Isoflurane enhances autophagy by activating AMPK/ULK1, inhibits NLRP3, and reduces cognitive impairment after cerebral ischemia-reperfusion injury in rats

Abstract

Background Cerebral ischemia-reperfusion injury (CIRI) is an important factor affecting the prognosis of patients with ischemic stroke. This study aimed to observe whether isoflurane posttreatment enhances autophagy after focal CIRI in rats by activating the AMPK/ULK1 signaling pathway, thereby inhibiting NLRP3 inflammation. The body releases inflammatory factors to reduce inflammation, thereby reducing neurological damage and improving cognitive and memory functions. Methods Eighty male SD rats were randomly divided into 5 groups: sham operation group (Sham), model group (MCAO), isoflurane posttreatment + model group (M + ISO), autophagy inhibitor Baf-A1 + isoflurane posttreatment + model group (M + I + B), AMPK inhibitor Compound C + isoflurane posttreatment + model group (M + I + C). Results Compared with the sham group, the MCAO group exhibited decreased neurobehavioral scores and cognitive memory function (P < 0.05). Compared with the MCAO group, the neurobehavioral score of rats in the M + ISO group was significantly reduced, the expression of AMPK, ULK1, Beclin1, and LC3B protein was significantly increased, and cognitive and memory function was significantly improved (P < 0.05). Compared with the M + ISO group, the neurobehavioral scores and the protein expression of NLRP3, IL-1β and IL-18 in the M + I + B and M + I + C groups increased significantly (P < 0.05). Conclusions This research indicated that isoflurane posttreatment may enhance autophagy by activating the AMPK/ULK1 signaling pathway and further inhibit the release of inflammatory factors from NLRP3 inflammasomes, thereby improving neurological function and cognitive impairment after focal CIRI in rats and exerting a protective effect on the brain.

Subsequent maternal sleep deprivation aggravates cognitive impairment by modulating hippocampal neuroinflammatory responses and synaptic function in maternal isoflurane‐exposed offspring mice

“…These pro‐inflammatory factors can cross the placenta and the immature fetal blood–brain barrier and reach the fetal brain, where they induce an inflammatory response after birth (Entringer et al., 2010; Zhao et al., 2015). A previous study found that isoflurane exposure downregulated the pro‐inflammatory factors (such as IL‐18 and IL‐1β) in rats suffering from cerebral ischemia–reperfusion injury, and improved neuroinflammation and cognitive function (Zhai et al., 2023). However, one study showed that IL‐6 was significantly upregulated in the brains of offspring mice exposed to sevoflurane for 3 h on GD15.5, and this was accompanied by learning impairment, as assessed in the Y ‐maze test (Hirotsu et al., 2019).…”

A bibliometric analysis of research foci and trends in cerebral ischemia-reperfusion injury involving autophagy during 2008 to 2022

“…[69] Man Long et al observed that electroacupuncture pretreatment diminished TRPV1 expression, thereby inhibiting the NF-κβ pathway's transcriptional activity and exerting antiapoptotic effects. [70] Isoflurane [71] and the proprietary Chinese medicine Pien Tze Huang (PTH) [72] upregulate autophagy through activation of the AMPK/ULK1 pathway, thereby inhibiting the release of NLRP3 and inflammatory factors such as IL-1β and IL-18. Li Mao et al deduced that heightened Toll-like receptor 4 expression could induce CIRI by modulating NLRP3 inflammasome and autophagy, though the precise mechanism remains under investigation.…”