Glibenclamide ameliorates the expression of neurotrophic factors in sevoflurane anaesthesia-induced oxidative stress and cognitive impairment in hippocampal neurons of old rats
2021
Several antidiabetic medications have been proposed as prospective treatments for cognitive impairments in type 2 diabetes patients, glibenclamide (GBC) among them. Our research aimed to evaluate the impact of GBC on hippocampal learning memory and inflammation due to enhanced neurotrophic signals induced by inhalation of sevoflurane. Rats (Sprague Dawley, both sexes) were assigned to four groups: a control (vehicle, p.o.), GBC (10 mg/kg b.w.; p.o.), low-dose sevoflurane and low-dose sevoflurane + GBC (10 mg/kg b.w.; p.o.) for 23 days. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining was performed to analyse the count of apoptotic cells and ELISA was conducted to assess the protein signals. A Western blot, a Y-maze test, and a Morris maze test were performed, and the results analysed. Blood and tissues were collected, and isolation of RNA was performed with qRT-PCR. The Morris maze test results revealed an improvement in the length of the escape latency on days 1 (P < 0.05), 2 (P < 0.01), 3, and 4 in the low-dose Sevo group. Time spent in the quadrant and crossing axis and the percentage of spontaneous alterations showed a substantial decrease in the low-dose Sevo group which received GBC at 10 mg/kg b.w. Significant increases were shown in IL-6 and TNF-α levels in the low-dose Sevo group, whereas a decrease was evident in the GBC group. Our results indicate that glibenclamide may be a novel drug to prevent sevoflurane inhalation-induced impaired learning and reduce brain-derived neurotrophic factor release, which may be a vital target for the development of potential therapies for cognitive deficits and neurodegeneration.
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