title: Dynamic cerebral microcirculatory changes in transient forebrain ischemia in rats: involvement of type I nitric oxide synthase.
abstract: The diameter of surface microvessels and the erythrocyte velocity and flux through intraparenchymal capillaries in the parietal cortex were measured during transient global cerebral ischemia and reperfusion using laser-scanning confocal fluorescence microscopy in anesthetized rats. The role of nitric oxide (NO) from neurons in the microcirculatory changes was also investigated using 7-nitro-indazole (7-NI, 25 mg/kg, i.p.). Wistar rats (4 per group) equipped with a closed cranial window were given fluorescein isothiocyanate (FITC)-Dextran and FITC-labeled erythrocytes intravenously to respectively visualize the microvessels and the erythrocytes in the capillaries. Experiments were videorecorded on-line. Forebrains were made ischemic for 15 minutes and then reperfused for 120 minutes under the microscope. Ischemia was associated with a flattened EEG, a low persistent blood flow, and a transient leakage of fluorescein across the arteriole wall. Unclamping the carotid arteries led to immediate high blood flow in the arterioles, but it was not 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 recruitment occurred. 7-Nitro-indazole significantly reduced the arteriole dilatation and prevented the increase in erythrocyte velocity and flux through capillaries in early reperfusion. 7-Nitroindazole had no influence on the fluorescein leakage. The current study suggests a partial role for NO released from neurons in the postischemic microcirculatory changes and provides new findings on the timing of arteriole dilatation and blood-brain barrier opening, and on erythrocyte capillary circulation in global ischemia.
authors.affiliation: Department of Cerebrovascular Research, CNRS UPR 646, University of Paris 7, France.
authors.forename: E
authors.initials: E
authors.lastname: Pinard
authors.forename: N
authors.initials: N
authors.lastname: Engrand
authors.forename: J
authors.initials: J
authors.lastname: Seylaz
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D017536:Carotid Artery, Common; D007191:Indazoles / Q000494:pharmacology; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D018613:Microscopy, Confocal; D009474:Neurons / Q000201:enzymology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D016548:Prosencephalon / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D013525:Surgical Instruments; D013997:Time Factors; D014664:Vasodilation / Q000502:physiology
chemical_list: D007191:Indazoles; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; C080122:7-nitroindazole