Neuroprotective Effect Of PKR Phosphorylation Inhibitor C16 In Neonatal Hypoxia-ischemia Encephalopathy

Objective: Neonatal hypoxic ischemic encephalopathy(HIE)is the disease caused by asphyxia of perinatal period leading to cerebral hypoxia ischemia injury.PKR(double-stranded-RNA-dependent protein kinase)is a serine/threonine kinase associated with inflammation,apoptosis and autophagy.So we explored whether PKR was participated in the pathologic processes of HIE,and if C16-inhibitor of PKR phosphorylation,could exhibit the neuroprotective effect in the neonatal hypoxia-ischemia encephalopathy.Methods: Seven-day-old Sprague-Dawley rats were randomly devided into three groups(n=6): Control,HIE model,C16 treatment.TTC stain for infarction area and TUNEL stain for apoptosis cell were assayed 24 hours after the brain hypoxia.Western blot was performed to quantify the expression of the PKR,p-PKR at 0h,3h,6h,12 h,24h and NF-?B,p-NF-?B at 12 h after hypoxia exposure.The Gene expression of IL-1?,IL-6 and TNF-?was performed at 0h,3h,6h,12 h and 24 h.Data was shown in (?)±s,one-way ANOVA was performed in analysis.Results:1)The p-PKR/PKR Ratios of HIE group were raised from 0h,and reached the peak value at 3h,then reversed to the basal line at 24 h.2)C16 post-treatment markedly reduced the activation of PKR,accompanied with the decrease of infarct volume.3)Gene expression of cytokine(TNF-?,IL-6 and IL-1?)evidently increased in HIE group,which could be reduced by C16.4)The ratio of p-NF-?B/NF-?B in HIE group is the most evidently increased,and C16 attenuated phosphorylation of NF-?B induced by hypoxia-ischemia insult.Conclusion: Phosphorylation of PKR takes important role in pathologic process of HIE.C16,inhibitor of PKR activation,displays neuroprotection effect in neonatal HIE rats,which might achieved through PKR/NF-?B signaling pathway by anti-neuroinflammation reactions.