title: Intrathecal treatment with anti-Nogo-A antibody improves functional recovery in adult rats after stroke.
abstract: 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.
authors: Neurology and Research Service, Hines VA Hospital, Roosevelt Road and Fifth Avenue, Hines, IL 60141, USA. shih-yen.tsai@va.gov
authors: Shih-Yen
authors: SY
authors: Tsai
authors: Tiffanie M
authors: TM
authors: Markus
authors: Ellen M
authors: EM
authors: Andrews
authors: Joseph L
authors: JL
authors: Cheatwood
authors: April J
authors: AJ
authors: Emerick
authors: Anis K
authors: AK
authors: Mir
authors: Martin E
authors: ME
authors: Schwab
authors: Gwendolyn L
authors: GL
authors: Kartje
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D007278:Injections, Spinal / Q000379:methods; D008297:Male; D009185:Myelin Proteins / Q000276:immunology*; D000070798:Nogo Proteins; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D020127:Recovery of Function / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D000906:Antibodies; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat
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