title: Inhibiting tumor necrosis factor-α signaling attenuates postoperative cognitive dysfunction in aged rats.
abstract: Postoperative cognitive dysfunction (POCD), commonly observed in elderly patients, is characterized by impaired concentration, memory and learning following surgery, and may persist for a long duration or progress into serious central nervous system diseases. It has been demonstrated neuroinflammation caused by surgery is involved in the development of POCD. However, the detailed molecular mechanism remains to be fully elucidated. The present study aimed to reveal the role of tumor necrosis factor (TNF)-α in the development of POCD in aged rats. Laparotomy was performed to mimic human abdominal surgery in the aged rats. Following surgery, the memory and learning functions were impaired, with significant upregulation of pro-inflammatory cytokines, including TNF-α, interleukin (IL)-1β, IL-4 and IL-6 in the hippocampal tissues. However, intracisternal administration of the TNF-α receptor antagonist, R-7050, during surgery attenuated these defects in cognitive function and inhibited the production of the pro-inflammatory cytokines in the hippocampal tissues. Furthermore, intracisternal administration of R-7050 inhibited the activation of the downstream nuclear factor-κB and mitogen-activated protein kinase signaling pathway in the hippocampal tissues. Therefore, the results of the present study suggested a key role of the TNF-α-mediated signaling pathway in the development of POCD.
authors.affiliation: Department of Anesthesiology, Dezhou People's Hospital, Dezhou, Shandong 253045, P.R. China.
authors.forename: Yuanzhong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, China Meitan General Hospital, Beijing 100028, P.R. China.
authors.forename: Qinghao
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Department of Anesthesiology, Dezhou People's Hospital, Dezhou, Shandong 253045, P.R. China.
authors.forename: Ermin
authors.initials: E
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, China Meitan General Hospital, Beijing 100028, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Dezhou People's Hospital, Dezhou, Shandong 253045, P.R. China.
authors.forename: Xubin
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000005:Abdomen / Q000601:surgery; D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation; D007276:Injections, Intraventricular; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D011183:Postoperative Complications; D011810:Quinoxalines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D011810:Quinoxalines; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4