Delayed Methylene Blue Improves Lesion Volume, Multi-Parametric Quantitative Magnetic Resonance Imaging Measurements, and Behavioral Outcome after Traumatic Brain Injury

Traumatic brain injury (TBI) remains a primary cause of death and disability in both civilian and military populations worldwide. There is a critical need for the development of neuroprotective agents that can circumvent damage and provide functional recovery. We previously showed that methylene blue (MB), a U.S. Food and Drug Administration-grandfathered drug with energy-enhancing and antioxidant properties, given 1 and 3h post-TBI, had neuroprotective effects in rats. This study aimed to further investigate the neuroprotection of delayed MB treatment (24h postinjury) post-TBI as measured by lesion volume and functional outcomes. Comparisons were made with vehicle and acute MB treatment. Multi-modal magnetic resonance imaging and behavioral studies were performed at 1 and 3h and 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. We found that delaying MB treatment 24h postinjury still minimized lesion volume and functional deficits, compared to vehicle-treated animals. The data further support the potential for MB as a neuroprotective treatment, especially when medical teatment is not readily available. MB has an excellent safety profile and is clinically approved for other indications. MB clinical trials on TBI can thus be readily explored.