TNF-α receptor antagonist attenuates isoflurane-induced cognitive impairment in aged rats

Yang,Nengli; Liang,Yafeng; Yang,Pei; Wang,Weijian; Zhang,Xuezheng; Wang,Junlu

doi:10.3892/etm.2016.3262

TNF-α receptor antagonist attenuates isoflurane-induced cognitive impairment in aged rats

Authors:
- Nengli Yang
- Yafeng Liang
- Pei Yang
- Weijian Wang
- Xuezheng Zhang
- Junlu Wang
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Affiliations: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: April 18, 2016 https://doi.org/10.3892/etm.2016.3262
Pages: 463-468

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Abstract

Postoperative cognitive dysfunction (POCD), a common clinical in aged patients, is characterized by deficits in cognitive functions in patients following anesthesia and surgery. It has been demonstrated that isoflurane may lead to cognitive impairment in aged rats; however, effective clinical interventions for preventing this disorder are limited. Tumor necrosis factor (TNF)-α has been suggested to be involved in neuroinflammation as well as the development of POCD. Accordingly, the present study aimed to investigate whether TNF‑α signaling is involved in the isoflurane‑induced cognitive impairment in aged rats, and whether TNF‑α receptor antagonist are able to attenuate isoflurane‑induced cognitive impairment in aged rats. A population of 20‑month‑old rats were administered TNF‑α receptor antagonist R‑7050 or an equal volume of saline by intraperitoneal injection 12 h prior to exposure to isoflurane to model cognitive impairment following anesthesia in old patients. Then the rats were exposed to 1.3% isoflurane for 4 h. In the control group, rats showed impaired cognitive functions evaluated by Morris water maze assay after isoflurane exposure. Furthermore, isoflurane exposure induced marked upregulation of proinflammatory cytokines, including interleukin (IL)‑1β, TNF‑α, IL‑6 and IL‑8 in the hippocampus tissue. In the experimental group, intracisternal administration of TNF‑α receptor antagonist R‑7050 significantly attenuated isoflurane‑induced cognitive impairment and upregulation of proinflammatory cytokines. Further investigation revealed that intracisternal administration of TNF‑α receptor antagonist R‑7050 notably suppressed isoflurane‑induced activation of NF‑κB and MAPK signaling. Collectively, the present results suggest that TNF-α receptor antagonist may serve as a potential agent for the prevention of anesthesia-induced cognitive decline in aged patients.

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