Edaravone dexborneol promotes oligodendrocyte precursor cell proliferation and differentiation to repair white matter and improve long-term outcomes after ischemic stroke.

BACKGROUND: White matter repair after ischemic stroke is critical for long-term recovery. Edaravone dexborneol (EDB) has antioxidative and anti-inflammatory properties, but its role in white matter integrity remains unclear.

METHODS: We enrolled 73 patients with first-ever left basal ganglia infarction, including the conventional treatment group (n = 33) and the EDB treatment group (n = 40). In addition, 32 healthy individuals were recruited as a control group. After 3 months, MRI (T1WI and DTI) was performed to assess FA values of 8 major tracts and rich-club network organization. In parallel, middle cerebral artery occlusion (MCAO) was induced in mice. Behavioral tests, histology, immunofluorescence, and Western blot were conducted to evaluate functional recovery, white matter injury, OPC proliferation/differentiation, and Akt/mTOR signaling. Primary OPC cultures were used to validate mechanisms in vitro.

RESULTS: Clinically, the conventional group showed reduced FA values and weakened rich-club connectivity, whereas both metrics were significantly improved in the EDB group. In MCAO mice, EDB alleviated brain atrophy and white matter injury, promoted sensorimotor and cognitive recovery, and enhanced OPC proliferation and differentiation via Akt/mTOR activation. In vitro, EDB stimulated OPC proliferation/differentiation, while Akt/mTOR inhibition abolished these effects.

CONCLUSION: EDB treatment was associated with improved local tract integrity and global network connectivity in stroke patients. In experimental models, EDB promoted OPC proliferation and differentiation via Akt/mTOR signaling, potentially contributing to remyelination and white matter repair, accompanied by improved long-term functional outcomes. These findings suggest that EDB may represent a promising strategy for post-stroke white matter repair.