Sevoflurane-induced inflammation development: involvement of cholinergic anti-inflammatory pathway.
BEHAVIOURAL PHARMACOLOGY(2019)
Abstract
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-alpha 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-alpha level in plasma and hippocampal tissue. Similarly, this sevoflurane-induced change of tumor necrosis factor-alpha 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.
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Key words
alpha-7 nicotinic acetylcholine receptor,cholinergic anti-inflammatory pathway,cognitive dysfunction,inflammation,rat,sevoflurane
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