Effects of early multisensory stimulation on the p-ERK/p-CREB/BDNF/TrkB signaling pathway in the hippocampus of neonatal rats with hypoxic-ischemic brain damage
Objective To observe the effects of early multisensory stimulation on the signaling pathway of phosphorylated extracellular signal-regulated kinase(p-ERK)/phosphorylated cAMP-response element binding protein(p-CREB)/brain-derived neur-otrophic factor(BDNF)/tyrosine kinase receptor B(TrkB)and its mediated synaptic remodeling in the hippocampus of neonatal rats with hypoxic-ischemic brain damage(HIBD).Methods Forty-eight healthy seven-day-old neonatal rats were randomized into sham-operated group,model group,and early multisensory stimulation group,with 16 rats in each group.A HIBD model was establ-ished in the model and early multisensory stimulation groups.The sham-operated group only had the common carotid arteries exposed without further intervention.The early multisensory stimulation group received continuous early multisensory stimulation interventions for 28 days starting 24 h post-modeling,while the other groups did not receive any treatment.Morris water maze test was performed to assess the spatial learning and memory ability of rats;transmission electron microscopy was utilized to observe changes in hippocampal synaptic ultrastructure;immunohistochemistry was used to measure the expression levels of BDNF and TrkB in the hippocampus;Western blot was employed to analyze the protein expression levels of p-ERK,p-CREB,BDNF,TrkB,and Syn1 in the hippocampus.Results Compared with the sham-operated group,the model group showed significantly prolonged escape latencies on training days 3,4,and 5(P＜0.01)and a significantly reduced number of platform crossings on training day 6(P＜0.01);the hippocampal synaptic ultrastructure was blurred,with decreases in synaptic density and synaptic vesicles;the protein expression levels of p-ERK,p-CREB,BDNF,TrkB,and Syn1 in the hippocampus were significantly downregulated(P＜0.01).Compared with the model group,the early multisensory stimulation group exhibited shorter escape latencies on training days 4 and 5(P＜0.01)and an increased number of platform crossings on training day 6(P＜0.05);there was an increase in hippocampal synaptic density,with more synaptic connections,and clear,round synaptic vesicles in the presynaptic enlargements;the protein expression levels of p-ERK,p-CREB,BDNF,TrkB,and Syn1 in the hippocampus were significantly upregulated(P＜0.01).Conclusion Early multisensory stimulation can effectively enhance cognitive function in neonatal rats with HIBD and promote synaptic remodeling in the ischemic hippocampus.The mechanism of action may be related to the activation of the p-ERK/p-CREB/BDNF/TrkB signaling pathway.
万方数据
维普
