AIM:To explore the impact of chronic stress on postoperative cognitive dysfunction in rats and to elucidate the mechanistic link to histone deacetylase 2(HDAC2).METHODS:A repeated social defeat stress model and a prolonged isoflurane anesthesia model were established in mice.The rats were randomly assigned to four groups:control(Ctrl)group,isoflurane anesthesia(Iso)group,chronic social defeat stress(RSDS)group,and chronic social de-feat stress combined with isoflurane anesthesia(RSDS+Iso)group.Anxiety-like behaviors were evaluated using the social avoidance test and the novelty-suppressed feeding test.Cognitive function was assessed through the novel object recogni-tion test and the Morris water maze.Plasma corticosterone levels were measured via enzyme-linked immunosorbent assay(ELISA).Primary hippocampal neurons were isolated from fetal mouse hippocampi and classified into four groups:con-trol group,chronic stress combined with prolonged isoflurane anesthesia(Cort+Iso)group,CAY-10683 intervention(CAY),and CAY-10683 treatment(CAY+Cort+Iso)group.Cell viability was determined using CCK-8 assay,and pro-tein expression levels of brain-derived neurotrophic factor(BDNF)and HDAC2 were analyzed by Western blot.RE-SULTS:The RSDS mouse model was successfully established,with ELISA results indicating a significant increase in plasma corticosterone levels in mice subjected to chronic stress combined with prolonged isoflurane anesthesia.Behavioral assessments and Western blot analyses revealed that mice exposed to prolonged isoflurane anesthesia following chronic stress showed marked declines in cognitive function and hippocampal BDNF protein expression levels.Additionally,chronic stress significantly elevated HDAC2 protein expression in the hippocampi of mice undergoing prolonged isoflurane anesthesia.Treatment with an HDAC2 inhibitor reduced HDAC2 protein expression in primary hippocampal neurons sub-jected to chronic stress combined with prolonged isoflurane anesthesia,concurrently increasing BDNF protein expression levels.CONCLUSION:Chronic stress significantly worsens postoperative cognitive dysfunction induced by prolonged isoflurane anesthesia,associated with increased HDAC2 protein expression in the hippocampus.Inhibition of HDAC2 ef-fectively counteracts the reduction in BDNF,a protein crucial for cognitive function,caused by the combination of chronic stress and prolonged isoflurane anesthesia.

AIM:To explore the impact of chronic stress on postoperative cognitive dysfunction in rats and to elucidate the mechanistic link to histone deacetylase 2(HDAC2).METHODS:A repeated social defeat stress model and a prolonged isoflurane anesthesia model were established in mice.The rats were randomly assigned to four groups:control(Ctrl)group,isoflurane anesthesia(Iso)group,chronic social defeat stress(RSDS)group,and chronic social de-feat stress combined with isoflurane anesthesia(RSDS+Iso)group.Anxiety-like behaviors were evaluated using the social avoidance test and the novelty-suppressed feeding test.Cognitive function was assessed through the novel object recogni-tion test and the Morris water maze.Plasma corticosterone levels were measured via enzyme-linked immunosorbent assay(ELISA).Primary hippocampal neurons were isolated from fetal mouse hippocampi and classified into four groups:con-trol group,chronic stress combined with prolonged isoflurane anesthesia(Cort+Iso)group,CAY-10683 intervention(CAY),and CAY-10683 treatment(CAY+Cort+Iso)group.Cell viability was determined using CCK-8 assay,and pro-tein expression levels of brain-derived neurotrophic factor(BDNF)and HDAC2 were analyzed by Western blot.RE-SULTS:The RSDS mouse model was successfully established,with ELISA results indicating a significant increase in plasma corticosterone levels in mice subjected to chronic stress combined with prolonged isoflurane anesthesia.Behavioral assessments and Western blot analyses revealed that mice exposed to prolonged isoflurane anesthesia following chronic stress showed marked declines in cognitive function and hippocampal BDNF protein expression levels.Additionally,chronic stress significantly elevated HDAC2 protein expression in the hippocampi of mice undergoing prolonged isoflurane anesthesia.Treatment with an HDAC2 inhibitor reduced HDAC2 protein expression in primary hippocampal neurons sub-jected to chronic stress combined with prolonged isoflurane anesthesia,concurrently increasing BDNF protein expression levels.CONCLUSION:Chronic stress significantly worsens postoperative cognitive dysfunction induced by prolonged isoflurane anesthesia,associated with increased HDAC2 protein expression in the hippocampus.Inhibition of HDAC2 ef-fectively counteracts the reduction in BDNF,a protein crucial for cognitive function,caused by the combination of chronic stress and prolonged isoflurane anesthesia.