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.