SODIUM-CHANNEL MODULATORS PREVENT OXYGEN AND GLUCOSE DEPRIVATION INJURY AND GLUTAMATE RELEASE IN RAT NEOCORTICAL CULTURES

Neocortical cultures were deprived of oxygen and glucose to model isch emic neuronal injury. We used a graded series of periods of oxygen and glucose deprivation, providing graded insults. Cell death was measure d by release of lactate dehydrogenase (LDH). One hundred and twenty to 240 min of deprivation caused graded increases in glutamate overflow, LDH release and Ca-45 influx. Curves of LDH release with respect to d eprivation time were shifted to longer intervals by treatment with tet rodotoxin (TTX; 3, 30 or 300 nM), phenytoin (10, 30 or 100 mu M), lido caine (10, 30 or 100 mu M) or the N-methyl-D-aspartate antagonist CPP [3(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid, 3, 10, 30 or 100 mu M]. Combined treatment with TTX and CPP caused pronounced rightwar d shifts of LDH deprivation curves. Our results indicate that Na+ chan nel blockade is neuroprotective in neocortex cultures. Our results als o suggest that neuroprotection with Na+ channel blockers may be due to inhibition of glutamate release. (C) 1997 Published by Elsevier Scien ce Ltd.