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The effects of acute Methylene Blue administration on cerebral blood flow and metabolism in humans and rats

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posted on 2023-06-10, 07:06 authored by Nisha Singh, Eilidh MacNicol, Ottavia DiPasquale, Karen Randall, David Lythgoe, Ndabezinhle Mazibuko, Camilla Simmons, Pierluigi Selvaggi, Stephanie Stephenson, Federico E Turkheimer, Dianna Cash, Fernando Zelaya, Alessandro ColasantiAlessandro Colasanti
Methylene Blue (MB) is a brain-penetrating drug with putative neuroprotective, antioxidant and metabolic enhancing effects. In vitro studies suggest that MB enhances mitochondrial complexes activity. However, no study has directly assessed the metabolic effects of MB in the human brain. We used in vivo neuroimaging to measure the effect of MB on cerebral blood flow (CBF) and brain metabolism in humans and in rats. Two doses of MB (0.5 and 1 mg/kg in humans; 2 and 4 mg/kg in rats; iv) induced reductions in global cerebral blood flow (CBF) in humans (F(1.74, 12.17)5.82, p = 0.02) and rats (F(1,5)26.04, p = 0.0038). Human cerebral metabolic rate of oxygen (CMRO2) was also significantly reduced (F(1.26, 8.84)8.01, p = 0.016), as was the rat cerebral metabolic rate of glucose (CMRglu) (t = 2.6(16) p = 0.018). This was contrary to our hypothesis that MB will increase CBF and energy metrics. Nevertheless, our results were reproducible across species and dose dependent. One possible explanation is that the concentrations used, although clinically relevant, reflect MB’s hormetic effects, i.e., higher concentrations produce inhibitory rather than augmentation effects on metabolism. Additionally, here we used healthy volunteers and healthy rats with normal cerebral metabolism where MB’s ability to enhance cerebral metabolism might be limited.

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Publication status

  • Published

File Version

  • Published version

Journal

Journal of Cerebral Blood Flow and Metabolism

ISSN

0271-678X

Publisher

SAGE Publications

Page range

1-11

Event location

United States

Department affiliated with

  • BSMS Neuroscience Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2023-05-19

First Open Access (FOA) Date

2023-05-19

First Compliant Deposit (FCD) Date

2023-05-19

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