Human epidermal growth factor (EGF) receptor mRNA was detected in cryopreserved tissue sections a... more Human epidermal growth factor (EGF) receptor mRNA was detected in cryopreserved tissue sections adherent to whole glass slides using in situ reverse transcriptase polymerase chain reaction. EGF receptor cDNA was synthesized in situ by reverse transcription using an EGF receptor-specific oligonucleotide primer. In situ polymerase chain reaction amplification in the presence of digoxigenin-11-dUTP and subsequent binding with an antidigoxigenin antibody conjugated to alkaline phosphatase allowed direct visualization. Because DNase, RNase, or proteinase K are not required, tissue integrity is maintained. EGF receptor mRNA is expressed in the basal layer of normal human skin epithelium and is significantly overexpressed in squamous cell tumor specimens, which is consistent with conventional analysis of EGF receptor expression. The assay is semiquantitative, quicker, more sensitive, and void of the nonspecific binding associated with in situ hybridization. In situ reverse transcriptase polymerase chain reaction using whole glass slides is ideally suited for detecting moderate to infrequently expressed transcripts in biopsy specimens.
ABSTRACTSpinal cord injury (SCI) is a debilitating disease resulting in an estimated 18,000 new c... more ABSTRACTSpinal cord injury (SCI) is a debilitating disease resulting in an estimated 18,000 new cases in the United States on an annual basis. Significant behavioral research on animal models has led to a large amount of data, some of which has been catalogued in the Open Data Commons for Spinal Cord Injury (ODC-SCI). More recently, high throughput sequencing experiments have been utilized to understand molecular mechanisms associated with SCI, with nearly 6,000 samples from over 90 studies available in the Sequence Read Archive. However, to date, no resource is available for efficiently mining high throughput sequencing data from SCI experiments. Therefore, we have developed a protocol for processing RNA-Seq samples from high-throughput sequencing experiments related to SCI resulting in both raw and normalized data that can be efficiently mined for comparisons across studies as well as homologous discovery across species. We have processed 1,196 publicly available RNA-seq samples f...
Spinal cord injury (SCI) is a devastating condition that results in whole-body dysfunction, notab... more Spinal cord injury (SCI) is a devastating condition that results in whole-body dysfunction, notably cardiovascular (CV) disruption and disease. Injury-induced destruction of autonomic pathways in conjunction with a progressive decline in physical fitness contribute to the poor CV status of SCI individuals. Despite the wide use of exercise training as a therapeutic option to reduce CV dysfunction, little is known about the acute hemodynamic responses to the exercise itself. We investigated CV responses to an exercise challenge (swimming) following both high and low thoracic contusion to determine if the CV system is able to respond appropriately to the challenge of swimming. Blood pressure (BP) telemetry and echocardiography were used to track the progression of dysfunction in rodents with T3 and T10 SCI (n = 8 each) for 10 weeks postcontusion. At 1 week postinjury, all animals displayed a drastic decline in heart rate (HR) during the exercise challenge, likely a consequence of neuro...
Joint contractures and spasticity are two common secondary complications of a severe spinal cord ... more Joint contractures and spasticity are two common secondary complications of a severe spinal cord injury (SCI), which can significantly reduce quality of life, and stretching is one of the top strategies for rehabilitation of these complications. We have previously shown that a daily static stretching protocol administered to rats at either acute or chronic time points after a moderate or moderate-severe T10 SCI significantly disrupts their hindlimb locomotor function. The objective of the current study was to examine the effects of dynamic range of motion (ROM) stretching on the locomotor function of rats with SCI as an alternative to static stretching. Starting at 6 weeks post-injury (T10 moderate contusion) eight adult Sprague-Dawley rats were subjected to hindlimb stretching for 4 weeks. Our standard stretching protocol (six maneuvers to stretch the major hindlimb muscle groups) was modified from 1 min static stretch-and-hold at the end ROM of each stretch position to a dynamic 2 sec hold, 1 sec release rhythm repeated for a duration of 1 min. Four weeks of daily (5 days/week) dynamic stretching led to significant disruption of locomotor function as assessed by the Basso, Beattie, Bresnahan (BBB) Open Field Locomotor Scale and three-dimensional (3D) kinematic and gait analyses. In addition, we identified and analyzed an apparently novel hindlimb response to dynamic stretch that resembles human clonus. The results of the current study extend the observation of the stretching phenomenon to a new modality of stretching that is also commonly used in SCI rehabilitation. Although mechanisms and clinical relevance still need to be established, our findings continue to raise concerns that stretching as a therapy can potentially hinder aspects of locomotor recovery.
Experimental Study. To characterize the specific hindlimb electromyographic (EMG) patterns in res... more Experimental Study. To characterize the specific hindlimb electromyographic (EMG) patterns in response to muscle stretch and to measure the applied forces during stretching in the rat model of moderate SCI. Kentucky Spinal Cord Injury Research Center, Louisville, KY, USA. Female Sprague Dawley rats (n = 4) were instrumented for telemetry-based EMG recording (right rectus femoris and biceps femoris) and received a moderate T10 spinal cord injury (SCI). The major hindlimb muscle groups were stretched using our clinically modeled protocol. The EMG responses were recorded biweekly for 8 weeks. The forces applied during stretching were measured using a custom-designed glove. Locomotor function was assessed using the BBB Open Field Locomotor Scale, 3D kinematics and gait analysis. Three main EMG patterns in response to stretch were identified: clonic-like, air-stepping, and spasms. Torques applied during stretching ranged from 0.4-8 N•cm, and with the exception of the quadriceps, did not ...
Locomotor training of rats with thoracic contusion spinal cord injuries can induce task-specific ... more Locomotor training of rats with thoracic contusion spinal cord injuries can induce task-specific changes in stepping but rarely results in improved overground locomotion, possibly due to a ceiling effect. Thus, the authors hypothesize that incompletely injured rats maximally retrain themselves while moving about in their cages over the first few weeks postinjury. To test the hypothesis using hindlimb immobilization after mild thoracic contusion spinal cord injury in adult female rats. A passive stretch protocol was included as an independent treatment. Wheelchairs were used to hold the hindlimbs stationary in an extended position leaving the forelimbs free. The wheelchairs were used for 15 to 18 hours per day, 5 days per week for 8 weeks, beginning at 4 days postinjury. A 20-minute passive hindlimb stretch therapy was applied to half of the animals. Hindlimb locomotor function of the wheelchair group was not different from controls at 1 week postinjury but declined significantly over the next 4 weeks. Passive stretch had no influence on wheelchair animals but limited functional recovery of normally housed animals, preventing them from regaining forelimb-hindlimb coordination. Following 8 weeks of wheelchair immobilization and stretch therapy, only the wheelchair group displayed an improvement in function when returned to normal housing but retained significant deficits in stepping and coordination out to 16 weeks. Hindlimb immobilization and passive stretch may hinder or conceal the normal course of functional recovery of spinal cord injured rats. These observations have implications for the management of acute clinical spinal cord injuries.
Journal of the American Association for Laboratory Animal Science : JAALAS, 2007
A variety of rehabilitation methods that increase social interaction and locomotor activity are r... more A variety of rehabilitation methods that increase social interaction and locomotor activity are reported to yield positive benefits in humans and animals with spinal cord injury (SCI). Environmental enrichment often incorporates group housing, increased cage size, and objects to increase social interaction and stimulate locomotor activity of animals. Others have reported that adult rats housed in enriched environments immediately after moderate contusion thoracic SCI show improvements in locomotion, but not in neurotransmission through or anatomy at the SCI site. In the present study, in contrast to previous reports, environmental enrichment did not improve the locomotion of rats with contusion thoracic SCI. Furthermore, as in previous reports, improvements were not observed for either electrophysiologic measures of neurotransmission through (transcranial magnetic motor-evoked potentials) and caudal to (magnetic-evoked interlimb reflex) the injury site or the amount of spared white ...
Locomotor training of rats with thoracic contusion spinal cord injuries can induce task-specific ... more Locomotor training of rats with thoracic contusion spinal cord injuries can induce task-specific changes in stepping but rarely results in improved overground locomotion, possibly due to a ceiling effect. Thus, the authors hypothesize that incompletely injured rats maximally retrain themselves while moving about in their cages over the first few weeks postinjury. To test the hypothesis using hindlimb immobilization after mild thoracic contusion spinal cord injury in adult female rats. A passive stretch protocol was included as an independent treatment. Wheelchairs were used to hold the hindlimbs stationary in an extended position leaving the forelimbs free. The wheelchairs were used for 15 to 18 hours per day, 5 days per week for 8 weeks, beginning at 4 days postinjury. A 20-minute passive hindlimb stretch therapy was applied to half of the animals. Hindlimb locomotor function of the wheelchair group was not different from controls at 1 week postinjury but declined significantly over the next 4 weeks. Passive stretch had no influence on wheelchair animals but limited functional recovery of normally housed animals, preventing them from regaining forelimb-hindlimb coordination. Following 8 weeks of wheelchair immobilization and stretch therapy, only the wheelchair group displayed an improvement in function when returned to normal housing but retained significant deficits in stepping and coordination out to 16 weeks. Hindlimb immobilization and passive stretch may hinder or conceal the normal course of functional recovery of spinal cord injured rats. These observations have implications for the management of acute clinical spinal cord injuries.
Activity-based rehabilitation is a promising strategy for improving functional recovery following... more Activity-based rehabilitation is a promising strategy for improving functional recovery following spinal cord injury (SCI). While results from both clinical and animal studies have shown that a variety of approaches can be effective, debate still exists regarding the optimal post-injury period to apply rehabilitation. We recently demonstrated that rats with moderately severe thoracic contusive SCI can be re-trained to swim when training is initiated 2 weeks after injury and that swim training had no effect on the recovery of overground locomotion. We concluded that swim training is a task-specific model of post-SCI activity-based rehabilitation. In the present study, we ask if re-training initiated acutely is more or less effective than when initiated at 2 weeks post-injury. Using the Louisville Swim Scale, an 18-point swimming assessment, supplemented by kinematic assessment of hindlimb movement during swimming, we report that acute re-training is less effective than training initiated at 2 weeks. Using the bioluminescent protein luciferase as a blood-borne macromolecular marker, we also show a significant increase in extravasation in and around the site of SCI following only 8 min of swimming at 3 days post-injury. Taken together, these results suggest that acute re-training in a rat model of SCI may compromise rehabilitation efforts via mechanisms that may involve one or more secondary injury cascades, including acute spinal microvascular dysfunction.
After spinal cord injury (SCI) many patients develop muscle contractures in their plegic limbs. P... more After spinal cord injury (SCI) many patients develop muscle contractures in their plegic limbs. Physical therapists commonly use stretching as an approach to avoid contractures and to maintain the extensibility of soft tissues. We found previously that a daily stretching protocol has a negative effect on locomotor recovery in rats with mild thoracic SCIs. The purpose of the current study was to determine the effects of stretching on locomotor function at acute and chronic time points following moderately-severe contusive SCIs. Female SD rats with 25g-cm T10 contusion injuries received our standard 24-minute stretching protocol starting 4 days (acutely) or 12 weeks (chronically) post-injury (5 days/week for 5 or 4 weeks respectively). Locomotor function was assessed using the BBB (Basso, Beattie, and Bresnahan) Open Field Locomotor Scale, video-based kinematics and gait analysis. Locomotor deficits were evident in the acute animals after only 5 days of stretching and increasing the perceived intensity of stretching at week 4 resulted in greater impairment. Stretching initiated chronically resulted in dramatic decrements in locomotor function as most animals had BBB scores of 0-3 for weeks 2, 3 and 4 of stretching. Locomotor function recovered to control levels for both groups within 2 weeks once daily stretching ceased. Histological analysis revealed no apparent signs of overt and persistent damage to muscles undergoing stretching. The current study extends our observations of the stretching phenomenon to a more clinically relevant moderately-severe SCI animal model. The results are in agreement with our previous findings and further demonstrate that spinal cord locomotor circuitry is especially vulnerable to the negative effects of stretching at chronic time points. While the clinical relevance of this phenomenon remains unknown, we speculate that stretching may contribute to the lack of locomotor recovery in some patients.
A rarely explored subject in animal research is the effect of pre-injury variables on behavioral ... more A rarely explored subject in animal research is the effect of pre-injury variables on behavioral outcome post-SCI. Low reporting of such variables may underlie some discrepancies in findings between laboratories. Particularly, intensive task-specific training before a SCI might be important, considering that sports injuries are one of the leading causes of SCI. Thus, individuals with SCI often underwent rigorous training before their injuries. In the present study, we asked whether training before SCI on a grasping task or a swimming task would influence motor recovery in rats. Swim pre-training impaired recovery of swimming 2 and 4 weeks post-injury. This result fits with the idea of motor learning interference, which posits that learning something new may disrupt learning of a new task; in this case, learning strategies to compensate for functional loss after SCI. In contrast to swimming, grasp pre-training did not influence grasping ability after SCI at any time point. However, grasp pre-trained rats attempted to grasp more times than untrained rats in the first 4 weeks post-injury. Also, lesion volume of grasp pre-trained rats was greater than that of untrained rats, a finding which may be related to stress or activity. The increased participation in rehabilitative training of the pre-trained rats in the early weeks post-injury may have potentiated spontaneous plasticity in the spinal cord and counteracted the deleterious effect of interference and bigger lesions. Thus, our findings suggest that pre-training plays a significant role in recovery after CNS damage and needs to be carefully controlled for.
Journal of the American Association for Laboratory Animal Science : JAALAS, 2007
A variety of rehabilitation methods that increase social interaction and locomotor activity are r... more A variety of rehabilitation methods that increase social interaction and locomotor activity are reported to yield positive benefits in humans and animals with spinal cord injury (SCI). Environmental enrichment often incorporates group housing, increased cage size, and objects to increase social interaction and stimulate locomotor activity of animals. Others have reported that adult rats housed in enriched environments immediately after moderate contusion thoracic SCI show improvements in locomotion, but not in neurotransmission through or anatomy at the SCI site. In the present study, in contrast to previous reports, environmental enrichment did not improve the locomotion of rats with contusion thoracic SCI. Furthermore, as in previous reports, improvements were not observed for either electrophysiologic measures of neurotransmission through (transcranial magnetic motor-evoked potentials) and caudal to (magnetic-evoked interlimb reflex) the injury site or the amount of spared white ...
Human epidermal growth factor (EGF) receptor mRNA was detected in cryopreserved tissue sections a... more Human epidermal growth factor (EGF) receptor mRNA was detected in cryopreserved tissue sections adherent to whole glass slides using in situ reverse transcriptase polymerase chain reaction. EGF receptor cDNA was synthesized in situ by reverse transcription using an EGF receptor-specific oligonucleotide primer. In situ polymerase chain reaction amplification in the presence of digoxigenin-11-dUTP and subsequent binding with an antidigoxigenin antibody conjugated to alkaline phosphatase allowed direct visualization. Because DNase, RNase, or proteinase K are not required, tissue integrity is maintained. EGF receptor mRNA is expressed in the basal layer of normal human skin epithelium and is significantly overexpressed in squamous cell tumor specimens, which is consistent with conventional analysis of EGF receptor expression. The assay is semiquantitative, quicker, more sensitive, and void of the nonspecific binding associated with in situ hybridization. In situ reverse transcriptase polymerase chain reaction using whole glass slides is ideally suited for detecting moderate to infrequently expressed transcripts in biopsy specimens.
ABSTRACTSpinal cord injury (SCI) is a debilitating disease resulting in an estimated 18,000 new c... more ABSTRACTSpinal cord injury (SCI) is a debilitating disease resulting in an estimated 18,000 new cases in the United States on an annual basis. Significant behavioral research on animal models has led to a large amount of data, some of which has been catalogued in the Open Data Commons for Spinal Cord Injury (ODC-SCI). More recently, high throughput sequencing experiments have been utilized to understand molecular mechanisms associated with SCI, with nearly 6,000 samples from over 90 studies available in the Sequence Read Archive. However, to date, no resource is available for efficiently mining high throughput sequencing data from SCI experiments. Therefore, we have developed a protocol for processing RNA-Seq samples from high-throughput sequencing experiments related to SCI resulting in both raw and normalized data that can be efficiently mined for comparisons across studies as well as homologous discovery across species. We have processed 1,196 publicly available RNA-seq samples f...
Spinal cord injury (SCI) is a devastating condition that results in whole-body dysfunction, notab... more Spinal cord injury (SCI) is a devastating condition that results in whole-body dysfunction, notably cardiovascular (CV) disruption and disease. Injury-induced destruction of autonomic pathways in conjunction with a progressive decline in physical fitness contribute to the poor CV status of SCI individuals. Despite the wide use of exercise training as a therapeutic option to reduce CV dysfunction, little is known about the acute hemodynamic responses to the exercise itself. We investigated CV responses to an exercise challenge (swimming) following both high and low thoracic contusion to determine if the CV system is able to respond appropriately to the challenge of swimming. Blood pressure (BP) telemetry and echocardiography were used to track the progression of dysfunction in rodents with T3 and T10 SCI (n = 8 each) for 10 weeks postcontusion. At 1 week postinjury, all animals displayed a drastic decline in heart rate (HR) during the exercise challenge, likely a consequence of neuro...
Joint contractures and spasticity are two common secondary complications of a severe spinal cord ... more Joint contractures and spasticity are two common secondary complications of a severe spinal cord injury (SCI), which can significantly reduce quality of life, and stretching is one of the top strategies for rehabilitation of these complications. We have previously shown that a daily static stretching protocol administered to rats at either acute or chronic time points after a moderate or moderate-severe T10 SCI significantly disrupts their hindlimb locomotor function. The objective of the current study was to examine the effects of dynamic range of motion (ROM) stretching on the locomotor function of rats with SCI as an alternative to static stretching. Starting at 6 weeks post-injury (T10 moderate contusion) eight adult Sprague-Dawley rats were subjected to hindlimb stretching for 4 weeks. Our standard stretching protocol (six maneuvers to stretch the major hindlimb muscle groups) was modified from 1 min static stretch-and-hold at the end ROM of each stretch position to a dynamic 2 sec hold, 1 sec release rhythm repeated for a duration of 1 min. Four weeks of daily (5 days/week) dynamic stretching led to significant disruption of locomotor function as assessed by the Basso, Beattie, Bresnahan (BBB) Open Field Locomotor Scale and three-dimensional (3D) kinematic and gait analyses. In addition, we identified and analyzed an apparently novel hindlimb response to dynamic stretch that resembles human clonus. The results of the current study extend the observation of the stretching phenomenon to a new modality of stretching that is also commonly used in SCI rehabilitation. Although mechanisms and clinical relevance still need to be established, our findings continue to raise concerns that stretching as a therapy can potentially hinder aspects of locomotor recovery.
Experimental Study. To characterize the specific hindlimb electromyographic (EMG) patterns in res... more Experimental Study. To characterize the specific hindlimb electromyographic (EMG) patterns in response to muscle stretch and to measure the applied forces during stretching in the rat model of moderate SCI. Kentucky Spinal Cord Injury Research Center, Louisville, KY, USA. Female Sprague Dawley rats (n = 4) were instrumented for telemetry-based EMG recording (right rectus femoris and biceps femoris) and received a moderate T10 spinal cord injury (SCI). The major hindlimb muscle groups were stretched using our clinically modeled protocol. The EMG responses were recorded biweekly for 8 weeks. The forces applied during stretching were measured using a custom-designed glove. Locomotor function was assessed using the BBB Open Field Locomotor Scale, 3D kinematics and gait analysis. Three main EMG patterns in response to stretch were identified: clonic-like, air-stepping, and spasms. Torques applied during stretching ranged from 0.4-8 N•cm, and with the exception of the quadriceps, did not ...
Locomotor training of rats with thoracic contusion spinal cord injuries can induce task-specific ... more Locomotor training of rats with thoracic contusion spinal cord injuries can induce task-specific changes in stepping but rarely results in improved overground locomotion, possibly due to a ceiling effect. Thus, the authors hypothesize that incompletely injured rats maximally retrain themselves while moving about in their cages over the first few weeks postinjury. To test the hypothesis using hindlimb immobilization after mild thoracic contusion spinal cord injury in adult female rats. A passive stretch protocol was included as an independent treatment. Wheelchairs were used to hold the hindlimbs stationary in an extended position leaving the forelimbs free. The wheelchairs were used for 15 to 18 hours per day, 5 days per week for 8 weeks, beginning at 4 days postinjury. A 20-minute passive hindlimb stretch therapy was applied to half of the animals. Hindlimb locomotor function of the wheelchair group was not different from controls at 1 week postinjury but declined significantly over the next 4 weeks. Passive stretch had no influence on wheelchair animals but limited functional recovery of normally housed animals, preventing them from regaining forelimb-hindlimb coordination. Following 8 weeks of wheelchair immobilization and stretch therapy, only the wheelchair group displayed an improvement in function when returned to normal housing but retained significant deficits in stepping and coordination out to 16 weeks. Hindlimb immobilization and passive stretch may hinder or conceal the normal course of functional recovery of spinal cord injured rats. These observations have implications for the management of acute clinical spinal cord injuries.
Journal of the American Association for Laboratory Animal Science : JAALAS, 2007
A variety of rehabilitation methods that increase social interaction and locomotor activity are r... more A variety of rehabilitation methods that increase social interaction and locomotor activity are reported to yield positive benefits in humans and animals with spinal cord injury (SCI). Environmental enrichment often incorporates group housing, increased cage size, and objects to increase social interaction and stimulate locomotor activity of animals. Others have reported that adult rats housed in enriched environments immediately after moderate contusion thoracic SCI show improvements in locomotion, but not in neurotransmission through or anatomy at the SCI site. In the present study, in contrast to previous reports, environmental enrichment did not improve the locomotion of rats with contusion thoracic SCI. Furthermore, as in previous reports, improvements were not observed for either electrophysiologic measures of neurotransmission through (transcranial magnetic motor-evoked potentials) and caudal to (magnetic-evoked interlimb reflex) the injury site or the amount of spared white ...
Locomotor training of rats with thoracic contusion spinal cord injuries can induce task-specific ... more Locomotor training of rats with thoracic contusion spinal cord injuries can induce task-specific changes in stepping but rarely results in improved overground locomotion, possibly due to a ceiling effect. Thus, the authors hypothesize that incompletely injured rats maximally retrain themselves while moving about in their cages over the first few weeks postinjury. To test the hypothesis using hindlimb immobilization after mild thoracic contusion spinal cord injury in adult female rats. A passive stretch protocol was included as an independent treatment. Wheelchairs were used to hold the hindlimbs stationary in an extended position leaving the forelimbs free. The wheelchairs were used for 15 to 18 hours per day, 5 days per week for 8 weeks, beginning at 4 days postinjury. A 20-minute passive hindlimb stretch therapy was applied to half of the animals. Hindlimb locomotor function of the wheelchair group was not different from controls at 1 week postinjury but declined significantly over the next 4 weeks. Passive stretch had no influence on wheelchair animals but limited functional recovery of normally housed animals, preventing them from regaining forelimb-hindlimb coordination. Following 8 weeks of wheelchair immobilization and stretch therapy, only the wheelchair group displayed an improvement in function when returned to normal housing but retained significant deficits in stepping and coordination out to 16 weeks. Hindlimb immobilization and passive stretch may hinder or conceal the normal course of functional recovery of spinal cord injured rats. These observations have implications for the management of acute clinical spinal cord injuries.
Activity-based rehabilitation is a promising strategy for improving functional recovery following... more Activity-based rehabilitation is a promising strategy for improving functional recovery following spinal cord injury (SCI). While results from both clinical and animal studies have shown that a variety of approaches can be effective, debate still exists regarding the optimal post-injury period to apply rehabilitation. We recently demonstrated that rats with moderately severe thoracic contusive SCI can be re-trained to swim when training is initiated 2 weeks after injury and that swim training had no effect on the recovery of overground locomotion. We concluded that swim training is a task-specific model of post-SCI activity-based rehabilitation. In the present study, we ask if re-training initiated acutely is more or less effective than when initiated at 2 weeks post-injury. Using the Louisville Swim Scale, an 18-point swimming assessment, supplemented by kinematic assessment of hindlimb movement during swimming, we report that acute re-training is less effective than training initiated at 2 weeks. Using the bioluminescent protein luciferase as a blood-borne macromolecular marker, we also show a significant increase in extravasation in and around the site of SCI following only 8 min of swimming at 3 days post-injury. Taken together, these results suggest that acute re-training in a rat model of SCI may compromise rehabilitation efforts via mechanisms that may involve one or more secondary injury cascades, including acute spinal microvascular dysfunction.
After spinal cord injury (SCI) many patients develop muscle contractures in their plegic limbs. P... more After spinal cord injury (SCI) many patients develop muscle contractures in their plegic limbs. Physical therapists commonly use stretching as an approach to avoid contractures and to maintain the extensibility of soft tissues. We found previously that a daily stretching protocol has a negative effect on locomotor recovery in rats with mild thoracic SCIs. The purpose of the current study was to determine the effects of stretching on locomotor function at acute and chronic time points following moderately-severe contusive SCIs. Female SD rats with 25g-cm T10 contusion injuries received our standard 24-minute stretching protocol starting 4 days (acutely) or 12 weeks (chronically) post-injury (5 days/week for 5 or 4 weeks respectively). Locomotor function was assessed using the BBB (Basso, Beattie, and Bresnahan) Open Field Locomotor Scale, video-based kinematics and gait analysis. Locomotor deficits were evident in the acute animals after only 5 days of stretching and increasing the perceived intensity of stretching at week 4 resulted in greater impairment. Stretching initiated chronically resulted in dramatic decrements in locomotor function as most animals had BBB scores of 0-3 for weeks 2, 3 and 4 of stretching. Locomotor function recovered to control levels for both groups within 2 weeks once daily stretching ceased. Histological analysis revealed no apparent signs of overt and persistent damage to muscles undergoing stretching. The current study extends our observations of the stretching phenomenon to a more clinically relevant moderately-severe SCI animal model. The results are in agreement with our previous findings and further demonstrate that spinal cord locomotor circuitry is especially vulnerable to the negative effects of stretching at chronic time points. While the clinical relevance of this phenomenon remains unknown, we speculate that stretching may contribute to the lack of locomotor recovery in some patients.
A rarely explored subject in animal research is the effect of pre-injury variables on behavioral ... more A rarely explored subject in animal research is the effect of pre-injury variables on behavioral outcome post-SCI. Low reporting of such variables may underlie some discrepancies in findings between laboratories. Particularly, intensive task-specific training before a SCI might be important, considering that sports injuries are one of the leading causes of SCI. Thus, individuals with SCI often underwent rigorous training before their injuries. In the present study, we asked whether training before SCI on a grasping task or a swimming task would influence motor recovery in rats. Swim pre-training impaired recovery of swimming 2 and 4 weeks post-injury. This result fits with the idea of motor learning interference, which posits that learning something new may disrupt learning of a new task; in this case, learning strategies to compensate for functional loss after SCI. In contrast to swimming, grasp pre-training did not influence grasping ability after SCI at any time point. However, grasp pre-trained rats attempted to grasp more times than untrained rats in the first 4 weeks post-injury. Also, lesion volume of grasp pre-trained rats was greater than that of untrained rats, a finding which may be related to stress or activity. The increased participation in rehabilitative training of the pre-trained rats in the early weeks post-injury may have potentiated spontaneous plasticity in the spinal cord and counteracted the deleterious effect of interference and bigger lesions. Thus, our findings suggest that pre-training plays a significant role in recovery after CNS damage and needs to be carefully controlled for.
Journal of the American Association for Laboratory Animal Science : JAALAS, 2007
A variety of rehabilitation methods that increase social interaction and locomotor activity are r... more A variety of rehabilitation methods that increase social interaction and locomotor activity are reported to yield positive benefits in humans and animals with spinal cord injury (SCI). Environmental enrichment often incorporates group housing, increased cage size, and objects to increase social interaction and stimulate locomotor activity of animals. Others have reported that adult rats housed in enriched environments immediately after moderate contusion thoracic SCI show improvements in locomotion, but not in neurotransmission through or anatomy at the SCI site. In the present study, in contrast to previous reports, environmental enrichment did not improve the locomotion of rats with contusion thoracic SCI. Furthermore, as in previous reports, improvements were not observed for either electrophysiologic measures of neurotransmission through (transcranial magnetic motor-evoked potentials) and caudal to (magnetic-evoked interlimb reflex) the injury site or the amount of spared white ...
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Papers by Alice Shum-Siu