Isoflurane Promotes Neuroinflammation and Induces Cognitive Impairment Through the miR‐3099‐5p/AQP4 Axis

Isoflurane is an inhalational anesthetic widely used in clinical practice. However, its potential neurotoxic mechanisms have not been fully elucidated. Recent studies have found that miR-3099-5p is stably expressed in the brain and is closely associated with neural injury, neurodevelopment, and stem cell differentiation. This study utilized an isoflurane-treated SD rat model to assess the effects of isoflurane on the spatial learning and memory capabilities of the rats through the Morris water maze experiment system. ELISA technology was employed to measure the levels of inflammatory factors, while the thiobarbituric acid reactive substance method and WST-1/NBT colorimetric method were used to determine oxidative stress indicators. Furthermore, qRT-PCR technology was applied to detect gene expression levels, and the regulatory relationships between target genes were further examined through dual-luciferase reporter gene assays. Exposure to isoflurane can lead to cognitive dysfunction in rats, accompanied by an upregulation of miR-3099-5p expression. Additionally, inhibiting miR-3099-5p not only significantly improves these cognitive deficits but also attenuates the isoflurane-induced inflammatory response of microglia and oxidative stress, with the mechanism being through direct targeting and inhibition of AQP4 expression. miR-3099-5p mediates isoflurane-induced neurotoxicity via AQP4 regulation. Its inhibition alleviates cognitive impairment and neuroinflammation, providing a novel therapeutic target for anesthesia-related neural damage and potential neuroprotective drug development.