Chronic inflammation plays an important role in the mechanisms underpinning the development of anesthesia-induced cognitive dysfunction. However, less is known about how anesthesia causes inflammation. One possibility is that the inflammation is related to alteration of the activity of the alpha 7 nicotinic acetylcholine receptor cholinergic anti-inflammatory pathway. This study analyzed the effect of sevoflurane administration on the cognitive function by using a novel object recognition test and Y-maze test, and on acetylcholinesterase activity and expression in hippocampal tissue by using an acetylcholinesterase assay kit and quantitative real-time PCR. This study also evaluated the effect of alpha 7 nicotinic acetylcholine receptor agonist PNU-282987 and antagonist methyllycaconitine on cognitive function and the level of hippocampal tumor necrosis factor-α in aged rats exposed to sevoflurane anesthesia. We found that 3% sevoflurane significantly impaired cognitive function and increased acetylcholinesterase activity by upregulating its expression in hippocampal tissue. Sevoflurane-induced impairment of cognitive function was significantly rescued by PNU-282987 but aggravated by methyllycaconitine. In addition to impairment of cognitive function, sevoflurane also significantly increased tumor necrosis factor-α level in plasma and hippocampal tissue. Similarly, this sevoflurane-induced change of tumor necrosis factor-α level in rats was antagonized by PNU-282987 but amplified by methyllycaconitine. In conclusion, our data show that the development of inflammation in sevoflurane-induced cognitive decline is associated with the downregulation of alpha 7 nicotinic acetylcholine receptor cholinergic anti-inflammatory pathway in aged rats.
aDepartment of Anesthesiology, North University of Hebei
bDepartment of Anesthesiology, the First Hospital of Zhangjiakou
cDepartment of Anesthesiology, The Fifth Hospital of Zhangjiakou
dDepartment of Blood Transfusion, Gansu Hospital of Traditional Chinese Medicine
eDepartment of Infection Management, the First affiliated Hospital of North University of Hebei, Zhangjiakou
fDepartment of Infection Management of the Affiliated Kailuan General Hospital of Hebei United University, Tangshan
gDepartment of Endocrinology, North University of Hebei, Hebei, China
* Jian Yin and Xin Zhao contributed equally to the writing of this article.
Received 9 February 2019 Accepted as revised 17 August 2019
Correspondence to Jinliang Teng, MD, The Department of anesthesiology, The First Affiliated Hospital of Hebei North University, No. 13, Changqing Road, Zhangjiakou, Hebei 075000, China, e-mail: email@example.com