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.
Glucose converted from a diet has been considered a high risk factor of type 2 diabetes mellitus (T2DM). However, it is not clear how it increases the risk of T2DM. Here, we investigated the effect of high glucose administration on glucose tolerence in wild type and toll like receptor 4 (TLR4) knockout mice. Mice were intragastrically administered with high glucose. The level of fasting blood glucose, insulin and intraperitoneal glucose tolerance were measured, and insulinogenic index and HOMA IR were calculated at 1 week. To understand mechanism of glucose action, we also assessed blood glucose, glucagon like peptide 1 and inflammatory cytokines levels at different time windows following high glucose load. Our results show that 20 g/kg glucose load leads to glucose tolerance impairment and insulin resistance in wild type mice. Following 20 g/kg glucose load, the levels of plasma interlukin 6 (IL 6) and tumor necrosis factor α (TNF α) increased significantly in wild type mice, but not in TLR4 knockout mice. Moreover, 20 g/kg glucose load also impaired glucose induced GLP 1 secretion in wild type and TLR4 knockout mice. Our results indicate that high glucose load leads to glucose intolerance with insulin resistance through impairment of GLP 1 secretion, increase of blood glucose levels via activating TLR4 and increasing levels of IL 6 and TNF α in mice.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.