Protective effect of nimodipine against ischemic neuronal damage in rat hippocampus without changing postischemic cerebral blood flow.
The purpose of the present study was to investigate the neuroprotective action of nimodipine. Furthermore, the influence of nimodipine on postischemic local CBF (LCBF) was examined. Forebrain ischemia of the rat was performed for 10 min by bilateral carotid clamping, administration of trimethaphan, and blood withdrawal to obtain an MABP of 40 mm Hg. LCBF was measured after 10 min of postischemic recirculation by injecting [14C]iodoantipyrine in saline solution. Nimodipine (0.1, 0.3, and 1.0 mg/kg) was suspended in miglyol oil and applied orally 60 min prior to ischemia. Histological evaluation was performed 7 days after ischemia. Hippocampal neuronal damage was determined as the percentage of necrotic neurons. After preischemic application of nimodipine, neuronal damage was significantly reduced in the hippocampal CA1 subfield. Postischemic LCBF was not affected by treatment with nimodipine. These findings show that nimodipine is able to protect neurons against ischemic damage. The neuroprotective effect of nimodipine was not mediated by a postischemic cerebral vasodilation, but by a direct action on the neurons.
Nuglisch
J
J
Institut für Pharmakologie und Toxikologie, Philipps-Universität, Marburg, F.R.G.
Karkoutly
C
C
Mennel
H D
HD
Rossberg
C
C
Krieglstein
J
J
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D002560:Cerebrovascular Circulation; D006624:Hippocampus / Q000473:pathology*; D008297:Male; D009336:Necrosis; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats
D009553:Nimodipine