Methylene blue is neuroprotective against mild traumatic brain injury.
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.
1 Research Imaging Institute, University of Texas Health Science Center , San Antonio, Texas.
Lora
L
Talley Watts
Justin Alexander
JA
Long
Jonathan
J
Chemello
Samantha
S
Van Koughnet
Angelica
A
Fernandez
Shiliang
S
Huang
Qiang
Q
Shen
Timothy Q
TQ
Duong
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D005456:Fluorescent Dyes; D008279:Magnetic Resonance Imaging; D008297:Male; D008751:Methylene Blue / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D005456:Fluorescent Dyes; D018696:Neuroprotective Agents; D008751:Methylene Blue
MRI; antioxidant; mitochondria; oxidative stress; vasogenic edema