Methylene blue is neuroprotective against mild traumatic brain injury

Lora Talley Watts, Justin Alexander Long, Jonathan Chemello, Samantha Van Koughnet, Angelica Fernandez, Shiliang Huang, Qiang Shen, Timothy Q. Duong

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


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 3h 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.

Original languageEnglish (US)
Pages (from-to)1063-1071
Number of pages9
JournalJournal of Neurotrauma
Issue number11
StatePublished - Jun 1 2014


  • MRI
  • antioxidant
  • mitochondria
  • oxidative stress
  • vasogenic edema

ASJC Scopus subject areas

  • Clinical Neurology


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