Methylene blue is neuroprotective against mild traumatic brain injury

J Neurotrauma. 2014 Jun 1;31(11):1063-71. doi: 10.1089/neu.2013.3193. Epub 2014 Apr 8.


Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Methylene blue (MB) has known energy-enhancing and antioxidant properties. This study tested the hypothesis that MB treatment reduces lesion volume and behavioral deficits in a rat model of mild TBI. In a randomized double-blinded design, animals received either MB (n=5) or vehicle (n=6) after TBI. Studies were performed on 0, 1, 2, 7, and 14 days following an impact to the primary forelimb somatosensory cortex. MRI lesion was not apparent 1 h after TBI, became apparent 3 h after TBI, and peaked at 2 days for both groups. The MB-treated animals showed significantly smaller MRI lesion volume than the vehicle-treated animals at all time points studied. The MB-treated animals exhibited significantly improved scores on forelimb placement asymmetry and foot fault tests than did the vehicle-treated animals at all time points studied. Smaller numbers of dark-stained Nissl cells and Fluoro-Jade(®) positive cells were observed in the MB-treated group than in vehicle-treated animals 14 days post-TBI. In conclusion, MB treatment minimized lesion volume, behavioral deficits, and neuronal degeneration following mild TBI. MB is already approved by the United States Food and Drug Administration (FDA) to treat a number of indications, likely expediting future clinical trials in TBI.

Keywords: MRI; antioxidant; mitochondria; oxidative stress; vasogenic edema.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antioxidants / therapeutic use*
  • Behavior, Animal
  • Brain / pathology
  • Brain Injuries / drug therapy*
  • Brain Injuries / pathology
  • Brain Injuries / psychology
  • Fluorescent Dyes
  • Magnetic Resonance Imaging
  • Male
  • Methylene Blue / therapeutic use*
  • Neuroprotective Agents / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley


  • Antioxidants
  • Fluorescent Dyes
  • Neuroprotective Agents
  • Methylene Blue