Cerebral Endothelial Nitric Oxide Synthase Expression After Focal Cerebral Ischemia in Rats

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Abstract

Background and Purpose

The purpose of this study was to measure the temporal profile of expression of the endothelial nitric oxide synthase (NOS) in cerebral microvessels after middle cerebral artery occlusion in the rat.

Methods

Middle cerebral artery occlusion was performed on 24 male Wistar rats by extracranial insertion of a 4-0 nylon monofilament into the internal artery. Three additional rats were used as controls. Animals were killed at 1, 2, 4, 6, 24, 48, 72, and 168 hours after middle cerebral artery occlusion (n=3 per time point). Rat brains were perfused with buffer, frozen, sectioned, and stained with a monoclonal antibody against endothelial NOS. Adjacent sections were stained with hematoxylin and eosin for evaluation of neuronal damage.

Results

The endothelial NOS in the cerebral vessels was upregulated at 1 hour after induction of ischemia throughout the ischemic region. The induction of the endothelial NOS progressively increased up to 24 hours of ischemia. In the periphery of the area of necrosis in the cortex, a delayed (24-hour) upregulation of the endothelial NOS remained constant throughout the duration of ischemia.

Conclusions

The rapid and intense differential expression of the endothelial NOS in the core and peripheral areas of the lesion indicates a role for endothelial NOS in ischemic cell damage and suggests that the increased expression of NOS may mediate changes in the cerebral blood flow.

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