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Anti-RAGE antibody attenuates isoflurane-induced cognitive dysfunction in aged rats.
Behav Brain Res 2017; 322(Pt A):167-176BB

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+Show Affiliations

Department of Anesthesiology, Peking University Third Hospital (PUTH), Beijing 100191, China.Department of Anesthesiology, Peking University Third Hospital (PUTH), Beijing 100191, China.Department of Anesthesiology, Peking University Third Hospital (PUTH), Beijing 100191, China.Department of Anesthesiology, Tsinghua University Yuquan Hospital, Beijing 100040, China.Department of Anesthesiology, Peking University Third Hospital (PUTH), Beijing 100191, China.Central Laboratory, Peking University Third Hospital (PUTH), Beijing 100191, China.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.Department of Anesthesiology, Peking University Third Hospital (PUTH), Beijing 100191, China. Electronic address: puthmzk@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28115220

Citation

Shi, Chengmei, et al. "Anti-RAGE Antibody Attenuates Isoflurane-induced Cognitive Dysfunction in Aged Rats." Behavioural Brain Research, vol. 322, no. Pt A, 2017, pp. 167-176.
Shi C, Yi D, Li Z, et al. Anti-RAGE antibody attenuates isoflurane-induced cognitive dysfunction in aged rats. Behav Brain Res. 2017;322(Pt A):167-176.
Shi, C., Yi, D., Li, Z., Zhou, Y., Cao, Y., Sun, Y., ... Guo, X. (2017). Anti-RAGE antibody attenuates isoflurane-induced cognitive dysfunction in aged rats. Behavioural Brain Research, 322(Pt A), pp. 167-176. doi:10.1016/j.bbr.2017.01.012.
Shi C, et al. Anti-RAGE Antibody Attenuates Isoflurane-induced Cognitive Dysfunction in Aged Rats. Behav Brain Res. 2017 03 30;322(Pt A):167-176. PubMed PMID: 28115220.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-RAGE antibody attenuates isoflurane-induced cognitive dysfunction in aged rats. AU - Shi,Chengmei, AU - Yi,Duan, AU - Li,Zhengqian, AU - Zhou,Yongde, AU - Cao,Yiyun, AU - Sun,Yan, AU - Chui,Dehua, AU - Guo,Xiangyang, Y1 - 2017/01/20/ PY - 2016/10/13/received PY - 2017/01/05/revised PY - 2017/01/06/accepted PY - 2017/1/25/pubmed PY - 2017/12/2/medline PY - 2017/1/25/entrez KW - Aβ KW - BBB KW - Cognitive dysfunction KW - Isoflurane KW - Neuroinflammation KW - RAGE SP - 167 EP - 176 JF - Behavioural brain research JO - Behav. Brain Res. VL - 322 IS - Pt A N2 - 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. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/28115220/Anti_RAGE_antibody_attenuates_isoflurane_induced_cognitive_dysfunction_in_aged_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(16)30828-2 DB - PRIME DP - Unbound Medicine ER -