Forebrain ischemia-induced nitric oxide synthase (iNOS) induction, neuronal apoptosis and drug action in rats

We examined the induction of nitric oxide synthase (iNOS) mRNA and neuronal death after forebrain ischemia by 4 vessel occlusion in rat hippocampus. In addition, we tried to characterize whether or not the delayed neuronal cell death is apoptosis or necrosis by means of TUNEL method and staining of chromatin dye, Hoechst 33258. Nuclei of the CA 1 pyramidal neurons were positive to TUNEL after ischemic insult, but not at the preceding stage. These results suggest that the delayed neuronal death following forebrain ischemia is apoptosis. Moreover, induction of iNOS mRNA was detected 3 days after ischemic insult in hippocampus. It seems to be a close causality between he neuronal death following transient ischemia and iNOS/NO in the hippocampus. We then found that herbimycin A, a potent tyrosine kinase inhibitor, and aspirin inhibited LPS/IFN-γ-induced iNOS induction in C6 glioma cells. It is interesting to examine whether or not both drugs inhibit brain ischemia-induced neuronal apoptosis. We presented and discussed the mechanism of NO-induced apoptosis using NG 10815 cells too.