Effects of glutamate receptor antagonists and protein synthesis inhibitor on delayed neuronal death induced by transient global ischemia in rat brain.
- Author:
Jun Seog KO
1
;
Choon Sang BAE
;
Jong Keun KIM
Author Information
1. Departments of Pharmacology, Chonnam University Medical School and Chonnam University Research Institute of Medical Sciences, Kwangju 501-190, Korea.
- Publication Type:Original Article
- Keywords:
Global cerebral ischemia;
Delayed neuronal death;
MK-801;
Kynurenic acid;
Cycloheximide;
Apoptosis
- MeSH:
Animals;
Apoptosis;
Brain*;
Cycloheximide;
Dizocilpine Maleate;
Excitatory Amino Acid Antagonists*;
Glutamic Acid*;
Humans;
In Situ Nick-End Labeling;
Ischemia*;
Kynurenic Acid;
Male;
N-Methylaspartate;
Neurons*;
Prosencephalon;
Pyramidal Cells;
Rats*;
Rats, Wistar;
Receptors, AMPA;
Receptors, Glutamate*
- From:The Korean Journal of Physiology and Pharmacology
1998;2(3):279-286
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
