Hypoglycaemic brain damage: effect of a dihydropyridine calcium channel antagonist in rats.
Hypoglycaemic brain damage consists of selective necrosis of cerebral neurons related to the extracellular release of excitatory amino acids. Neuronal excitatory amino acid receptors are activated and calcium channels are opened. The present investigation was designed to test the effectiveness of dihydropyridine blockade of voltage-sensitive calcium channels in hypoglycaemic brain damage. Sixty-four rats were given either high-dose nimodipine, consisting of an initial bolus of 300 micrograms/kg nimodipine administered at the stage of EEG slowing (blood glucose levels of 1.0-1.5 mmol/l), followed by continuous intravenous nimodipine infusion at 1.5 micrograms.kg-1.min-1, low-dose nimodipine, consisting of an initial bolus of 30 micrograms/kg at the time of EEG slowing, followed by 0.15 microgram.kg-1.min-1, an equal volume of vehicle solution, or 154 mmol/l NaCl. Animals receiving either low- or high-dose nimodipine had higher mortality, and increased brain damage compared with controls. Examination of the perfusion-fixed brains 1 week after recovery with glucose revealed that quantitated neuronal necrosis was worsened by nimodipine in the hippocampus, caudate nucleus and cerebral cortex. The present results in profound hypoglycaemia (accompanied by a flat EEG) contrast with the beneficial effect of nimodipine in brain ischaemia.
Auer
R N
RN
Department of Pathology, University of Calgary, Alberta, Canada.
Anderson
L G
LG
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001831:Body Temperature; D001925:Brain Damage, Chronic / Q000209:etiology / Q000503:physiopathology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004569:Electroencephalography / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D007003:Hypoglycemia / Q000150:complications / Q000503:physiopathology*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007328:Insulin; D008297:Male; D009336:Necrosis; D009553:Nimodipine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007328:Insulin; D009553:Nimodipine