title: Isoflurane anesthesia results in reversible ultrastructure and occludin tight junction protein expression changes in hippocampal blood-brain barrier in aged rats.
abstract: The underlying mechanism of isoflurane-induced cognitive dysfunction in older individuals is unknown. In this study, the effects of isoflurane exposure on the hippocampal blood-brain barrier (BBB) in aged rats were investigated because it was previously shown that BBB disruption involves in cognitive dysfunction. Twenty-month-old rats randomly received 1.5% isoflurane or vehicle gas as control. Hippocampal BBB ultrastructure was analyzed by transmission electron microscopy and expression of tight junction proteins was measured by western blot analysis. BBB permeability was detected with sodium fluorescein extravasation and further confirmed by immunoglobulin G immunohistochemistry. Spatial learning and memory were assessed by the Morris water maze test. Isoflurane anesthesia resulted in reversible time-dependent BBB ultrastructure morphological damage and significant decreases in expression of the tight junction proteins occludin, which contributed to sodium fluorescein and IgG leakage. Rats with isoflurane exposure also showed significant cognitive deficits in the Morris water maze test. This in vivo data indicate that occludin down-regulation may be one of the mediators of isoflurane-induced hippocampus BBB disruption, and may contribute to hippocampus-dependent cognitive impairment after isoflurane exposure in aged rats.
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Ni
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Zhengqian
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Lunxu
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Chunyi
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Peking University, Beijing 100191, China. Electronic address: zhongyf@bjmu.edc.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Neuroscience Research Institute, Department of Neurobiology, Peking University, Beijing 100191, China. Electronic address: dchui@bjmu.edu.
authors.forename: Dehua
authors.initials: D
authors.lastname: Cui
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China. Electronic address: puthmzk@163.com.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Guo
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000523:psychology; D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D003071:Cognition / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007530:Isoflurane / Q000009:adverse effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D062793:Occludin / Q000378:metabolism*; D010539:Permeability; D017207:Rats, Sprague-Dawley; D065853:Spatial Learning / Q000187:drug effects; D019108:Tight Junctions / Q000378:metabolism*
chemical_list: D018685:Anesthetics, Inhalation; D062793:Occludin; C568987:Ocln protein, rat; D007530:Isoflurane
keywords: Blood–brain barrier; Hippocampus; Postoperative cognitive dysfunction; Tight junction protein