抄録
The time course of changes in activity of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), a marker for nitric oxide (NO) synthase, was studied histochemically in the rat cerebral cortex after focal Ischemia induced by middle cerebral artery occlusion. In the cerebral cortex of sham-operated animals, NADPH-d activity was present mostly in scattered, isolated cells that resembled medium-to-large neurons. Granular cells of the cerebral cortex showed abundant NADPH-d activity, but few pyramidal cells of layers III or V were stained. Most NADPH-d-positive neurons were located in the white matter immediately below the cerebral cortex; only a small number of NADPH-d-positive cells were detected in the superficial layers. Most of the heavily stained neurons were located in the proximity of blood vessels; in some instances, cell bodies were apposed to the vascular profiles and their processes encircled the vessel walls. NADPH-d activity was not detected in vascular endothelial cells in the cerebral cortex of sham-operated rats. After 5 min of Ischemia, the number of NADPH-d-positive neurons was increased markedly in the parietal cortex. After 60 min of Ischemia, the number of NADPH-d-positive neurons in the parietal cortex had decreased to below that detected in sham-operated animals; however, the number of stained neurons in the piriform and cingulate cortex was increased. NADPH-d-positive endothelial cells were detected in small vessels and capillaries in all layers of the parietal cortex after 5 min of Ischemia. NADPH-d activity in endothelial cells had decreased to almost basal levels after 60 min of ischemia. Pretreatment animals with N-nitro-L-arginine methyl ester (a NO synthase inhibitor) or MK-801 (a N-methyl-D-asparate-sensitive glutamate receptor antagonist) markedly inhibited the ische-mia-induced increase in NADPH-d activity in both neurons and endothelial cells. These results suggest that NO synthesized by neurons or endothelial cells contributes to the regulation of cerebral blood flow. Moreover, glutamate may be an important determinant of NO synthase expression after focal cerebral ischemia.
