title: Anti-RAGE antibody attenuates isoflurane-induced cognitive dysfunction in aged rats.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital (PUTH), Beijing 100191, China.
authors.forename: Chengmei
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital (PUTH), Beijing 100191, China.
authors.forename: Duan
authors.initials: D
authors.lastname: Yi
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital (PUTH), Beijing 100191, China.
authors.forename: Zhengqian
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Tsinghua University Yuquan Hospital, Beijing 100040, China.
authors.forename: Yongde
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital (PUTH), Beijing 100191, China.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Central Laboratory, Peking University Third Hospital (PUTH), Beijing 100191, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Neuroscience Research Institute & Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education & Ministry of Public Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Dehua
authors.initials: D
authors.lastname: Chui
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital (PUTH), Beijing 100191, China. Electronic address: puthmzk@163.com.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Guo
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D000906:Antibodies / Q000008:administration & dosage*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D060825:Cognitive Dysfunction / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007530:Isoflurane / Q000633:toxicity*; D008297:Male; D018697:Nootropic Agents / Q000008:administration & dosage*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C000593873:Ager protein, mouse; D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies; D018697:Nootropic Agents; D000067759:Receptor for Advanced Glycation End Products; D014409:Tumor Necrosis Factor-alpha; D007530:Isoflurane
keywords: Aβ; BBB; Cognitive dysfunction; Isoflurane; Neuroinflammation; RAGE