Subacute but not acute generation of nitric oxide in focal cerebral ischemia

Background and Purpose-Excessive release of nitric oxide (NO) has been impl icated in the pathophysiology of neurodegeneration in ischemic stroke. We c ompared intracerebral release of indicators of NO generation at the acute a nd subacute stages of transient focal cerebral ischemia. Methods-In vivo microdialysis in the rat striatum was performed at the acut e (first hours) and subacute (after 24 or 48 hours) stages of cerebral isch emia or sham operation to monitor intracerebral release of the stable NO me tabolites nitrite and nitrate. Results-Whereas only a nonsignificant trend toward increased release of the se NO metabolites was evidenced in acute cerebral ischemia, a significant N O generation was observed subacutely, 48 hours after induction of cerebral ischemia. Aminoguanidine, a selective inhibitor of inducible NO synthase, s uppressed this delayed release of nitrite and nitrate. Conclusions-Whereas these observations do not support a major NO generation in acute cerebral ischemia, they indicate an inducible NO synthase-depende nt NO generation predominantly at the subacute phase of ischemic neurodegen eration. Therefore, NO generation may play a pathophysiological role in del ayed ischemic neurodegeneration.