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Back seat driving: hindlimb corticospinal neurons assume forelimb control following ischaemic stroke


Starkey, Michelle Louise; Bleul, Christiane; Zörner, Björn; Lindau, Nicolas Thomas; Mueggler, Thomas; Rudin, Markus; Schwab, Martin Ernst (2012). Back seat driving: hindlimb corticospinal neurons assume forelimb control following ischaemic stroke. Brain, 135(Pt 11):3265-3281.

Abstract

Whereas large injuries to the brain lead to considerable irreversible functional impairments, smaller strokes or traumatic lesions are often associated with good recovery. This recovery occurs spontaneously, and there is ample evidence from preclinical studies to suggest that adjacent undamaged areas (also known as peri-infarct regions) of the cortex 'take over' control of the disrupted functions. In rodents, sprouting of axons and dendrites has been observed in this region following stroke, while reduced inhibition from horizontal or callosal connections, or plastic changes in subcortical connections, could also occur. The exact mechanisms underlying functional recovery after small- to medium-sized strokes remain undetermined but are of utmost importance for understanding the human situation and for designing effective treatments and rehabilitation strategies. In the present study, we selectively destroyed large parts of the forelimb motor and premotor cortex of adult rats with an ischaemic injury. A behavioural test requiring highly skilled, cortically controlled forelimb movements showed that some animals recovered well from this lesion whereas others did not. To investigate the reasons behind these differences, we used anterograde and retrograde tracing techniques and intracortical microstimulation. Retrograde tracing from the cervical spinal cord showed a correlation between the number of cervically projecting corticospinal neurons present in the hindlimb sensory-motor cortex and good behavioural recovery. Anterograde tracing from the hindlimb sensory-motor cortex also showed a positive correlation between the degree of functional recovery and the sprouting of neurons from this region into the cervical spinal cord. Finally, intracortical microstimulation confirmed the positive correlation between rewiring of the hindlimb sensory-motor cortex and the degree of forelimb motor recovery. In conclusion, these experiments suggest that following stroke to the forelimb motor cortex, cells in the hindlimb sensory-motor area reorganize and become functionally connected to the cervical spinal cord. These new connections, probably in collaboration with surviving forelimb neurons and more complex indirect connections via the brainstem, play an important role for the recovery of cortically controlled behaviours like skilled forelimb reaching.

Abstract

Whereas large injuries to the brain lead to considerable irreversible functional impairments, smaller strokes or traumatic lesions are often associated with good recovery. This recovery occurs spontaneously, and there is ample evidence from preclinical studies to suggest that adjacent undamaged areas (also known as peri-infarct regions) of the cortex 'take over' control of the disrupted functions. In rodents, sprouting of axons and dendrites has been observed in this region following stroke, while reduced inhibition from horizontal or callosal connections, or plastic changes in subcortical connections, could also occur. The exact mechanisms underlying functional recovery after small- to medium-sized strokes remain undetermined but are of utmost importance for understanding the human situation and for designing effective treatments and rehabilitation strategies. In the present study, we selectively destroyed large parts of the forelimb motor and premotor cortex of adult rats with an ischaemic injury. A behavioural test requiring highly skilled, cortically controlled forelimb movements showed that some animals recovered well from this lesion whereas others did not. To investigate the reasons behind these differences, we used anterograde and retrograde tracing techniques and intracortical microstimulation. Retrograde tracing from the cervical spinal cord showed a correlation between the number of cervically projecting corticospinal neurons present in the hindlimb sensory-motor cortex and good behavioural recovery. Anterograde tracing from the hindlimb sensory-motor cortex also showed a positive correlation between the degree of functional recovery and the sprouting of neurons from this region into the cervical spinal cord. Finally, intracortical microstimulation confirmed the positive correlation between rewiring of the hindlimb sensory-motor cortex and the degree of forelimb motor recovery. In conclusion, these experiments suggest that following stroke to the forelimb motor cortex, cells in the hindlimb sensory-motor area reorganize and become functionally connected to the cervical spinal cord. These new connections, probably in collaboration with surviving forelimb neurons and more complex indirect connections via the brainstem, play an important role for the recovery of cortically controlled behaviours like skilled forelimb reaching.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Balgrist University Hospital, Swiss Spinal Cord Injury Center
04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology

04 Faculty of Medicine > Institute of Biomedical Engineering
04 Faculty of Medicine > Brain Research Institute
Dewey Decimal Classification:570 Life sciences; biology
170 Ethics
610 Medicine & health
Language:English
Date:November 2012
Deposited On:19 Dec 2012 14:46
Last Modified:06 Aug 2018 14:54
Publisher:Oxford University Press
ISSN:0006-8950
OA Status:Green
Publisher DOI:https://doi.org/10.1093/brain/aws270
PubMed ID:23169918

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