Bilateral cervical contusion spinal cord injury in rats

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.     

Recovery of forepaw gripping ability and reorganization of cortical motor control following cervical spinal cord injuries in mice

Previous studies using a grip strength meter (GSM) revealed a loss of gripping ability following cervical hemisection injuries in mice, followed by partial recovery. Here, we assess whether normal gripping ability and the recovered gripping ability after cervical hemisection depend on the cerebral cortex. First, we assessed grip strength of both forepaws of 18-week-old C57Bl/6 mice before and after a left sensorimotor cortex lesion or right lateral hemisection at C5. Both lesions led to a complete loss of gripping ability by the right forepaw and caused only minor deficits in the left. After cortical lesions, gripping ability re-appeared at about 17 days post-injury, and grip strength recovered to near-normal levels by 24 days post-injury. After C5 hemisections, gripping ability re-appeared after 31 days post-injury in 50% of the mice. Follow-up experiments were then carried out in which 10-week-old mice received C4 hemisection injuries and were tested for 28 days; then mice received secondary lesions of the sensorimotor cortex ipsi- or contralateral to the hemisection. Younger mice with cervical hemisections recovered gripping ability between 12 and 28 days post-hemisection. Cortical lesions on the side contralateral to the hemisection led to a complete loss of recovered gripping ability in all mice; cortical lesions on the side ipsilateral to the hemisection also disrupted recovered gripping ability in some animals. Surprisingly, lesions of the cortex ipsilateral to the hemisection did not impair gripping ability of the contralateral (left) forepaw. Finally, we assessed the effects of a third lesion of whichever side of the sensorimotor cortex remained, so that the sensorimotor cortex was ablated bilaterally. Remarkably, gripping function by the forepaw contralateral to the original hemisection was completely unaffected, and the recovered gripping function by the forepaw ipsilateral to the hemisection was disrupted in only some of the animals. These results indicate a substantial reorganization of motor control of gripping function after cervical injuries in mice so that gripping ability by both forepaws becomes largely independent of cortical control.     

An investigation of the cortical control of forepaw gripping after cervical hemisection injuries in rats

Previous studies in mice have demonstrated that forepaw gripping ability, as measured by a grip strength meter (GSM), is dependent on the contralateral sensorimotor cortex, but this dependency changes after hemisection injury at cervical level 4 (C4). Initially, the mouse fails to grip with the forepaw ipsilateral to the hemisection but gripping recovers. Additionally, a mouse's gripping by the contralateral paw becomes independent of the sensorimotor cortex, indicating a reorganization of cortical control of gripping function (Blanco, J.E., Anderson, K.D., Steward, O. 2007. Recovery of forepaw gripping ability and reorganization of cortical motor control following cervical spinal cord injuries in mice. Exp. Neurol. 203, 333-348.). Here we explore whether a similar reorganization occurs after cervical hemisection injuries in rats. We show that as in mice, unilateral lesions of the sensorimotor cortex impair rats' griping by the contralateral paw. We also confirm from previous studies that cervical hemisections impair rats' griping by the ipsilateral paw. In contrast to mice, however there is minimal recovery of gripping after complete lateral hemisections and secondary lesions of the sensorimotor cortex continue to impair rats' gripping by the contralateral paw. Thus, forelimb gripping ability as measured by the GSM is dependent on the contralateral sensorimotor cortex in rats even after a cervical hemisection.     

Spinal pathways involved in the control of forelimb motor function in rats

There is increasing interest in developing rodent models for cervical spinal cord injury (SCI) and techniques to assess forelimb motor function. Previously, we demonstrated that in rats, complete unilateral hemisection at cervical level five (C5) permanently eliminated the ability to grip and caused severe impairments in food retrieval by the forepaw ipsilateral to the lesion [Anderson, K.D., Gunawan, A., Steward, O., 2005. Quantitative behavioral analysis of forepaw function after cervical spinal cord injury in rats: Relationship to the corticospinal tract. Exp. Neurol. 194, 161-174]. Here, we analyzed the functional consequences of partial lesions that damaged tracts/cells located in the medial vs. lateral portion of the spinal cord. Female Sprague-Dawley rats were trained on the Grip Strength Meter (GSM) and the food pellet reaching task. Rats then received either a "medial lesion" that destroyed an approximately 0.5 mm wide zone from the midline laterally (which included the dorsal column) or "lateral lesion" that destroyed the lateral column at C5 and were tested for 8 weeks. Rats with histologically-verified medial lesions exhibited a complete loss of gripping ability for 7 weeks post-injury; only 1 of 4 animals exhibited any recovery of grip strength, and this occurred at 54 days. In contrast, rats with lateral lesions exhibited deficits, but the majority (7/10) recovered the ability to grip by 43 days post-injury. Interestingly, when tested on the food retrieval task, rats with medial lesions exhibited deficits that recovered; rats with lateral lesions exhibited more permanent deficits. These results suggest that different spinal circuits are involved in recovery of grip strength vs. recovery of skilled reaching.     

Quantitative assessment of forelimb motor function after cervical spinal cord injury in rats: relationship to the corticospinal tract

Approximately 50% of human spinal cord injuries (SCI) are at the cervical level, resulting in impairments in motor function of the upper extremity. Even modest recovery of upper extremity function could have an enormous impact on quality of life for quadriplegics. Thus, there is a critical need to develop experimental models for cervical SCI and techniques to assess deficits and recovery of forelimb motor function. Here, we analyze forelimb and forepaw motor function in rats after a lateral hemisection at C5 and assessed the relationship between the functional impairments and the extent of damage to one descending motor system, the corticospinal tract (CST). Female Sprague-Dawley rats were trained on various behavioral tasks that require the forelimb, including a task that measures gripping ability by the hand (as measured by a grip strength meter, GSM), a food reaching task, and horizontal rope walking. After 8 weeks of post-injury testing, the distribution of the CST was evaluated by injecting BDA into the sensorimotor cortex either ipsi- or contralateral to the cervical lesion. Complete unilateral hemisection injuries eliminated the ability to grip and caused severe impairments in food retrieval by the forepaw ipsilateral to the lesion. There was no indication of recovery in either task. In cases in which hemisections spared white matter near the midline, there was some recovery of forelimb motor function over time. Assessment of rope climbing ability revealed permanent impairments in forelimb use and deficits in hindlimb use and trunk stability. Sensory testing using a dynamic plantar aesthesiometer revealed that there was no increase in touch sensitivity in the affected forelimb. For the cases in which both histological and behavioral data were available, spared forelimb motor function was greatest in rats in which there was sparing of the dorsal CST.     

Forelimb locomotor assessment scale (FLAS): Novel assessment of forelimb dysfunction after cervical spinal cord injury

We describe here a novel forelimb locomotor assessment scale (FLAS) that assesses forelimb use during locomotion in rats injured at the cervical level. A quantitative scale was developed that measures movements of shoulder, elbow, and wrist joints, forepaw position and digit placement, forelimb–hindlimb coordination, compensatory behaviors adopted while walking, and balance. Female Sprague-Dawley rats received graded cervical contusions ranging from 200 to 230 (“mild,” n = 11) and 250–290 kdyn (“moderate,” n = 13) between C5 and C8. Rats were videotaped post-injury as they walked along an alley to determine deficits and recovery of forelimb function. Recovery of shoulder and elbow joint movement occurred rapidly (within 1–7 days post-injury), whereas recovery of wrist joint movement was slower and more variable. Most rats in all groups displayed persistent deficits in forepaw and digit movement, but developed compensatory behaviors to allow functional forward locomotion within 1–2 weeks post-injury. Recovery of forelimb function as measured by the FLAS reached a plateau by 3 weeks post-injury in all groups. Rats with mild contusions displayed greater locomotor recovery than rats with moderate contusions, but exhibited persistent deficits compared to sham controls. Reliability was tested by having seven raters (three internal, four external) from different laboratories, independently and blindly score videos of all rats. The multivariate correlation between all raters, all animals, and all time points ranged from r² = 0.88–0.96 (p < 0.0001), indicating a high inter-rater reliability. Thus, the FLAS is a simple, inexpensive, sensitive, and reliable measure of forelimb function during locomotion following cervical SCI.     

Quantitative assessment of deficits and recovery of forelimb motor function after cervical spinal cord injury in mice

A large proportion of spinal cord injuries (SCIs) in humans are at the cervical (C) level, but there are few tests to quantitatively assess forelimb motor function after cervical spinal cord injury in rodents. Here, we describe a simple and reliable technique for assessing forelimb grip strength over time. Female C57Bl/6 mice were trained on the Grip Strength Meter (GSM, TSE-Systems), then received a lateral hemisection of the spinal cord at level C5, C6, C7, or T1. Gripping ability by each forepaw was then tested for 4 weeks postinjury. Before injury, there was no significant difference in the force exerted by either forepaw. After hemisections at C5, C6, or C7, the forepaw ipsilateral to the injury was initially completely unable to grip (day 2 postinjury), and there was a slight transient decrease in the strength of the contralateral paw compared to presurgical levels. The ipsilateral forepaw exhibited no ability to grip until about 10-14 days postlesion, at which time grip reappeared and strength then recovered over a period of a few days to a level that was about 50% of preinjury levels. Grip strength was minimally and transiently affected by hemisection at T1. The grip strength analysis provides a convenient, quantitative measure of the loss and recovery of forelimb function after cervical injury.     

Functional and electrophysiological changes after graded traumatic spinal cord injury in adult rat

A graded contusion spinal cord injury (SCI) was created in the adult rat spinal cord using the Infinite Horizons (IH) impactor to study the correlation between injury severity and anatomical, behavioral, and electrophysiological outcomes. Adult Fisher rats were equally divided into five groups and received contusion injuries at the ninth thoracic level (T9) with 100, 125, 150, 175, or 200 kdyn impact forces, respectively. Transcranial magnetic motor-evoked potentials (tcMMEPs) and BBB open-field locomotor analyses were performed weekly for 4 weeks postinjury. Our results demonstrated that hindlimb locomotor function decreased in accordance with an increase in injury severity. The locomotor deficits were proportional to the amount of damage to the ventral and lateral white matter (WM). Locomotor function was strongly correlated to the amount of spared WM, which contains the reticulospinal and propriospinal tracts. Normal tcMMEP latencies were recorded in control, all of 100-kdyn-injured and half of 125-kdyn-injured animals. Delayed latency responses were recorded in some of 125-kdyn-injured and all of 150-kdyn-injured animals. No tcMMEP responses were recorded in 175- and 200-kdyn-injured animals. Comparison of tcMMEP responses with areas of WM loss or demyelination identified the medial ventrolateral funiculus (VLF) as the location of the tcMMEP pathway. Immunohistochemical and electromicroscopic (EM) analyses showed the presence of demyelinated axons in WM tracts surrounding the lesion cavities at 28 days postinjury. These data support the notion that widespread WM damage in the ventral and lateral funiculi may be a major cause for locomotor deficits and lack of tcMMEP responses after SCI.     

Aspiration of a cervical spinal contusion injury in preparation for delayed peripheral nerve grafting does not impair forelimb behavior or axon regeneration

A peripheral nerve graft model was used to examine axonal growth after a unilateral cervical (C) contusion injury in adult rats and to determine if manipulation of an injury site prior to transplantation affects spontaneous behavioral recovery. After a short delay (7 d) the epicenter of a C4 contusion was exposed and aspirated without harming the cavity walls followed by apposition with one end of a pre-degenerated tibial nerve to the rostral cavity wall. After a longer delay (28 d) the aspirated cavity was treated with GDNF to promote regeneration by chronically injured neurons. In both groups forelimb and hindlimb locomotor scores decreased significantly 2 d after lesion site manipulation, but by 7 d, the forelimb score was not different from the pre-manipulation score. There was no significant difference in grid walking or grip strength scores for the affected forelimb in either group 7 d after contusion vs. 7 d after manipulation. Over 1500 brain stem and propriospinal neurons grew axons into the graft with either delay. These results demonstrate that a contusion injury site can be manipulated prior to transplantation without causing long-lasting forelimb or hindlimb behavioral deficits and that peripheral nerve grafts support axonal growth after acute or chronic contusion injury.     

Cervical spinal cord injury in the adult rat: assessment of forelimb dysfunction

Traumatic injury to the adult human spinal cord most frequently occurs at the mid-to-low cervical segments and produces tetraplegia. To investigate treatments for improving upper extremity function after cervical spinal cord injury (SCI), three behavioral tests were examined for their potential usefulness in evaluating forelimb function in an adult rat model that mimics human low cervical SCI. Testing was conducted pre- and up to 4 weeks post-operation in adult female rats subjected to either contusion injury at the C7 spinal cord segment or sham-surgery. Modified Forelimb Tarlov scales revealed significant proximal and distal forelimb extension dysfunction in lesion rats at l-to-4 weeks post-cervical SCI. The Forelimb Grip Strength Test showed a significant decrease in forelimb grip strength of lesion rats throughout the 4 weeks post-cervical SCI. Significant deficits in reach and pellet retrieval by lesion rats were measured at l-to-4 weeks post-cervical SCI with the conditioned pellet retrieval Staircase Test. The results demonstrate that these qualitative and quantitative forelimb behavioral tests can be used to evaluate forelimb function following low cervical SCI and may be useful to investigate treatments for improving forelimb function in these lesions.     

One day of motor training with amphetamine impairs motor recovery following spinal cord injury

It has previously been reported that a single dose of amphetamine paired with training on a beam walking task can enhance locomotor recovery following brain injury (Feeney et al., 1982). Here, we investigated whether this same drug/training regimen could enhance functional recovery following either thoracic (T9) or cervical (C5) spinal cord injury. Different groups of female Sprague-Dawley rats were trained on a beam walking task, and in a straight alley for assessment of hindlimb locomotor recovery using the BBB locomotor scale. For rats that received C5 hemisections, forelimb grip strength was assessed using a grip strength meter. Three separate experiments assessed the consequences of training rats on the beam walking task 24 h following a thoracic lateral hemisection with administration of either amphetamine or saline. Beginning 1 h following drug administration, rats either received additional testing/retraining on the beam hourly for 6 h, or they were returned to their home cages without further testing/retraining. Rats with thoracic spinal cord injuries that received amphetamine in conjunction with testing/retraining on the beam at 1 day post injury (DPI) exhibited significantly impaired recovery on the beam walking task and BBB. Rats with cervical spinal cord injuries that received training with amphetamine also exhibited significant impairments in beam walking and locomotion, as well as impairments in gripping and reaching abilities. Even when administered at 14 DPI, the drug/training regimen significantly impaired reaching ability in cervical spinal cord injured rats. Impairments were not seen in rats that received amphetamine without training. Histological analyses revealed that rats that received training with amphetamine had significantly larger lesions than saline controls. These data indicate that an amphetamine/training regimen that improves recovery after cortical injury has the opposite effect of impairing recovery following spinal cord injury because early training with amphetamine increases lesion severity.     

PEGylated interferon-β modulates the acute inflammatory response and recovery when combined with forced exercise following cervical spinal contusion injury

Secondary degeneration leads to an expansion of the initial tissue damage sustained during a spinal cord injury (SCI). Dampening the cellular inflammatory response that contributes to this progressive tissue damage is one possible strategy for neuroprotection after acute SCI. We initially examined whether treatment with a PEGylated form of rat interferon-beta (IFN-β) would modulate the expression of several markers of inflammation and neuroprotection at the site of a unilateral cervical level 5 contusion injury. Adult female Sprague–Dawley rats were injured using the Infinite Horizon Impactor at a force of 200 kdyn (equivalent to a severe injury) and a mean displacement of 1600–1800 μm. A single dose (5 × 10⁶ units) of PEGylated IFN-β or vehicle was administered 30 min following SCI. Here we demonstrate temporal changes in pro- and anti-inflammatory cytokine levels and the expression of heat shock proteins and iNOS (involved in neuroprotection) at the lesion epicenter and one segment caudally after SCI and PEG IFN-β treatment. The results suggested a potential therapeutic treatment strategy for modulation of secondary damage after acute SCI. Therefore, we examined whether acute treatment with PEG IFN-β would improve forelimb function alone or when combined with forced exercise (Ex). Animals began the Ex paradigm 5 days post SCI and continued for 5 days/week over 8 weeks. Locomotion (forelimb locomotor scale [FLS], hindlimb BBB, and TreadScan) and sensorimotor function (grid walking) was tested weekly. Additional outcome measures included lesion size and glial cell reactivity. Significant FLS improvements occurred at 1 week post SCI in the PEGylated IFN-β-treated group but not at any other time point or with any other treatment approaches. These results suggest that this acute neuroprotective treatment strategy does not translate into long term behavioral recovery even when combined with forced exercise.     

Respiratory function following bilateral mid-cervical contusion injury in the adult rat

The consequences of spinal cord injury (SCI) are often viewed as the result of white matter damage. However, injuries occurring at any spinal level, especially in cervical and lumbar enlargement regions, also entail segmental neuronal loss. Yet, the contributions of gray matter injury and plasticity to functional outcomes are poorly understood. The present study addressed this issue by investigating changes in respiratory function following bilateral C(3)/C(4) contusion injuries at the level of the phrenic motoneuron (PhMN) pool which in the adult rat extends from C(3) to C(5/6) and provides innervation to the diaphragm. Despite extensive white and gray matter pathology associated with two magnitudes of injury severity, ventilation was relatively unaffected during both quiet breathing and respiratory challenge (hypercapnia). On the other hand, bilateral diaphragm EMG recordings revealed that the ability to increase diaphragm activity during respiratory challenge was substantially, and chronically, impaired. This deficit has not been seen following predominantly white matter lesions at higher cervical levels. Thus, the impact of gray matter damage relative to PhMNs and/or interneurons becomes evident during conditions associated with increased respiratory drive. Unaltered ventilatory behavior, despite significant deficits in diaphragm function, suggests compensatory neuroplasticity involving recruitment of other spinal respiratory networks which may entail remodeling of connections. Transynaptic tracing, using pseudorabies virus (PRV), revealed changes in PhMN-related interneuronal labeling rostral to the site of injury, thus offering insight into the potential anatomical reorganization and spinal plasticity following cervical contusion.     

Responses to cortical injury: I. Methodology and local effects of contusions in the rat

In order to develop some understanding of the evolution of cortical contusions, interdisciplinary studies including behavior, morphology and histochemistry were conducted at varying intervals after standardized injuries. A method for producing graded and reproducible focal cortical contusions in the rat is described. When these impact injuries are made in the ‘hindpaw cortical area, ’ specific trauma dose dependent behavioral deficits can be readily observed in the contralateral hindlimb. While most functional recovery occurs in the first two weeks after trauma, with severe contusions, deficits persist beyond 90 days. Morphologically these injuries progress from hemorrhages in white matter directly under contused cortex during the first hours after injury to the development of a necrotic cavity by 24 hours. The cativation appears to expand over the subsequent two weeks and by 15 days is lined with fibroblast-like elements and macrophages. Intense acid phosphatase activity is seen on the borders of the area of necrosis. This lysosomal enzyme may participate in autolysis and development of focal cavitation following cortical contusion.     

Comparing deficits following excitotoxic and contusion injuries in the thoracic and lumbar spinal cord of the adult rat

The majority of human spinal cord injuries involve gray matter loss from the cervical or lumbar enlargements. However, the deficits that arise from gray matter damage are largely masked by the severe deficits due to associated white matter damage. We have developed a model to examine gray matter-specific deficits and therapeutic strategies that uses intraspinal injections of the excitotoxin kainic acid into the T9 and L2 regions of the spinal cord. The resulting deficits have been compared to those from standard contusion injuries at the same levels. Injuries were assessed histologically and functional deficits were determined using the Basso, Beattie, and Bresnahan (BBB) 21-point open field locomotor scale and transcranial magnetic motor evoked potentials (tcMMEPs). Kainic acid injections into T9 resulted in substantial gray matter damage; however, BBB scores and tcMMEP response latencies were not different from those of controls. In contrast, kainic acid injections into L2 resulted in paraplegia with BBB scores similar to those following contusion injuries at either T9 or L2, without affecting tcMMEP response latencies. These observations demonstrate that gray matter loss can result in significant functional deficits, including paraplegia, in the absence of a disruption of major descending pathways.     

Traumatic Brown-Séquard-plus syndrome

BACKGROUND: In the 1840s Brown-Séquard described the motor and sensory effects of sectioning half of the spinal cord. Penetrating injuries can cause Brown-Séquard or, more frequently, Brown-Séquard-plus syndromes. OBJECTIVE: To report the case of a 25-year-old man who developed left-sided Brown-Séquard syndrome at the C8 level and left-sided Horner syndrome plus urinary retention and bilateral extensor responses following a stab wound in the right side of the neck. RESULTS: Magnetic resonance imaging demonstrated a low cervical lesion and somatosensory evoked potentials confirmed the clinical finding of left-side dorsal column disturbance. At follow-up, the patient's mobility and bladder function had returned to normal. CONCLUSION: This patient recovered well after a penetrating neck injury that disturbed function in more than half the lower cervical spinal cord (Brown-Séquard-plus syndrome).     

Graded unilateral cervical spinal cord injury in the rat: evaluation of forelimb recovery and histological effects

The purpose of this study was to develop a model of unilateral cervical (C4-C5) spinal cord contusion injury in the rat and to characterize the functional and histological consequences following three injury levels using a new weight-drop spinal cord injury device. We evaluated forepaw/forelimb and hindlimb functions by: (1) a horizontal ladder beam measuring paw misplacements and slips; and (2) the forelimb preference test which measures the forelimb used for pushing off to rear, for support, and to land on after rearing. Rats with a mild spinal cord injury displayed primarily a forepaw deficit (forepaw misplacements) for 8 weeks after injury. Paw preference also improved after injury, but failed to reach control levels even after 12 weeks. These rats had damage primarily to the rubrospinal, spinocervicothalamic, and the uncrossed lateral corticospinal tracts in the dorsolateral funiculus a well as some loss of the lateral spinothalamic tracts in the lateral funiculus. Rats with a moderate injury had a prominent forepaw deficit still evident at 12 weeks after injury as well as a mild but not significant hindlimb deficit. Paw preference improved slightly 12 weeks. There was a larger lesion in the dorsolateral and lateral funiculi than in mildly injured rats which extended into the ventrolateral funiculi. There was a significant loss of gray matter compared to rats with a mild injury. Rats with a severe injury displayed significant forelimb and hindlimb deficits throughout the 12 week testing period compared to rats with a mild or moderate injury, and also had a more severe paw preference bias (90%). The lesion encompassed the entire dorsolateral, lateral and ventrolateral funiculi with some disruption of the ventral funiculus. There was more significant gray matter necrosis compared to rats with either a mild or moderate injury. Thus, the spinal cord injury device we used may be useful for studying graded cervical spinal cord injury in rats and potential treatments or interventions, because both the behavioral and histological effects are reproducible and consistent.     

Adult rat forelimb dysfunction after dorsal cervical spinal cord injury

Repairing upper extremity function would significantly enhance the quality of life for persons with cervical spinal cord injury (SCI). Repair strategy development requires investigations of the deficits and the spontaneous recovery that occurs when cervical spinal cord axonal pathways are damaged. The present study revealed that both anatomically and electrophysiologically complete myelotomies of the C4 spinal cord dorsal columns significantly increased the adult rat's averaged times to first attend to adhesive stickers placed on the palms of their forepaws at 1 week. Complete bilateral myelotomies of the dorsal funiculi and dorsal hemisection, but not bilateral dorsolateral funiculi injuries, also similarly increased these times at 1 week. These data extend a previous finding by showing that a forepaw tactile sensory deficit that occurred in the adult rat after bilateral C4 spinal cord dorsal funiculi injury is due to damage of the dorsal columns. Averaged times to first attend to the stickers also decreased to those of sham-operated rats at 3 and 4 weeks post-dorsal hemisection with weekly testing. In contrast, a separate group of rats with dorsal hemisections had significantly increased times when tested only at 4 weeks. These data indicate that frequent assessment of this particular behavior in rats with dorsal hemisections extinguishes it and/or engenders a learned response in the absence of sensory axons in the dorsal columns and dorsolateral funiculi. This finding contrasted with weekly testing of grid walking where increased forelimb footfall numbers persisted for 4 weeks post-dorsal hemisection.     

Behavioral and histological outcomes following graded spinal cord contusion injury in the C57Bl/6 mouse

A computer-controlled electromagnetic spinal cord injury device (ESCID) has been adapted to develop a mouse model of spinal cord contusion injury. In the present study, we have extended this model in C57Bl/6 mice with behavioral and histopathological outcome assessment. Three groups of mice received a laminectomy at the T(9) vertebral level followed by a contusion injury from a predetermined starting load of 1500 dynes. Contusion was produced by rapid displacement of the spinal cord to a peak distance of 0.3, 0.5, or 0.8 mm, with the entire injury and retraction procedure completed over a 23-ms epoch. Control groups received laminectomy alone or complete transection. Functional recovery was examined for 9 weeks after injury using the BBB locomotor rating scale, grid walking, and footprint analysis. Distinct patterns of locomotor recovery were evident across the five groups. Measurements of spared white matter at the epicenter, lesion length, and cross-sectional area of fibronectin-immunopositive scar tissue were also significantly different between injury groups. The severity of injury corresponded with the biomechanical measures recorded at the time of impact as well as with behavioral and histological parameters. The results demonstrate that graded contusion injuries can be produced reliably in mice using the ESCID. The data provide a thorough and quantitative analysis of the effects of contusion injury on long-term behavioral and histological outcome measures in this strain and species.     

Functional subdivisions of the rat somatic sensorimotor cortex

The behavioural impairments and subsequent recovery were studied in rats with circumscribed unilateral lesions in the somatic sensorimotor cortex (SMC). Lesions were made in the caudal forelimb region (CFL), the rostral forelimb region (RFL), the anteromedial cortex (AMC) or the hindlimb area. Rats with damage in the CFL produced a deficit in placing the forelimb contralateral to the lesion during exploratory locomotion on a grid surface. Rats with AMC damage circled in the direction ipsilateral to the lesion. Lesions in the CFL or AMC produced an ipsilateral somatosensorimotor asymmetry on the bilateral-stimulation test (responding to adhesive patches placed on the contralateral forelimb was slower) that recovered in 7 days following AMC lesions or 28 days following CFL lesions. Finally, RFL lesions produced an ipsilateral asymmetry on the bilateral-stimulation task that was more severe and enduring (recovery in 60 days). After behavioral recovery, the effects of an additional lesion placed in the homotopic contralateral cortex were examined (two-stage bilateral lesion). Rats receiving two-stage bilateral lesions in the RFL or CFL responded slower to tactile stimulation of the forelimb contralateral to the second lesion. In the case of CFL-damaged rats, placing deficits also appeared contralateral to the most recent injury. In contrast, rats receiving two-stage bilateral AMC lesions did not exhibit behavioral asymmetries following the second lesion. These results provide evidence to suggest that subdivisions of the rat SMC can be distinguished with lesion/behavioral experiments. Moreover, a comparison of the effects of unilateral and two-stage bilateral lesions may help in the parcellation of the rat SMC into functionally distinct subareas and provide a basis for studying the processes of recovery and maintenance of function following brain damage.