The Effects And Mechanism Of Isofluane On Learning And Memory Capacity In Aged Rats

Postoperative cognitive dysfunction(POCD)is an important clinical complication after anesthesia and major surgery,which predisposes to impairments in patients' daily functioning and an increased morbidity and mortality.Because of the special physiological characteristics of the elderly,the incidence of central nervous system complications in perioperative period was significantly higher than that in young people.A growing body of preclinical evidence supports the view that exposure to general anesthetics may contribute to neuronal loss and cognitive impairments in aged rats,however,the underlying pathophysiological mechanisms are complex and still not completely established.Endoplasmic reticulum stress may be one of the mechanisms of neurotoxicity.Moderate endoplasmic reticulum stress can activate the unfolded protein response(UPR),maintain the normal intracellular environment,prolonged or high-intensity stress response may lead to neuronal disability or even apoptosis.In our study,twenty-month-old rats were randomly divided into four groups: control group(C),isoflurane group(ISO),isoflurane plus salubrinal group(ISO + SAL)and salubrinal group(SAL)(n = 15 in each group).All rats were subjected to water maze training for 5 consecutive days before exposed to isoflurane to form a stable memory.Group ISO received 1.5% isoflurane 2 h,SAL group received Salubrinal(1 mg/kg)by intraperitoneally injected.For ISO+SAL group,Salubrinal was intraperitoneally injected 30 min before exposure to isoflurane(1 mg/kg).Non-anaesthetized rats served as control group(C).The Morris water maze test was performed 24 hours after the administration,including the navigation experiment and the space exploration experiment,respectively,to determine the time of escape latency and the percentage of time spent in the previous platform quadrant.Results show that: compared with C group,ISO group escaping latency extended(P<0.05),the number of times through the target platform(P<0.05)is reducing;compared with ISO group,ISO+SAL group escaping latency shorted(P<0.05),the number of times through the target platform(P<0.05)is increasing;the escape latency time and the number of times through the target platform of SAL group was no significant difference compare with C group.At the end of the water maze test,the left hippocampus and left frontal lobe were collected and the gene transcription level of GRP78?ATF4 and CHOP was detected by real-time quantitative PCR(RT-PCR).Results show that: compared with C group,the expression of GRP78?ATF4 ? CHOP of ISO group were significantly increased(P<0.05);compared with ISO group,the expression of GRP78?ATF4?CHOP of ISO+SAL group were significantly decreased(P<0.05);the mRNA levels of SAL group has no statistical significance compared with C group(P>0.05).The expression of GRP78 ? ATF4 and CHOP was detected by immunofluorescence.Results show that: compared with C group,the expression of GRP78?ATF4?CHOP of ISO group were significantly increased(P<0.05);compared with ISO group,the expression of GRP78?ATF4?CHOP of ISO+SAL group was significantly decreased(P<0.05);the protein levels of SAL group has no statistical significance compared with C group(P>0.05).Analyze the experimental results and draw the following conclusions:1.Isoflurane anesthesia can induce the short-term memory disability of rats,and this effect can be alleviated by salubrinal before anesthesia.2.The expression of GRP78? ATF4 and CHOP in hippocampus and frontal lobe of rats were up-regulated by isoflurane anesthesia,and these effects could be down-regulated by salubrinal,indicating that the isoflurane may cause short-term memory decline and related to the activation of the endoplasmic reticulum stress pathway in hippocampus and frontal lobe neurons.