Limits on recovery in the corticospinal tract of the rat: Partial lesions impair skilled reaching and the topographic representation of the forelimb in motor cortex

Piecharka, Dionne M.; Kleim, Jeffrey A.; Whishaw, Ian Q.

doi:10.1016/j.brainresbull.2005.04.013

Cited by 50 publications

(35 citation statements)

References 62 publications

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“…Interruption of CST input to the cervical spinal cord resulted in a permanent impairment of skilled forelimb function as shown in previous studies (Whishaw et al, 1993;Piecharka et al, 2005). The same result was obtained in injured rats with immobilized impaired forelimbs.…”

Section: Forced Limb Use Leads To Functional Recoverysupporting

confidence: 86%

Constraint-Induced Movement Therapy in the Adult Rat after Unilateral Corticospinal Tract Injury

Maier¹,

Baumann²,

Thallmair³

et al. 2008

J. Neurosci.

168

128

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Smaller spinal cord injuries often allow some degree of spontaneous behavioral improvements because of structural rearrangements within different descending fiber tracts or intraspinal circuits. In this study, we investigate whether rehabilitative training of the forelimb (forced limb use) influences behavioral recovery and plastic events after injury to a defined spinal tract, the corticospinal tract (CST). Female adult Lewis rats received a unilateral CST injury at the brainstem level. Use of the contralateral impaired forelimb was either restricted, by a cast, or forced, by casting the unimpaired forelimb immediately after injury for either 1 or 3 weeks. Forced use of the impaired forelimb was followed by full behavioral recovery on the irregular horizontal ladder, whereas animals that could not use their affected side remained impaired. BDA (biotinylated dextran amine) labeling of the intact CST showed lesion-induced growth across the midline where CST collaterals increased their innervation density and extended fibers toward the ventral and the dorsal horn in response to forced limb use. Gene chip analysis of the denervated ventral horn revealed changes in particular for growth factors, adhesion and guidance molecules, as well as components of synapse formation suggesting an important role for these factors in activity-dependent intraspinal reorganization after unilateral CST injury.

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Section: Forced Limb Use Leads To Functional Recoverysupporting

confidence: 86%

Constraint-Induced Movement Therapy in the Adult Rat after Unilateral Corticospinal Tract Injury

Maier¹,

Baumann²,

Thallmair³

et al. 2008

J. Neurosci.

168

128

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“…[51][52][53] In standard ICMS studies, forelimb movements can be evoked at £60 uA. [37][38][39][54][55][56] However, we and others have previously found that post-CCI of the CMS requires higher current to drive ICMS-evoked movements. 57,58 The fact that wrist and elbow movements are primarily elicited above 60 uA indicates that, even 41 days post-CCI, the motor cortex is highly dysfunctional, further supporting our previous findings that dendrites in peri-injury remaining MC are sparse, and NOGO is upregulated compared to control animals.…”

Section: Discussionmentioning

confidence: 99%

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

Combs

Jones

Kozlowski

et al. 2016

Journal of Neurotrauma

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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.

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“…These skillful voluntary forepaw movements require training prior to injury, and involve more supraspinal descending inputs than unskilled movement such as reflex or postural support movements (Alaverdashvili and Whishaw, 2008;Anderson et al, 2007;McKenna and Whishaw, 1999;Zai et al, 2009). The supraspinal descending tracts involved in skilled forepaw movement include the corticospinal Piecharka et al, 2005;Starkey et al, 2005), and rubrospinal tracts (McKenna and Whishaw, 1999;Whishaw et al, 1998), with the latter being more important for digit movements in rats (Kuchler et al, 2002). In this study we report that SCI significantly reduced the number of ipsilateral forepaw adjustments made per piece of vermicelli, a result consistent with previous literature in which this test was used to assess functional recovery after unilateral middle cerebral artery occlusion, an electrolytic somatosensory cortex lesion, or a striatal dopamine-depleting lesion (Allred et al, 2008).…”

Section: Assessment Of Skilled and Unskilled Behavioral Tasksmentioning

confidence: 99%

Characterization of a Graded Cervical Hemicontusion Spinal Cord Injury Model in Adult Male Rats

Dunham

Siriphorn

Chompoopong

et al. 2010

Journal of Neurotrauma

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Most experimental models of spinal cord injury (SCI) in rodents induce damage in the thoracic cord and subsequently examine hindlimb function as an indicator of recovery. In these models, functional recovery is most attributable to white-matter preservation and is less influenced by grey-matter sparing. In contrast, most clinical cases of SCI occur at the lower cervical levels, a region in which both grey-matter and white-matter sparing contribute to functional motor recovery. Thus experimental cervical SCI models are beginning to be developed and used to assess protective and pharmacological interventions following SCI. The objective of this study was to characterize a model of graded cervical hemicontusion SCI with regard to several histological and behavioral outcome measures, including novel forelimb behavioral tasks. Using a commercially available rodent spinal cord impactor, adult male rats received hemicontusion SCI at vertebral level C5 at 100, 200, or 300 kdyn force, to produce mild, moderate, or severe injury severities. Tests of skilled and unskilled forelimb and locomotor function were employed to assess functional recovery, and spinal cord tissue was collected to assess lesion severity. Deficits in skilled and unskilled forelimb function and locomotion relating to injury severity were observed, as well as decreases in neuronal numbers, white-matter area, and white-matter gliosis. Significant correlations were observed between behavioral and histological data. Taken together, these data suggest that the forelimb functional and locomotor assessments employed here are sensitive enough to measure functional changes, and that this hemicontusion model can be used to evaluate potential protective and regenerative therapeutic strategies.

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Limits on recovery in the corticospinal tract of the rat: Partial lesions impair skilled reaching and the topographic representation of the forelimb in motor cortex

Cited by 50 publications

References 62 publications

Constraint-Induced Movement Therapy in the Adult Rat after Unilateral Corticospinal Tract Injury

Constraint-Induced Movement Therapy in the Adult Rat after Unilateral Corticospinal Tract Injury

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

Characterization of a Graded Cervical Hemicontusion Spinal Cord Injury Model in Adult Male Rats

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