Use of brain slices in the study of pathogenic role of inducible nitric oxide synthase in cerebral ischemia-reperfusion

We have recently demonstrated that inducible nitric oxide synthase (iNOS) i s expressed in rat forebrain slices exposed to oxygen and glucose deprivati on (OGD). Now, we have found that the expression of iNOS after OGD is time- dependent since 20 min of OGD produces the appearance of iNOS at earlier ti mes than 10 min of OGD. OGD also causes neurotoxicity in this model, as rev ealed by the increase in excitatory amino acid, neuron specific enolase and lactate dehydrogenase (LDH) efflux to the incubation solution. Finally, th e administration of the NMDA receptor antagonist MK-801 (100 nM) inhibits b oth the expression of iNOS and the release of LDH. Our findings demonstrate that this method may be considered an useful in vitro model of ischemia-re perfusion to determine the therapeutic role of neuroprotective tools. (C) 1 999 Elsevier Science Inc. All rights reserved.