) or 1.0 g/kg i.p. once), and amputation associated with those agents application. BPC 157 counteracting regimens (i.v., i.p., i.g. (immediately after any challenge)) correspondingly follow the route of bleeding-agents application. All heparin-, warfarin-, and aspirin-rats and normal-rats that received BPC 157 exhibited lesser fall in platelets count. BPC 157 attenuated over-increased APTT-, TT-values in 10mg/kg heparin-rats, but did not influence heparin activity (anti-Xa test). Indicatively, unless counteracted in BPC 157 rats, excessive bleeding-acute thrombocytopenia (<20% of initial values in heparin-rats) approaches substantial fall in platelets count known in type II HIT. Also, BPC 157 markedly prolongs the survival time (heparin-rats, 25mg/kg, right foot amputation). Copyright © 2011 Elsevier Ltd. All rights reserved.

Withania coagulans Fruit Extract Reduces Oxidative Stress and Inflammation in Kidneys of Streptozotocin-Induced Diabetic Rats

PubMed Central

Ojha, Shreesh; Alkaabi, Juma; Amir, Naheed; Sheikh, Azimullah; Agil, Ahmad; Fahim, Mohamed Abdelmonem; Adem, Abdu

2014-01-01

The present study was carried out to investigate the changes in oxidative and inflammatory status in streptozotocin-induced diabetic rat's kidneys and serum following treatment with Withania coagulans, a popular herb of ethnomedicinal significance. The key markers of oxidative stress and inflammation such as inflammatory cytokines (IL-1β, IL-6, and TNF-α) and immunoregulatory cytokines (IL-4 and IFN-γ) were increased in kidneys along with significant hyperglycemia. However, treatment of four-month diabetic rats with Withania coagulans (10 mg/kg) for 3 weeks significantly attenuated hyperglycemia and reduced the levels of proinflammatory cytokines in kidneys. In addition, Withania coagulans treatment restored the glutathione levels and inhibited lipid peroxidation along with marked reduction in kidney hypertrophy. The present study demonstrates that Withania coagulans corrects hyperglycemia and maintained antioxidant status and reduced the proinflammatory markers in kidneys, which may subsequently reduce the development and progression of renal injury in diabetes. The results of the present study are encouraging for its potential use to delay the onset and progression of diabetic renal complications. However, the translation of therapeutic efficacy in humans requires further studies. PMID:25295146

Budesonide ameliorates lung function of the cigarette smoke-exposed rats through reducing matrix metalloproteinase-1 content

PubMed Central

Sun, Jiawei; Zhang, Ping; Zhang, Bin; Li, Kang; Li, Zhu; Li, Junhong; Zhang, Yongjian; Sun, Wuzhuang

2015-01-01

Objectives: This study was conducted to investigate an effect of inhaled budesonide on cigarette smoke-exposed lungs with a possible mechanism involved in the event. Methods: Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of budesonide. Inflammatory cell count in bronchoalveolar lavage fluid (BALF), lung function testing, mean liner intercept (MLI) in lung tissue, mean alveolar number (MAN) and a ratio of bronchial wall thickness and external diameter (BWT/D) were determined in the grouped rats, respectively. Contents of matrix metalloproteinase (MMP)-1, MMP-2 and tissue inhibitor of metalloproteinase (TIMP)-2 productions in BALF were examined as well. Results: There were significant changes in the above assessments in the smoking rats as compared to those in the control rats (all P < 0.01 and 0.05). Budesonide inhalation significantly decreased the numbers of the BALF cells and partly reversed lung function decline in the challenged rats (P < 0.01 and 0.05). However, this corticosteroid did not influence pathological changes in fine structures of the tobacco smoke-exposed lungs. Treatment with budesonide resulted in an obvious decrease in the MMP-1 but not MMP-2 and TIMP-2 productions (P < 0.05). Conclusion: Inhaled budesonide mitigates the ongoing inflammatory process in the smoked lungs and ameliorates declining lung function through reducing MMP-1 content. PMID:26191209

Budesonide ameliorates lung function of the cigarette smoke-exposed rats through reducing matrix metalloproteinase-1 content.

PubMed

Sun, Jiawei; Zhang, Ping; Zhang, Bin; Li, Kang; Li, Zhu; Li, Junhong; Zhang, Yongjian; Sun, Wuzhuang

2015-01-01

This study was conducted to investigate an effect of inhaled budesonide on cigarette smoke-exposed lungs with a possible mechanism involved in the event. Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of budesonide. Inflammatory cell count in bronchoalveolar lavage fluid (BALF), lung function testing, mean liner intercept (MLI) in lung tissue, mean alveolar number (MAN) and a ratio of bronchial wall thickness and external diameter (BWT/D) were determined in the grouped rats, respectively. Contents of matrix metalloproteinase (MMP)-1, MMP-2 and tissue inhibitor of metalloproteinase (TIMP)-2 productions in BALF were examined as well. There were significant changes in the above assessments in the smoking rats as compared to those in the control rats (all P<0.01 and 0.05). Budesonide inhalation significantly decreased the numbers of the BALF cells and partly reversed lung function decline in the challenged rats (P<0.01 and 0.05). However, this corticosteroid did not influence pathological changes in fine structures of the tobacco smoke-exposed lungs. Treatment with budesonide resulted in an obvious decrease in the MMP-1 but not MMP-2 and TIMP-2 productions (P<0.05). Inhaled budesonide mitigates the ongoing inflammatory process in the smoked lungs and ameliorates declining lung function through reducing MMP-1 content.

Soluble Milk Protein Supplementation with Moderate Physical Activity Improves Locomotion Function in Aging Rats.

PubMed

Lafoux, Aude; Baudry, Charlotte; Bonhomme, Cécile; Le Ruyet, Pascale; Huchet, Corinne

2016-01-01

Aging is associated with a loss of muscle mass and functional capacity. Present study was designed to compare the impact of specific dairy proteins on muscular function with or without a low-intensity physical activity program on a treadmill in an aged rat model. We investigated the effects of nutritional supplementation, five days a week over a 2-month period with a slow digestible protein, casein or fast digestible proteins, whey or soluble milk protein, on strength and locomotor parameters in sedentary or active aged Wistar RjHan rats (17-19 months of age). An extensive gait analysis was performed before and after protein supplementation. After two months of protein administration and activity program, muscle force was evaluated using a grip test, spontaneous activity using an open-field and muscular mass by specific muscle sampling. When aged rats were supplemented with proteins without exercise, only minor effects of different diets on muscle mass and locomotion were observed: higher muscle mass in the casein group and improvement of stride frequencies with soluble milk protein. By contrast, supplementation with soluble milk protein just after physical activity was more effective at improving overall skeletal muscle function in old rats compared to casein. For active old rats supplemented with soluble milk protein, an increase in locomotor activity in the open field and an enhancement of static and dynamic gait parameters compared to active groups supplemented with casein or whey were observed without any differences in muscle mass and forelimb strength. These results suggest that consumption of soluble milk protein as a bolus immediately after a low intensity physical activity may be a suitable nutritional intervention to prevent decline in locomotion in aged rats and strengthen the interest to analyze the longitudinal aspect of locomotion in aged rodents.

Soluble Milk Protein Supplementation with Moderate Physical Activity Improves Locomotion Function in Aging Rats

PubMed Central

Lafoux, Aude; Baudry, Charlotte; Bonhomme, Cécile; Le Ruyet, Pascale; Huchet, Corinne

2016-01-01

Aging is associated with a loss of muscle mass and functional capacity. Present study was designed to compare the impact of specific dairy proteins on muscular function with or without a low-intensity physical activity program on a treadmill in an aged rat model. We investigated the effects of nutritional supplementation, five days a week over a 2-month period with a slow digestible protein, casein or fast digestible proteins, whey or soluble milk protein, on strength and locomotor parameters in sedentary or active aged Wistar RjHan rats (17–19 months of age). An extensive gait analysis was performed before and after protein supplementation. After two months of protein administration and activity program, muscle force was evaluated using a grip test, spontaneous activity using an open-field and muscular mass by specific muscle sampling. When aged rats were supplemented with proteins without exercise, only minor effects of different diets on muscle mass and locomotion were observed: higher muscle mass in the casein group and improvement of stride frequencies with soluble milk protein. By contrast, supplementation with soluble milk protein just after physical activity was more effective at improving overall skeletal muscle function in old rats compared to casein. For active old rats supplemented with soluble milk protein, an increase in locomotor activity in the open field and an enhancement of static and dynamic gait parameters compared to active groups supplemented with casein or whey were observed without any differences in muscle mass and forelimb strength. These results suggest that consumption of soluble milk protein as a bolus immediately after a low intensity physical activity may be a suitable nutritional intervention to prevent decline in locomotion in aged rats and strengthen the interest to analyze the longitudinal aspect of locomotion in aged rodents. PMID:27973615

Reduced glucose-induced insulin secretion in low-protein-fed rats is associated with altered pancreatic islets redox status.

PubMed

Cappelli, Ana Paula G; Zoppi, Claudio C; Silveira, Leonardo R; Batista, Thiago M; Paula, Flávia M; da Silva, Priscilla M R; Rafacho, Alex; Barbosa-Sampaio, Helena C; Boschero, Antonio C; Carneiro, Everardo M

2018-01-01

In the present study, we investigated the relationship between early life protein malnutrition-induced redox imbalance, and reduced glucose-stimulated insulin secretion. After weaning, male Wistar rats were submitted to a normal-protein-diet (17%-protein, NP) or to a low-protein-diet (6%-protein, LP) for 60 days. Pancreatic islets were isolated and hydrogen peroxide (H 2 O 2 ), oxidized (GSSG) and reduced (GSH) glutathione content, CuZn-superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and catalase (CAT) gene expression, as well as enzymatic antioxidant activities were quantified. Islets that were pre-incubated with H 2 O 2 and/or N-acetylcysteine, were subsequently incubated with glucose for insulin secretion measurement. Protein malnutrition increased CAT mRNA content by 100%. LP group SOD1 and CAT activities were 50% increased and reduced, respectively. H 2 O 2 production was more than 50% increased whereas GSH/GSSG ratio was near 60% lower in LP group. Insulin secretion was, in most conditions, approximately 50% lower in LP rat islets. When islets were pre-incubated with H 2 O 2 (100 μM), and incubated with glucose (33 mM), LP rats showed significant decrease of insulin secretion. This effect was attenuated when LP islets were exposed to N-acetylcysteine. © 2017 Wiley Periodicals, Inc.

Chronic ibuprofen administration reduces neuropathic pain but does not exert neuroprotection after spinal cord injury in adult rats.

PubMed

Redondo-Castro, Elena; Navarro, Xavier

2014-02-01

Ibuprofen is commonly used as an anti-inflammatory analgesic drug, although it is not amongst the first-line treatments for neuropathic pain. Its main effects are mediated by non-specific inhibition of COX enzymes, but it also exerts some COX-independent effects, such as the inhibition of RhoA signaling and the modulation of glial activity. These effects have boosted the use of ibuprofen as a tool to promote axonal regeneration and to increase functional recovery after neural injuries, although with controversial results showing positive and negative outcomes of ibuprofen treatment in several experimental models. We have evaluated the effects of ibuprofen administered at 60 mg/kg twice a day to rats subjected to a mild spinal cord contusion. Our results indicate that ibuprofen ameliorates mechanical hyperalgesia in rats by reducing central hyperexcitability, but failed to produce improvements in the recovery of locomotion. Despite an early effect on reducing microglial reactivity, the ibuprofen treatment did not provide histological evidence of neuroprotection; indeed the volume of cord tissue spared rostral to the lesion was decreased in ibuprofen treated rats. In summary, the early modulation of neuroinflammation produced by the administration of ibuprofen seems to eventually lead to a worse resolution of detrimental events occurring in the secondary injury phase, but also to reduce the development of neuropathic pain. Copyright © 2013 Elsevier Inc. All rights reserved.

Post-conditioning experience with acute or chronic inflammatory pain reduces contextual fear conditioning in the rat

PubMed Central

Johnston, Ian N.; Maier, Steven F.; Rudy, Jerry W.; Watkins, Linda R.

2017-01-01

There is evidence that pain can impact cognitive function in people. The present study evaluated whether Pavlovian fear conditioning in rats would be reduced if conditioning were followed by persistent inflammatory pain induced by a subcutaneous injection of dilute formalin or complete Freund's adjuvant (CFA) on the dorsal lumbar surface of the back. Formalin-induced pain specifically impaired contextual fear conditioning but not auditory cue conditioning (Experiment 1A). Moreover, formalin pain only impaired contextual fear conditioning if it was initiated within 1 h of conditioning and did not have a significant effect if initiated 2, 8 or 32 h after (Experiments 1A and 1B). Experiment 2 showed that formalin pain initiated after a session of context pre-exposure reduced the ability of that pre-exposure to facilitate contextual fear when the rat was limited to a brief exposure to the context during conditioning. Similar impairments in context- but not CS-fear conditioning were also observed if the rats received an immediate post-conditioning injection with CFA (Experiment 3). Finally, we confirmed that formalin and CFA injected s.c. on the back induced pain-indicative behaviours, hyperalgesia and allodynia with a similar timecourse to intraplantar injections (Experiment 4). These results suggest that persistent pain impairs learning in a hippocampus-dependent task, and may disrupt processes that encode experiences into long-term memory. PMID:21920390

Losartan reduces liver expression of plasminogen activator inhibitor-1 (PAI-1) in a high fat-induced rat nonalcoholic fatty liver disease model.

PubMed

Rosselli, Maria Soledad; Burgueño, Adriana L; Carabelli, Julieta; Schuman, Mariano; Pirola, Carlos J; Sookoian, Silvia

2009-09-01

To evaluate the effect of losartan-an angiotensin II type 1 receptor (AT1R) antagonist- and telmisartan-an AT1R blocker with insulin-sensitizing properties-, on the hepatic expression of plasminogen activator inhibitor-1 (PAI-1) in a rat model of nonalcoholic fatty liver disease (NAFLD). Rats were given a high-fat diet (HFD) for 8 weeks and after this period were randomly divided into 3 groups. For 12 weeks along with the same access to HFD, one group (9 rats) received losartan and another group received telmisartan (10 rats), both at 10mg/kg intraperitoneally (ip) every 24h. The third group (8 rats) received saline ip along with the HFD. Finally, a control group (6 rats) was fed with standard chow diet for 20 weeks. Fatty liver was reverted by both losartan and telmisartan. Both drugs had beneficial effects on insulin resistance, reaching statistical significance in telmisartan group. Expression of hepatic mRNA of PAI-1 showed a 42% decrease in losartan-treated rats in comparison with both HFD group and telmisartan-treated rats. To further evaluate this differential effect on PAI-1 expression, we explored the effect of the drugs on liver expression of TNFalpha, PEPCK-C and PPARalpha, and no significant differences were observed. These results indicate that AT1R blockers could be eligible drugs for reducing hepatic lipid accumulation in patients with NAFLD. However, only 12 weeks of losartan treatment strongly reduced hepatic PAI-1 gene expression. These differences could provide even more effective options for preventing fatty liver disease and its cardiovascular complications.

[The selenium haemostasis during experimental anaphylaxis reaction in rats treated with reduced glutathione and selenium enriched spirulina].

PubMed

Golubkina, N A; Mazo, V K; Gmoshinskiĭ, I V; Zorin, S N; Tambiev, A Kh; Kirikova, N N

2000-01-01

The main events caused by anaphilaxis in selenium haemostasis in rats include significant increase of selenium excretion with urine (6.36 +/- 1.18 nM Se/18 h., n = 10, compared with 1.72 +/- 0.38 nM Se/18 h., n = 10) and decrease of selenium plasma/selenium erythrocytes ratio from 0.939 to 0.791. Reduced glutathione (G-SH) administration led to 1.5-fold decrease of plasma selenium level and 1.3-fold increase of selenium concentration in intestinal walls of sensitized rats (r = -0.720, P < 0.001). Chromatographic separation of plasma proteins showed that intragastric intubation of G-SH to sensibilized rats significantly decreased the protein P content and did not influence the concentration of Se-GSHPx, thus indicating the local selenium acceptor role of G-SH. G-SH administration did not influence the intestinal permeability in sensitised rats while use of complex additive: G-SH and selenium enriched spirulina--normalized the latter parameter and the ratio of protein P/Se-GSHPx in plasma.

Branched-Chain Amino Acid Supplementation Reduces Oxidative Stress and Prolongs Survival in Rats with Advanced Liver Cirrhosis

PubMed Central

Mifuji-Moroka, Rumi; Hara, Nagisa; Miyachi, Hirohide; Sugimoto, Ryosuke; Tanaka, Hideaki; Fujita, Naoki; Gabazza, Esteban C.; Takei, Yoshiyuki

2013-01-01

Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05). The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver. PMID:23936183