Inhibition of neuronal nitric oxide synthase improves microregional O₂balance 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 O 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 O saturations (20-60 μm in diameter) using cryomicrospectrophotometry were determined. Results Ischaemia-reperfusion decreased the average venular O saturation and the ratio of O supply/consumption. But, 7-NI treatment improved the average O supply/consumption ratio and venular O saturation (57.6 ± 1.3 vs 52.0 ± 3.8%) in ischaemia-reperfusion. The heterogeneity of venular O 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 O 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 O balance in the ischaemic-reperfused cortex (IR-C). The improvement in microregional O balance could be one of the contributing factors to the reduced size of cortical infarct.

Antioxidant-Based Therapy Reduces Early-Stage Intestinal Ischemia-Reperfusion Injury in Rats

“…Regarding the use of nitroindazole in reperfusion injury, most studies have been performed in experimental models of cerebral ischemia. It has been shown that various markers of damage due to oxidative stress, such as MDA, glutathione (GSH) or lipid peroxidation, are greatly reduced with nitroindazole, and reached levels close to those of control groups [27,40,41]. It has been proposed that the prophylactic effect of this compound involves more than its action as an NOS inhibitor, since it is also involved in other enzymatic pathways.…”

Genetic Deletion of PGF2α-FP Receptor Exacerbates Brain Injury Following Experimental Intracerebral Hemorrhage

“…Anisomorphic astrogliosis can inhibit neurite outgrowth and increase levels of the inducible form of nitric oxide synthase (iNOS) and nitric oxide (NO) which can possess cytotoxic properties and contribute to neuronal death (Gibbons and Dragunow, 2006 ). The elevated levels of NO released from activated astrocytes might be the most relevant in ICH-induced injury as NO is a vasodilator (Chi et al, 2015 ; Crobeddu et al, 2015 ; Munoz et al, 2015 ). Therefore, increased vasodilation could lead to greater ICH-induced secondary injury.…”