TY - JOUR
T1 - The effects of acute Methylene Blue administration on cerebral blood flow and metabolism in humans and rats
AU - Singh, Nisha
AU - MacNicol, Eilidh
AU - DiPasquale, Ottavia
AU - Randall, Karen
AU - Lythgoe, David
AU - Mazibuko, Ndabezinhle
AU - Simmons, Camilla
AU - Selvaggi, Pierluigi
AU - Stephenson, Stephanie
AU - Turkheimer, Federico E
AU - Cash, Diana
AU - Zelaya, Fernando
AU - Colasanti, Alessandro
N1 - Publisher Copyright:
© The Author(s) 2023.
PY - 2023/11
Y1 - 2023/11
N2 - 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 (CMRO
2) 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.
AB - 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 (CMRO
2) 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.
UR - http://www.scopus.com/inward/record.url?scp=85148646668&partnerID=8YFLogxK
U2 - 10.1177/0271678X231157958
DO - 10.1177/0271678X231157958
M3 - Article
C2 - 36803299
SN - 0271-678X
VL - 43
SP - 95
EP - 105
JO - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
JF - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
IS - 2_suppl
ER -
