Dynamic cerebral microcirculatory changes in transient forebrain ischemia in rats: Involvement of type I nitric oxide synthase

The diameter of surface microvessels and the erythrocyte velocity and flux through intraparenchymal capillaries in the parietal cortex were measured d uring transient global cerebral ischemia and reperfusion using laser-scanni ng confocal fluorescence microscopy in anesthetized rats. The role of nitri c oxide (NO) from neurons in the microcirculatory changes was also investig ated using 7-nitro-indazole (7-NI, 25 mg/kg, TP). Wistar rats (4 per group) equipped with a closed cranial window were given fluorescein isothiocyanat e (FITC)-Dextran and FITC-labded erythrocytes intravenously to respectively visualize the microvessels and the erythrocytes in the capillaries. Experi ments were videorecorded on-line. Forebrains were made ischemic for 15 minu tes and then reperfused for 120 minutes under the microscope. Ischemia was associated with a flattened EEG, a low persistent blood flow, and a transie nt leakage of fluorescein across the arteriole wall. Unclamping the carotid arteries led to immediate high blood flow in the arterioles, but it was no t until 5 minutes later that the arterioles dilated significantly (181% +/- 27%) and erythrocyte velocity in the capillaries increased significantly ( 460% +/- 263%). Neither nonperfused capillaries nor erythrocyte capillary r ecruitment occurred. 7-Nitro-indazole significantly reduced the arteriole d ilatation and prevented the increase in erythrocyte velocity and flux throu gh capillaries in early reperfusion. 7-Nitroindazole had no influence on th e fluorescein leakage. The current study suggests a partial role for NO rel eased from neurons in the postischemic microcirculatory changes and provide s new findings on the timing of arteriole dilatation and brood-brain barrie r opening, and on erythrocyte capillary circulation in global ischemia.