Melatonin Promotes Neuroprotective Effects Of Microglia In HIE

Introduction:The benefits of melatonin in improving the recovery of hypoxic-ischemic perinatal brain damage(HIBD)have been well documented,mediated via its anti-oxidant,anti-apoptotic,and anti-inflammatory properties.Nevertheless,the effects of melatonin in the inter-regulation between inflammatory,oxidative and ER stress,as well as how this inter-regulation affects the crosstalk between activated microglia and injured neurons remain unclear.Methods and Results:Our study demonstrated that in the acute phase of HIBD,melatonin exhibited a therapeutic role not only by directly improving the resistance of neurons to HI,but also by reducing the second injury exerted by microglia activation.Specifically,melatonin converted microglia from neurotoxic into neuro-protective based on the analyses of secretion and phagocytosis.By restricting the infiltration of proinflammatory mediators,melatonin decreased levels of ER stress,oxidative response and neuronal apoptosis.Most interestingly,despite of executioner caspase activation,some neurons exited the apoptotic process and underwent anastasis.The scope of ischemic penumbra,which the above reactions converged inwas significantly narrowed.Discussion:By inhibiting deterioration of the penumbra tissues,melatonin reduced the expansion of ischemic infarction,which would certainly delay the progression of HIE and effectively prolong the time window for clinical treatment of HIE.