Objectives: Methylene blue, the FDA-grandfathered drug was proved to be neuroprotective in ischemic stroke in rat. However, the mechanism of the protective effect was unknown. In this study, we used different animal models to investigate the effect of MB administration given within and beyond the therapeutic time window on behavioral deficits and infarct volume and related mechanism about the white matter protection.

Methods: Middle cerebral artery occlusion and reperfusion (MCAO) and photothrombotic middle cerebral artery occlusion (PT-MCAO) models were used. Behavioral deficits and infarct volume were measured by foot fault test, Garcia neurological score and TTC staining. Black gold staining and western blot were used to evaluate the brain white matter injury.

Results: We found that intraperitoneal administration of MB immediately or 24h after the MCAO or PT-MCAO surgery reduced infarct volume, improved the neurological deficits, reduced the white matter injury via myelin Basic Protein (BMP) protection.

Conclusion: These findings suggested that MB relieved white matter injury besides neuronal protection and has potential therapeutic effects on ischemic stroke.

All data were obtained from randomized, double-blind, and vehicle-controlled design.