Effects of glutamate receptor antagonists and protein synthesis inhibitor on delayed neuronal death induced by transient global ischemia in rat brain

It has been well documented that transient forebrain global ischemia causes selective neuronal degeneration in hippocampal CA1 pyramidal neurons with a delay of a few days. The mechanism of this delayed hippocampal CA1 pyramidal neuronal death (DND) is still controversial. To delineate the mechanisms of the DND, the effects of treatment with MK-801, an NMDA receptor antagonist, kynurenic acid, a NMDA/non-NMDA receptor antagonist, and/or cycloheximide, a protein synthesis inhibitor, on the DND were investigated in male Wistar rats. To examine the participation of apoptotic neuronal death in the DND, TUNEL staining was performed in ischemic brain section. Global ischemia was induced by 4-vessel occlusion for 20 min. All animals in this study showed the DND 3 and 7 days after the ischemic insult. The DND that occurred 3 days and 7 days after the ischemia were not affected by pretreatment with MK-801 (I mg/kg), but markedly attenuated by the pretreatment with kynurenic acid (500 mg/kg). Treatment with cycloheximide (1 mg/kg) also markedly inhibited the DND. The magnitudes of attenuation by the two drugs were similar. The magnitude of attenuation by co-treatments with kynurenic acid and cycloheximide was not greater than that with any single treatment. TUNEL staining was negative in the sections obtained 1 or 2 days after the ischemic insults, but it was positive at hippocampal CA1 pyramidal cells in sections collected 3 days after the ischemia. These results suggested that the DND should be mediated by the activation of non-NMDA receptor, not by the activation of NMDA receptor and that the activation of AMPA receptor should induce the apoptotic process in the DND.

Study on Contractile Responses Induced by Anoxia in Porcine Cerebral Artery

This study was designed to observe anoxia-induced responses and to clarify their possible mechanisms in porcine basilar and circle of Willis arteries. Anoxia produced a transient vasoconstriction, which then recovered to the basal tension of a 3-5 min. later, and the reoxygenation that follows produced the biphasic(relaxation-contraction) response in the intact endothelial rings under resting tension. The anoxia-induced contraction was potentiated by pretreatment with KC1 and PGF2alpha. Reoxygenation produced only sustained relaxation. Removal of the endothelium and pretreatment with nimodipine or indomethacine markedly attenuated the anoxia-induced contractions. Anoxia transiently and significantly increased cyclic GMP contents in the endothelium-intact preparations, but did not affect them in the endothelium-removed ones. The above results suggest that anoxia-induced contraction is endothelium-dependent and is resultant to the release of a Prostaglandin-like substance(s) .