Unilateral dorsal column and rubrospinal tract injuries affect overground locomotion in the unrestrained rat

Webb, Aubrey A.; Muir, Gillian D.

doi:10.1046/j.1460-9568.2003.02768.x

Cited by 77 publications

(57 citation statements)

References 36 publications

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“…This activity is similar to behavior in their home cages; therefore, repeated trials fail to bias paw usage (Schallert et al, 2000). Previous studies have shown that unilateral cortical aspiration (Woodlee et al, 2005), cervical hemisection (Schallert et al, 2000), and more subtle lesions of exclusive descending motor and ascending sensory spinal tracts (Liu et al, 1999(Liu et al, , 2002Webb and Muir, 2003) reduce ipsilateral paw usage (rats normally use both paws with equal frequency for initial contact with the cylinder wall and lateral movement). Consistent with these reports, we observed a shift in paw usage to the contralateral side in vehicle-treated animals after lesion.…”

Section: Restitution Of Sensory Functionmentioning

confidence: 88%

Chondroitinase ABC-Mediated Plasticity of Spinal Sensory Function

Cafferty¹,

Bradbury²,

Lidierth³

et al. 2008

J. Neurosci.

102

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Experimental therapeutics designed to enhance recovery from spinal cord injury (SCI) primarily focus on augmenting the growth of damaged axons by elevating their intrinsic growth potential and/or by nullifying the influence of inhibitory proteins present in the mature CNS. However, these strategies may also influence the wiring of intact pathways. The direct contribution of such effects to functional restoration after injury has been mooted, but as yet not been described. Here, we provide evidence to support the hypothesis that reorganization of intact spinal circuitry enhances function after SCI. Adult rats that underwent unilateral cervical spared-root lesion (rhizotomy of C5, C6, C8, and T1, sparing C7) exhibited profound sensory deficits for 4 weeks after injury. Delivery of a focal intraspinal injection of the chondroitin sulfate proteoglycan-degrading enzyme chondroitinase ABC (ChABC) was sufficient to restore sensory function after lesion. In vivo electrophysiological recordings confirm that behavioral recovery observed in ChABC-treated rats was consequent on reorganization of intact C7 primary afferent terminals and not regeneration of rhizotomized afferents back into the spinal cord within adjacent segments. These data confirm that intact spinal circuits have a profound influence on functional restoration after SCI. Furthermore, comprehensive understanding of these targets may lead to therapeutic interventions that can be spatially tailored to specific circuitry, thereby reducing unwanted maladaptive axon growth of distal pathways.

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Section: Restitution Of Sensory Functionmentioning

confidence: 88%

Chondroitinase ABC-Mediated Plasticity of Spinal Sensory Function

Cafferty¹,

Bradbury²,

Lidierth³

et al. 2008

J. Neurosci.

102

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“…Prior studies have reported this tract to be important for unrestrained overground locomotion, captured here by performance on the CatWalk. [29][30][31] Such findings suggest that the lack of myelinated RST in the 0.8 mm groups may have produced the more prolonged proximal forelimb deficits seen on the CatWalk and IBB tasks in comparison to the 0.6 mm group.…”

Section: Distal Forelimb Motor Function Exhibits the Greatest And Mosmentioning

confidence: 89%

A Cervical Hemi-Contusion Spinal Cord Injury Model for the Investigation of Novel Therapeutics Targeting Proximal and Distal Forelimb Functional Recovery

Mondello

Sunshine

Fischedick

et al. 2015

Journal of Neurotrauma

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Cervical spinal cord contusion is the most common human spinal cord injury, yet few rodent models replicate the pathophysiological and functional sequela of this injury. Here, we modified an electromechanical injury device and characterized the behavioral and histological changes occurring in response to a lateralized C4 contusion injury in rats. A key feature of the model includes a non-injurious touch phase where the spinal cord surface is dimpled with a consistent starting force. Animals were either left intact as a control, received a non-injury-producing touch on the surface of the cord (''sham''), or received a 0.6 mm or a 0.8 mm displacement injury. Rats were then tested on the forelimb asymmetry use test, CatWalk, and the Irvine, Beatties, and Bresnahan (IBB) cereal manipulation task to assess proximal and distal upper limb function for 12 weeks. Injuries of moderate (0.6 mm) and large (0.8 mm) displacement showed consistent differences in forelimb asymmetry, metrics of the CatWalk, and sub-scores of the IBB. Overall findings indicated long lasting proximal and distal upper limb deficits following 0.8 mm injury but transient proximal with prolonged distal limb deficits following 0.6 mm injury. Significant differences in loss of ipsilateral unmyelinated and myelinated white matter was detected between injury severities. Demyelination was primarily localized to the dorsolateral region of the hemicord and extended further rostral following 0.8 mm injury. These findings establish the C4 hemi-contusion injury as a consistent, graded model for testing novel treatments targeting forelimb functional recovery.

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“…It is conceivable, however, that thoracic lesions could in the meantime affect axial musculature and posture; the same may be true for cervical spinal injuries. 77,78 Recent studies in which gray matter was pharmacologically rescued after a thoracic contusion injury showed an increase in the control of trunk musculature, although.hindlimb locomotion did not improve. 79,80 From a clinical rehabilitative perspective, axial musculature stability is vital.…”

Section: Neuronal Replacement In the Injured Spinal Cordmentioning

confidence: 99%

Cellular transplantation strategies for spinal cord injury and translational neurobiology

Reier

2004

Neurotherapeutics

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Summary: Basic science advances in spinal cord injury and regeneration research have led to a variety of novel experimental therapeutics designed to promote functionally effective axonal regrowth and sprouting. Among these interventions are cell-based approaches involving transplantation of neural and non-neural tissue elements that have potential for restoring damaged neural pathways or reconstructing intraspinal synaptic circuitries by either regeneration or neuronal/glial replacement. Notably, some of these strategies (e.g., grafts of peripheral nerve tissue, olfactory ensheathing glia, activated macrophages, marrow stromal cells, myelin-forming oligodendrocyte precursors or stem cells, and fetal spinal cord tissue) have already been translated to the clinical arena, whereas others have imminent likelihood of bench-to-bedside application. Although this progress has generated considerable enthusiasm about treating what once was thought to be a totally incurable condition, there are many issues to be considered relative to treatment safety and efficacy. The following review reflects on different experimental applications of intraspinal transplantation with consideration of the underlying pathological, pathophysiological, functional, and neuroplastic responses to spinal trauma that such treatments may target along with related issues of procedural and biological safety. The discussion then moves to an overview of ongoing and completed clinical trials to date. The pros and cons of these endeavors are considered, as well as what has been learned from them. Attention is primarily directed at preclinical animal modeling and the importance of patterning clinical trials, as much as possible, according to laboratory experiences.

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Unilateral dorsal column and rubrospinal tract injuries affect overground locomotion in the unrestrained rat

Cited by 77 publications

References 36 publications

Chondroitinase ABC-Mediated Plasticity of Spinal Sensory Function

Chondroitinase ABC-Mediated Plasticity of Spinal Sensory Function

A Cervical Hemi-Contusion Spinal Cord Injury Model for the Investigation of Novel Therapeutics Targeting Proximal and Distal Forelimb Functional Recovery

Cellular transplantation strategies for spinal cord injury and translational neurobiology

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