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 (HIF-1) is activated by inhaled anesthetics. The aim of the present study was to determine the role of HIF-1 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 protein, activation of nuclear factor (NF)-B signaling and increased expression of TNF-1 were observed in the hippocampus of isoflurane-exposed rats compared with the control group. Pharmacological inhibition of HIF-1 activation by 5-[1-(phenylmethyl)-1H-indazol-3-yl]-2-furanmethanol (YC-1) markedly suppressed the enhanced expression of HIF-1, disrupted NF-B signaling pathway activity and inhibited the isoflurane-induced increase of TNF-1 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 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 as a potential therapeutic target for POCD.
[1]Shanghai Univ Med & Hlth Sci, Peoples Hosp East Campus 6, Dept Anesthesiol, Shanghai 200233, Peoples R China.
[2]Peking Univ, Dept Anesthesiol, Hosp 3, 49 North Garden St, Beijing 100191, Peoples R China.
[3]North Minzu Univ, Dept Med Imaging, Ningxia 750021, Peoples R China.
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