miR‐330‐5p Attenuates Isoflurane‐Induced Neuroinflammation and Cognitive Dysfunction by Regulating EPHB3

ABSTRACT It has been shown that isoflurane induces persistent neuroinflammation, which can cause morphological and functional changes in brain, leading to cognitive impairment. It is known that miRNAs play an important regulatory role in hippocampal neurodevelopment and plasticity. This study was to investigate the effect of miR‐330‐5p on isoflurane‐induced cognitive deficits in rats and hippocampal neuronal cell lines and to study the underlying mechanisms. Cognitive performance in rats exposed to isoflurane was assessed using the Morris water maze (MWM) test. The levels of inflammation and oxidative stress markers were quantified using enzyme‐linked immunosorbent assays (ELISA). Additionally, luciferase reporter assays were employed to validate the interaction between miR‐330‐5p and its target genes. Isoflurane exposure led to increased miR‐330‐5p expression in the hippocampal tissues of rats. Suppression of miR‐330‐5p enhanced cognitive performance, as evidenced by longer durations spent in the target quadrant and reduced escape latencies. Furthermore, isoflurane‐induced hippocampal neuronal apoptosis, inflammation, and oxidative stress were alleviated by both a miR‐330‐5p inhibitor and EPHB3 silencing. Notably, EPHB3 was identified as a direct regulatory target of miR‐330‐5p. MiR‐330‐5p exerts neuroprotective effects in rats by regulating EPHB3, which is associated with inflammatory responses, oxidative stress and neuronal apoptosis mediated by the miR‐330‐5p/EPHB3 axis.