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.
Conflict of interest statement
Disclosure/Conflict of Interest
The authors declare no conflict of interest
Figures
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
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
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
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
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.
Similar articles
- Effects of hypoxia, hyperoxia, and hypercapnia on baseline and stimulus-evoked BOLD, CBF, and CMRO2 in spontaneously breathing animals.
Sicard KM, Duong TQ. Sicard KM, et al. Neuroimage. 2005 Apr 15;25(3):850-8. doi: 10.1016/j.neuroimage.2004.12.010. Neuroimage. 2005. PMID: 15808985 Free PMC article. - Cerebral blood flow and BOLD fMRI responses to hypoxia in awake and anesthetized rats.
Duong TQ. Duong TQ. Brain Res. 2007 Mar 2;1135(1):186-94. doi: 10.1016/j.brainres.2006.11.097. Epub 2007 Jan 2. Brain Res. 2007. PMID: 17198686 Free PMC article. - Measurement of CMRO2 and its relationship with CBF in hypoxia with an extended calibrated BOLD method.
Zhang Y, Yin Y, Li H, Gao JH. Zhang Y, et al. J Cereb Blood Flow Metab. 2020 Oct;40(10):2066-2080. doi: 10.1177/0271678X19885124. Epub 2019 Oct 30. J Cereb Blood Flow Metab. 2020. PMID: 31665954 Free PMC article. - Blood oxygenation level-dependent (BOLD)-based techniques for the quantification of brain hemodynamic and metabolic properties - theoretical models and experimental approaches.
Yablonskiy DA, Sukstanskii AL, He X. Yablonskiy DA, et al. NMR Biomed. 2013 Aug;26(8):963-86. doi: 10.1002/nbm.2839. Epub 2012 Aug 28. NMR Biomed. 2013. PMID: 22927123 Free PMC article. Review. - Biophysical and physiological origins of blood oxygenation level-dependent fMRI signals.
Kim SG, Ogawa S. Kim SG, et al. J Cereb Blood Flow Metab. 2012 Jul;32(7):1188-206. doi: 10.1038/jcbfm.2012.23. Epub 2012 Mar 7. J Cereb Blood Flow Metab. 2012. PMID: 22395207 Free PMC article. Review.
Cited by
- Mitochondrial Dysfunction in Stroke: Implications of Stem Cell Therapy.
Sarmah D, Kaur H, Saraf J, Vats K, Pravalika K, Wanve M, Kalia K, Borah A, Kumar A, Wang X, Yavagal DR, Dave KR, Bhattacharya P. Sarmah D, et al. Transl Stroke Res. 2018 Jun 20. doi: 10.1007/s12975-018-0642-y. Online ahead of print. Transl Stroke Res. 2018. PMID: 29926383 Review. - Methylene blue treatment delays progression of perfusion-diffusion mismatch to infarct in permanent ischemic stroke.
Rodriguez P, Jiang Z, Huang S, Shen Q, Duong TQ. Rodriguez P, et al. Brain Res. 2014 Nov 7;1588:144-9. doi: 10.1016/j.brainres.2014.09.007. Epub 2014 Sep 8. Brain Res. 2014. PMID: 25218555 Free PMC article. - Intraarterial transplantation of human umbilical cord blood mononuclear cells in hyperacute stroke improves vascular function.
Huang L, Liu Y, Lu J, Cerqueira B, Misra V, Duong TQ. Huang L, et al. Stem Cell Res Ther. 2017 Mar 22;8(1):74. doi: 10.1186/s13287-017-0529-y. Stem Cell Res Ther. 2017. PMID: 28330501 Free PMC article. - Mitochondria in Cell-Based Therapy for Stroke.
Monsour M, Gordon J, Lockard G, Alayli A, Borlongan CV. Monsour M, et al. Antioxidants (Basel). 2023 Jan 12;12(1):178. doi: 10.3390/antiox12010178. Antioxidants (Basel). 2023. PMID: 36671040 Free PMC article. Review. - Effect of Methylene Blue on White Matter Injury after Ischemic Stroke.
Cheng Q, Chen X, Ma J, Jiang X, Chen J, Zhang M, Wu Y, Zhang W, Chen C. Cheng Q, et al. Oxid Med Cell Longev. 2021 Feb 2;2021:6632411. doi: 10.1155/2021/6632411. eCollection 2021. Oxid Med Cell Longev. 2021. PMID: 33603949 Free PMC article.
References
- 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
- 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
- Clifton J, 2nd, Leikin JB. Methylene blue. Am J Ther. 2003;10:289–291. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- 8UL1TR000149/TR/NCATS NIH HHS/United States
- R01 EY018855/EY/NEI NIH HHS/United States
- UL1 TR000149/TR/NCATS NIH HHS/United States
- UL1 TR001120/TR/NCATS NIH HHS/United States
- EY018855/EY/NEI NIH HHS/United States
- R01 NS045879/NS/NINDS NIH HHS/United States
- R01-NS45879/NS/NINDS NIH HHS/United States
- R01 EY014211/EY/NEI NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous