The Effects Of Intraoperative Hypothermia On Postoperative Cognitive Function In The Rat And Its Possible Mechanisms

AimsIntraoperative hypothermia(IPH)is a common complication during operations and is associated with several adverse events.Postoperative cognitive dysfunction(POCD)and its adverse consequences have drawn increasing attention in recent years.There are currently no relevant studies investigating the correlation between IPH and POCD.The aim of this study was to assess the effects of IPH on postoperative cognitive function in rats undergoing exploratory laparotomies and to investigate the possible related mechanisms.MethodsAdult male Sprague-Daweley rats were randomly assigned to Hypothermic group,Normothermic group and Control group.Hypothermic and Normothermic group received exploratory laparotomies.The body temperatures of rats in Hypothermic group were maintained at 33 ± 0.5℃ and the Normothermic group were maintained at 37 ± 0.5℃.The Control group was fed normally without operation.We used the Y-maze and Morris Water Maze tests to assess postoperative spatial working memory ability,spatial learning,and memory ability.Following the behavioral tests,the morphological changes in hippocampal neurons were examined by haematoxylin-eosin staining.Subsequently,western blot analysis was performed to measure the hippocampal synaptic plasticity-related protein expression levels of activity-regulated cytoskeletal-associated protein(Arc),cyclic adenosine monophosphate-response element-binding protein(CREB),S133-phosphorylated CREB(p-CREB[S133]),α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor 1(AMPAR1),and S831-phosphorylated AMPAR1(p-AMPAR1[S831]).ResultsOur results suggest a correlation between IPH and POCD in rats and that IPH may lead to POCD regarding impairments in spatial working memory,spatial learning,and memory.Moreover,we also observed that IPH increased the damage of neurons in the dentate gyrus(DG)region of the hippocampus,inhibited the expression of hippocampal synaptic plasticity-related proteins Arc,p-CREB(S133)and p-AMPAR1(S831).ConclusionsPOCD induced by IPH might be due to neurons damage in the DG region of the hippocampus and decreased expression of hippocampal synaptic plasticity-related proteins Arc,p-CREB(S133),and p-AMPAR1(S831).This study was only a preliminary exploration of the mechanisms underlying intraoperative hypothermia effect on POCD;the precise mechanism requires further investigation.AimsIntraoperative hypothermia(IPH)is very common among patients undergoing surgery and can lead to cognitive impairment.The hippocampus is responsible for memory formation and retention.As a functional core area,the cornu ammonis 1(CA1)region of hippocampus contains abundant blood vessels and is susceptible to ischemia and critical for memory.The part Ⅰ suggests that IPH may lead to postoperative cognitive dysfunction(POCD).On this basis,using a rat model of POCD induced by IPH,the present study was undertaken to explore the relationship between vascular function and neuronal state in the CA1 region of hippocampus.MethodsAdult male Sprague-Daweley rats used for this study were randomly divided into three groups:Hypothermic group(33 ±0.5 ℃),Normothermic group(37±0.5 ℃)and Control group.The rats in groups Hypothermic and Normothermic were subjected to exploratory laparotomies,while the rats in group Control were fed normally without operation.The postoperative cognitive function of rats was evaluated using the Y-maze and Morris Water Maze(MWM)tests.The immunohistochemistry(IHC)staining,Dihydroethidium(DHE)staining,haematoxylin-eosin staining(HE)and immunofluorescence(IF)staining were performed to detect vascular endothelial cell(VECs)function changes,vascular smooth muscle cells(VSMCs)phenotypic transformation,reactive oxygen species(ROS)levels,the neuronal morphological change in the hippocampal CA1 region and memory-related activity-regulated cytoskeletal-associated protein(Arc)expression.ResultsIPH leads to impairments of spatial working memory,spatial learning,and memory after surgery,that is,POCD occurred in rats.Furthermore,this research indicated that IPH disturb VECs function in hippocampal CA1 region,inhibit the expressions of vascular endothelial growth factor(VEGF)and endothelial nitric oxide synthase(eNOS).Subsequently,the destruction of endothelial integrity led to reactive oxygen species(ROS)accumulation.Additionally,IPH reduced the expression of VSMCs contractile phenotypic marker smooth muscle myosin heavy chain(SMMHC)and increased the expression of VSMCs synthetic phenotypic marker osteopontin(OPN)in hippocampal CA1 region,which eventually led to the overexpression of retinol-binding protein 1(RBP1).This indicated that VSMCs transformed from contractile phenotype in physiological state to synthetic phenotype in pathological state.Ultimately,this study suggested that vascular dysfunction cause the damage of neurons in the hippocampal CA1 region and reduce the expression level of memory-related protein Arc.ConclusionsBased on the research in the part I,the study further explored the possible mechanism of IPH-induced POCD in rats,and revealed it may be caused by neuronal damages induced by vascular dysfunction in the hippocampal CA1 region.This study could provide novel insights into exploring the effects of IPH on the hippocampus and postoperative cognitive function,which might allow the identification of a new research target and treatment strategy.