title: Delayed treatment with monoclonal antibody IN-1 1 week after stroke results in recovery of function and corticorubral plasticity in adult rats.
abstract: Neuronal death due to ischemic stroke results in permanent deficits in sensory, language, and motor functions. The growth-restrictive environment of the adult central nervous system (CNS) is an obstacle to functional recovery after stroke and other CNS injuries. In this regard, Nogo-A is a potent neurite growth-inhibitory protein known to restrict neuronal plasticity in adults. Previously, we have found that treatment with monoclonal antibody (mAb) IN-1 to neutralize Nogo-A immediately after stroke enhanced motor cortico-efferent plasticity and recovery of skilled forelimb function in rats. However, immediate treatment for stroke is often not clinically feasible. Thus, the present study was undertaken to determine whether cortico-efferent plasticity and functional recovery would occur if treatment with mAb IN-1 was delayed 1 week after stroke. Adult rats were trained on a forelimb-reaching task, and the middle cerebral artery was occluded to induce focal cerebral ischemia to the forelimb sensorimotor cortex. After 1 week, animals received mAb IN-1 treatment, control antibody, or no treatment, and were tested for 9 more weeks. To assess cortico-efferent plasticity, the sensorimotor cortex opposite the stroke lesion was injected with an anterograde neuroanatomical tracer. Behavioral analysis demonstrated a recovery of skilled forelimb function, and anatomical studies revealed neuroplasticity at the level of the red nucleus in animals treated with mAb IN-1, thus demonstrating the efficacy of this treatment even if administered 1 week after stroke.
authors.affiliation: Neurology and Research Service, Hines VA Hospital, Roosevelt Road and Fifth Avenue, Hines, Illinois, USA. aseymo1@lumc.edu
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Seymour
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Andrews
authors.forename: Shih-Yen
authors.initials: SY
authors.lastname: Tsai
authors.forename: Tiffanie M
authors.initials: TM
authors.lastname: Markus
authors.forename: Melanie R
authors.initials: MR
authors.lastname: Bollnow
authors.forename: Miranda M
authors.initials: MM
authors.lastname: Brenneman
authors.forename: Timothy E
authors.initials: TE
authors.lastname: O'Brien
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Castro
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
authors.forename: Gwendolyn L
authors.initials: GL
authors.lastname: Kartje
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000503:physiopathology; D004525:Efferent Pathways / Q000502:physiology; D005552:Forelimb / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D009185:Myelin Proteins / Q000276:immunology*; D009473:Neuronal Plasticity / Q000187:drug effects*; D000070798:Nogo Proteins; D051381:Rats; D020318:Rats, Long-Evans; D020521:Stroke / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat