N-omega-nitro-L-arginine attenuates early ischemic neuronal damage of prolonged focal cerebral ischemia and recirculation in rats

The present study aimed to examine the effects of N-omega-nitro-L-arginine (LNA) on the early ischemic neuronal damage (EIND), All the experiments were carried out under general anesthesia, maintaining the blood gases and the body temperature within the physiological ranges. The local CBF, the topographically corresponding cortical specific gravity, and the volume of EIND were determined in each rat, which was subjected to prolonged or temporary occlusion of middle cerebral artery (MCA) using our original miniclip. Significant cortical edema developed only in the brain area where the local CBF value was below 200 ml 100 g(-1) min(-1). The prolonged MCA occlusion for 1, 2, and 4 h induced a time-dependent increase in the severity of cortical edema and the volume of EIND. Removal of the clip invariably induced recirculation. Compared to that induced by 4 h prolonged ischemia, the brain damage was improved by 1 h MCA occlusion followed by 3 h recirculation, whereas it was significantly worsened by 2 h ischemia followed by 2 h recirculation. While LNA 1 mg, i.p., given two times during the experiment only partially inhibited the activity of brain nitric oxide synthase it remarkably ameliorated EIND of both prolonged ischemia and recirculation in this model. The above findings indicate the pathogenic role of nitric oxide in prolonged ischemia as well as recirculation.