DAMAGE FROM OXYGEN AND GLUCOSE DEPRIVATION IN HIPPOCAMPAL SLICES IS PREVENTED BY TETRODOTOXIN, LIDOCAINE AND PHENYTOIN WITHOUT BLOCKADE OF ACTION-POTENTIALS

In vitro ischemia (IVI) was simulated with rat hippocampal slices in m edium lacking D-glucose, equilibrated with 95% nitrogen, 5% carbon dio xide. Within 5-8 min, synaptic potentials disappeared and a DC negativ e shift (5-15 mV) occurred. Prolonged application of 95% oxygen and D- glucose 12 min later did not allow synaptic potentials to recover. Sli ces pretreated with sodium channel blocking drugs allowed synaptic pot entials to recover after IVI. Tetrodotoxin (TTX, 100-600 nM), the anti convulsant phenytoin (5.0 to 100 mu M) and the local anesthetic lidoca ine (2.0 to 200 mu M) each delayed or prevented negative DC shifts fro m IVI. Histological examination showed that drug treatments also preve nted CA1 pyramidal cell damage from IVI. Neuroprotection occurred with out blocking synaptic potentials or presynaptic fiber volleys, suggest ing relevance for treatment of brain ischemia.