Sevoflurane-induced memory impairment in the postnatal developing mouse brain

Abstract

The aim of the present study was to confirm that sevoflurane induces memory impairment in the postnatal developing mouse brain and determine its mechanism of action. C57BL/6 mice 7 days old were randomly assigned into a 2.6% sevoflurane (n=68), a 1.3% sevoflurane (n=68) and a control (n=38) group. Blood gas analysis was performed to evaluate hypoxia and respiratory depression during anesthesia in 78 mice. Measurements for expression of caspase-3 by immunohistochemistry, cleavage of poly adenosine diphosphate-ribose polymerase (PARP) by western blotting, as well as levels of brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor type 2 (Ntrk2), pro-BDNF, p75 neurotrophin receptor (p75NTR) and protein kinase B (PKB/Akt) by enzyme-linked immunosorbent assay were performed in the hippocampus of 12 mice from each group. A total of 60 mice underwent the Morris water maze (MWM) test. Results from the MWM test indicated that the time spent in the northwest quadrant and platform site crossovers by mice in the 2.6 and 1.3% sevoflurane groups was significantly lower than that of the control group. Meanwhile, levels of caspase-3 and cleaved PARP in the 2.6 and 1.3% sevoflurane groups were significantly higher than that in the control group. Levels of pro-BDNF and p75NTR were significantly increased and the level of PKB/Akt was significantly decreased following exposure to 2.6% sevoflurane. Finally, the memory of postnatal mice was impaired by sevoflurane, this was determined using a MWM test. Therefore, the results of the current study suggest that caspase-3 induced cleavage of PARP, as well as pro-BDNF, p75NTR and PKB/Akt may be important in sevoflurane-induced memory impairment in the postnatal developing mouse brain.

Efficacy of melatonin in alleviating disorders arising from repeated exposure to sevoflurane in males and females of the Wistar rats during preadolescence

“…Our study additionally found a connection between caspase-3 and sevoflurane-induced memory impairment in rats, with increased caspase-3 expression and Poly (ADP-ribose) polymerase (PARP) cleavage in hippocampus tissue contributing to neuronal death and significant memory impairment 42,43 . This suggests that caspase-3-induced PARP cleavage may be a mechanism for hippocampal neuronal death and memory impairment in postnatal mice 44 .…”

LncRNA Rik-203 Contributes to Sevoflurane Induced Neurotoxicity?

“…Aberrant neural differentiation has been shown to contribute to cognitive impairment and neurogenesis inhibition in young and offspring rodents ( 18 ). Sevoflurane regulates neurogenesis in offspring rats by down-regulating the expression of brain-derived neurotrophic factor (BDNF), which is the critical neural development and disease related gene ( 19 – 22 ) and induces neurotoxicity and cognitive impairment in young mice ( 23 , 24 ). But, the underlying mechanism by which sevoflurane regulates the expression of BDNF remains largely unknown, which impedes further research into anesthesia neurotoxicity in the developing brain.…”

Sevoflurane regulating LncRNA Rik-203 contributes to neural differentiation via microRNA-466l-3p /BDNF pathway

“…Aberrant neural differentiation has been shown to contribute to cognitive impairment and neurogenesis inhibition in young and offspring rodents [34]. Sevoflurane regulates neurogenesis in offspring rats by down-regulated the expression of brain-derived neurotrophic factor (BDNF) that is the critical neural development and disease related gene [19,[35][36][37] and induces neurotoxicity and cognitive impairment in young mice [38,39]. But, the underlying mechanism by which sevoflurane regulates the expression of BDNF remains largely unknown, which impedes further research into anesthesia neurotoxicity in the developing brain.…”