Title: Nitric Oxide Production during Cerebral Ischemia and Reperfusion in eNOS- and nNOS-Knockout Mice
Volume: 7
Issue: 1
Author(s): Yasuo Ito, Takeshi Ohkubo, Yoshio Asano, Kimihiko Hattori, Tomokazu Shimazu, Masamizu Yamazato, Harumitsu Nagoya, Yuji Kato and Nobuo Araki
Affiliation:
Keywords:
Nitric oxide (NO), endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), microdialysis, global ischemia, CA1 neuron
Abstract: The purpose of this study was to clarify the kinetics of nitric oxide (NO) induced by either endothelial NO synthase (eNOS) or neuronal NO synthase (nNOS) after transient global forebrain ischemia. We investigated NO production and ischemic changes to hippocampal CA1 neurons in eNOS knockout (-/-) mice and nNOS (-/-) mice during cerebral ischemia and reperfusion. NO production was continuously monitored by in vivo microdialysis. Global forebrain ischemia was produced by occlusion of both common carotid arteries for 10 minutes. Levels of nitrite (NO2-) and nitrate (NO3-), as NO metabolites, in dialysate were determined using the Griess reaction. Two hours after the start of reperfusion, animals were perfused with 4% paraformaldehyde. Hippocampal CA1 neurons were divided into three phases (severely ischemic, moderately ischemic, surviving), and the ratio of surviving neurons to degenerated neurons was calculated as the survival rate. The relative cerebral blood flow (rCBF) was significantly higher in nNOS (-/-) mice than in control mice after reperfusion. Levels of NO3- were significantly lower in eNOS (-/-) mice and nNOS (-/-) mice than in control mice during ischemia and reperfusion. NO3- levels were significantly lower in nNOS (-/-) mice than in eNOS (-/-) mice after the start of reperfusion. Survival rate tended to be higher in nNOS (-/-) mice than in control mice, but not significantly. These in vivo data suggest that NO production in the striatum after reperfusion is closely related to activities of both nNOS and eNOS, and is mainly related to nNOS following reperfusion. Theme: Disorders of the nervous system. Topic: Ischemia.
