Date of Award

2015

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

Abstract

Stroke related death ranks as the fourth most common cause of mortality in the United States. Current therapeutic options following stroke are limited. One potential therapy involves the use of anti-Nogo-A immunotherapy post-stroke. Our laboratory has shown that the administration of this novel treatment results in sensorimotor recovery in adult and aged rats. This therapy has been shown to be efficacious when applied immediately, 24 hours, and 1 week post-stroke in rats with mild to moderate sensorimotor deficits. In addition, recent results suggest that administration of anti-Nogo-A immunotherapy up to 9 weeks after stroke still induces functional recovery and neuroanatomical plasticity in adult rats with mild to moderate sensorimotor deficits. However, whether and how long anti-Nogo-A immunotherapy is efficacious when administered in the chronic stroke phase in rats with moderate to very severe sensorimotor deficits is unknown. In the present project we sought to investigate the effectiveness of anti-Nogo-A immunotherapy as a therapeutic intervention to improve sensorimotor recovery when applied to chronic stroke-impaired adult rats with moderate to very severe sensorimotor deficits. Prior to testing the efficacy of anti-Nogo-A immunotherapy we set out to evaluate the spontaneous motor recovery profiles in adult rats after stroke. We found that animals displayed different recovery profiles based on initial deficit severity after stroke and overall, all spontaneous recovery occurred within the first 4 weeks post-stroke. Therefore, the neurological deficit in the stroke animals had plateaued by the time anti-Nogo-A immunotherapy was given at 9 and 25 weeks post-stroke. We found that animals with moderate to very severe deficits treated with anti-Nogo-A immunotherapy at 9 or 25 weeks post-stroke showed improved sensorimotor recovery at both time points. However, the improved sensorimotor function was not associated with dendritic changes in either the perilesional or contralesional cortex. Our finding of improved sensorimotor recovery even when treatment was started 25 weeks post-stroke demonstrates the promising therapeutic potential for anti-Nogo-A immunotherapy to treat stroke sufferers long after the initial ischemic damage has taken place.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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