Sevoflurane attenuates brain damage through inhibiting autophagy and apoptosis in cerebral ischemia‑reperfusion rats

Abstract

The present study aimed to investigate the effects of sevoflurane post-conditioning in a rat brain cerebral ischemia-reperfusion (I/R) model and examine its possible mechanism. Rats were randomly divided into six groups: Sham control group (Sham), I/R group, sevoflurane group (Se), Toll-like receptor-4 (TLR4) inhibitor group (Tak-242), nuclear factor (NF)-κB inhibitor group (QNZ) and Sevoflurane post-conditioning combined with TLR4-NF-κB signaling pathway inhibitor group (Se + Tak-242). Morris water maze test and tetrazolium chloride staining were used to investigate the I/R injury. The nerve cell apoptosis and autophagy in cortical tissue were detected by TUNEL and transmission electron microscopy, respectively. The expression of TLR4 protein in cortical tissue was observed by immunohistochemical staining. The expression of autophagy and apoptotic associated proteins in cortical tissues and the activity of TLR4-NF-κB signaling pathway were assayed by western blot analysis. Sevoflurane post-conditioning improved the learning and memory dysfunction caused by cerebral I/R injury. The cerebral infarction area, nerve cell apoptosis and formation of autophagic vacuoles were reduced after sevoflurane administration. The expression of light chain 3II/I, Beclin-1, Bad and Cleaved-Caspase-3 proteins were inhibited and the expression of Bcl-2 protein was upregulated after sevoflurane administration. Sevoflurane post-conditioning also inhibited the TLR4 protein and NF-κB phosphorylation, and increased inhibitor of kBα phosphorylation. The treatment effect of Tak-242 and QNZ groups were not significantly different compared with the Se group (P>0.05), and the Se + Tak-242 group had the best results. The present study demonstrated that sevoflurane post-conditioning could protect middle cerebral artery occlusion-induced brain injury rats by inhibiting autophagy and apoptosis, and that its mechanism is related to the TLR4-NF-κB signaling pathway.

Sevoflurane Inhibits Traumatic Brain Injury-Induced Neuron Apoptosis via EZH2-Downregulated KLF4/p38 Axis

“…One of the most instrumental findings in our study was the neuroprotective effect of sevoflurane against TBI by curbing neuron apoptosis, as evidenced by down-regulated expressions of Bax (pro-apoptotic protein) and Cleaved Caspase-3 and up-regulated Bcl-2 levels (anti-apoptotic protein). Similarly, administration of sevoflurane has been previously documented to augment Bcl-2 protein levels and decrease those of Cleaved Caspase-3 in rat brain cerebral ischemia-reperfusion models, a reflection of diminished neuron apoptosis ( Shi et al, 2020 ). In addition, another study highlighted that sevoflurane post-conditioning conferred an inhibitory effect on cell apoptosis in cerebral ischemia-reperfusion injury, which is largely in agreement with our findings ( Kim et al, 2017 ).…”

“…TBI, caused by a blow, bump or jolt to the head, results in brain dysfunction yet no officially approved therapeutic modalities are currently available for TBI ( Wang et al, 2018 ; Capizzi et al, 2020 ). Sevoflurane post-conditioning has been indicated to protect against brain injury induced by middle cerebral artery occlusion in rat models by inhibiting autophagy and apoptosis ( Shi et al, 2020 ), highly suggestive of its neuroprotective ability. In an effort to expand our understanding, the current study set out to uncover the mechanism underlying the functional role of sevoflurane in neuron apoptosis induced by TBI.…”

Suppression of lncRNA MALAT1 Reduces LPS- or IL-17A-Induced Inflammatory Response in Human Middle Ear Epithelial Cells via the NF-κB Signaling Pathway

“…Moreover, we observed that the contents of proinflammatory cytokines (TNF- α , IL-1 β , and IL-6) were increased by MALAT1 overexpression in LPS- or IL-17A-treated HMEECs. QNZ, an inhibitor of NF- κ B signaling, was widely used to suppress NF- κ B signaling [ 25 – 27 ]. In addition, the effects of MALAT1 on proinflammatory cytokines were significantly reversed by QNZ (Figures 5(b) – 5(g) ) ( Figure 5(b) , p = 0.002; Figure 5(c) , p = 0.015; Figure 5(d) , p < 0.001; Figure 5(e) , p = 0.006; Figure 5(f) , p = 0.002; Figure 5(g) , p < 0.001).…”

The neuroprotection effects of exosome in central nervous system injuries: A new target for therapeutic intervention

“…Up to now, the dual role of autophagy in protective or destructive of CNS injuries remains controversial. Shi et al found that in cerebral ischemia-reperfusion rats, inhibiting autophagy by sevo urane attenuated brain damage, demonstrating a detrimental role of autophagy [91]. Conversely, Ahsan et al reported that Urolithin A-activated autophagy protected against ischemic neuronal injury by inhibiting endoplasmic reticulum (ER) stress both in vitro and in vivo, suggesting that autophagy played a bene cial role in stroke [92].…”