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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


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).


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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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