?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.title=Post-ischaemic+treatment+with+the+cyclooxygenase-2+inhibitor+nimesulide+reduces+blood-brain+barrier+disruption+and+leukocyte+infiltration+following+transient+focal+cerebral+ischaemia+in+rats&rft.creator=Candelario-Jalil%2C+Eduardo&rft.creator=Gonzalez-Falcon%2C+Armando&rft.creator=Garcia-Cabrera%2C+Michel&rft.creator=Leon%2C+Olga+Sonia&rft.creator=Fiebich%2C+Bernd&rft.subject=Neurochemistry&rft.description=Several+studies+suggest+that+cyclooxygenase+(COX)-2+plays+a+pivotal+role+in+the+progression+of+ischemic+brain+damage.+In+the+present+study%2C+we+investigated+the+effects+of+selective+inhibition+of+COX-2+with+nimesulide+(12+mg%2Fkg)+and+selective+inhibition+of+COX-1+with+valeryl+salicylate+(VAS%2C+12-120+mg%2Fkg)+on+prostaglandin+E2+(PGE2)+levels%2C+myeloperoxidase+(MPO)+activity%2C+Evans+Blue+(EB)+extravasation+and+infarct+volume+in+a+standardized+model+of+transient+focal+cerebral+ischemia+in+the+rat.+Postischemic+treatment+with+nimesulide+markedly+reduced+the+increase+in+PGE2+levels+in+the+ischemic+cerebral+cortex+24+h+after+stroke+and+diminished+infarct+size+by+48+%25+with+respect+to+vehicle-treated+animals+after+3+days+of+reperfusion.+Furthermore%2C+nimesulide+significantly+attenuated+the+blood-brain+barrier+(BBB)+damage+and+leukocyte+infiltration+(as+measured+by+EB+leakage+and+MPO+activity%2C+respectively)+seen+at+48+h+after+the+initial+ischemic+episode.+These+studies+provide+the+first+experimental+evidence+that+COX-2+inhibition+with+nimesulide+is+able+to+limit+BBB+disruption+and+leukocyte+infiltration+following+transient+focal+cerebral+ischemia.+Neuroprotection+afforded+by+nimesulide+is+observed+even+when+the+treatment+is+delayed+until+6+h+after+the+onset+of+ischemia%2C+confirming+a+wide+therapeutic+window+of+COX-2+inhibitors+in+experimental+stroke.+On+the+other+hand%2C+selective+inhibition+of+COX-1+with+VAS+had+no+significant+effect+on+the+evaluated+parameters.+These+data+suggest+that+COX-2+activity%2C+but+not+COX-1+activity%2C+contributes+to+the+progression+of+focal+ischemic+brain+injury%2C+and+that+the+beneficial+effects+observed+with+non-selective+COX+inhibitors+are+probably+associated+to+COX-2+rather+than+to+COX-1+inhibition.+&rft.publisher=Blackwell+Publishing&rft.contributor=Murphy%2C+Prof.+Sean&rft.contributor=Turner%2C+Prof.+Anthony&rft.date=2007-02&rft.type=Journal+(Paginated)&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.identifier=http%3A%2F%2Fcogprints.org%2F5393%2F1%2FJ_Neurochem_2007_Candelario-Jalil_et_al.pdf&rft.identifier=++Candelario-Jalil%2C+Eduardo+and+Gonzalez-Falcon%2C+Armando+and+Garcia-Cabrera%2C+Michel+and+Leon%2C+Olga+Sonia+and+Fiebich%2C+Bernd++(2007)+Post-ischaemic+treatment+with+the+cyclooxygenase-2+inhibitor+nimesulide+reduces+blood-brain+barrier+disruption+and+leukocyte+infiltration+following+transient+focal+cerebral+ischaemia+in+rats.++%5BJournal+(Paginated)%5D+++++&rft.relation=http%3A%2F%2Fcogprints.org%2F5393%2F