Olfactory ensheathing cells exosomes enhance neurological recovery in brain‐injured rats by modulating Nrf2‐ferroptosis pathway

Abstract This study aimed to evaluate the therapeutic potential of the olfactory ensheathing cells (OECs) exosomes (EXOs) in traumatic brain injury (TBI) and the regulatory role of nuclear factor E2‐related factor (Nrf2). Rats were divided into Sham, TBI, OECs‐EXOs (EXO), and OECs‐EXOs plus Nrf2 inhibitor (ML385) groups. Neurological function was assessed using the modified neurological severity score, the Morris water maze (MWM), and the Barnes maze tests. Brain injury, Fe 2+ accumulation, and mitochondrial damage were evaluated using histopathological imaging and ELISA kits. Expression levels of Nrf2 and ferroptosis‐related proteins were analyzed using western blot and qPCR. TBI rats exhibited significant neurological dysfunction, elevated serum injury markers and inflammatory cytokines, increased brain Fe 2+ and malondialdehyde (MDA), and altered expression of ferroptosis‐related proteins compared with Sham rats. The ML385 group exhibited reduced Nrf2 expression and attenuated OECs‐EXOs‐mediated therapeutic effects, suggesting a critical role of Nrf2 in the efficacy of OECs‐EXOs. Overall, OECs‐EXOs attenuated TBI‐induced neuroinflammation and oxidative stress and promoted neuronal repair and neurological recovery, likely via Nrf2‐regulated ferroptosis‐related pathways.