Shi Chengmei, Yi Duan, Li Zhengqian, Zhou Yongde, Cao Yiyun, Sun Yan, Chui Dehua, Guo Xiangyang
Department of Anesthesiology, Peking University Third Hospital (PUTH), Beijing 100191, China.
Department of Anesthesiology, Tsinghua University Yuquan Hospital, Beijing 100040, China.
Behav Brain Res. 2017 Mar 30;322(Pt A):167-176. doi: 10.1016/j.bbr.2017.01.012. Epub 2017 Jan 20.
Several animal studies demonstrated that the volatile anesthetic isoflurane could influence the blood-brain barrier (BBB) integrity, which involved the cognitive impairment. Increasing evidence has also shown that the receptor for advanced glycation end-products (RAGE) played a major role in maintaining the integrity of BBB. The present study aimed to determine whether the RAGE-specific antibody protects against BBB disruption and cognitive impairment induced by isoflurane exposure in aged rats. 108 aged rats were randomly divided into four groups: (1) control group (Control); (2) 4h of 2% isoflurane exposure group (ISO); (3) RAGE antibody (20μL, 2.5μg/μL) treated+4h of 2% isoflurane exposure group (anti-RAGE+ISO); (4) RAGE antibody (20μL, 2.5μg/μL) treated group (anti-RAGE). The isoflurane anesthesia resulted in the upregulation of hippocampal RAGE expression, disruption of BBB integrity, neuroinflammation, and beta-amyloid (Aβ) accumulation in aged rats. In addition, significant cognitive deficits in the Morris water maze test was also observed. The antibody pretreatment resulted in significant improvements in BBB integrity. Furthermore, the expression of RAGE and proinflammatory mediators, as well as, Aβ accumulation were attenuated. Moreover, the antibody administration attenuated the isoflurane-induced cognitive impairment in aged rats. These results demonstrate that RAGE signaling is involved in BBB damage after isoflurane exposure. Thus, the RAGE antibody represents a novel therapeutic intervention to prevent isoflurane-induced cognitive impairment.
多项动物研究表明，挥发性麻醉剂异氟烷可影响血脑屏障（BBB）的完整性，这与认知功能障碍有关。越来越多的证据还表明，晚期糖基化终产物受体（RAGE）在维持血脑屏障的完整性方面起主要作用。本研究旨在确定RAGE特异性抗体是否能预防异氟烷暴露诱导的老年大鼠血脑屏障破坏和认知功能障碍。108只老年大鼠被随机分为四组：（1）对照组（Control）；（2）2%异氟烷暴露4小时组（ISO）；（3）RAGE抗体（20μL，2.5μg/μL）处理+2%异氟烷暴露4小时组（抗RAGE+ISO）；（4）RAGE抗体（20μL，2.5μg/μL）处理组（抗RAGE）。异氟烷麻醉导致老年大鼠海马RAGE表达上调、血脑屏障完整性破坏、神经炎症和β-淀粉样蛋白（Aβ）积累。此外，在莫里斯水迷宫试验中还观察到明显的认知缺陷。抗体预处理使血脑屏障完整性得到显著改善。此外，RAGE和促炎介质的表达以及Aβ积累均减弱。此外，抗体给药减轻了异氟烷诱导的老年大鼠认知功能障碍。这些结果表明，RAGE信号通路参与了异氟烷暴露后的血脑屏障损伤。因此，RAGE抗体是预防异氟烷诱导的认知功能障碍的一种新型治疗干预措施。
