Silencing CircHIPK3 improves sevoflurane-explore learning and memory dysfunction and nerve damage via enhancing miR-338-3p.

Background: Sevoflurane (Sev), a widely used volatile anesthetic, can cause neurotoxicity, and impair learning and memory.

Objective: This study investigates the role and mechanisms of circHIPK3 in Sev-exposed neurotoxicity and learning and memory impairment.

Methods: SD rats and hippocampal neuronal cells were exposed to Sev. RT-qPCR analysis of circHIPK3 and miR-338-3p levels. MWM test was performed to examine the behavioral changes in rats. The levels of circHIPK3 and miR-338-3p levels were investigated using RT-qPCR. ELISA assay to analyze the expression of pro-inflammatory factors. CCK-8, flow cytometry, and commercial ROS assay kits were analyzed to detect cell viability, apoptosis, and ROS production. DLR and RIP assays validate circHIPK3 binding to miR-338-3p.

Results: Sev increased circHIPK3 expression in rat hippocampal tissue as well as in neuronal cells but decreased miR-338-3p levels compared to controls. circHIPK3 binding to miR-338-3p. Furthermore, silencing of circHIPK3 rats attenuated Sev-induced decline in learning and memory functions . silencing circHIPK3 also reduced Sev-induced secretion of inflammatory factors in rat and neuronal cells. Reducing circHIPK3 partially reversed the Sev-induced decrease in cell viability, increased apoptosis, and overproduction of ROS. However, the inhibitory effect of circHIPK3 on Sev neurotoxicity was restored upon downregulation of miR-338-3p.

Conclusion: Collectively, silencing circHIPK3 alleviates Sev exposure-induced learning and memory deficits and neurotoxicity by enhancing miR-338-3p expression.