Methylene Blue as a Cerebral Metabolic and Hemodynamic Enhancer

Ai Ling Lin, Ethan Poteet, Fang Du, Roy C. Gourav, Ran Liu, Yi Wen, Andrew Bresnen, Shiliang Huang, Peter T. Fox, Shao Hua Yang, Timothy Q. Duong

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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 (CMRO2) 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 CMRO2 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.

Original languageEnglish
Article numbere46585
JournalPLoS ONE
Volume7
Issue number10
DOIs
StatePublished - 9 Oct 2012

Fingerprint

methylene blue
Methylene Blue
Hemodynamics
hemodynamics
Brain
Cerebrovascular Circulation
brain
blood flow
Neuroimaging
uptake mechanisms
Glucose
glucose
Blood
normoxia
Parkinson disease
Magnetic resonance
Alzheimer disease
Oxygen
magnetic resonance imaging
Metabolism

Cite this

Lin, A. L., Poteet, E., Du, F., Gourav, R. C., Liu, R., Wen, Y., ... Duong, T. Q. (2012). Methylene Blue as a Cerebral Metabolic and Hemodynamic Enhancer. PLoS ONE, 7(10), [e46585]. https://doi.org/10.1371/journal.pone.0046585
Lin, Ai Ling ; Poteet, Ethan ; Du, Fang ; Gourav, Roy C. ; Liu, Ran ; Wen, Yi ; Bresnen, Andrew ; Huang, Shiliang ; Fox, Peter T. ; Yang, Shao Hua ; Duong, Timothy Q. / Methylene Blue as a Cerebral Metabolic and Hemodynamic Enhancer. In: PLoS ONE. 2012 ; Vol. 7, No. 10.
@article{b2af6c380a054240981a348a20faeec1,
title = "Methylene Blue as a Cerebral Metabolic and Hemodynamic Enhancer",
abstract = "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 (CMRO2) 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 CMRO2 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.",
author = "Lin, {Ai Ling} and Ethan Poteet and Fang Du and Gourav, {Roy C.} and Ran Liu and Yi Wen and Andrew Bresnen and Shiliang Huang and Fox, {Peter T.} and Yang, {Shao Hua} and Duong, {Timothy Q.}",
year = "2012",
month = "10",
day = "9",
doi = "10.1371/journal.pone.0046585",
language = "English",
volume = "7",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

Lin, AL, Poteet, E, Du, F, Gourav, RC, Liu, R, Wen, Y, Bresnen, A, Huang, S, Fox, PT, Yang, SH & Duong, TQ 2012, 'Methylene Blue as a Cerebral Metabolic and Hemodynamic Enhancer', PLoS ONE, vol. 7, no. 10, e46585. https://doi.org/10.1371/journal.pone.0046585

Methylene Blue as a Cerebral Metabolic and Hemodynamic Enhancer. / Lin, Ai Ling; Poteet, Ethan; Du, Fang; Gourav, Roy C.; Liu, Ran; Wen, Yi; Bresnen, Andrew; Huang, Shiliang; Fox, Peter T.; Yang, Shao Hua; Duong, Timothy Q.

In: PLoS ONE, Vol. 7, No. 10, e46585, 09.10.2012.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Methylene Blue as a Cerebral Metabolic and Hemodynamic Enhancer

AU - Lin, Ai Ling

AU - Poteet, Ethan

AU - Du, Fang

AU - Gourav, Roy C.

AU - Liu, Ran

AU - Wen, Yi

AU - Bresnen, Andrew

AU - Huang, Shiliang

AU - Fox, Peter T.

AU - Yang, Shao Hua

AU - Duong, Timothy Q.

PY - 2012/10/9

Y1 - 2012/10/9

N2 - 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 (CMRO2) 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 CMRO2 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.

AB - 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 (CMRO2) 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 CMRO2 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.

UR - http://www.scopus.com/inward/record.url?scp=84867287360&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0046585

DO - 10.1371/journal.pone.0046585

M3 - Article

C2 - 23056355

AN - SCOPUS:84867287360

VL - 7

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 10

M1 - e46585

ER -