Beneficial effect of nimodipine on metabolic and functional disturbances in rabbit hippocampus following complete cerebral ischemia.
We investigated the effects of intravenous application of nimodipine on the neurophysiologic, biochemical, and morphologic consequences of 15 minutes of global cerebral ischemia in seven rabbits. In vivo dialysis of the hippocampus was used to determine changes in extracellular concentrations of extracellular calcium and amino acids and blood-brain barrier permeability. Ischemia without treatment produced a rapid disappearance of electroencephalographic activity, a decrease in the concentration of extracellular calcium, the release of neuroactive amino acids, and leakage of methionine to the tissue fluid, plus a significant increase of the blood-brain barrier permeability to fluorescein. Except for permeability and electroencephalographic activity, these parameters normalized during 45 minutes of recirculation; permeability and activity failed to normalize completely during 3 hours of recirculation. After 3 hours of recirculation, morphologic changes in the CA1 hippocampal area were observed. Treatment with nimodipine significantly enhanced electroencephalographic activity recovery and normalization during recirculation, reduced the decrease in extracellular calcium concentration, and prevented the increased permeability of the blood-brain barrier. Nimodipine protected the CA1 area from early morphologic changes and reduced leakage of methionine from brain cells. The beneficial cytoprotective effect of nimodipine, probably related to normalization of calcium homeostasis and blood-brain barrier permeability after ischemia, may reflect both vascular and cellular sites of action.
Lazarewicz
J W
JW
Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Warsaw.
Pluta
R
R
Salinska
E
E
Puka
M
M
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D004569:Electroencephalography; D019793:Fluorescein; D005452:Fluoresceins; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology; D009553:Nimodipine / Q000494:pharmacology*; D009994:Osmolar Concentration; D011817:Rabbits; D013997:Time Factors
D000596:Amino Acids; D005452:Fluoresceins; D009553:Nimodipine; D002118:Calcium; D019793:Fluorescein