Crebanine protects aged rats from anesthesia-induced cognitive deficits by restoring mitophagy

In a preprint study using aged male Sprague-Dawley rats and BV2 microglial cells, researchers examined how the plant alkaloid crebanine counters sevoflurane-induced cognitive impairment. In cell cultures, sevoflurane exposure disrupted mitophagy, leading to reactive oxygen species accumulation and cytosolic leakage of mitochondrial DNA. This leakage activated the cGAS-STING pathway, driving pro-inflammatory microglial polarization. Crebanine treatment restored mitophagic flux, reduced mitochondrial DNA release, and promoted an anti-inflammatory microglial phenotype. Blocking mitophagy or chemically activating STING eliminated these protective effects. In aged rats exposed to sevoflurane, crebanine administration reduced hippocampal neuroinflammation and neuronal apoptosis. These cellular improvements translated to preserved spatial learning and memory performance during Morris water maze testing.