Intrathecal treatment with anti-Nogo-A antibody improves functional recovery in adult rats after stroke
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Stroke often results in devastating neurological disabilities with no specific treatment available to improve functional recovery. Neurite growth inhibitory proteins such as Nogo-A play a critical role in impeding regain of function after stroke. We have reported that treatment with anti-Nogo-A antibody using the intracerebroventricular route resulted in improvement of function and neuroplasticity in adult or aged rats after stroke. This present study tested a more clinically accessible route for applying anti-Nogo-A antibodies, the intrathecal route. Anti-Nogo-A or control antibody was administered intrathecally at lower lumbar levels 1 week after middle cerebral artery occlusion in adult rats. Our results show that anti-Nogo-A antibody delivered by this intrathecal route for 2 weeks penetrated into brain parenchyma and bound to myelin-enriched structures such as the corpus callosum and striatal white matter. Animals receiving anti-Nogo-A antibody treatment significantly improved recovery of function on the skilled forelimb reaching task as compared to stroke only and stroke/control antibody animals. These findings show that anti-Nogo-A antibody delivered through the intrathecal route is as effective in restoring lost functions after stroke as the intracerebroventricular route. This is of great importance for the future application of anti-Nogo-A immunotherapy for ischemic stroke treatment.
KeywordsIschemic Stroke Middle Cerebral Artery Occlusion Perivascular Space Prefer Limb Intrathecal Route
Supported by the Department of Veterans Affairs, MREP, NIH (Grant NS40960), Neuroscience Institute and Falk Foundation, Novartis Pharmatheuticals, and the Swiss NSF. We thank Dr. Chung-Sung Sung (VGH Taipei, Taiwan) for assisting in intrathecal catheterization, and Sam and Josh Rosales for their technical assistance.
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