Neuroprotective efficacy of methylene blue in ischemic stroke: an MRI study

PLoS One. 2013 Nov 21;8(11):e79833. doi: 10.1371/journal.pone.0079833. eCollection 2013.


Methylene blue (MB) has unique energy-enhancing and antioxidant properties and is FDA-approved drug to treat methemoglobinemia and cyanide poisoning. This study evaluated the efficacy of MB to treat ischemic stroke in rats using longitudinal MRI and behavioral measures. Rats were subjected to 60-minute middle-cerebral-artery occlusion. In a randomized double-blinded design, vehicle or MB was administered after reperfusion. The initial lesion volumes at 30 minutes post-ischemia were not significantly different between the two groups (P = 0.92). The final infarct volumes two days after stroke increased in the vehicle group but decreased in the MB group, yielding a 30% difference in infarct volume (P = 0.03). Tracking tissue fate on a pixel-by-pixel basis showed that MB salvaged more initial core pixels compared to controls (22±3% versus 11±3%, P = 0.03), and more mismatch pixels compared to controls (83±3% versus 61±8%, P = 0.02). This study demonstrates MB treatment minimizes ischemic brain injury and improves functional outcomes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyanides / toxicity
  • Magnetic Resonance Imaging
  • Male
  • Methemoglobinemia / drug therapy*
  • Methylene Blue / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley


  • Cyanides
  • Methylene Blue