Inhibition of neuronal nitric oxide synthase improves microregional O2 balance in cerebral ischemia-reperfusion.

Abstract

Objectives Return of regional cerebral blood flow (rCBF) in focal cerebral ischaemia may not ensure proper distribution of blood flow to meet metabolic demand. This study was performed to determine how inhibition of neuronal nitric oxide synthase (NOS) during ischaemia-reperfusion would affect microregional O2 supply/consumption balances and their variation. Methods Twenty minutes before middle cerebral artery (MCA) occlusion, a NOS inhibitor 7-nitroindazole (7-NI) 50 mg/kg ip (7-NI group) or vehicle (control group) was administered. At 1 hour of ischaemia and 2 hours of reperfusion, rCBF, the size of cortical infarct and arteriolar and venular O2 saturations (20-60 μm in diameter) using cryomicrospectrophotometry were determined. Results Ischaemia-reperfusion decreased the average venular O2 saturation and the ratio of O2 supply/consumption. But, 7-NI treatment improved the average O2 supply/consumption ratio and venular O2 saturation (57.6 ± 1.3 vs 52.0 ± 3.8%) in ischaemia-reperfusion. The heterogeneity of venular O2 saturations reported as coefficient of variation (CV = 100 × SD/mean) was much smaller in the 7-NI than the control group (8.8 vs 15.5). The number of veins with low O2 saturation ( < 50%) was also smaller with the 7-NI (4/70) than the control group (18/70). The size of cortical infarct was smaller with 7-NI treatment. Discussion Our data suggest that inhibition of neuronal NOS by 7-NI improved microregional O2 balance in the ischaemic-reperfused cortex (IR-C). The improvement in microregional O2 balance could be one of the contributing factors to the reduced size of cortical infarct.

• Authors: Oak Z Chi, Kang H Rah, Sylviana Barsoum, Xia Liu, Harvey R Weiss
• Journal: Neurological research (Neurol Res) Pg. (Jun 29 2015) ISSN: 1743-1328 [Electronic] England
• PMID: 26119517 (Publication Type: Journal Article)