Role of hippocampal β-amyloid 42 deposition-induced accumulation of neutrophils in blood-brain barrier damage caused by sevoflurane anesthesia in aged rats
10.3760/cma.j.cn131073.20210714.00814
- VernacularTitle:海马Aβ 42沉积诱发中性粒细胞聚集在七氟烷麻醉导致老龄大鼠血脑屏障损伤中的作用
- Author:
Munan HAN
1
;
Qi ZHAO
;
Beibei DONG
;
Yang YU
;
Yonghao YU
;
Guolin WANG
;
Lianbing GU
Author Information
1. 南京医科大学第一临床医学院 211166
- Keywords:
Anesthetics, inhalation;
Cognitive dysfunction;
Blood-brain barrier;
Amyloid beta-peptides;
Neutrophils;
Aged
- From:
Chinese Journal of Anesthesiology
2021;41(8):955-958
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the role of hippocampal β-amyloid 42 (Aβ 42) deposition-induced accumulation of neutrophils in blood-brain barrier damage caused by sevoflurane anesthesia in aged rats. Methods:Seventy-two healthy male Wistar rats in which IT catheters were successfully planted, aged 18-20 months, weighing 600-650 g, were divided into 4 groups ( n=18 each) using a random number table method: control group (group C), γ-secretase inhibitor DAPT group (group D), sevoflurane anesthesia group (group S) and DAPT plus sevoflurane anesthesia group (group DS). Dimethyl sulfoxide 10 μl was intrathecally injected in group C and group S, and 30 min later group C inhaled 60% oxygen for 2 h, and group S inhaled 3.6% sevoflurane and 60% oxygen for 2 h and tibial fracture surgery was performed at the same time.DAPT 10 μl was intrathecally injected in group D and group DS, and 30 min later group D inhaled 60% oxygen for 2 h, and group DS inhaled 3.6% sevoflurane and 60% oxygen for 2 h and tibial fracture surgery was performed at the same time.The fear conditioning test was performed at 12 h after the end of treatment in each group, and the ratio of time spent freezing was calculated.The rats were sacrificed after the end of behavioral test, and hippocampal tissues were removed for determination of the expression of Aβ 42, occludin and matrix metalloproteinase-9 (MMP-9) (by Western blot), neutrophil count (by immuno-histochemistry), and content of Evans blue (EB) (by EB staining). Results:Compared with group C, the ratio of time spent freezing was significantly decreased, the expression of Aβ 42 and MMP-9 was up-regulated, the expression of occludin was down-regulated, the neutrophil count and content of EB were increased in group S and group DS ( P<0.05), and no significant change was found in the parameters mentioned above in group D ( P>0.05). Compared with group S, the ratio of time spent freezing was significantly increased, the expression of Aβ 42 and MMP-9 was down-regulated, the expression of occludin was up-regulated, the neutrophil count and content of EB were decreased in group DS ( P<0.05). Conclusion:The mechanism by which sevoflurane anesthesia leads to postoperative cognitive dysfunction is related to hippocampal Aβ 42 deposition-induced accumulation of neutrophils and causing damage to blood-brain barrier in aged rats.
