Role of oxytocin in neonatal rat hippocampal neurons after hypoxic-ischemic injury

AIM: To investigate whether oxytocin has neuroprotective effects on hippocampal CA1 pyramidal neurons from neonatal rats exposed to hypoxic-ischemic brain injury and the underlying mechanisms. METHODS: An in vitro model of hypoxic-ischemic injury was used by exposing the brain slices to oxygen-glucose deprivation (OGD) solution. Acute dissociated brain slices (6~8 slices per rat) from 8 Sprague-Dawely rats of 7~10 d old were used. The slices were randomly divided into 4 groups:control group, OGD 20 min group, OGD 40 min group and OGD+oxytocin group. The effect of oxytocin on neuronal death was evaluated by TO-PRO-3 staining. Fresh brain slices from other 20 neonatal rats were divided into OGD group, OGD+oxytocin group, OGD+dVOT (oxytocin receptor antagonist)+oxytocin group, and OGD+bicucuclline (GABA_A receptor antagonist)+oxytocin group. The onset of anoxic depolarization in the hippocampal neurons treated with different drugs was recorded by whole-cell patch-clamp techniques. RESULTS: The results of TO-PRO-3 staining showed that neuronal deaths in hippocampal CA1 area were increased over the prolonged OGD time. Oxytocin significantly reduced the hypoxic-ischemic deaths. Oxytocin dramatically prolonged the onset time of anoxic depolarization after the application of OGD solution. Both dVOT and bicuculline blocked this effect. CONCLUSION: Oxytocin plays a neuroprotective role in neonatal rat hippocampal CA1 pyramidal neurons by enhancing the inhibitory synaptic transmission via oxytocin receptors. Therefore, oxytocin is useful as a candidate for neuroprotective treatment after neonatal hypoxic-ischemic brain injury.