Isoflurane-induced postoperative cognitive dysfunction is mediated by hypoxia-inducible factor-1[alpha]-dependent neuroinflammation in aged rats

Elderly patients are at high risk of developing postoperative cognitive dysfunction (POCD) after prolonged exposure to inhaled anesthetics. However, the pathogenesis of POCD remains unknown. Hypoxia-inducible factor-1[alpha] (HIF-1[alpha]) is activated by inhaled anesthetics. The aim of the present...

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Published inMolecular medicine reports Vol. 17; no. 6; p. 7730
Main Authors Cao, Yiyun, Li, Zhengqian, Ma, Lijun, Ni, Cheng, Li, Lunxu, Yang, Ning, Shi, Chengmei, Guo, Xiangyang
Format Journal Article
LanguageEnglish
Published Spandidos Publications 01.06.2018
Subjects
Care and treatment
Cognitive disorders
Development and progression
Elderly patients
Genetic aspects
Health aspects
Transcription factors
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Summary:Elderly patients are at high risk of developing postoperative cognitive dysfunction (POCD) after prolonged exposure to inhaled anesthetics. However, the pathogenesis of POCD remains unknown. Hypoxia-inducible factor-1[alpha] (HIF-1[alpha]) is activated by inhaled anesthetics. The aim of the present study was to determine the role of HIF-1[alpha] in isoflurane-induced neuroinflammation and the resulting cognitive impairment. Following a 4-h exposure to 1.5% isoflurane in 20-month-old rats, increased expression of HIF-1[alpha] protein, activation of nuclear factor (NF)-[kappa]B signaling and increased expression of TNF-1[alpha] were observed in the hippocampus of isoflurane-exposed rats compared with the control group. Pharmacological inhibition of HIF-1[alpha] activation by 5-[1-(phenylmethyl)-1H-indazol-3-yl]-2-furanmethanol (YC-1) markedly suppressed the enhanced expression of HIF-1[alpha], disrupted NF-[kappa]B signaling pathway activity and inhibited the isoflurane-induced increase of TNF-1[alpha] expression. YC-1 pretreatment also significantly attenuated isoflurane-induced cognitive deficits according to the results of the Morris water maze task. These results suggest that hippocampal HIF-1[alpha] appears to be involved in an upstream mechanism of isoflurane-induced cognitive impairment. Further research is warranted to fully clarify the pathogenesis and investigate HIF-1[alpha] as a potential therapeutic target for POCD. Key words: isoflurane, postoperative cognitive dysfunction, hypoxia-inducible factor-1[alpha], nuclear factor-[kappa]B
ISSN:1791-2997
1791-3004
DOI:10.3892/mmr.2018.8850