Delayed treatment with monoclonal antibody IN-1 1 week after stroke results in recovery of function and corticorubral plasticity in adult rats.
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.
Seymour
Andrew B
AB
Neurology and Research Service, Hines VA Hospital, Roosevelt Road and Fifth Avenue, Hines, Illinois, USA. aseymo1@lumc.edu
Andrews
Ellen M
EM
Tsai
Shih-Yen
SY
Markus
Tiffanie M
TM
Bollnow
Melanie R
MR
Brenneman
Miranda M
MM
O'Brien
Timothy E
TE
Castro
Anthony J
AJ
Schwab
Martin E
ME
Kartje
Gwendolyn L
GL
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*
D000911:Antibodies, Monoclonal; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat