Combination of Isoflurane and Propofol as General Anesthesia During Orthopedic Surgery of Perioperative Cerebral Hypoperfusion Rats to Avoid Cognitive Impairment

Frontiers in Medicine

article

Xinyue Bu¹  Ji Ma³  Zhuo Yang⁴  Guolin Wang⁵  Tang Li¹  Haiyun Wang¹  Zhengyuan Xia⁷  Di Guo¹  Jinxin Wang¹  Yi Sun²  Chenyi Yang²  Guoqiang Liu² 

[1] Department of Anesthesiology, The Third Central Clinical College of Tianjin Medical University;Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease;The Third Central Hospital of Tianjin;State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials for Ministry of Education, College of Medicine, Nankai University;Tianjin Research Institute of Anesthesiology;Tianjin Third Central Hospital, Nankai University;Department of Anesthesiology, University of Hong Kong

关键词: cerebral hypoperfusion;    cognitive function;    isoflurane;    propofol;    GABA A R α1;    BiP;   

DOI  :  10.3389/fmed.2020.549081

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Background: Perioperative cerebral hypoperfusion (CH) is common, although the underlying mechanism of cognitive impairment that results due to perioperative cerebral hypoperfusion remains to be determined. Isoflurane anesthesia induces neuronal injury via endoplasmic reticulum (ER) stress, whereas a sub-anesthetic dose of propofol improves postoperative cognitive function. However, the effects of the combination of isoflurane plus propofol, which is a common aesthetic combination administered to patients, on ER stress and cognition remain unknown. Methods: We sought to determine the effects of isoflurane plus propofol on ER stress and cognitive function in rats insulted by cerebral hypoperfusion. Ligation of the bilateral common carotid arteries (CCA) was adopted to develop the cerebral hypoperfusion rat model. A second surgery, open reduction and internal fixation (ORIF), requiring general anesthesia, was performed 30 days later so that the effects of anesthetics on the cognitive function of CH rats could be assessed. Rats received isoflurane alone (1.9%), propofol alone (40 mg·kg −1 ·h −1 ) or a combination of isoflurane and propofol (1% and 20 mg·kg −1 ·h −1 or 1.4% and 10 mg·kg −1 ·h −1 ). Behavioral studies (contextual fear conditioning [FC] test), histological analyses (Nissl staining) and biochemical analyses (western blotting of the harvested rat brain tissues) were employed. Results: Hippocampus-dependent memory of rats in group IP 1 (1% isoflurane plus 20 mg·kg −1 ·h −1 propofol) was not impaired, and expression level of γ-aminobutyric acid A type receptor α1 subunit, a key cognition-related protein, remained normal. ER stress alleviator, binding immunoglobulin protein, increased extremely while ER stress transcription factor, C/EBP homologous protein, showed no statistical difference compared with the control group. Numbers of surviving neurons confirmed the substantial neuronal damage caused by propofol or isoflurane alone. Conclusions: These data suggest that ER stress contributes to the underlying mechanism of cognitive impairment and that the combination of isoflurane and propofol did not aggravate cognitive impairment and ER stress in aging rats with CH that were further subjected to ORIF surgery.

【 授权许可】

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