Original Research

Surgery Induces Activation of Indoleamine 2, 3-Dioxygenase, Increases in Pro-Inflammatory Cytokines and Cognitive Impairment in Old Rats

Xiao Wang , Li Chen , Hui-Wei Zhang , Chun-Yu Gong , Kang Yi , Zhuo Li , Huai-ming Wang , Jin Liu , Zhongcong Xie , Jing Yang
Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China, Department of Surgery, NO. 4 West China Teaching Hospital,Sichuan University, Chengdu, China Department of pharmacy, Shaanxi provincial people's hospital, Xi'an, China Geriatric Anesthesia Research Unit, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, USA
J Anesth Perioper Med 2015; 2(1): 14- 21 . Published on Jan 16, 2015 . doi:10.24015/JAPM.2015.0003
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Background: Postoperative cognitive dysfunction (POCD) is one of the most common complications in senior patients after surgery. However, the cause is largely unknown. Activation of indoleamine 2, 3-dioxygenase (IDO), a rate-limiting enzyme of kynurenine pathway, which converts tryptophan into kynurenine in extrahepatic tissues, may contribute to cognitive impairment. We therefore set out to assess whether surgery under anesthesia can induce activation of IDO, neuroinflammation and cognitive impairment in old rats.

Methods: Male Sprague-Dawley rats (24-month-old) were randomly assigned into three groups: 40% oxygen inhalation, 1.8% isoflurane anesthesia and left nephrectomy under 1.8% isoflurane anesthesia. Cognitive function was assessed daily in Y maze. Levels of interferon gamma (IFN-γ) and interleukin-6 (IL-6), IDO, tryptophan and kynurenine in serum and hippocampus were determined at 6 hours, 1, 3 and 7 days after anesthesia or surgery by using MILLIPLEX MAP Rat Cytokine Panel, enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), respectively. 

Results: Anesthesia with 1.8% isoflurane for three hours increased IL-6 level in serum at six hours which returned to normal level at 24 hours after the anesthesia. The isoflurane anesthesia alone did not induce cognitive impairment. Nephrectomy plus isoflurane elevated IFN-γ level in serum, increased levels of IL-6 and IDO, and IDO activity, determined by the ratio of tryptophan and kynurenine, in both serum and hippocampus, and finally induced cognitive impairment. These data showed that surgery under isoflurane anesthesia may induce activation of IDO, neuroinflammation and cognitive impairment in old rats.

Conclusions: These results suggested the potential role of IDO pathway in POCD pathogenesis, pending on further studies.



Citation: Xiao Wang, Li Chen, Hui-Wei Zhang, Chun-Yu Gong, Kang Yi, Zhuo Li, et al. Surgery induces activation of indoleamine 2,3-dioxygenase, increases in pro-inflammatory cytokines and cognitive impairment in old rats. J Anesth Perioper Med 2015; 2: 14-21. doi: 10.24015/JAPM.2015.0003
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