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

Abstract

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.

Recent advances in mechanistic, therapeutic, and diagnostic research of cerebrovascular diseases: updates from brain & BrainPET 2022

“…They assume that these findings, consistent between species and dose-dependent, may be related to the relatively high doses of methylene blue used. 23 In summary, the findings presented in this special collection may pave the way toward novel diagnostic and treatment strategies for cerebrovascular diseases. Nevertheless, these interesting contributions represent small steps toward clinical application, and some findings still await verification in large-scale clinical studies.…”

“…They assume that these findings, consistent between species and dose-dependent, may be related to the relatively high doses of methylene blue used. 23…”