Methylene blue potentiates stimulus-evoked fMRI responses and cerebral oxygen consumption during normoxia and hypoxia - PubMed (original) (raw)

Methylene blue potentiates stimulus-evoked fMRI responses and cerebral oxygen consumption during normoxia and hypoxia

Shiliang Huang et al. Neuroimage. 2013.

Abstract

Methylene blue USP (MB) at low doses has metabolic-enhancing and antioxidant properties and exhibits experimental neurotherapeutic benefits, but little is known about its in vivo effects on cerebral blood flow (CBF), functional evoked responses, and the associated changes in cerebral metabolic rate of oxygen (CMRO2). This study used magnetic resonance imaging (MRI) to evaluate the in vivo effects of a single intravenous MB therapeutic dose (0.5mg/kg) on basal CBF, blood oxygenation level-dependent (BOLD) and CBF responses to hypercapnic (5% CO2 in air) inhalation, as well as changes in BOLD, CBF, and CMRO2 during forepaw stimulation in the rat brain. MB did not have significant effects on arterial oxygen saturation, heart rate and fMRI responses to hypercapnia. However, MB significantly potentiated forepaw-evoked BOLD and CBF changes under normoxia. To further evaluate in vivo effects of MB under metabolic stress conditions, MRI measurements were also made under mild hypoxia (15% O2). Hypoxia per se increased evoked functional MRI responses. MB under hypoxia further potentiated forepaw-evoked BOLD, CBF and oxygen consumption responses relative to normoxia. These findings provide insights into MB's effects on cerebral hemodynamics in vivo and could help to optimize treatments in neurological diseases with mitochondrial dysfunction and oxidative stress.

Copyright © 2013 Elsevier Inc. All rights reserved.

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Conflict of interest statement

Disclosure/Conflict of Interest

The authors declare no conflict of interest

Figures

Figure 1

Figure 1

Schematic of the experimental design. The measurements are basal CBF, fMRI associated with CO2 challenge, and fMRI of forepaw stimulation. Vehicle was injected first followed by MB in the same animals. The reverse was not possible because MB has sustained effects.

Figure 2

Figure 2

Group-averaged basal CBF, BOLD and CBF fMRI responses to 5% CO2 and forepaw stimulation for before and after methylene blue (MB). fMRI data were overlaid on anatomical MRI. CBF grayscale bar ranges from 0 to 1.5 ml/gram/min. Color bars are cross-correlation coefficients.

Figure 3

Figure 3

Group-averaged BOLD and CBF fMRI responses to 5% CO2 challenge before and after methylene blue (MB) injection in the same animals (normoxia). Two ROI’s (~6×6 pixels each) which were determined from group data of the forepaw stimulation and used in the quantitative analysis are shown. Values are in mean ± SEM (N = 8). * indicates P < 0.05 with paired t-test.

Figure 4

Figure 4

Group-averaged basal CBF, BOLD, CBF and CMRO2 fMRI responses to forepaw stimulation before and after methylene blue (MB) injection in the same animals (normoxia). Values are in mean ± SEM (N = 10). Forepaw-evoked CBF and BOLD responses were statistically different between pre- and post-MB. * indicates P < 0.05 with paired t-test.

Figure 5

Figure 5

Group-averaged basal CBF, BOLD, CBF and CMRO2 fMRI responses to forepaw stimulation before and after methylene blue (MB) injection in the same animals (hypoxia). Values are in mean ± SEM (N = 6). All measures post-MB were statistically different (higher) from pre-MB. * indicates P < 0.05 with paired t-test.

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References

    1. Bandettini PA, Wong EC, Hinks RS, Rikofsky RS, Hyde JS. Time course EPI of human brain function during task activation. Magn Reson Med. 1992;25:390–397. - PubMed
    1. Boxerman JL, Bandettini PA, Kwong KK, Baker JR, Davis TL, Rosen BR, Weisskoff RM. The intravascular contribution to fMRI signal change: Monte Carlo modeling and diffusion-weighted studies in vivo. Magn Reson Med. 1995;34:4–10. - PubMed
    1. Bruchey AK, Gonzalez-Lima F. Behavioral, physiological and biochemical hormetic responses to the autoxidizable dye methylene blue. Am J Pharmacol Toxicol. 2008;3:72–79. - PMC - PubMed
    1. Clifton J, 2nd, Leikin JB. Methylene blue. Am J Ther. 2003;10:289–291. - PubMed
    1. Davis TL, Kwong KK, Weisskoff RM, Rosen BR. Calibrated functional MRI: Mapping the dynamics of oxidative metabolism. Proc Natl Acad Sci USA. 1998;95:1834–1839. - PMC - PubMed

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