METHYLCOBALAMIN ATTENUATES THE HYPOXIA HYPOGLYCEMIA-INDUCED OR GLUTAMATE-INDUCED REDUCTION IN HIPPOCAMPAL FIBER SPIKES IN-VITRO/

The effects of methylcobalamin, a vitamin B-12 analogue, on the hypoxi a/hypoglycemia- or glutamate-induced reduction in hippocampal CA1 pres ynaptic fiber spikes elicited by Schaffer collateral stimulation in ra t brain slices were evaluated. Hippocampal slices were exposed to 15 m in of hypoxia/hypoglycemia, and then these slices were returned to oxy genated and glucose-containing buffer for 3 h. Hypoxia/hypoglycemia re duced CA1 presynaptic potentials in vitro. Treatment with 10 mu M meth ylcobalamin attenuated the impairment of CA1 presynaptic potentials in duced by hypoxia/hypoglycemia or glutamate application (10 mM). Daily injection of methylcobalamin (0.5 mg/kg i.p./day) for 3 days in vivo a lso attenuated the hypoxia/hypoglycemia- or glutamate-induced reductio n in presynaptic potentials in hippocampal slices. Pretreatment with c yanocobalamin at 10 mu M failed to attenuate the impairment of CA1 pre synaptic potentials. However, daily injection of cyanocobalamin (0.5 m g/kg i.p./day) for 3 days caused a protective action against the hypox ia/hypoglycemia- or glutamate-induced functional deficit. Furthermore, co-treatment of L-arginine (100 mu M), a substrate for nitric oxide s ynthase, with methylcobalamin in vitro reversed the methylcobalamin-in duced functional recovery. The present results demonstrate that methyl cobalamin application in vivo or in vitro leads to functional recovery from hypoxia/hypoglycemia- or glutamate-induced impairment of CA1 pre synaptic potentials. Neuroprotection was obtained by in vivo applicati on of cyanocobalamin, but not by its in vitro application. It is repor ted that in vivo injected cyanocobalamin converted to methylcobalamin in the hepatic cells. Therefore, the results suggest that a transmethy lation reaction in the hippocampal regions may be involved in the meth ylcobalamin-induced functional recovery from ischemic impairment.