Document Detail

Combined antiapoptotic and antioxidant approach to acute neuroprotection for stroke in hypertensive rats.
MedLine Citation:
PMID:  23632970     Owner:  NLM     Status:  Publisher    
We hypothesized that targeting key points in the ischemic cascade with combined neuroglobin (Ngb) overexpression and c-jun N-terminal kinase (JNK) inhibition (SP600125) would offer greater neuroprotection than single treatment after in vitro hypoxia/reoxygenation and in a randomized, blinded in vivo experimental stroke study using a clinically relevant rat strain. Male spontaneously hypertensive stroke-prone rats underwent transient middle cerebral artery occlusion (tMCAO) and were divided into the following groups: tMCAO; tMCAO+control GFP-expressing canine adenovirus-2, CAVGFP; tMCAO+Ngb-expressing CAV-2, CAVNgb; tMCAO+SP600125; tMCAO+CAVNgb+SP600125; or sham procedure. Rats were assessed till day 14 for neurologic outcome before infarct determination. In vitro, combined lentivirus-mediated Ngb overexpression+SP600125 significantly reduced oxidative stress and apoptosis compared with single treatment(s) after hypoxia/reoxygenation in B50 cells. In vivo, infarct volume was significantly reduced by CAVNgb, SP600125, and further by CAVNgb+SP600125. The number of Ngb-positive cells in the peri-infarct cortex and striatum was significantly increased 14 days after tMCAO in animals receiving CAVNgb. Neurologic outcome, measured using a 32-point neurologic score, significantly improved with CAVNgb+SP600125 compared with single treatments at 14 days after tMCAO. Combined Ngb overexpression with JNK inhibition reduced hypoxia/reoxygenation-induced oxidative stress and apoptosis in cultured neurons and reduced infarct and improved neurologic outcome more than single therapy after in vivo experimental stroke in hypertensive rats.Journal of Cerebral Blood Flow & Metabolism advance online publication, 1 May 2013; doi:10.1038/jcbfm.2013.70.
Emily N J Ord; Rachel Shirley; John D McClure; Christopher McCabe; Eric J Kremer; I Mhairi Macrae; Lorraine M Work
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-5-01
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  -     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-5-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
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