PMID- 25450597 OWN - NLM STAT- MEDLINE DCOM- 20150429 LR - 20240209 IS - 1095-8673 (Electronic) IS - 0022-4804 (Linking) VI - 194 IP - 1 DP - 2015 Mar TI - Alpha 7 nicotinic acetylcholine receptor agonist GTS-21 mitigates isoflurane-induced cognitive impairment in aged rats. PG - 255-61 LID - S0022-4804(14)00904-4 [pii] LID - 10.1016/j.jss.2014.09.043 [doi] AB - BACKGROUND: Postoperative cognitive dysfunction is increasingly recognized as an important clinical syndrome. Inhalation anesthetics are commonly used during surgery, and it has been proposed that inhalation anesthetics impair cognitive function. However, there are few clinical interventions and treatments available to prevent this disorder. GTS-21, a selective agonist of alpha 7 nicotinic acetylcholine receptor, has been indicated to exert neuroprotective effects in the experimental animal models of neurodegenerative diseases. Therefore, we hypothesized that pretreatment with GTS-21 attenuates isoflurane-induced cognitive decline in aged rats. METHODS: In the present study, 20-mo-old rats were administered GTS-21 or an equal volume of saline by intraperitoneal injection 30 min before exposure to isoflurane. Then the rats were exposed to 1.3% isoflurane for 4 h. Spatial learning and memory of the rats were assessed at 2 wk after isoflurane exposure. The expression levels of interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha in the hippocampus and cerebral cortex were determined by enzyme-linked immunosorbent assay. Simultaneously, neuronal apoptosis in the hippocampus was also observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and Nissl staining. RESULTS: We found that exposure to isoflurane induces learning and memory deficits of old rats. IL-1beta in the hippocampus was increased at 4 h after isoflurane exposure. Isoflurane also increased neuroapoptosis in the hippocampus and decreased neuronal density in the CA1 region. And GTS-21 pretreatment effectively alleviated these changes. CONCLUSIONS: The study demonstrated that pretreatment with alpha7 nicotinic acetylcholine receptor agonist GTS-21 attenuates isoflurane-induced learning and memory impairment in aged rats. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Kong, Fei-Juan AU - Kong FJ AD - Department of Endocrinology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Department of Anesthesiology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China. FAU - Ma, Lei-Lei AU - Ma LL AD - Department of cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Zhang, Hong-Hai AU - Zhang HH AD - Department of Anesthesiology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China. FAU - Zhou, Jia-Qiang AU - Zhou JQ AD - Department of Endocrinology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: xzzzju@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141005 PL - United States TA - J Surg Res JT - The Journal of surgical research JID - 0376340 RN - 0 (Anesthetics, Inhalation) RN - 0 (Benzylidene Compounds) RN - 0 (IL1B protein, rat) RN - 0 (Interleukin-1beta) RN - 0 (Nicotinic Agonists) RN - 0 (Pyridines) RN - 8S399XDN2K (3-(2,4-dimethoxybenzylidene)anabaseine) RN - CYS9AKD70P (Isoflurane) SB - IM MH - Anesthetics, Inhalation/*toxicity MH - Animals MH - Apoptosis/drug effects MH - Benzylidene Compounds/*pharmacology MH - Cognition Disorders/chemically induced/*drug therapy MH - Hippocampus/chemistry/drug effects MH - Interleukin-1beta/analysis MH - Isoflurane/*toxicity MH - Male MH - Nicotinic Agonists/*pharmacology MH - Pyridines/*pharmacology MH - Rats MH - Rats, Sprague-Dawley OTO - NOTNLM OT - Aged rats OT - Alpha 7 nicotinic acetylcholine receptor OT - Apoptosis OT - Isoflurane OT - Learning and memory EDAT- 2014/12/03 06:00 MHDA- 2015/04/30 06:00 CRDT- 2014/12/03 06:00 PHST- 2014/07/28 00:00 [received] PHST- 2014/09/19 00:00 [revised] PHST- 2014/09/29 00:00 [accepted] PHST- 2014/12/03 06:00 [entrez] PHST- 2014/12/03 06:00 [pubmed] PHST- 2015/04/30 06:00 [medline] AID - S0022-4804(14)00904-4 [pii] AID - 10.1016/j.jss.2014.09.043 [doi] PST - ppublish SO - J Surg Res. 2015 Mar;194(1):255-61. doi: 10.1016/j.jss.2014.09.043. Epub 2014 Oct 5.