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Nogo-A antibodies and training reduce muscle spasms in spinal cord-injured rats


Gonzenbach, R R; Gasser, P; Zörner, B; Hochreutener, E; Dietz, V; Schwab, M E (2010). Nogo-A antibodies and training reduce muscle spasms in spinal cord-injured rats. Annals of Neurology, 68(1):48-57.

Abstract

OBJECTIVE: Spinal cord injury (SCI) leads to permanent motor and sensory deficits due to the damage of ascending and descending fiber tracts. In addition, malfunctions such as neuropathic pain or muscle spasms develop in many patients, possibly caused by injury-induced plastic changes of neuronal circuits above and below the lesion. New treatment strategies for spinal cord injury aim at enhancing plasticity and neurite growth, for example, by blocking the key neurite growth inhibitor Nogo-A or its downstream effectors. It is therefore crucial to investigate potential effects of such treatments on malfunctions such as muscle spasms. In addition, locomotor training, now a standard therapeutic tool to improve walking ability in incomplete SCI subjects, can be expected to influence the rearrangement of spinal cord circuits and the development of muscle spasms and other malfunctions. METHODS AND RESULTS: Here we present and validate a new rat model for muscle spasms after incomplete SCI and show that both intrathecal anti-Nogo-A antibody treatment and locomotor training, started early after injury, permanently reduce the development of muscle spasms. INTERPRETATION: The results show that an antibody-mediated suppression of the growth inhibitory protein Nogo-A leads to functional recovery and a lower level of malfunctions, suggesting the formation of functionally meaningful connections in the damaged spinal cord. Treadmill training early after SCI also has a beneficial effect.

Abstract

OBJECTIVE: Spinal cord injury (SCI) leads to permanent motor and sensory deficits due to the damage of ascending and descending fiber tracts. In addition, malfunctions such as neuropathic pain or muscle spasms develop in many patients, possibly caused by injury-induced plastic changes of neuronal circuits above and below the lesion. New treatment strategies for spinal cord injury aim at enhancing plasticity and neurite growth, for example, by blocking the key neurite growth inhibitor Nogo-A or its downstream effectors. It is therefore crucial to investigate potential effects of such treatments on malfunctions such as muscle spasms. In addition, locomotor training, now a standard therapeutic tool to improve walking ability in incomplete SCI subjects, can be expected to influence the rearrangement of spinal cord circuits and the development of muscle spasms and other malfunctions. METHODS AND RESULTS: Here we present and validate a new rat model for muscle spasms after incomplete SCI and show that both intrathecal anti-Nogo-A antibody treatment and locomotor training, started early after injury, permanently reduce the development of muscle spasms. INTERPRETATION: The results show that an antibody-mediated suppression of the growth inhibitory protein Nogo-A leads to functional recovery and a lower level of malfunctions, suggesting the formation of functionally meaningful connections in the damaged spinal cord. Treadmill training early after SCI also has a beneficial effect.

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19 citations in Web of Science®
24 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Brain Research Institute
04 Faculty of Medicine > Balgrist University Hospital, Swiss Spinal Cord Injury Center
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:July 2010
Deposited On:04 Jan 2011 08:10
Last Modified:07 Dec 2017 04:27
Publisher:Wiley-Blackwell
ISSN:0364-5134
Publisher DOI:https://doi.org/10.1002/ana.22009
PubMed ID:20582944

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