NP-2 GSK-3βInhibitor Reduced Neonatal Hypoxic-Ischemic Brain Injury in Mice

NP-2 GSK-3βInhibitor Reduced Neonatal Hypoxic-Ischemic Brain Injury in Mice

FENG Zhong-ping

【期刊名称】《《神经药理学报》》 【年(卷),期】2018(008)004

【摘要】Hypoxia-ischemia is an important cause of brain injury and neurological morbidity in the newborn infants.Glycogen synthase kinase 3β(GSK-3β)is

activated

and

upregulated

following

hypoxic-

ischemic(HI)brain injury.We have investigated the effects of GSK-3βinhibitors,Tideglusib and TDZD-8,on HI brain injury in neonatal mice.Specifically,postnatal day 7(P7)mouse pups subjected to unilateral common carotid artery ligation followed by 1 h of hypoxia.HI experimental or sham control groups were administered either the GSK-3βinhibitor or vehicle intraperitoneally 20 min prior to the onset of ischemia.The brain infarct volume and whole brain images were used in conjunction with Nissl staining to evaluate the protective effects of GSK-3βinhibitors.Either tideglusib or TDZD-8 significantly reduced cerebral infarct volume and improved neurobehavioral outcomes following HI injury.Western

blotting

showed

that

either

drug

increased

phosphorylated GSK-3βand Akt,and reduced the expression of GFAP and p-STAT3.Pretreatment with tideglusib also enhanced the protein level of Notch1,and reduced the cleavage of pro-apoptotic signal