Exogenous recombinant Hsp70 attenuates sevoflurane anesthesia‐induced cognitive dysfunction in aged mice

• Published in: Brain and behavior Vol. 13; no. 1; pp. e2861 - n/a
• Main Authors: Xie, Yongxiang, Huang, Jianzhong, Chen, Yijia
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.01.2023; John Wiley and Sons Inc; Wiley
• Subjects: Aged; Aging; Alzheimer's disease; Anesthesia; Anesthetics, Inhalation; Animal cognition; Animal memory; Animals; Antibodies; Apoptosis; Cognitive ability; Cognitive Dysfunction - chemically induced; Cognitive Dysfunction - drug therapy; Cognitive Dysfunction - prevention & control; cognitive function; Cytokines; Enzymes; Heat shock proteins; Hippocampus - metabolism; HSP70 Heat-Shock Proteins - metabolism; HSP70 Heat-Shock Proteins - pharmacology; Humans; Mice; neuroinflammation; Neurotoxicity; NF-kappa B - metabolism; Original; Parkinson's disease; Pathogenesis; Polymerase chain reaction; recombinant Hsp70; sevoflurane; Sevoflurane - pharmacology; Variance analysis; cognitive function; recombinant Hsp70; sevoflurane; aging; neuroinflammation
• ISSN: 2162-3279; 2162-3279
• DOI: 10.1002/brb3.2861

Background Postoperative cognitive dysfunction (POCD) is a severe postoperative neurological sequela in elderly patients, and there is currently no standard treatment for POCD. In this study, whether recombinant human heat shock protein 70 (rHsp70) could alleviate sevoflurane‐induced cognitive impairment in aged mice is investigated. Methods To determine the prophylactic effect of rHsp70 in sevoflurane‐induced cognitive dysfunction, aged mice were pretreated with different concentrations of rHsp70 (29.4, 58.8, and 117.6 μg/kg; intranasal injected; N = 12) every day for 1 week; then, 3% sevoflurane was utilized to anesthetize the aged mice. Cognitive function, neurotoxicity, and serum and hippocampal Hsp70 levels in aged mice undergoing sevoflurane anesthesia were assessed by the Morris water maze test and enzyme‐linked immunosorbent assay. The effects of rHsp70 on inflammatory response were assessed by proinflammatory cytokine production and nuclear factor‐κB (NF‐κB) activation assays. Results We found that aged mice exposed to sevoflurane showed reduced learning and memory ability and reduced Hsp70 expression, which were both restored by rHsp70 pretreatment. RHsp70 also reversed sevoflurane‐induced up‐regulated Bax and Bcl‐2 expression and interleukin‐1, IL‐6, and monocyte chemoattractant protein‐1 overproduction. Finally, rHsp70 pretreatment suppressed sevoflurane‐induced NF‐κB activation. Our study indicated that rHsp70 was sufficient to suppress sevoflurane‐induced cognitive decline and neurotoxicity. Conclusion Our important finding warrants further study on the clinical application of rHsp70 in elderly patients undergoing anesthesia. 1. rHsp70 pretreatment suppressed sevoflurane induced NF‐?B activation. 2>. rHsp70 is sufficient to suppress sevoflurane induced cognitive decline and neurotoxicity.