The neuroprotective effects of dextromethorphan on guinea pig-derived hippocampal slices during hypoxia

Abstract

The purpose of this study was to determine whether dextromethorphan, an opioid class antitussive, prevents hypoxia-induced loss of nerve function in an in vitro hippocampal slice preparation. The evoked population spike (PS) was recorded from CA1 pyramidal cells of guinea pig-derived hippocampal slices. Hippocampal slices were superfused with O 2 (95%) CO 2 (5%) gassed artificial cerebral spinal fluid (ACSF) at 37°C. The PS did not recover during reoxygenation in slices that were made hypoxic for 30 min by exposure to N 2 (95%) CO 2 (5%) gassed ACSF in place of oxygenated ACSF. The PS recovered during reoxygenation, following 30 min of hypoxia, in 9 of 10 slices treated with dextromethorphan (100 μM) and in 4 of 6 slices treated with d,l-2-amino-5-phosphono-valerate (AP-5) (100 μM), an NMDA receptor antagonist. The mean PS amplitudes, one hour after perfusion with oxygenated ACSF, were 42% and 51%, respectively, of the pre-hypoxia amplitude. The PS recovered during reoxygenation in all of seven slices superfused with lowered temperature ACSF (25°C) during 30 min of hypoxia. The results show that dextromethorphan, like the NMDA antagonist AP-5 and lowered temperature, protected neurons from hypoxia-induced injury in the hippocampus.