Expression of endothelial nitric oxide synthase in the ischemic penumbra: relationship to expression of neuronal nitric oxide synthase and vascular endothelial growth factor

Expressional patterns of the endothelial and neuronal forms of nitric oxide synthase (NOS) in cerebral ischemia were studied utilizing a permanent mid dle cerebral artery occlusion (PMCAO) model. Motor performance and infarct volumes were determined in the rats. Immunohistochemical staining for eNOS, nNOS and neurofilament were performed at 1, 2, 3, 5, 7 and 14 days after P MCAO. Vascular endothelial growth factor (VEGF) expression was determined b y in-situ hybridization. PMCAO caused a reproducible cortical infarct with motor deficits in the rats. Double immunohistochemical stainings indicated that eNOS and nNOS were induced in ischemic neurons. Most stained neurons w ere positive for both NOS forms but some reacted with only one NOS antibody . nNOS expression peaked at 24-48 h after PMCAO, stained mainly the cytopla sm of core neurons, and disappeared after the 3rd day. eNOS expression incr eased until the 7th day, stained mainly the cytoplasm and membrane of penum bral cells and disappeared by the 14th day after PMCAO. VEGF expression was significantly induced in the penumbral zone in a similar distribution to e NOS. The anatomical and temporal pattern of VEGF and eNOS induction in the brain after permanent ischemia suggest that these mediators may play a role in protecting penumbral tissue from additional ischemic damage. (C) 2001 E lsevier Science B.V. All rights reserved.