Chronic oral methylene blue treatment in a rat model of focal cerebral ischemia/reperfusion.

Abstract

A single acute low-dose methylene blue (MB), an FDA-grandfathered drug, has been shown to ameliorate behavioral deficits and reduces MRI-defined infarct volume in experimental ischemic stroke when administered intravenously or intraperitoneally. The efficacy of chronic MB treatment in ischemic stroke remains unknown. In a randomized, double-blinded and vehicle-controlled design, we investigated the efficacy of chronic oral MB administration in ischemic stroke longitudinally up to 60 days post injury using MRI and behavioral tests, with end-point histology. The major findings were chronic oral MB treatment, compared to vehicle, i) improves functional behavioral outcomes starting on day 7 and up to 60 days, ii) reduces MRI-defined total lesion volumes from day 14 and up to 60 days where some initial abnormal MRI-defined core and perfusion-diffusion mismatch were salvaged, iii) reduces white-matter damage, iv) gray matter and white matter damages are consistent with Nissl stains and Black Gold stain histology. These findings provide further evidence that long-term oral administration of low-dose MB is safe and has positive therapeutic effects in chronic ischemic stroke.

• Authors: Lei Huang, Jianfei Lu, Bianca Cerqueira, Yichu Liu, Zhao Jiang, Timothy Q Duong
• Journal: Brain research (Brain Res) Vol. 1678 Pg. 322-329 (Jan 01 2018) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 29108817 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Neuroprotective Agents
• Spin Labels
• Methylene Blue

Topics

• Administration, Oral
• Analysis of Variance
• Animals
• Disease Models, Animal
• Double-Blind Method
• Image Processing, Computer-Assisted
• Infarction, Middle Cerebral Artery (diagnostic imaging, drug therapy, physiopathology)
• Magnetic Resonance Imaging
• Male
• Methylene Blue (administration & dosage)
• Neuroprotective Agents (administration & dosage)
• Rats
• Rats, Sprague-Dawley
• Reperfusion
• Sensory Gating (drug effects, physiology)
• Silver Staining
• Spin Labels