Local nimodipine application improves early functional recovery in the rabbit hippocampus after 15-min global cerebral ischemia.
Microdialysis was used to apply 10 microM nimodipine to the hippocampus of rabbits submitted to 15-min global cerebral ischemia. Analysis of dialysate allowed determination of changes in extracellular fluid concentrations of calcium (Ca2+e) and amino acids and in blood-brain barrier (BBB) permeability to fluorescein. General physiological parameters and EEG were recorded throughout the experiments, and morphological changes in the hippocampus 3 h following ischemia were evaluated. Ischemia caused rapid disappearance of EEG activity, a decrease of Ca2+e, and a release of neuroactive amino acids. Enhanced BBB permeability to fluorescein and early morphological changes in hippocampal pyramidal neurones were noted. Intrahippocampal nimodipine infusion only slightly reduced the decrease of Ca2+e and did not change amino acid release and BBB permeability after ischemia. However, nimodipine accelerated reappearance of hippocampal EEG activity and improved its pattern. A reduction of morphological changes of hippocampal pyramidal neurones in the vicinity of the dialysis probe was noted in the nimodipine-treated group. These results suggest that nimodipine-sensitive L channels do not play a critical role in ischemia-evoked Ca2+ redistribution in the rabbit hippocampus. It seems that a portion of the direct neuroprotective action of nimodipine may not be related to the inhibition of calcium influx into neurones.
Lazarewicz
J W
JW
Department of Neurochemistry, Polish Academy of Sciences, Warsaw.
Pluta
R
R
Puka
M
M
Salińska
E
E
D000287:Administration, Topical; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D017551:Microdialysis; D009553:Nimodipine / Q000008:administration & dosage* / Q000627:therapeutic use; D011817:Rabbits
D009553:Nimodipine