Regional difference in nitric oxide production during forebrain ischemia

The hippocampus has been shown to exhibit particular vulnerability to ischemia, suggesting the existence of inherent processes leading to neuronal death. Nitric oxide (NO) has been implicated in neurotoxicity due to ischemia. The relationship between regional distribution of NO synthesis induced by ischemia and the areas vulnerable to ischemia remains elusive. In the present study, we explored regional variation in NO synthesis by determining the concentrations of nitrite (NO^-₇), a major metabolite of NO, in the brain in vivo microdialysis samples obtained from the hippocampus and the striatum subjected to ischemia. Sprague-Dawley rats were anesthetized with pentobarbital (40 mg/kg, i.p.). An in vivo microdialysis probe was implanted into the hippocampus or the striatum. Subsequently, the animals were subjected to forebrain ischemia for 20 min by occlusion of both common carotid arteries and induced hypotension. Forebrain ischemia gave rise to a significant change in NO^-₂ level only in the hippocampus, resulting in an increase to 111.2 ± 5.4 (mean ± SEM) % of the preischemia level. This finding suggests the presence of a regional difference in NO production during ischemia, which may be concerned with the underlying mechanism of ischemic vulnerability.