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Licensed Unlicensed Requires Authentication Published by De Gruyter May 30, 2019

Role of the GABAA receptors in the long-term cognitive impairments caused by neonatal sevoflurane exposure

Tao Li, Zeyi Huang, Xianwen Wang, Ju Zou and Sijie Tan

Abstract

Sevoflurane is a widely used inhalational anesthetic in pediatric surgeries, which is considered reasonably safe and reversible upon withdrawal. However, recent preclinical studies suggested that peri-neonatal sevoflurane exposure may cause developmental abnormalities in the brain. The present review aimed to present and discuss the accumulating experimental data regarding the undesirable effects of sevoflurane on brain development as revealed by the laboratory studies. First, we summarized the long-lasting side effects of neonatal sevoflurane exposure on cognitive functions. Subsequently, we presented the structural changes, namely, neuroapoptosis, neurogenesis and synaptogenesis, following sevoflurane exposure in the immature brain. Finally, we also discussed the potential mechanisms underlying subsequent cognitive impairments later in life, which are induced by neonatal sevoflurane exposure and pointed out potential strategies for mitigating sevoflurane-induced long-term cognitive impairments. The type A gamma-amino butyric acid (GABAA) receptor, the main targets of sevoflurane, is excitatory rather than inhibitory in the immature neurons. The excitatory effects of the GABAA receptors have been linked to increased neuroapoptosis, elevated serum corticosterone levels and epigenetic modifications following neonatal sevoflurane exposure in rodents, which might contribute to sevoflurane-induced long-term cognitive abnormalities. We proposed that the excitatory GABAA receptor-mediated HPA axis activity might be a novel mechanism underlying sevoflurane-induced long-term cognitive impairments. More studies are needed to investigate the effectiveness and mechanisms by targeting the excitatory GABAA receptor as a prevention strategy to alleviate cognitive deficits induced by neonatal sevoflurane exposure in future.

Funding source: Hunan Provincial Natural Science Foundation of China

Award Identifier / Grant number: 2019JJ40250

Funding source: Provincial Education Department of Hunan

Award Identifier / Grant number: 18B262

Funding source: University of South China

Award Identifier / Grant number: 2018XQD32

Award Identifier / Grant number: 2018XJXZ159

Funding source: Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study

Award Identifier / Grant number: 2015-351

Funding statement: The authors would like to thank Professor Anatoly E. Martynyuk at the University of Florida for his critical reading of the manuscript. S.T. and J.Z. were supported by the Hunan Provincial Natural Science Foundation of China (2019JJ40250), the Provincial Education Department of Hunan (18B262) and the University of South China (2018XQD32). T.L and X.W. were supported by a grant from University of South China (NO. 2018XJXZ159). The authors would also like to acknowledge the financial support provided by the Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study (2015-351).

References

Alvarado, M.C., Murphy, K.L., and Baxter, M.G. (2017). Visual recognition memory is impaired in rhesus monkeys repeatedly exposed to sevoflurane in infancy. Br. J. Anaesth. 119, 517–523.10.1093/bja/aew473Search in Google Scholar PubMed PubMed Central

Amrock, L.G., Starner, M.L., Murphy, K.L., and Baxter, M.G. (2015). Long-term effects of single or multiple neonatal sevoflurane exposures on rat hippocampal ultrastructure. Anesthesiology 122, 87–95.10.1097/ALN.0000000000000477Search in Google Scholar PubMed

Bale, T.L., Baram, T.Z., Brown, A.S., Goldstein, J.M., Insel, T.R., McCarthy, M.M., Nemeroff, C.B., Reyes, T.M., Simerly, R.B., Susser, E.S., et al. (2010). Early life programming and neurodevelopmental disorders. Biol. Psychiatry 68, 314–319.10.1016/j.biopsych.2010.05.028Search in Google Scholar PubMed PubMed Central

Ben-Ari, Y. (2002). Excitatory actions of gaba during development: the nature of the nurture. Nat. Rev. Neurosci. 3, 728–739.10.1038/nrn920Search in Google Scholar PubMed

Ben-Ari, Y. (2014). The GABA excitatory/inhibitory developmental sequence: a personal journey. Neuroscience 279, 187–219.10.1016/j.neuroscience.2014.08.001Search in Google Scholar PubMed

Boscolo, A., Ori, C., Bennett, J., Wiltgen, B., and Jevtovic-Todorovic, V. (2013). Mitochondrial protectant pramipexole prevents sex-specific long-term cognitive impairment from early anaesthesia exposure in rats. Br. J. Anaesth. 110(Suppl 1), i47–i52.10.1093/bja/aet073Search in Google Scholar PubMed PubMed Central

Briner, A., de Roo, M., Dayer, A., Muller, D., Habre, W., and Vutskits, L. (2010). Volatile anesthetics rapidly increase dendritic spine density in the rat medial prefrontal cortex during synaptogenesis. Anesthesiology 112, 546–556.10.1097/ALN.0b013e3181cd7942Search in Google Scholar PubMed

Brioni, J.D., Varughese, S., Ahmed, R., and Bein, B. (2017). A clinical review of inhalation anesthesia with sevoflurane: from early research to emerging topics. J. Anesth. 31, 764–778.10.1007/s00540-017-2375-6Search in Google Scholar PubMed PubMed Central

Brohan, J. and Goudra, B.G. (2017). The role of GABA receptor agonists in anesthesia and sedation. CNS Drugs 31, 845–856.10.1007/s40263-017-0463-7Search in Google Scholar PubMed

Campagna, J.A., Miller, K.W., and Forman, S.A. (2003). Mechanisms of actions of inhaled anesthetics. N. Engl. J. Med. 348, 2110–2124.10.1056/NEJMra021261Search in Google Scholar PubMed

Cao, W., Pavlinec, C., Gravenstein, N., Seubert, C.N., and Martynyuk, A.E. (2012). Roles of aldosterone and oxytocin in abnormalities caused by sevoflurane anesthesia in neonatal rats. Anesthesiology 117, 791–800.10.1097/ALN.0b013e318266c62dSearch in Google Scholar PubMed PubMed Central

Castaneda, A.E., Tuulio-Henriksson, A., Marttunen, M., Suvisaari, J., and Lönnqvist, J. (2008). A review on cognitive impairments in depressive and anxiety disorders with a focus on young adults. J. Affect. Disord. 106, 1–27.10.1016/j.jad.2007.06.006Search in Google Scholar PubMed

Chen, C., Shen, F-Y., Zhao, X., Zhou, T., Xu, D-J., Wang, Z-R., and Wang, Y-W. (2015). Low-dose sevoflurane promotes hippocampal neurogenesis and facilitates the development of dentate gyrus-dependent learning in neonatal rats. ASN Neuro 7.10.1177/1759091415575845Search in Google Scholar PubMed PubMed Central

Chinn, G.A., Sasaki Russell, J.M., and Sall, J.W. (2016). Is a short anesthetic exposure in children safe? Time will tell: a focused commentary of the GAS and PANDA trials. Ann. Transl. Med. 4, 408.10.21037/atm.2016.10.43Search in Google Scholar PubMed PubMed Central

Chung, W., Park, S., Hong, J., Park, S., Lee, S., Heo, J., Kim, D., and Ko, Y. (2015). Sevoflurane exposure during the neonatal period induces long-term memory impairment but not autism-like behaviors. Paediatr. Anaesth. 25, 1033–1045.10.1111/pan.12694Search in Google Scholar PubMed

Coleman, K., Robertson, N.D., Dissen, G.A., Neuringer, M.D., Martin, L.D., Cuzon Carlson, V.C., Kroenke, C., Fair, D., and Brambrink, A.M. (2017). Isoflurane anesthesia has long-term consequences on motor and behavioral development in infant rhesus macaques. Anesthesiology 126, 74–84.10.1097/ALN.0000000000001383Search in Google Scholar PubMed PubMed Central

Cooper, J.M., Vargha-Khadem, F., Gadian, D.G., and Maguire, E.A. (2011). The effect of hippocampal damage in children on recalling the past and imagining new experiences. Neuropsychologia 49, 1843–1850.10.1016/j.neuropsychologia.2011.03.008Search in Google Scholar PubMed PubMed Central

Cornejo, B.J., Mesches, M.H., Coultrap, S., Browning, M.D., and Benke, T.A. (2007). A single episode of neonatal seizures permanently alters glutamatergic synapses. Ann. Neurol. 61, 411–426.10.1002/ana.21071Search in Google Scholar PubMed

Cullinan, W.E., Ziegler, D.R., and Herman, J.P. (2008). Functional role of local GABAergic influences on the HPA axis. Brain Struct. Funct. 213, 63–72.10.1007/s00429-008-0192-2Search in Google Scholar PubMed

Dalla Massara, L., Osuru, H.P., Oklopcic, A., Milanovic, D., Joksimovic, S.M., Caputo, V., DiGruccio, M.R., Ori, C., Wang, G., Todorovic, S.M., et al. (2016). General anesthesia causes epigenetic histone modulation of c-Fos and Brain-derived neurotrophic factor, target genes important for neuronal development in the immature rat hippocampus. Anesthesiology 124, 1311–1327.10.1097/ALN.0000000000001111Search in Google Scholar PubMed PubMed Central

Davidson, A.J., Disma, N., de Graaff, J.C., Withington, D.E., Dorris, L., Bell, G., Stargatt, R., Bellinger, D.C., Schuster, T., Arnup, S.J., et al. (2016). Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet 387, 239–250.10.1016/S0140-6736(15)00608-XSearch in Google Scholar PubMed

DeFrances, C.J., Cullen, K.A., and Kozak, L.J. (2007). National hospital discharge survey: 2005 annual summary with detailed diagnosis and procedure data. Vital Health Stat. 13, 1–209.Search in Google Scholar

Deng, W., Aimone, J.B., and Gage, F.H. (2010). New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat. Rev. Neurosci. 11, 339–350.10.1038/nrn2822Search in Google Scholar PubMed PubMed Central

Ding, M.-L., Ma, H., Man, Y.-G., and Lv, H.-Y. (2017). Protective effects of a green tea polyphenol, epigallocatechin-3-gallate, against sevoflurane-induced neuronal apoptosis involve regulation of CREB/BDNF/TrkB and PI3K/Akt/mTOR signalling pathways in neonatal mice. Can. J. Physiol. Pharmacol. 95, 1396–1405.10.1139/cjpp-2016-0333Search in Google Scholar PubMed

Edwards, D.A., Shah, H.P., Cao, W., Gravenstein, N., Seubert, C.N., and Martynyuk, A.E. (2010). Bumetanide alleviates epileptogenic and neurotoxic effects of sevoflurane in neonatal rat brain. Anesthesiology 112, 567–575.10.1097/ALN.0b013e3181cf9138Search in Google Scholar PubMed

Fang, F., Xue, Z., and Cang, J. (2012). Sevoflurane exposure in 7-day-old rats affects neurogenesis, neurodegeneration and neurocognitive function. Neurosci. Bull. 28, 499–508.10.1007/s12264-012-1260-4Search in Google Scholar PubMed PubMed Central

Fang, F., Song, R., Ling, X., Peng, M., Xue, Z., and Cang, J. (2017). Multiple sevoflurane anesthesia in pregnant mice inhibits neurogenesis of fetal hippocampus via repressing transcription factor Pax6. Life Sci. 175, 16–22.10.1016/j.lfs.2017.03.003Search in Google Scholar PubMed

Garcia, P.S., Kolesky, S.E., and Jenkins, A. (2010). General anesthetic actions on GABA(A) receptors. Curr. Neuropharmacol. 8, 2–9.10.2174/157015910790909502Search in Google Scholar PubMed PubMed Central

Goyagi, T. (2018). The additional oxygen as a carrier gas during long-duration sevoflurane exposure ameliorate the neuronal apoptosis and improve the long-term cognitive function in neonatal rats. Brain Res. 1678, 220–230.10.1016/j.brainres.2017.10.014Search in Google Scholar PubMed

Hong, S., Zheng, G., and Wiley, J.W. (2015). Epigenetic regulation of genes that modulate chronic stress-induced visceral pain in the peripheral nervous system. Gastroenterology 148, 148–157.e7.10.1053/j.gastro.2014.09.032Search in Google Scholar PubMed PubMed Central

Huang, H., Liu, C.-M., Sun, J., Jin, W.-J., Wu, Y.-Q., and Chen, J. (2017). Wiederholte Anwendung von Sevofluran 2% bei 7 und 60 Tage alten Ratten: Neurotoxizität und neurokognitive Dysfunktion (Repeated 2% sevoflurane administration in 7- and 60-day-old rats: neurotoxicity and neurocognitive dysfunction). Anaesthesist 66, 850–857.10.1007/s00101-017-0359-4Search in Google Scholar PubMed

Ikonomidou, C., Bosch, F., Miksa, M., Bittigau, P., Vöckler, J., Dikranian, K., Tenkova, T.I., Stefovska, V., Turski, L., and Olney, J.W. (1999). Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 283, 70–74.10.1126/science.283.5398.70Search in Google Scholar PubMed

Istaphanous, G.K., Howard, J., Nan, X., Hughes, E.A., McCann, J.C., McAuliffe, J.J., Danzer, S.C., and Loepke, A.W. (2011). Comparison of the neuroapoptotic properties of equipotent anesthetic concentrations of desflurane, isoflurane, or sevoflurane in neonatal mice. Anesthesiology 114, 578–587.10.1097/ALN.0b013e3182084a70Search in Google Scholar PubMed

Jevtovic-Todorovic, V., Hartman, R.E., Izumi, Y., Benshoff, N.D., Dikranian, K., Zorumski, C.F., Olney, J.W., and Wozniak, D.F. (2003). Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J. Neurosci. 23, 876–882.10.1523/JNEUROSCI.23-03-00876.2003Search in Google Scholar PubMed

Ji, M.-H., Wang, X.-M., Sun, X.-R., Zhang, H., Ju, L.-S., Qiu, L.-L., Yang, J.-J., Jia, M., Wu, J., and Yang, J. (2015). Environmental enrichment ameliorates neonatal sevoflurane exposure-induced cognitive and synaptic plasticity impairments. J. Mol. Neurosci. 57, 358–365.10.1007/s12031-015-0627-1Search in Google Scholar PubMed

Ji, M.-H., Wang, Z.-Y., Sun, X.-R., Tang, H., Zhang, H., Jia, M., Qiu, L.-L., Zhang, G.-F., Peng, Y.G., and Yang, J.-J. (2017). Repeated neonatal sevoflurane exposure-induced developmental delays of parvalbumin interneurons and cognitive impairments are reversed by environmental enrichment. Mol. Neurobiol. 54, 3759–3770.10.1007/s12035-016-9943-xSearch in Google Scholar PubMed

Jia, M., Liu, W.-X., Yang, J.-J., Xu, N., Xie, Z.-M., Ju, L.-S., Ji, M.-H., Martynyuk, A.E., and Yang, J.-J. (2016). Role of histone acetylation in long-term neurobehavioral effects of neonatal exposure to sevoflurane in rats. Neurobiol. Dis. 91, 209–220.10.1016/j.nbd.2016.03.017Search in Google Scholar PubMed PubMed Central

Ju, L.-S., Jia, M., Sun, J., Sun, X.-R., Zhang, H., Ji, M.-H., Yang, J.-J., and Wang, Z.-Y. (2016). Hypermethylation of hippocampal synaptic plasticity-related genes is involved in neonatal sevoflurane exposure-induced cognitive impairments in rats. Neurotox. Res. 29, 243–255.10.1007/s12640-015-9585-1Search in Google Scholar PubMed

Ju, L.-S., Yang, J.-J., Morey, T.E., Gravenstein, N., Seubert, C.N., Resnick, J.L., Zhang, J.-Q., and Martynyuk, A.E. (2018). Role of epigenetic mechanisms in transmitting the effects of neonatal sevoflurane exposure to the next generation of male, but not female, rats. Br. J. Anaesth. 121, 406–416.10.1016/j.bja.2018.04.034Search in Google Scholar PubMed PubMed Central

Kempermann, G., Song, H., and Gage, F.H. (2015). Neurogenesis in the adult hippocampus. Cold Spring Harb. Perspect. Biol. 7, a018812.10.1101/cshperspect.a018812Search in Google Scholar PubMed PubMed Central

Lee, J.-R., Lin, E.P., Hofacer, R.D., Upton, B., Lee, S.Y., Ewing, L., Joseph, B., and Loepke, A.W. (2017). Alternative technique or mitigating strategy for sevoflurane-induced neurodegeneration: a randomized controlled dose-escalation study of dexmedetomidine in neonatal rats. Br. J. Anaesth. 119, 492–505.10.1093/bja/aex219Search in Google Scholar PubMed PubMed Central

Lei, X., Zhang, W., Liu, T., Xiao, H., Liang, W., Xia, W., and Zhang, J. (2013). Perinatal supplementation with omega-3 polyunsaturated fatty acids improves sevoflurane-induced neurodegeneration and memory impairment in neonatal rats. PLoS One 8, e70645.10.1371/journal.pone.0070645Search in Google Scholar PubMed PubMed Central

Liang, G., Ward, C., Peng, J., Zhao, Y., Huang, B., and Wei, H. (2010). Isoflurane causes greater neurodegeneration than an equivalent exposure of sevoflurane in the developing brain of neonatal mice. Anesthesiology 112, 1325–1334.10.1097/ALN.0b013e3181d94da5Search in Google Scholar PubMed PubMed Central

Liang, X., Zhang, Y., Zhang, C., Tang, C., Wang, Y., Ren, J., Chen, X., Zhang, Y., and Zhu, Z. (2017). Effect of repeated neonatal sevoflurane exposure on the learning, memory and synaptic plasticity at juvenile and adult age. Am. J. Transl. Res. 9, 4974–4983.Search in Google Scholar PubMed

Lim, B.-G., Shen, F.-Y., Kim, Y.-B., Kim, W.B., Kim, Y.S., Han, H.C., Lee, M.-K., Kong, M.-H., and Kim, Y.I. (2014). Possible role of GABAergic depolarization in neocortical neurons in generating hyperexcitatory behaviors during emergence from sevoflurane anesthesia in the rat. ASN Neuro 6.10.1042/AN20140004Search in Google Scholar PubMed PubMed Central

Lin, D., Feng, C., Cao, M., and Zuo, Z. (2011). Volatile anesthetics may not induce significant toxicity to human neuron-like cells. Anesth. Analg. 112, 1194–1198.10.1213/ANE.0b013e3181fdf69dSearch in Google Scholar PubMed

Lin, X.F., Han, Y.Q., Li, H.L., Zhao, Y.P., Fei, X.J., Sheng, J.X., Lu, H.H., Liu, S., and Zhang, L. (2014). SAHA attenuates sevoflurane-induced learning and memory impairments in fetal mice. Genet. Mol. Res. 13, 10769–10778.10.4238/2014.December.18.18Search in Google Scholar PubMed

Lin, D., Liu, J., Kramberg, L., Ruggiero, A., Cottrell, J., and Kass, I.S. (2016). Early-life single-episode sevoflurane exposure impairs social behavior and cognition later in life. Brain Behav. 6, e00514.10.1002/brb3.514Search in Google Scholar PubMed PubMed Central

Liston, C. and Gan, W.-B. (2011). Glucocorticoids are critical regulators of dendritic spine development and plasticity in vivo. Proc. Natl. Acad. Sci. U.S.A. 108, 16074–16079.10.1073/pnas.1110444108Search in Google Scholar PubMed PubMed Central

Liu, G., Zhu, T., Zhang, A., Li, F., Qian, W., and Qian, B. (2016). Heightened stress response and cognitive impairment after repeated neonatal sevoflurane exposures might be linked to excessive GABAAR-mediated depolarization. J. Anesth. 30, 834–841.10.1007/s00540-016-2215-0Search in Google Scholar PubMed

Liu, Y., Liu, C., Zeng, M., Han, X., Zhang, K., Fu, Y., Li, J., and Li, Y. (2018). Influence of sevoflurane exposure on mitogen-activated protein kinases and Akt/GSK-3β/CRMP-2 signaling pathways in the developing rat brain. Exp. Ther. Med. 15, 2066–2073.10.3892/etm.2017.5651Search in Google Scholar PubMed PubMed Central

Lu, Y., Wang, J., Yan, J., Yang, Y., Sun, Y., Huang, Y., Hu, R., Zhang, Y., and Jiang, H. (2015). Sevoflurane attenuate hypoxia-induced VEGF level in tongue squamous cell carcinoma cell by upregulating the DNA methylation states of the promoter region. Biomed. Pharmacother. 71, 139–145.10.1016/j.biopha.2015.02.032Search in Google Scholar PubMed

Lu, Y., Huang, Y., Jiang, J., Hu, R., Yang, Y., Jiang, H., and Yan, J. (2016). Neuronal apoptosis may not contribute to the long-term cognitive dysfunction induced by a brief exposure to 2% sevoflurane in developing rats. Biomed. Pharmacother. 78, 322–328.10.1016/j.biopha.2016.01.034Search in Google Scholar PubMed

Martynyuk, A.E., Yang, J.-J., and Zhang, J.-Q. (2017). Neurodevelopmental effects of anesthesia and environmental factors. Oncotarget 8, 9009–9010.10.18632/oncotarget.14694Search in Google Scholar PubMed PubMed Central

Mori, K., Iijima, N., Higo, S., Aikawa, S., Matsuo, I., Takumi, K., Sakamoto, A., and Ozawa, H. (2014). Epigenetic suppression of mouse Per2 expression in the suprachiasmatic nucleus by the inhalational anesthetic, sevoflurane. PLoS One 9, e87319.10.1371/journal.pone.0087319Search in Google Scholar PubMed PubMed Central

Nie, H., Peng, Z., Lao, N., Dong, H., and Xiong, L. (2013). Effects of sevoflurane on self-renewal capacity and differentiation of cultured neural stem cells. Neurochem. Res. 38, 1758–1767.10.1007/s11064-013-1074-4Search in Google Scholar PubMed

Peng, S., Yan, H.-Z., Liu, P.-R., Shi, X.-W., Liu, C.-L., Liu, Q., and Zhang, Y. (2018). Phosphodiesterase 4 inhibitor roflumilast protects rat hippocampal neurons from sevoflurane induced injury via modulation of MEK/ERK signaling pathway. Cell Physiol. Biochem. 45, 2329–2337.10.1159/000488180Search in Google Scholar PubMed

Qiu, J., Shi, P., Mao, W., Zhao, Y., Liu, W., and Wang, Y. (2015). Effect of apoptosis in neural stem cells treated with sevoflurane. BMC Anesthesiol. 15, 25.10.1186/s12871-015-0018-8Search in Google Scholar PubMed PubMed Central

Qiu, L., Zhu, C., Bodogan, T., Gómez-Galán, M., Zhang, Y., Zhou, K., Li, T., Xu, G., Blomgren, K., Eriksson, L.I., et al. (2016). Acute and long-term effects of brief sevoflurane anesthesia during the early postnatal period in rats. Toxicol. Sci. 149, 121–133.10.1093/toxsci/kfv219Search in Google Scholar PubMed

Radley, J.J., Rocher, A.B., Miller, M., Janssen, W.G.M., Liston, C., Hof, P.R., McEwen, B.S., and Morrison, J.H. (2006). Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex. Cereb. Cortex 16, 313–320.10.1093/cercor/bhi104Search in Google Scholar PubMed

Ramage, T.M., Chang, F.L., Shih, J., Alvi, R.S., Quitoriano, G.R., Rau, V., Barbour, K.C., Elphick, S.A., Kong, C.L., Tantoco, N.K., et al. (2013). Distinct long-term neurocognitive outcomes after equipotent sevoflurane or isoflurane anaesthesia in immature rats. Br. J. Anaesth. 110(Suppl 1), i39–i46.10.1093/bja/aet103Search in Google Scholar PubMed PubMed Central

Raper, J., de Biasio, J.C., Murphy, K.L., Alvarado, M.C., and Baxter, M.G. (2018). Persistent alteration in behavioural reactivity to a mild social stressor in rhesus monkeys repeatedly exposed to sevoflurane in infancy. Br. J. Anaesth. 120, 761–767.10.1016/j.bja.2018.01.014Search in Google Scholar PubMed PubMed Central

Sanders, R.D., Hassell, J., Davidson, A.J., Robertson, N.J., and Ma, D. (2013). Impact of anaesthetics and surgery on neurodevelopment: an update. Br. J. Anaesth. 110(Suppl 1), i53–i72.10.1093/bja/aet054Search in Google Scholar PubMed PubMed Central

Satomoto, M., Satoh, Y., Terui, K., Miyao, H., Takishima, K., Ito, M., and Imaki, J. (2009). Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice. Anesthesiology 110, 628–637.10.1097/ALN.0b013e3181974fa2Search in Google Scholar PubMed

Satomoto, M., Sun, Z., Adachi, Y.U., and Makita, K. (2016). Sugammadex-enhanced neuronal apoptosis following neonatal sevoflurane exposure in mice. Anesthesiol. Res. Pract. 2016, 9682703.10.1155/2016/9682703Search in Google Scholar PubMed PubMed Central

Satomoto, M., Sun, Z., Adachi, Y.U., and Makita, K. (2018). Neonatal sevoflurane exposure induces adulthood fear-induced learning disability and decreases glutamatergic neurons in the basolateral amygdala. J. Neurosurg. Anesthesiol. 30, 59–64.10.1097/ANA.0000000000000387Search in Google Scholar PubMed

Servick, K. (2014). Biomedical research. Researchers struggle to gauge risks of childhood anesthesia. Science 346, 1161–1162.10.1126/science.346.6214.1161Search in Google Scholar PubMed

Seubert, C.N., Zhu, W., Pavlinec, C., Gravenstein, N., and Martynyuk, A.E. (2013). Developmental effects of neonatal isoflurane and sevoflurane exposure in rats. Anesthesiology 119, 358–364.10.1097/ALN.0b013e318291c04eSearch in Google Scholar PubMed PubMed Central

Shi, Y., Wang, G., Li, J., and Yu, W. (2017). Hydrogen gas attenuates sevoflurane neurotoxicity through inhibiting nuclear factor κ-light-chain-enhancer of activated B cells signaling and proinflammatory cytokine release in neonatal rats. Neuroreport 28, 1170–1175.10.1097/WNR.0000000000000899Search in Google Scholar PubMed

Stevens, R.A., Butler, B.D., Kokane, S.S., Womack, A.W., and Lin, Q. (2017). Neonatal inhibition of Na+-K+-2Cl-cotransporter prevents ketamine induced spatial learning and memory impairments. Neurotoxicol. Teratol. 60, 82–86.10.1016/j.ntt.2016.11.001Search in Google Scholar PubMed PubMed Central

Tagawa, T., Sakuraba, S., Kimura, K., and Mizoguchi, A. (2014). Sevoflurane in combination with propofol, not thiopental, induces a more robust neuroapoptosis than sevoflurane alone in the neonatal mouse brain. J. Anesth. 28, 815–820.10.1007/s00540-014-1822-xSearch in Google Scholar PubMed

Tan, S., Xu, C., Zhu, W., Willis, J., Seubert, C.N., Gravenstein, N., Sumners, C., and Martynyuk, A.E. (2014). Endocrine and neurobehavioral abnormalities induced by propofol administered to neonatal rats. Anesthesiology 121, 1010–1017.10.1097/ALN.0000000000000366Search in Google Scholar PubMed PubMed Central

Tan, S., Wang, Y., Chen, K., Long, Z., and Zou, J. (2017). Ketamine alleviates depressive-like behaviors via down-regulating inflammatory cytokines induced by chronic restraint stress in mice. Biol. Pharm. Bull. 40, 1260–1267.10.1248/bpb.b17-00131Search in Google Scholar PubMed

Veyckemans, F. (2001). Excitation phenomena during sevoflurane anaesthesia in children. Curr. Opin. Anaesthesiol. 14, 339–343.10.1097/00001503-200106000-00010Search in Google Scholar PubMed

Vutskits, L. and Xie, Z. (2016). Lasting impact of general anaesthesia on the brain: mechanisms and relevance. Nat. Rev. Neurosci. 17, 705–717.10.1038/nrn.2016.128Search in Google Scholar PubMed

Wang, L.-Y., Tang, Z.-J., and Han, Y.-Z. (2016). Neuroprotective effects of caffeic acid phenethyl ester against sevoflurane-induced neuronal degeneration in the hippocampus of neonatal rats involve MAPK and PI3K/Akt signaling pathways. Mol. Med. Rep. 14, 3403–3412.10.3892/mmr.2016.5586Search in Google Scholar PubMed

Willis, J., Zhu, W., Perez-Downes, J., Tan, S., Xu, C., Seubert, C., Gravenstein, N., and Martynyuk, A. (2015). Propofol-induced electroencephalographic seizures in neonatal rats: the role of corticosteroids and γ-aminobutyric acid type A receptor-mediated excitation. Anesth. Analg. 120, 433–439.10.1213/ANE.0000000000000529Search in Google Scholar PubMed PubMed Central

Xia, Y., Xu, H., Jia, C., Hu, X., Kang, Y., Yang, X., Xue, Q., Tao, G., and Yu, B. (2017). Tanshinone IIA attenuates sevoflurane neurotoxicity in neonatal mice. Anesth. Analg. 124, 1244–1252.10.1213/ANE.0000000000001942Search in Google Scholar PubMed

Xiao, H., Liu, B., Chen, Y., and Zhang, J. (2016). Learning, memory and synaptic plasticity in hippocampus in rats exposed to sevoflurane. Int. J. Dev. Neurosci. 48, 38–49.10.1016/j.ijdevneu.2015.11.001Search in Google Scholar PubMed

Xie, S.-N., Ye, H., Li, J.-F., and An, L.-X. (2017). Sevoflurane neurotoxicity in neonatal rats is related to an increase in the GABAA R α1/GABAA R α2 ratio. J. Neurosci. Res. 95, 2367–2375.10.1002/jnr.24118Search in Google Scholar PubMed

Xu, C., Tan, S., Zhang, J., Seubert, C.N., Gravenstein, N., Sumners, C., Vasilopoulos, T., and Martynyuk, A.E. (2015). Anesthesia with sevoflurane in neonatal rats: developmental neuroendocrine abnormalities and alleviating effects of the corticosteroid and Cl(−) importer antagonists. Psychoneuroendocrinology 60, 173–181.10.1016/j.psyneuen.2015.06.016Search in Google Scholar PubMed PubMed Central

Yang, Z.-J., Wang, Y.-W., Li, C.-L., Ma, L.-Q., and Zhao, X. (2015). Pre-treatment with a Xingnaojing preparation ameliorates sevoflurane-induced neuroapoptosis in the infant rat striatum. Mol. Med. Rep. 11, 1615–1622.10.3892/mmr.2014.2934Search in Google Scholar PubMed PubMed Central

Yang, Z., Lv, J., Li, X., Meng, Q., Yang, Q., Ma, W., Li, Y., and Ke, Z.J. (2017a). Sevoflurane decreases self-renewal capacity and causes c-Jun N-terminal kinase-mediated damage of rat fetal neural stem cells. Sci. Rep. 7, 46304.10.1038/srep46304Search in Google Scholar PubMed PubMed Central

Yang, J., Ju, L., Jia, M., Zhang, H., Sun, X., Ji, M., Yang, J., and Martynyuk, A.E. (2017b). Subsequent maternal separation exacerbates neurobehavioral abnormalities in rats neonatally exposed to sevoflurane anesthesia. Neurosci. Lett. 661, 137–142.10.1016/j.neulet.2017.09.063Search in Google Scholar PubMed PubMed Central

Yonamine, R., Satoh, Y., Kodama, M., Araki, Y., and Kazama, T. (2013). Coadministration of hydrogen gas as part of the carrier gas mixture suppresses neuronal apoptosis and subsequent behavioral deficits caused by neonatal exposure to sevoflurane in mice. Anesthesiology 118, 105–113.10.1097/ALN.0b013e318275146dSearch in Google Scholar PubMed

Yu, Y., Zhang, P., Yan, J., Sun, Y., Wu, X., Xi, S., Zhang, L., Sun, Y., Hu, R., and Jiang, H. (2016). Sevoflurane induces cognitive impairments via the MiR-27b/LIMK1-signaling pathway in developing rats. Inhal. Toxicol. 28,731–738.10.1080/08958378.2016.1266532Search in Google Scholar PubMed

Yufune, S., Satoh, Y., Akai, R., Yoshinaga, Y., Kobayashi, Y., Endo, S., and Kazama, T. (2016). Suppression of ERK phosphorylation through oxidative stress is involved in the mechanism underlying sevoflurane-induced toxicity in the developing brain. Sci. Rep. 6, 21859.10.1038/srep21859Search in Google Scholar PubMed PubMed Central

Zhang, Y., Dong, Y., Zheng, H., Shie, V., Wang, H., Busscher, J.J., Yue, Y., Xu, Z., and Xie, Z. (2013). Sevoflurane inhibits neurogenesis and the Wnt-catenin signaling pathway in mouse neural progenitor cells. Curr. Mol. Med. 13, 1446–1454.10.2174/15665240113139990073Search in Google Scholar PubMed

Zhang, M.Q., Ji, M.H., Zhao, Q.S., Jia, M., Qiu, L.L., Yang, J.J., Peng, Y.G., and Martynyuk, A.E. (2015). Neurobehavioural abnormalities induced by repeated exposure of neonatal rats to sevoflurane can be aggravated by social isolation and enrichment deprivation initiated after exposure to the anaesthetic. Br. J. Anaesth. 115, 752–760.10.1093/bja/aev339Search in Google Scholar PubMed PubMed Central

Zhang, X., Shen, F., Xu, D., and Zhao, X. (2016a). A lasting effect of postnatal sevoflurane anesthesia on the composition of NMDA receptor subunits in rat prefrontal cortex. Int. J. Dev. Neurosci. 54, 62–69.10.1016/j.ijdevneu.2016.01.008Search in Google Scholar PubMed

Zhang, X., Liu, S., Newport, G.D., Paule, M.G., Callicott, R., Thompson, J., Liu, F., Patterson, T.A., Berridge, M.S., Apana, S.M., et al. (2016b). In vivo monitoring of sevoflurane-induced adverse effects in neonatal nonhuman primates using small-animal positron emission tomography. Anesthesiology 125, 133–146.10.1097/ALN.0000000000001154Search in Google Scholar PubMed

Zhang, J., Xu, C., Puentes, D.L., Seubert, C.N., Gravenstein, N., and Martynyuk, A.E. (2016c). Role of steroids in hyperexcitatory adverse and anesthetic effects of sevoflurane in neonatal rats. Neuroendocrinology 103, 440–451.10.1159/000437267Search in Google Scholar PubMed PubMed Central

Zhao, Y.L., Xiang, Q., Shi, Q.Y., Li, S.Y., Tan, L., Wang, J.T., Jin, X.G., and Luo, A.L. (2011). GABAergic excitotoxicity injury of the immature hippocampal pyramidal neurons’ exposure to isoflurane. Anesth. Analg. 113, 1152–1160.10.1213/ANE.0b013e318230b3fdSearch in Google Scholar PubMed

Zheng, S.-Q., Chen, X., Wang, Y.-J., An, L.-X. (2015). Effects of sevoflurane on brain neuroapoptosis and ability of long-term learning and memory in newborn rats. Beijing Da Xue Xue Bao 47, 674–678.Search in Google Scholar PubMed

Zhou, X., Song, F.-H., He, W., Yang, X.-Y., Zhou, Z.-B., Feng, X., and Zhou, L.-H. (2012). Neonatal exposure to sevoflurane causes apoptosis and reduces nNOS protein expression in rat hippocampus. Mol. Med. Rep. 6, 543–546.10.3892/mmr.2012.976Search in Google Scholar PubMed

Zhou, L., Wang, Z., Zhou, H., Liu, T., Lu, F., Wang, S., Li, J., Peng, S., and Zuo, Z. (2015). Neonatal exposure to sevoflurane may not cause learning and memory deficits and behavioral abnormality in the childhood of Cynomolgus monkeys. Sci. Rep. 5, 11145.10.1038/srep11145Search in Google Scholar PubMed PubMed Central

Zhou, X., Li, W., Chen, X., Yang, X., Zhou, Z., Lu, D., and Feng, X. (2016a). Dose-dependent effects of sevoflurane exposure during early lifetime on apoptosis in hippocampus and neurocognitive outcomes in Sprague-Dawley rats. Int. J. Physiol. Pathophysiol. Pharmacol. 8, 111–119.Search in Google Scholar

Zhou, X., da Li, W., Yuan, B.-L., Niu, L.-J., Yang, X.-Y., Zhou, Z.-B., Chen, X.-H., and Feng, X. (2016b). Lithium treatment prevents apoptosis in neonatal rat hippocampus resulting from sevoflurane exposure. Neurochem. Res. 41, 1993–2005.10.1007/s11064-016-1909-xSearch in Google Scholar PubMed

Zimering, J.H., Dong, Y., Fang, F., Huang, L., Zhang, Y., and Xie, Z. (2016). Anesthetic sevoflurane causes rho-dependent filopodial shortening in mouse neurons. PLoS One 11, e0159637.10.1371/journal.pone.0159637Search in Google Scholar PubMed PubMed Central

Zou, J., Wu, D., Li, T., Wang, X., Liu, Y., and Tan, S. (2019). Association of luteinizing hormone/choriogonadotropin receptor gene polymorphisms with polycystic ovary syndrome risk: a meta-analysis. Gynecol. Endocrinol. 35, 81–85.10.1080/09513590.2018.1498834Search in Google Scholar PubMed

Received: 2019-01-05
Accepted: 2019-03-29
Published Online: 2019-05-30
Published in Print: 2019-11-26

©2019 Walter de Gruyter GmbH, Berlin/Boston

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