A potent AMPA/kainate receptor antagonist, YM90K, attenuates the loss of N-acetylaspartate in the hippocampal CA1 area after transient unilateral forebrain ischemia in gerbils.
By analyzing histological damages and the regional N-acetylaspartate (NAA) level simultaneously, we evaluated the effect of an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor antagonist, YM90K [6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione monohydrochloride], in unilateral forebrain ischemia in gerbils. The right common carotid artery was clipped for 5 min under ether anesthesia, and reperfused for 7 days. The frozen brain sections were lyophilized and the hippocampal CA1 area was dissected out for HPLC assay of NAA. An adjacent section was stained with hematoxylin-eosin for counting survived neurons per 1 mm pyramidal layer of the hippocampal CA1 area. Postischemic administration of YM90K at 20 mg/kg and 25 mg/kg attenuated the decrease of both the number of survived neurons and the NAA level on the ischemic side in a dose-dependent manner. A significant linear correlation was observed between the NAA level and the number of intact neurons. These results indicated that the NAA level could be used as an index of neuroprotective effects of pharmacological agents in global cerebral ischemia.
Nakano
M
M
Department of Neurology, Osaka University Graduate School of Medicine, Suita, Japan.
Ueda
H
H
Li
J Y
JY
Matsumoto
M
M
Yanagihara
T
T
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016548:Prosencephalon / Q000378:metabolism / Q000473:pathology*; D011810:Quinoxalines / Q000494:pharmacology*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors*
D001224:Aspartic Acid; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; C086162:6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione; C000179:N-acetylaspartate