Low-dose Sevoflurane Attenuates Cardiopulmonary Bypass (CPB)- induced Postoperative Cognitive Dysfunction (POCD) by Regulating Hippocampus Apoptosis via PI3K/AKT Pathway

Author(s): Jianhua Qin, Qingjun Ma, Dongmei Ma*

Journal Name: Current Neurovascular Research

Volume 17 , Issue 3 , 2020


DOI : 10.2174/1567202617666200513085403

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Abstract:

Background: Cardiopulmonary bypass (CPB) caused postoperative cognitive dysfunction (POCD) was characterized by hippocampus apoptosis, which seriously limited the therapeutic efficacy and utilization of CPB in clinic. Recent data indicated that sevoflurane anesthesia might alleviate CPB-induced POCD, however, the underlying mechanisms are still unclear.

Methods: In the present study, the in vivo CPB-POCD models were established by using aged Sprague-Dawley (SD) male rats and the in vitro hypoxia/reoxygenation (H/R) models were inducted by using the primary hippocampus neuron (PHN) cells.

Results: The results showed that CPB impaired cognitive functions and induced hippocampus apoptosis in rat models, which were alleviated by pre-treating rats with low-dose sevoflurane. In addition, the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signal pathway was inactivated in the hippocampus tissues of CPB-POCD rats, which were rescued by low-dose sevoflurane treatment. Of note, the PI3K/AKT inhibitor (LY294002) abrogated the protective effects of low-dose sevoflurane on CPB-POCD rats. Consistently, the in vitro results showed that H/R treatment induced cell apoptosis and inhibited cell viability in PHN cells, which were attenuated by low-dose sevoflurane. Similarly, LY294002 abrogated the inhibiting effects of low-dose sevoflurane on H/R-induced PHN cell death.

Conclusion: Taken together, low-dose sevoflurane attenuated CPB-induced POCD by inhibiting hippocampus apoptosis through activating PI3K/AKT signal pathway.

Keywords: Cardiopulmonary bypass, postoperative cognitive dysfunction, sevoflurane, hippocampus apoptosis, PI3K/AKT pathway, heart surgery.

[1]
Wu T, Liu J, Wang Q, Li P, Shi G. Superior blood-saving effect and postoperative recovery of comprehensive blood-saving strategy in infants undergoing open heart surgery under cardiopulmonary bypass. Medicine (Baltimore) 2018; 97(27): e11248
[http://dx.doi.org/10.1097/MD.0000000000011248] [PMID: 29979388]
[2]
Hirata Y. Cardiopulmonary bypass for pediatric cardiac surgery. Gen Thorac Cardiovasc Surg 2018; 66(2): 65-70.
[http://dx.doi.org/10.1007/s11748-017-0870-1] [PMID: 29185163]
[3]
Chen K, Sun Y, Dong W, et al. Activated A7nachr improves postoperative cognitive dysfunction and intestinal injury induced by cardiopulmonary bypass in rats: Inhibition of the proinflammatory response through the Th17 immune response. Cell Physiol Biochem 2018; 46(3): 1175-88.
[http://dx.doi.org/10.1159/000489068] [PMID: 29672286]
[4]
Yi SQ, Yang M, Duan KM. Immune-mediated metabolic kynurenine pathways are involved in the postoperative cognitive dysfunction after cardiopulmonary bypass. Thorac Cardiovasc Surg 2015; 63(7): 618-23.
[http://dx.doi.org/10.1055/s-0034-1393704] [PMID: 25893921]
[5]
Wu W, Wu Y, Cheng G, Zhang C, Wang H, Li Y. A mouse model of hepatic ischemia-reperfusion injury demonstrates potentially reversible effects on hippocampal neurons and postoperative cognitive function. Med Sci Monit 2019; 25: 1526-36.
[http://dx.doi.org/10.12659/MSM.912658] [PMID: 30808858]
[6]
Yuan S, Zhang X, Bo Y, Li W, Zhang H, Jiang Q. The effects of electroacupuncture treatment on the postoperative cognitive function in aged rats with acute myocardial ischemia-reperfusion. Brain Res 2014; 1593: 19-29.
[http://dx.doi.org/10.1016/j.brainres.2014.10.005] [PMID: 25446007]
[7]
Benson RA, Ozdemir BA, Matthews D, Loftus IM. A systematic review of postoperative cognitive decline following open and endovascular aortic aneurysm surgery. Ann R Coll Surg Engl 2017; 99(2): 97-100.
[http://dx.doi.org/10.1308/rcsann.2016.0338] [PMID: 27809575]
[8]
Bilotta F, Qeva E, Matot I. Anesthesia and cognitive disorders: A systematic review of the clinical evidence. Expert Rev Neurother 2016; 16(11): 1311-20.
[http://dx.doi.org/10.1080/14737175.2016.1203256] [PMID: 27329271]
[9]
Kong ZH, Chen X, Hua HP, Liang L, Liu LJ. The oral pretreatment of glycyrrhizin prevents surgery-induced cognitive impairment in aged mice by reducing neuroinflammation and alzheimer’s-related pathology via HMGB1 inhibition. J Mol Neurosci 2017; 63(3-4): 385-95.
[http://dx.doi.org/10.1007/s12031-017-0989-7] [PMID: 29034441]
[10]
Chen H, Iinuma M, Onozuka M, Kubo KY. Chewing maintains hippocampus-dependent cognitive function. Int J Med Sci 2015; 12(6): 502-9.
[http://dx.doi.org/10.7150/ijms.11911] [PMID: 26078711]
[11]
Ye JS, Chen L, Lu YY, Lei SQ, Peng M, Xia ZY. Honokiol-mediated mitophagy ameliorates postoperative cognitive impairment induced by surgery/sevoflurane via inhibiting the activation of NLRP3 inflammasome in the hippocampus. Oxid Med Cell Longev 2019.: 20198639618
[http://dx.doi.org/10.1155/2019/8639618] [PMID: 30918581]
[12]
Zheng J, Min S, Hu B, Liu Q, Wan Y. Nrdp1 is involved in hippocampus apoptosis in cardiopulmonary bypass-induced cognitive dysfunction via the regulation of ErbB3 protein levels. Int J Mol Med 2019; 43(4): 1747-57.
[http://dx.doi.org/10.3892/ijmm.2019.4080] [PMID: 30720051]
[13]
Ma J, Williams J, Eastwood D, et al. High-dose propofol anesthesia reduces the occurrence of postoperative cognitive dysfunction via maintaining cytoskeleton. Neuroscience 2019; 421: 136-43.
[http://dx.doi.org/10.1016/j.neuroscience.2019.09.024] [PMID: 31682819]
[14]
Zhang N, Ye W, Wang T, Wen H, Yao L. Up-regulation of miR-106a targets LIMK1 and contributes to cognitive impairment induced by isoflurane anesthesia in mice. Genes Genomics 2020; 42(4): 405-12.
[http://dx.doi.org/10.1007/s13258-019-00913-8] [PMID: 31933141]
[15]
Tian Y, Chen KY, Liu LD, Dong YX, Zhao P, Guo SB. Sevoflurane exacerbates cognitive impairment induced by aβ1-40 in rats through initiating neurotoxicity, neuroinflammation, and neuronal apoptosis in rat hippocampus. Mediators Inflamm 2018.: 20183802324
[http://dx.doi.org/10.1155/2018/3802324] [PMID: 30402039]
[16]
Zhao X, Sun Y, Ding Y, Zhang J, Li K. miR-34a inhibitor may effectively protect against sevoflurane-induced hippocampal apoptosis through the Wnt/β-Catenin pathway by targeting Wnt1. Yonsei Med J 2018; 59(10): 1205-13.
[http://dx.doi.org/10.3349/ymj.2018.59.10.1205] [PMID: 30450855]
[17]
Peng S, Li P, Liu P, et al. Cistanches alleviates sevoflurane-induced cognitive dysfunction by regulating PPAR-γ-dependent antioxidant and anti-inflammatory in rats. J Cell Mol Med 2020; 24(2): 1345-59.
[http://dx.doi.org/10.1111/jcmm.14807] [PMID: 31802591]
[18]
Yang X, Zhang W, Wu H, et al. Downregulation of CDK5 restores sevoflurane-induced cognitive dysfunction by promoting SIRT1-mediated autophagy. Cell Mol Neurobiol 2020; 40(6): 955-65.
[http://dx.doi.org/10.1007/s10571-020-00786-6] [PMID: 31950315]
[19]
Zhu J, Zhang Z, Jia J, et al. Sevoflurane induces learning and memory impairment in young mice through a reduction in neuronal glucose transporter 3. Cell Mol Neurobiol 2019; 40(6): 879-95.
[http://dx.doi.org/10.1007/s10571-019-00779-0] [PMID: 31884568]
[20]
Shi CX, Jin J, Wang XQ, et al. Sevoflurane attenuates brain damage through inhibiting autophagy and apoptosis in cerebral ischemia reperfusion rats. Mol Med Rep 2020; 21(1): 123-30.
[PMID: 31746402]
[21]
Liu C, Ding R, Huang W, Miao L, Li J, Li Y. Sevoflurane protects against intestinal ischemia-reperfusion injury by activating peroxisome proliferator-activated receptor gamma/nuclear factor-kappaB pathway in rats. Pharmacology 2020; 105(3-4): 231-42.
[PMID: 31655824]
[22]
Xie D, Zhao J, Guo R, et al. Sevoflurane Pre-conditioning ameliorates diabetic myocardial ischemia/reperfusion injury via differential regulation of p38 and ERK. Sci Rep 2020; 10(1): 23.
[http://dx.doi.org/10.1038/s41598-019-56897-8] [PMID: 31913350]
[23]
Hirai T, Konishi Y, Mizuno S, Rui Z, Sun Y, Nishiwaki K. Differential effects of sevoflurane on the growth and apoptosis of human cancer cell lines. J Anesth 2020; 34(1): 47-57.
[http://dx.doi.org/10.1007/s00540-019-02701-w] [PMID: 31667585]
[24]
Wang Z, Cui R, Wang K. Effects of sevoflurane pretreatment on the apoptosis of rat H9c2 cardiomyocytes and the expression of GRP78. Exp Ther Med 2018; 15(3): 2818-23.
[http://dx.doi.org/10.3892/etm.2018.5799] [PMID: 29599827]
[25]
Kalhori MR, Arefian E, Fallah Atanaki F, Kavousi K, Soleimani M. miR-548x and miR-4698 controlled cell proliferation by affecting the PI3K/AKT signaling pathway in Glioblastoma cell lines. Sci Rep 2020; 10(1): 1558.
[http://dx.doi.org/10.1038/s41598-020-57588-5] [PMID: 32005873]
[26]
Sun L, Zhang Y, Zhang W, et al. Green tea and black tea inhibit proliferation and migration of HepG2 cells via the PI3K/Akt and MMPs signalling pathway. Biomed Pharmacother 2020; 2020: 125109893
[http://dx.doi.org/10.1016/j.biopha.2020.109893] [PMID: 32004975]
[27]
Xing X, Guo S, Zhang G, et al. miR-26a-5p protects against myocardial ischemia/reperfusion injury by regulating the PTEN/PI3K/AKT signaling pathway. Braz J Med Biol Res 2020; 53(2): e9106
[http://dx.doi.org/10.1590/1414-431x20199106] [PMID: 31994603]
[28]
Zhou J, Huang Z, Ni X, Lv C. Piperlongumine induces apoptosis and G2/M phase arrest in human osteosarcoma cells by regulating ROS/PI3K/Akt pathway. Toxicol In Vitro 2020; 2020: 65104775
[http://dx.doi.org/10.1016/j.tiv.2020.104775] [PMID: 31987842]
[29]
Su R, Sun P, Zhang D, Xiao W, Feng C, Zhong L. Neuroprotective effect of miR-410-3p against sevoflurane anesthesia-induced cognitive dysfunction in rats through PI3K/Akt signaling pathway via targeting C-X-C motif chemokine receptor 5. Genes Genomics 2019; 41(10): 1223-31.
[http://dx.doi.org/10.1007/s13258-019-00851-5] [PMID: 31350734]
[30]
Wang YB, Xie JQ, Liu W, Zhang RZ, Huang SH, Xing YH. BACE1 gene silencing alleviates isoflurane anesthesia induced postoperative cognitive dysfunction in immature rats by activating the PI3K/Akt signaling pathway. Mol Med Rep 2018; 18(5): 4259-70.
[http://dx.doi.org/10.3892/mmr.2018.9453] [PMID: 30221701]
[31]
Wu Q, Yi X. Down-regulation of Long Noncoding RNA MALAT1 Protects Hippocampal Neurons Against Excessive Autophagy and Apoptosis via the PI3K/Akt Signaling Pathway in Rats with Epilepsy. J Mol Neurosci 2018; 65(2): 234-45.
[http://dx.doi.org/10.1007/s12031-018-1093-3] [PMID: 29858824]
[32]
Xing N, Xing F, Li Y, et al. Dexmedetomidine improves propofol-induced neuronal injury in rat hippocampus with the involvement of miR-34a and the PI3K/Akt signaling pathway. Life Sci 2020.: 247117359
[http://dx.doi.org/10.1016/j.lfs.2020.117359] [PMID: 32001264]
[33]
He H, Liu W, Zhou Y, et al. Sevoflurane post-conditioning attenuates traumatic brain injury-induced neuronal apoptosis by promoting autophagy via the PI3K/AKT signaling pathway. Drug Des Devel Ther 2018; 12: 629-38.
[http://dx.doi.org/10.2147/DDDT.S158313] [PMID: 29606856]
[34]
Liu TJ, Wang B, Li QX, Dong XL, Han XL, Zhang SB. Effects of microRNA-206 and its target gene IGF-1 on sevoflurane-induced activation of hippocampal astrocytes in aged rats through the PI3K/AKT/CREB signaling pathway. J Cell Physiol 2018; 233(5): 4294-306.
[http://dx.doi.org/10.1002/jcp.26248] [PMID: 29052839]


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Article Details

VOLUME: 17
ISSUE: 3
Year: 2020
Published on: 28 September, 2020
Page: [232 - 240]
Pages: 9
DOI: 10.2174/1567202617666200513085403
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