Document Detail


Delayed treatment with monoclonal antibody IN-1 1 week after stroke results in recovery of function and corticorubral plasticity in adult rats.
MedLine Citation:
PMID:  15889044     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Andrew B Seymour; Ellen M Andrews; Shih-Yen Tsai; Tiffanie M Markus; Melanie R Bollnow; Miranda M Brenneman; Timothy E O'Brien; Anthony J Castro; Martin E Schwab; Gwendolyn L Kartje
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  25     ISSN:  0271-678X     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-09-23     Completed Date:  2005-11-30     Revised Date:  2013-09-25    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1366-75     Citation Subset:  IM    
Affiliation:
Neurology and Research Service, Hines VA Hospital, Roosevelt Road and Fifth Avenue, Hines, Illinois, USA. aseymo1@lumc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / therapeutic use*
Brain Ischemia / physiopathology
Efferent Pathways / physiology
Forelimb / physiology
Infarction, Middle Cerebral Artery / physiopathology
Male
Motor Cortex / physiology*
Myelin Proteins / immunology*
Neuronal Plasticity / drug effects*
Rats
Rats, Long-Evans
Stroke / drug therapy*
Grant Support
ID/Acronym/Agency:
NS 40960/NS/NINDS NIH HHS; R01 NS040960/NS/NINDS NIH HHS; R56 NS040960/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Myelin Proteins; 0/Nogo protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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