Calcium entry blocker ameliorates ischemic neuronal damage in monkey hippocampus.
Effects of treatment with (+/-)-1-(3,4-dimethoxyphenyl)-2-(4- diphenylmethylpiperazinyl)ethanol dihydrochloride (NC-1100), a calcium entry blocker, on ischemic neuronal damage were investigated. Monkeys were subjected to temporary occlusion of eight (bilateral common carotid, internal and external carotid, and vertebral arteries) major arteries. Blood flow was restored after 5, 10, 13, and 15 min occlusion, and NC-1100 (1 mg/kg) was then immediately infused intravenously. Monkeys were killed by perfusion fixation 5 days after occlusion. All brain regions were then histologically investigated for ischemic neuronal changes. Physiological data of NC-1100-treated subjects were not significantly different than those of untreated subjects. Heart rate tended to decrease after ischemia in treated subjects. Occlusion of 8 arteries for 10 to 15 min produced ischemic neuronal damage confined exclusively to the CA1 subfield of the hippocampus. Treatment with NC-1100 markedly reduced ischemic neuronal damage in the CA1 subfield of the hippocampus. It is suggested that postischemic treatment with the calcium entry blocker, NC-1100, might protect the brain from the ischemic damage produced in patients suffering from transient ischemia.
Nishijo
H
H
Department of Physiology, Toyama Medical and Pharmaceutical University, Japan.
Kuze
S
S
Ono
T
T
Tabuchi
E
E
Endo
S
S
Kogure
K
K
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000378:metabolism; D004569:Electroencephalography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008251:Macaca; D009474:Neurons / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001786:Blood Glucose; D002121:Calcium Channel Blockers; D010879:Piperazines; D014665:Vasodilator Agents; C050134:tamolarizine; D002245:Carbon Dioxide