Phenytoin and carbamazepine delay the initial depression of the population spike upon exposure to in vitro ischemia and promote its post-ischemic functional recovery in rat hippocampal slices

Abstract

Antiepileptic drugs have been shown to reduce the severity of neurodegeneration resulting from stroke or brain injury. In the present study, we evaluated the effects of the antiepileptic drugs phenytoin and carbamazepine on the time course of changes in the population spike (PS) during brief oxygen/glucose deprivation (OGD) in the CA1 pyramidal region of rat hippocampal slices in vitro. After introducing simulated ischemia by OGD, the PS was initially inhibited, followed by transient recovery and subsequent reinhibition again concomitantly with disappearance of the presynaptic volley (PV). The slices were then reperfused with oxygen/glucose-containing solution. Both phenytoin and carbamazepine (30 and 100 μM each) concentration-dependently delayed the initial inhibition and the time to transient recovery of the PS during OGD, thus prolonging the time until disappearance of the PV. However, they significantly promoted restoration of the PS after reperfusion. These results suggest that treatment with phenytoin and carbamazepine increases the resistance of tissue to energy deprivation, as evidenced by the facilitated post-ischemic recovery of the PS, despite prolonged ischemia.