Methylene blue as a cerebral metabolic and hemodynamic enhancer.
By restoring mitochondrial function, methylene blue (MB) is an effective neuroprotectant in many neurological disorders (e.g., Parkinson's and Alzheimer's diseases). MB has also been proposed as a brain metabolic enhancer because of its action on mitochondrial cytochrome c oxidase. We used in vitro and in vivo approaches to determine how MB affects brain metabolism and hemodynamics. For in vitro, we evaluated the effect of MB on brain mitochondrial function, oxygen consumption, and glucose uptake. For in vivo, we applied neuroimaging and intravenous measurements to determine MB's effect on glucose uptake, cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO(2)) under normoxic and hypoxic conditions in rats. MB significantly increases mitochondrial complex I-III activity in isolated mitochondria and enhances oxygen consumption and glucose uptake in HT-22 cells. Using positron emission tomography and magnetic resonance imaging (MRI), we observed significant increases in brain glucose uptake, CBF, and CMRO(2) under both normoxic and hypoxic conditions. Further, MRI revealed that MB dramatically increased CBF in the hippocampus and in the cingulate, motor, and frontoparietal cortices, areas of the brain affected by Alzheimer's and Parkinson's diseases. Our results suggest that MB can enhance brain metabolism and hemodynamics, and multimetric neuroimaging systems offer a noninvasive, nondestructive way to evaluate treatment efficacy.
Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. lina3@uthscsa.edu
Ai-Ling
AL
Lin
Ethan
E
Poteet
Fang
F
Du
Roy C
RC
Gourav
Ran
R
Liu
Yi
Y
Wen
Andrew
A
Bresnen
Shiliang
S
Huang
Peter T
PT
Fox
Shao-Hua
SH
Yang
Timothy Q
TQ
Duong
D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D006439:Hemodynamics; D006801:Humans; D008751:Methylene Blue / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism
D008751:Methylene Blue