?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.title=Wide+therapeutic+time+window+for+nimesulide+neuroprotection+in+a+model+of+transient+focal+cerebral+ischemia+in+the+rat&rft.creator=Candelario-Jalil%2C+Eduardo&rft.creator=Gonz%C3%A1lez-Falc%C3%B3n%2C+Armando&rft.creator=Garc%C3%ADa-Cabrera%2C+Michel&rft.creator=Le%C3%B3n%2C+Olga+S.&rft.creator=Fiebich%2C+Bernd+L.&rft.subject=Neurochemistry&rft.description=Results+from+several+studies+indicate+that+cyclooxygenase-2+(COX-2)+is+involved+ischemic+brain+injury.+The+purpose+of+this+study+was+to+evaluate+the+neuroprotective+effects+of+the+selective+COX-2+inhibitor+nimesulide+on+cerebral+infarction+and+neurological+deficits+in+a+standardized+model+of+transient+focal+cerebral+ischemia+in+rats.+Three+doses+of+nimesulide+(3%2C+6+and+12+mg%2Fkg%3B+i.p.)+or+vehicle+were+administered+immediately+after+stroke+and+additional+doses+were+given+at+6%2C+12%2C+24%2C+36+and+48+h+after+ischemia.+In+other+set+of+experiments%2C+the+effect+of+nimesulide+was+studied+in+a+situation+in+which+its+first+administration+was+delayed+for+3+to+24+h+after+ischemia.+Total%2C+cortical+and+subcortical+infarct+volumes+and+functional+outcome+(assessed+by+neurological+deficit+score+and+rotarod+performance)+were+determined+3+days+after+ischemia.+The+effect+of+nimesulide+on+prostaglandin+E2+(PGE2)+levels+in+the+injured+brain+was+also+investigated.+Nimesulide+dose-dependently+reduced+infarct+volume+and+improved+functional+recovery+when+compared+to+vehicle.+Of+interest+is+the+finding+that+neuroprotection+conferred+by+nimesulide+(reduction+of+infarct+size+and+neurological+deficits+and+improvement+of+rotarod+performance)+was+also+observed+when+treatment+was+delayed+until+24+h+after+ischemia.+Further%2C+administration+of+nimesulide+in+a+delayed+treatment+paradigm+completely+abolished+PGE2+accumulation+in+the+postischemic+brain%2C+suggesting+that+COX-2+inhibition+is+a+promising+therapeutic+strategy+for+cerebral+ischemia+to+target+the+late-occurring+inflammatory+events+which+amplify+initial+damage.+&rft.publisher=Elsevier&rft.contributor=Bloom%2C+Floyd&rft.date=2004-05&rft.type=Journal+(Paginated)&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.identifier=http%3A%2F%2Fcogprints.org%2F5617%2F1%2FBrain_Res_2004_nimesulide_stroke.pdf&rft.identifier=++Candelario-Jalil%2C+Eduardo+and+Gonz%C3%A1lez-Falc%C3%B3n%2C+Armando+and+Garc%C3%ADa-Cabrera%2C+Michel+and+Le%C3%B3n%2C+Olga+S.+and+Fiebich%2C+Bernd+L.++(2004)+Wide+therapeutic+time+window+for+nimesulide+neuroprotection+in+a+model+of+transient+focal+cerebral+ischemia+in+the+rat.++%5BJournal+(Paginated)%5D+++++&rft.relation=http%3A%2F%2Fcogprints.org%2F5617%2F