Behavioral, Physiological and Biochemical Hormetic Responses to the Autoxidizable Dye Methylene Blue

Bruchey, Aleksandra K.; González-Lima, Francisco

doi:10.3844/ajptsp.2008.72.79

Cited by 67 publications

(79 citation statements)

References 39 publications

(55 reference statements)

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“…4 At low doses, MB forms a reversible reduction-oxidation system with auto-oxidizing capacity. 5 Low-dose MB has redox recycling properties in that it acts as an electron cycler and facilitates electron transfer in the mitochondrial electron transport chain by accepting electrons from nicotinamide adenine dinucleotide (NADH), and transferring them to cytochrome c, bypassing complex I-III. 6 MB thus enhances or sustains ATP production in cells [7][8][9] and brain oxygen consumption in vitro.…”

Section: Introductionmentioning

confidence: 99%

Methylene Blue Is Neuroprotective against Mild Traumatic Brain Injury

Watts

Long

Chemello

et al. 2014

Journal of Neurotrauma

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Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Methylene blue (MB) has known energy-enhancing and antioxidant properties. This study tested the hypothesis that MB treatment reduces lesion volume and behavioral deficits in a rat model of mild TBI. In a randomized double-blinded design, animals received either MB (n = 5) or vehicle (n = 6) after TBI. Studies were performed on 0, 1, 2, 7, and 14 days following an impact to the primary forelimb somatosensory cortex. MRI lesion was not apparent 1 h after TBI, became apparent 3 h after TBI, and peaked at 2 days for both groups. The MB-treated animals showed significantly smaller MRI lesion volume than the vehicle-treated animals at all time points studied. The MB-treated animals exhibited significantly improved scores on forelimb placement asymmetry and foot fault tests than did the vehicle-treated animals at all time points studied. Smaller numbers of darkstained Nissl cells and Fluoro-Jade Ò positive cells were observed in the MB-treated group than in vehicle-treated animals 14 days post-TBI. In conclusion, MB treatment minimized lesion volume, behavioral deficits, and neuronal degeneration following mild TBI. MB is already approved by the United States Food and Drug Administration (FDA) to treat a number of indications, likely expediting future clinical trials in TBI.

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Section: Introductionmentioning

confidence: 99%

Methylene Blue Is Neuroprotective against Mild Traumatic Brain Injury

Watts

Long

Chemello

et al. 2014

Journal of Neurotrauma

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“…Methylene blue also prevented memory impairment in rats with local inhibition of mitochondrial respiration in the posterior cingulate cortex by maintaining cingulo-thalamo-hippocampal effective connectivity (13). Besides improving mitochondrial respiration, methylene blue could have pleiotropic effects on the brain from its redox interactions with various proteins and cellular processes (14,15). However, the memoryenhancing effects of methylene blue do not depend on inhibition of tau aggregation (16,17).…”

Section: Methodsmentioning

confidence: 99%

“…For delayed match-tosample and psychomotor vigilance tasks, 0.5-4 mg/kg, but it has opposite effects at doses greater than 10 mg/kg and displays a hormetic dose response (15). The capsules were stored in sequentially labeled plastic containers by a separate research nurse, who used the randomization key created by the statistician; this nurse did not participate in any other aspect of the study.…”

Section: Experimental Tasks and Image Acquisitionmentioning

confidence: 99%

“…For the CVR and mean CBF only, PCASL data for CO 2 challenge were also processed with the ASL data processing toolbox (https://cfn.upenn.edu/~zewang/ ASLtbx.php) to generate absolute mean CBF maps and preprocess data for CVR analysis (15). The ASL data processing toolbox applies motion correction, realignment, and a validated CBF quantification model.…”

Section: Neuroradiology: Functional Mr Imaging Of the Effects Of Methmentioning

confidence: 99%

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Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain

Rodriguez¹,

Zhou²,

Barrett³

et al. 2016

Radiology

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Purpose:To investigate the sustained-attention and memory-enhancing neural correlates of the oral administration of methylene blue in the healthy human brain. Materials and Methods:The institutional review board approved this prospective, HIPAA-compliant, randomized, double-blinded, placebocontrolled clinical trial, and all patients provided informed consent. Twenty-six subjects (age range, 22-62 years) were enrolled. Functional magnetic resonance (MR) imaging was performed with a psychomotor vigilance task (sustained attention) and delayed match-to-sample tasks (short-term memory) before and 1 hour after administration of low-dose methylene blue or a placebo. Cerebrovascular reactivity effects were also measured with the carbon dioxide challenge, in which a 2 3 2 repeatedmeasures analysis of variance was performed with a drug (methylene blue vs placebo) and time (before vs after administration of the drug) as factors to assess drug 3 time between group interactions. Multiple comparison correction was applied, with cluster-corrected P , .05 indicating a significant difference. Results:Administration of methylene blue increased response in the bilateral insular cortex during a psychomotor vigilance task (Z = 2.9-3.4, P = .01-.008) and functional MR imaging response during a short-term memory task involving the prefrontal, parietal, and occipital cortex (Z = 2.9-4.2, P = .03-.0003). Methylene blue was also associated with a 7% increase in correct responses during memory retrieval (P = .01). Conclusion:Low-dose methylene blue can increase functional MR imaging activity during sustained attention and short-term memory tasks and enhance memory retrieval.q RSNA, 2016

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“…The FST is the most widely used pharmacological in vivo test for assessing antidepressant activity (Bruchey andGonzalez-Lima, 2008, Tong-Un et al, 2010). The development of immobility when the rat is placed in an inescapable cylinder filled with water, reflects the cessation of persistent escape-directed behavior (Porsolt et al, 1977).…”

Section: Forced Swimming Test (Fst)mentioning

confidence: 99%

EVALUATION OF NEUROPHARMACOLOGICAL ACTIVITIES OF <i>STEPHANIA VENOSA</i> HERB CONSUMPTION IN HEALTHY RATS

Tong-Un¹,

Phachonpai²,

Muchimapura³

et al. 2012

American Journal of Agricultural and Biological Sciences

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Public concern on mental health has noticeably increased given the high prevalence of neuropsychiatric disorders especially anxiety and depression. Most of the drugs for these conditions used nowadays have adverse side effects so the need for newer, better-tolerated and more efficacious treatments is remaining high. Growing attention is being paid to traditional herbal medicines. Stephania venosa Spreng (S. venosa; SV) is a Thai traditional herb which has been used for cancer treatment as well as an aphrodisiac. In addition, accumulating lines of evidence reported that the ethanol extract of SV exhibited an antioxidant and exerted acetylcholinesterase inhibitory. However, the in vivo neurophamacological activities of this plant have never been studied. The aim of this study was to examine the neurophamacological effects of a crude extract of SV introduced orally at various doses ranging from 5, 10 and 20 mg kg −1 BW once daily for a period of 2 weeks. The anxiolytic and anti-depression like activities were determined after single administration, 1 and 2 weeks of treatment using elevated plus maze and forced swimming test respectively. Only SV 20 mg kg −1 treated rats exhibited a significant anxiolytic effect at all treatment duration. Unfortunately, this substance failed to show anti-depression like activity. Our findings provide a potential of the SV consumption might be used as a novel therapeutic strategy for the anti-anxiety disorder. However, further investigations about possible active ingredients and the precise underlying mechanisms are still necessary.

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Behavioral, Physiological and Biochemical Hormetic Responses to the Autoxidizable Dye Methylene Blue

Cited by 67 publications

References 39 publications

Methylene Blue Is Neuroprotective against Mild Traumatic Brain Injury

Methylene Blue Is Neuroprotective against Mild Traumatic Brain Injury

Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain

EVALUATION OF NEUROPHARMACOLOGICAL ACTIVITIES OF <i>STEPHANIA VENOSA</i> HERB CONSUMPTION IN HEALTHY RATS

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