Nanoscale magnesium hydride alleviates hypoxia-induced myelination deficits in zebrafish

 Can't our fucking failures of stroke associations and stroke medical 'professionals' look at this and see that further research is needed for our myelin damage

Nanoscale magnesium hydride alleviates hypoxia-induced myelination deficits in zebrafish

Li, Jia-Lin^1,2,#; Chen, Qiang^1,#; Li, Zheng-Hao^1,#; Xu, Dao-Jie³; He, Cheng^1,*; Liu, Peng^1,*

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Medical Gas Research ():10.4103/mgr.MEDGASRES-D-25-00104, January 23, 2026. | DOI: 10.4103/mgr.MEDGASRES-D-25-00104

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Abstract

Defects in myelination impair nerve impulse conduction and functional connectivity, which could lead to cognitive, behavioral and motor deficits in various neurological disorders. Adequate oxygen delivery is vital for brain development, while hypoxia in newborns tends to result in developmental deficiencies in myelination of the brain. The disruption of oligodendrocytes and their progenitor cells caused by hypoxia has been well researched. Nonetheless, the impairing dynamic myelination process is still unclear. Utilizing zebrafish as a model, we established hypoxia via cobalt chloride exposure or low oxygen (8%) incubation. Hypoxia significantly reduced oligodendrocyte progenitor cell numbers in the dorsal spinal cord, impaired migration velocity and suppressed proliferation. Myelination deficits were evident through decreased myelin sheath segment intensity in Tg(MBP:eGFP-CAAX) larvae. Time-lapse imaging revealed compromised dynamic myelination by individual oligodendrocytes under hypoxia, with fewer sheaths and reduced extension rates. Mechanistically, hypoxia elevated reactive oxygen species levels and disrupted mitochondrial membrane potential in cultured rat oligodendrocyte progenitor cells. Nanoscale magnesium hydride, a hydrogen-releasing agent, attenuated these effects. In vivo, magnesium hydride treatment rescued oligodendrocyte progenitor cell numbers and enhanced myelinogenesis capacity in hypoxic zebrafish. These findings demonstrate that magnesium hydride mitigates hypoxia-induced oxidative stress and mitochondrial dysfunction, thereby alleviating myelination deficits.

Fujian tablet regulates the Foxo3a/GPX4 axis to promote remyelination and improve motor function in ischemic stroke

 Your competent? doctor KNOWS EXACTLY HOW MUCH DEMYELINATION HAS OCCURRED and has EXACT PROTOCOLS TO FIX THAT! RIGHT? NO? So your doctor knows nothing and is completely fucking incompetent? Will your doctor once again prove incompetence by not getting human testing done?

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demyelinating (24 posts to May 2012)

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Fujian tablet regulates the Foxo3a/GPX4 axis to promote remyelination and improve motor function in ischemic stroke

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Abstract

Ethnopharmacological relevance

Fujian Tablet (FJT), a traditional Chinese herbal compound formulation developed under the theoretical framework of “nourishing the liver and kidney, replenishing essence and marrow”, has been clinically applied for over two decades to treat post-stroke neurological deficits. Preliminary studies demonstrated its efficacy in improving motor function and promoting cervical spinal cord neuroaxonal growth in a middle cerebral artery occlusion (MCAO) rat model. Building upon these findings, this study integrates metabolomic evidence of Foxo3a-GPX4 axis activation to systematically elucidate Fujian Tablet's neurorestorative mechanisms through three interconnected pathways: regulation of ferroptosis, promotion of oligodendrocyte proliferation, and remyelination. By bridging traditional TCM therapeutic principles with contemporary molecular neuroscience, this investigation aims to provide mechanistic insights for optimizing Fujian Tablet's clinical application and advancing its global recognition in neurorehabilitation.

Aim of the study

This study aims to verify the molecular mechanism by which FJT activates Forkhead box O3a (Foxo3a) to promote glutathione peroxidase 4 (GPX4) expression, thereby regulating oligodendrocyte survival and remyelination, based on the regulatory network of “traditional Chinese medicine compound - target - cellular function”. This study provides experimental evidence for explaining the material basis and action targets of the compound's efficacy.

Materials and methods

The middle cerebral artery embolization method was employed to establish a rat model of MCAO. Then, FJT was used for intervention via intragastric administration at doses of 0.72 g/kg and 1.44 g/kg, twice daily for 14 consecutive days. Behavioral observations of the rats were carried out using the Catwalk system and beam walking test (BWT). remyelination was assessed via luxol fast blue (LFB) staining and transmission electron microscopy. In addition, in vitro experiments with oligodendrocytes were conducted in combination. The expressions of myelin basic protein (MBP) was detected by immunofluorescence. The expressions of Ferritin, and GPX4 were detected by RT-qPCR and Western blot.

The levels of ferroptosis - related metabolites were measured using flow cytometry and enzyme - linked immunosorbent assay (ELISA). The transcriptional regulatory effect of Foxo3a on GPX4 was examined by ChIP-qPCR.

Results

Fujian Tablet dose-dependently improved the motor function of MCAO rats, and upregulated the expression of Foxo3a to enhance its binding activity to the GPX4 promoter, thereby increasing GPX4 expression. Knockdown of Foxo3a or treatment with the GPX4 inhibitor (RSL3) reversed the inhibitory effect of FJT on ferroptosis (decrease in lipid reactive oxygen species (ROS) and malondialdehyde (MDA), and increase in reduced glutathione (GSH)). This reversal led to a reduction in the expression of MBP and myelin oligodendrocyte glycoprotein (MOG), inhibited the level of remyelination (decrease in LFB optical density and increase in the electron microscopy G-ratio), and hindered the recovery of motor function. In vitro experiments confirmed that serum containing FJT inhibited ferroptosis through the Foxo3a-GPX4 axis, and promoted the proliferation of oligodendrocytes.

Conclusions

FJT exerts a neuroprotective effect by activating the Foxo3a - GPX4 axis to inhibit ferroptosis, promote the proliferation of oligodendrocytes and remyelination, and ultimately improve motor function. This study clarifies that Fujian Tablet exerts a neuroprotective effect through regulating the “ferroptosis - oligodendrocyte proliferation - remyelination” axis, providing a scientific basis for its clinical application in ethnic medicine.

Graphical abstract

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Repeated intermittent administration of 3,4-methylenedioxymethamphetamine mitigates demyelination in the brain from cuprizone-treated mice

 

 Your competent? doctor has known of myelin problems from your stroke a long time ago, was anything done to solve it? NO? So, pure incompetence in action! A competent doctor would ensure human testing gets done to prevent demyelination post stroke.

WELL, DO YOU HAVE A COMPETENT DOCTOR OR NOT?

demyelinating (23 posts to May 2012)

demyelination (7 posts to November 2021)

Repeated intermittent administration of 3,4-methylenedioxymethamphetamine mitigates demyelination in the brain from cuprizone-treated mice

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https://doi.org/10.1016/j.ejphar.2025.177345

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Abstract

3,4-Methylenedioxymethamphetamine (MDMA), commonly known as a recreational drug, may also offer therapeutic benefits for mental health. Population-based studies suggest that MDMA users have a lower risk of demyelinating diseases, such as depression. Given the role of the gut microbiota in mediating MDMA's effects, we hypothesized that MDMA might confer mental health benefits via the gut-brain axis. Cuprizone (CPZ) induces demyelination by chelating copper, which leads to oligodendrocyte death and subsequent myelin loss. This study investigated the impact of MDMA on brain demyelination in CPZ-treated mice, focusing on the gut-brain axis. Repeated intermittent MDMA administration (10 mg/kg, three times weekly for 6 weeks) significantly reduced demyelination in the corpus callosum (CC) of CPZ-treated mice. Gut microbiota and non-targeted metabolomics analyses revealed notable differences in specific gut bacteria and plasma (β-D-allose and L-sorbose) or fecal metabolite (carnitine) levels between MDMA-treated and vehicle-treated CPZ-exposed mice. Negative correlations were found between the levels of metabolites (β-D-allose, L-sorbose, and carnitine) and the relative abundance of Romboutsia and Romboutsia timonensis. These findings suggest that intermittent MDMA administration may alleviate demyelination in the CC of CPZ-treated mice via the gut–brain axis. Further research is needed to elucidate the roles of gut microbiota and metabolites in MDMA's effects on brain demyelination and to investigate other demyelination models.

White matter aging and its impact on brain function

 You competent? doctor has known of myelin problems from your stroke a long time ago, was anything done to solve it? NO? So, pure incompetence in action!

(My doctor told me I had a bunch of white matter hyperintensities but never showed me them on any scan, so I don't know the size, location or any intervention needed, because my doctor knew nothing and did nothing.)

demyelinating (23 posts to May 2012)

demyelination (7 posts to November 2021)

White matter aging and its impact on brain function

Janos Groh^1,2,3 janos.groh@tum.de ∙ Mikael Simons^1,2,3,4 mikael.simons@dzne.de

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Summary

Aging has a detrimental impact on white matter, resulting in reduced volume, compromised structural integrity of myelinated axons, and an increase in white matter hyperintensities. These changes are closely linked to cognitive decline and neurological disabilities. The deterioration of myelin and its diminished ability to regenerate as we age further contribute to the progression of neurodegenerative disorders. Understanding these changes is crucial for devising effective disease prevention strategies. Here, we will discuss the structural alterations in white matter that occur with aging and examine the cellular and molecular mechanisms driving these aging-related transformations. We highlight how the progressive disruption of white matter may initiate a self-perpetuating cycle of inflammation and neural damage.

Keywords

1. aging
2. white matter
3. myelin
4. neuroinflammation

Introduction

In his pioneering work, De Humani Corporis Fabrica (1543), Renaissance anatomist Andreas Vesalius provided one of the earliest descriptions of white matter structure, noting the corpus callosum as a whitish substance distinct from the softer, yellowish cerebrum.¹ Although Vesalius recognized that the corpus callosum connected the two hemispheres, he did not understand that its fibers originated from nerve cell bodies. At the time, white matter was believed to be composed of excretory ducts filled with a “spongy substance” and was thought to be the center of spirit and imagination.¹ Now, we know that white matter primarily consists of myelinated axons, glial cells, blood vessels, and extracellular matrix. Oligodendrocytes, the main cells in white matter, produce myelin sheaths that are crucial for fast signal transmission and for maintaining the functional and structural integrity of axons.^2,3 Because white matter largely lacks neuronal cell bodies and mainly serves to connect different gray matter areas, it has not received as much as attention as the cortical areas of the brain. Yet, its significance becomes evident when looking at its evolution in primates. Unlike neocortical gray matter, which grows in direct proportion to brain size, white matter mass has increased at a much higher rate, highlighting the crucial role of enhanced connectivity for higher brain function.⁴ Consequently, the proportion of white matter in the human brain has risen to about 40%, with myelinated axons being a major component.⁴ However, this expansion of white matter also introduces risks, providing a surface for diseases and the effects of aging. As we age, our white matter undergoes several changes. It experiences a reduction in overall volume and exhibits a decline in its microstructural integrity, and there is an accumulation of focal lesions, contributing to a decline in cognitive functions and to the risk for age-related neurological diseases, including dementia and stroke.^5,6,7,8 Many of these changes follow non-linear kinetics, starting slowly and then accelerating at a certain age.⁹ In this context, we explore the structural changes in white matter associated with aging and investigate the cellular and molecular mechanisms underlying these age-related transformations. We hypothesize that chronic inflammation and vascular changes are closely linked to the degeneration of myelin and axons with age.