HYPOGLYCEMIC 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 c hannels are opened. The present investigation was designed to test the effectiveness of dihydropyridine blockade of voltage-sensitive calciu m channels in hypoglycaemic brain damage. Sixty-four rats were given e ither high-dose nimodipine, consisting of an initial bolus of 300 mu g /kg nimodipine administered at the stage of EEG slowing (blood glucose levels of 1.0-1.5 mmol/l), followed by continuous intravenous nimodip ine infusion at 1.5 mu g . kg(-1). min(-1), low-dose nimodipine, consi sting of an initial bolus of 30 mu g/kg at the time of EEG slowing, fo llowed by 0.15 mu g . kg(-1). min(-1), an equal volume of vehicle solu tion, or 154 mmol/l NaCl. Animals receiving either low- or high-dose n imodipine had higher mortality, and increased brain damage compared wi th controls. Examination of the perfusion-fixed brains 1 week after re covery with glucose revealed that quantitated neuronal necrosis was wo rsened 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.