Neuroprotective Effects And The Underlying Mechanisms Of Oxytocin On Hypoxic-ischemic Induced Brain Injury In Neonatal Rats

Objective:Neonatal hypoxic-ischemic encephalopathy does great harm to children’s health.Since the lack of effective curative therapy,neonatal mortality and severe morbidity caused by NHIE is still high.So it’s high time to seek for new therapeutic strategies for NHIE.It has been reported that an endogenous neuropeptide,oxytocin(OT),is able to protect hippocampal neuronal function in adult rats against cerebral ischemia,however,to date,the effect of oxytocin on hippocampal neurons of neonatal rats still remains unknown.Here we investigate whether this peptide also has neuroprotective effects on hypoxic-ischemic brain injury in neonatal rats and uncover the underlying mechanisms.Methods:First of all,acute hippocampal slices(350μm thick)obtained from 54neonatal rats(7-10-day old)were used.Then,animal models of hypoxic-ischemic brain injury were made by using oxygen-glucose deprivation solution(OGD).After that,the effect of oxytocin on OGD-induced hippocampal CA1 neuronal death by TOPRO-3 staining.And,the onset time of anoxic depolarization recorded from CA1pyramidal neurons by using whole-cell patch-clamp technique.Also,the effect of oxytocin on inhibitory postsynaptic currents(IPSCs)and excitatory postsynaptic currents(EPSCs)were also studied by using whole-cell patch-clamp technique.Results:1.OT largely reduced OGD-induced hippocampal CA1 neuronal death in stratum pyramidale.2.OT significantly delayed the onset time of anoxic depolarization recorded in CA1 pyramidal neurons.This effect of OT was blocked by either dVOT(OT receptor antagonist)or bicuculline(GABA_A receptor antagonist).3.OT increased both the frequency and amplitude of spontaneous IPSCs in CA1pyramidal neurons which is neuronal activity-dependent and fully abolished by dVOT.4.OT did not alter the excitatory neurotransmission in pyramidal neurons.Instead,OT induced an inward current in 86%of the pyramidal neurons tested.Conclusions:These findings reveal a neuroprotective role of OT in neonatal hippocampal CA1 neurons following hypoxic-ischemic injury,likely by enhancing the inhibitory neurotransmission through OT receptors.