Abstract
BACKGROUND: Ischemic stroke significantly threatens human health, and current treatments remain limited, necessitating novel strategies. Mitochondrial transfer between neurons represents a crucial endogenous neuroprotective mechanism. OBJECTIVE: This study investigated whether electroacupuncture enhances mitochondrial transfer from astrocytes to damaged neurons during acute cerebral ischemia, promoting neuroprotection. METHODS: A middle cerebral artery occlusion (MCAO) model in Sprague-Dawley (SD) rats and an oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro were employed. Neurobehavioral assessments, electron microscopy, multiplex immunofluorescence, tissue quantification, western blotting, qRT-PCR, transcriptomics, and proteomics were conducted to evaluate mitochondrial distribution, function, and intercellular transfer under electroacupuncture preconditioning and intervention. RESULTS: Electroacupuncture significantly improved neurological outcomes and reduced brain tissue damage in MCAO rats. It facilitated mitochondrial transfer from astrocytes to neurons, increased functional mitochondria within neurons, and reduced neuronal apoptosis. These effects may involve regulation of the CD38-cADPR-Ca2 + signaling pathway and proteins associated with tunneling nanotubes (TNTs), such as F-actin, Miro1, TRAK1, and KIF5b. CONCLUSION: Electroacupuncture enhances mitochondrial transfer and function, exerting neuroprotective effects during acute ischemic stroke. This study highlights the potential of electroacupuncture as a therapeutic approach and identifies novel targets for brain protection strategies.