Neuroprotective Effects of Methylene Blue In Vivo and In Vitro

Stelmashook, E. V.; Генрихс, Е. Е.; Mukhaleva, Elizaveta; Kapkaeva, Marina R.; Kondratenko, R. V.; Skrebitsky, V. G.; Isaev, N. K.

doi:10.1007/s10517-019-04548-3

Cited by 17 publications

(4 citation statements)

References 14 publications

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“… 56 In a rat model of traumatic brain injury, 1 mg/kg intravenous MB before or after brain injury attenuated deficits in responses to tactile and proprioceptive stimulation of the contralateral fore and hind paws. 57 In studies in vitro , MB (0.05–1 μM) increased survival of cerebellar granule neurons in response to mitochondrial toxins. 58 Low concentrations of MB (alone or combined with near-infrared light) protected against neuronal degeneration and improved memory function through effects on mitochondrial electron transport chains.…”

Section: Discussionmentioning

confidence: 99%

Adverse effects of methylene blue in peripheral neurons: An in vitro electrophysiology and cell culture study

et al. 2022

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Methylene blue (MB) is an effective treatment for methemoglobinemia, ifosfamide-induced encephalopathy, cyanide poisoning, and refractory vasoplegia. However, clinical case reports and preclinical studies indicate potentially neurotoxic activity of MB at certain concentrations. The exact mechanisms of MB neurotoxicity are not known, and while the effects of MB on neuronal tissue from different brain regions and myenteric ganglia have been examined, its effects on primary afferent neurons from dorsal root ganglia (DRG) have not been studied. Mouse DRG were exposed to MB (0.3–10 µM) in vitro to assess neurite outgrowth. Increasing concentrations of MB (0.3–10 µM) were associated with neurotoxicity as shown by a substantial loss of cells with neurite formation, particularly at 10 µM. In parallel experiments, cultured rat DRG neurons were treated with MB (100 µM) to examine how MB affects electrical membrane properties of small-diameter sensory neurons. MB decreased peak inward and outward current densities, decreased action potential amplitude, overshoot, afterhyperpolarization, increased action potential rise time, and decreased action potential firing in response to current stimulation. MB induced dose-dependent toxicity in peripheral neurons, in vitro. These findings are consistent with studies in brain and myenteric ganglion neurons showing increased neuronal loss and altered membrane electrical properties after MB application. Further research is needed to parse out the toxicity profile for MB to minimize damage to neuronal structures and reduce side effects in clinical settings.

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Section: Discussionmentioning

confidence: 99%

Adverse effects of methylene blue in peripheral neurons: An in vitro electrophysiology and cell culture study

et al. 2022

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“…Similarly, MB can act on components of the mitochondrial electron transport chain (ETC) [27][28][29][30][31][32] , and has been used to treat cyanide poisoning characterized by inhibition of the electron transport chain via noncompetitive binding to complex IV 33,34 . MB is, due to its described action on mitochondria, furthermore investigated as a potential treatment for aging and/or neurodegeneration [35][36][37][38][39][40][41] , and has been shown to mitigate pesticide effects on mitochondria in wildlife, such as bumblebees 42 .…”

Section: Introductionmentioning

confidence: 99%

Challenging the status quo: Methylene blue at recommended concentrations alters metabolism in early zebrafish development

Mennigen,

Nipu,

Wei

et al. 2024

Preprint

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Methylene blue (MB) is an antifungal agent widely used during critical stages of zebrafish development. Most guidelines recommend 0.00005% or 0.0001% of MB for embryo/larval rearing. The Organisation for Economic Co-operation and Development zebrafish embryo toxicity test guideline omits MB recommendations, leading to inconsistent MB use in zebrafish research. Because MB affects oxidative energy metabolism in vitro and in vivo, we investigated possible metabolic effects of recommended MB concentrations in developing zebrafish (1-5 days post-fertilization (dpf)). MB increased O2 consumption rate at 1 dpf, followed by an overall reduction in oxidative energy metabolism in post-hatch eleutheroembryos (4-5 dpf). Concomitantly, mitochondrial transcripts decreased in 1 and 4 dpf zebrafish. Our findings show that MB, at recommended husbandry concentrations, affects oxidative metabolism and can thus confound experiments. Since the zebrafish embryo/larval model is gaining traction as a high-throughput New Approach Methodology (NAM) for toxicity assessment, researchers should reconsider MB use.

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“…One such drug that can be used in a multivalent therapeutic strategy is methylene blue (MB). According to some studies, MB can exhibit antioxidant properties, as well as protects cells from death induced by the action of inhibitors of the complex I of the electron transport chain [5][6][7]. Several studies showed that MB diminishes cerebral damage caused by TBI [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…According to some studies, MB can exhibit antioxidant properties, as well as protects cells from death induced by the action of inhibitors of the complex I of the electron transport chain [5][6][7]. Several studies showed that MB diminishes cerebral damage caused by TBI [7][8][9]. MB is able to penetrate the blood brain barrier following intravenous injection and its concentration in the brain rapidly (approximately in one hour) becomes 20 times greater than in plasma [10].…”

Section: Introductionmentioning

confidence: 99%

The Delayed Neuroprotective Effect of Methylene Blue in Experimental Rat Brain Trauma

et al. 2020

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After traumatic brain injury (TBI), an increase in dysfunction of the limbs contralateral to injury focus was observed. Using different behavioral tests, we found that a single intravenous injection of methylene blue (MB, 1 mg/kg) 30 min after the injury reduced the impairment of the motor functions of the limbs from 7 to 120 days after TBI. Administration of methylene blue 30 min after the injury and then monthly (six injections in total) was the most effective both in terms of preservation of limb function and duration of therapeutic action. This therapeutic effect was clearly manifested from the seventh day and continued until the end of the experiment—by the 180th day after TBI. MB is known to possess antioxidant properties; it has a protective effect against TBI by promoting autophagy and minimizing lesion volume in the first two weeks after TBI. Studies of the brains on the 180th day after TBI demonstrated that the monthly treatment of animals with MB statistically significantly prevented an increase in the density of microglial cells in the ipsilateral hemisphere and a decrease in the thickness of the corpus callosum in the contralateral hemisphere in comparison with untreated animals. However, on the 180th day after TBI, the magnetic resonance imaging scan of the animal brains did not show a significant reduction in the volume of the lesion in MB-treated animals. These findings are important for understanding the development of the long-term effects of TBI and expand the required therapeutic window for targeted neuroprotective interventions.

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Neuroprotective Effects of Methylene Blue In Vivo and In Vitro

Cited by 17 publications

References 14 publications

Adverse effects of methylene blue in peripheral neurons: An in vitro electrophysiology and cell culture study

Adverse effects of methylene blue in peripheral neurons: An in vitro electrophysiology and cell culture study

Challenging the status quo: Methylene blue at recommended concentrations alters metabolism in early zebrafish development

The Delayed Neuroprotective Effect of Methylene Blue in Experimental Rat Brain Trauma

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