Protective Effect of NA-1 on Hypoxic-ischemic Brain Damage in Neonatal Rats Based on CREB/BDNF Signaling Pathway
XIA Li
YIN Huaiqing
YIN Chongjuan
BAI Dan
SHI Rui
Abstract：Objective:To investigate the effect of postsynaptic densitin-95(PSD-95)inhibitor(NA-1)on cyclic adenosine phosphate response element binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway in hippocampus of neonatal rats with hypoxic-ischemic brain damage(HIBD).Methods:Neonatal SD rats of 7 d-old were randomly divided into normal control group,HIBD group,NA-1 group(intraperitoneally injected with 10 μg/g NA-1 solution)and NA-1+CREB inhibitor H89 group(intraperitoneally injected with 10 μg/g NA-1 solution+2 μg/L H89 solution),with 15 rats in each group.HIBD model was established by Rice method to evaluate the neurobehavioral changes of rats.The 2,3,5-triphenyltetrazolium chloride(TTC)staining and Nissl staining were used to observe the pathological changes of rat brain.The expression of PSD-95 and CREB/BDNF signaling pathway in the hippocampus of rats was detected by Western Blot.Results:Compared with the normal control group,the time of ground reflex and cliff escape reflex in the HIBD group was prolonged,the time of forelimb grip strength was shortened,the volume of cerebral infarction and the expression of PSD-95 protein in hippocampus increased,and the number of Nissl positive cells,phosphorylated CREB(p-CREB)/CREB and BDNF protein decreased(P＜0.05).Compared with the HIBD group,the time of ground reflex and cliff escape reflex in the NA-1 group was shortened,the time of forelimb grip strength was prolonged,the volume of cerebral infarction and the expression of PSD-95 protein in hippocampus decreased,and the number of Nissl positive cells,p-CREB/CREB and BDNF protein were increased(P＜0.05),while adding H89 partially reversed the effect of NA-1.Conclusion:NA-1 could improve the neurobehavior of neonatal rats after HIBD,reduce the volume of cerebral infarction and neuronal apoptosis,which might be related to the activation of CREB/BDNF signaling pathway.
Keywords：neonatal hypoxic-ischemic brain damagepostsynaptic density-95 inhibitorcyclic adenosine phosphate reaction element binding protein/brain-derived neurotrophic factor signaling pathwayneuron injuryratsexperimental study
Publication Date：2025-01-31
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 223-227 )