The Effect Of Vitamin C On Isoflurane-induced Cytotoxicity And Cognitive Impairment

Postoperative cognitive dysfunction (postoperative cognitivedysfunction, POCD) is a central nervous system complication after theoperation, performance as memory impaired, mental disorder, anxiety andpersonality changes for a period after anesthesia surgery, which occurscommonly in the elderly patients. POCD can lead to prolong the patient’srecovery time, increase the economic burden, and even improve the chanceof getting permanent cognitive dysfunction (Alzheimer’sdiseases, AD).Given the current research data, anesthesia is the second risk factorwhich can cause of postoperative cognitive dysfunction besidesage.Anesthetic cytotoxicity and inhibitory effects on the central nervoussystem, may be the pathogenesis of postoperative cognitive dysfunction.Meanwhile elderly patients take up a large proportion in the clinical cases.There are66million people over the age of65need to receive anesthesiatreatment every year. Therefore, exploring the anesthetic neural toxicmechanism, mitigating the neurotoxicity of anesthetic drugs and ensuringa better anesthesia for patients, are the main target of currentneurobiology and anesthesia research.For further exploring the cytotoxic mechanism of isoflurane and theprotect effect by vitamin C, molecular biologic and cellar biologicmethods were used in this study. We found antioxidant drug vitamin Ccan attenuate the cytotoxicity induced by isoflurane, including protectcells from apoptosis and keep mice apart from cognitive decline. Theresults are showed as following:(1) The results of reactive oxygenspecies (ROS) assay in H4-APP cells showed that compared with the isoflurane treatment group, the cells of vitamin C pretreatment group hada lower level of ROS accumulation. Indicated vitamin C can providecation to oxide free radical, and reduce the accumulation of reactiveoxygen species in cells.(2) Through the detection of mitochondrialmembrane permeability transition pore, JC-1and TMRE staining assay,ATP assay, we found that vitamin C can inhibit cell mitochondrialmembrane permeability transition pore opening, mitigate mitochondrialmembrane potential and ATP production decreasing. These resultsindicated vitamin C can maintain mitochondrial membrane structureintegrity and the balance of the electrochemical gradient.(3) Throughwestern blotting and MTT assay, we found vitamin C can attenuateisoflurane-induced caspase3activation and apoptosis in H4-APP cells,and improve cell viability.(4) The fear conditioning test (FCT) is themost commonly used behavioral test to detectlearningand memoryimpairment of mice. The findings in this study that vitamin C can reverseisoflurane-induced freezing time decrease in both the context and tonetests suggested that vitamin C can protect both hippocampus-dependentand hippocampus-independent learning and memory.The findings in this study further demonstrate the protect effect ofvitamin C against the cytotoxic mechanism of anesthetic isoflurane,which including ROS accumulation, destroying the mitochondrialstructure integrity and cell apoptosis. The results of Fear ConditioningSystem suggested that vitamin C can protect learning and memory ofmice in mice behavioral model. In conclusion, all the findings of currentstudy provid the theoretical and experiment support for the treatment andprevention of postoperative cognitive dysfunction.