?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.title=Delayed+treatment+with+nimesulide+reduces+measures+of+oxidative+stress+following+global+ischemic+brain+injury+in+gerbils&rft.creator=Candelario-Jalil%2C+Eduardo&rft.creator=Alvarez%2C+Dalia&rft.creator=Merino%2C+Nelson&rft.creator=Leon%2C+Olga+S.&rft.subject=Neurochemistry&rft.description=Metabolism+of+arachidonic+acid+by+cyclooxygenase+is+one+of+the+primary+sources+of+reactive+oxygen+species+in+the+ischemic+brain.+Neuronal+overexpression+of+cyclooxygenase-2+has+recently+been+shown+to+contribute+to+neurodegeneration+following+ischemic+injury.+In+the+present+study%2C+we+examined+the+possibility+that+the+neuroprotective+effects+of+the+cyclooxygenase-2+inhibitor+nimesulide+would+depend+upon+reduction+of+oxidative+stress+following+cerebral+ischemia.+Gerbils+were+subjected+to+5+min+of+transient+global+cerebral+ischemia+followed+by+48+h+of+reperfusion+and+markers+of+oxidative+stress+were+measured+in+hippocampus+of+gerbils+receiving+vehicle+or+nimesulide+treatment+at+three+different+clinically+relevant+doses+(3%2C+6+or+12+mg%2Fkg).+Compared+with+vehicle%2C+nimesulide+significantly+(P%3C0.05)+reduced+hippocampal+glutathione+depletion+and+lipid+peroxidation%2C+as+assessed+by+the+levels+of+malondialdehyde+(MDA)%2C+4-hydroxy-alkenals+(4-HDA)+and+lipid+hydroperoxides+levels%2C+even+when+the+treatment+was+delayed+until+6+h+after+ischemia.+Biochemical+evidences+of+nimesulide+neuroprotection+were+supported+by+histofluorescence+findings+using+the+novel+marker+of+neuronal+degeneration+Fluoro-Jade+B.+Few+Fluoro-Jade+B+positive+cells+were+seen+in+CA1+region+of+hippocampus+in+ischemic+animals+treated+with+nimesulide+compared+with+vehicle.+These+results+suggest+that+nimesulide+may+protect+neurons+by+attenuating+oxidative+stress+and+reperfusion+injury+following+the+ischemic+insult+with+a+wide+therapeutic+window+of+protection.&rft.publisher=Elsevier&rft.date=2003&rft.type=Journal+(Paginated)&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.identifier=http%3A%2F%2Fcogprints.org%2F5642%2F1%2FCandelario-Jalil_et_al_2003_Neurosci_Res.pdf&rft.identifier=++Candelario-Jalil%2C+Eduardo+and+Alvarez%2C+Dalia+and+Merino%2C+Nelson+and+Leon%2C+Olga+S.++(2003)+Delayed+treatment+with+nimesulide+reduces+measures+of+oxidative+stress+following+global+ischemic+brain+injury+in+gerbils.++%5BJournal+(Paginated)%5D+++++&rft.relation=http%3A%2F%2Fcogprints.org%2F5642%2F