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Исправление: Фитохормоновая абсциссовая кислота усиливает ремиелионацию в мышах моделей множественного склероза.

[Это корректирует статью ДОИ: 10.3389/fimmu.2024.1500697.]

Коллаген типа I, скрытый в повреждениях белой материи, препятствует восстановлению и функциональному восстановлению.

Повреждения белой материи вызваны церебральным кровопотоком, связанным с инсультом и демиелинизирующими заболеваниями, такими, как множественный склероз. Ремилинизация происходит спонтанно после травмы белой материи, но прогрессирующий множественный склероз и инсульт белой материи обычно характеризуются провалом ремиэлации. Однако механизмы, лежащие в основе слабого воспоминания о повреждениях, вызванных обезвоживанием и инсультом, остаются неясными. В текущем исследовании мы продемонстрировали, что коллагенные волокна, накопившиеся в демиелионированных повреждениях нескольких склерозных пацие

Совпадение в аннотации оригинала
White matter injury is caused by cerebral blood flow disturbances associated with stroke and demyelinating diseases such as multiple sclerosis. Remyelination is induced spontaneously after white matter injury, but progressive multiple sclerosis and white matter stroke are usually characterised by remyelination failure. However, the mechanisms underlying impa…

Preventing production of new oligodendrocytes impairs remyelination and sustains behavioural deficits after demyelination.

Damage to oligodendrocytes (OLs) and myelin sheaths (demyelination) has been shown to be associated with numerous neurological and psychiatric disorders. Remyelination is a rare and reliable regenerative response that occurs in the central nervous system (CNS). It is generally believed that OL progenitor cells (OPCs) are the cell source to generate new OLs to remyelinate the demyelinated axons. However, several recent studies have argued that pre-existing mature OLs that survive within the demyelinated area are responsible for remyelination. Here, by conditional knock-out (KO) of a transcripti…

Paired vagus nerve stimulation drives precise remyelination and motor recovery after myelin loss.

Myelin loss in the central nervous system can cause permanent motor or cognitive deficits in patients with multiple sclerosis (MS). While cu … njury and measured longitudinal myelin dynamics and functional recovery. We found that VNS promotes remyelination by increasing the generation of myelinating oligodendrocytes. Pairing VNS with a skilled reach task leads to the regeneration of myelin sheaths on previously myelinated axon segments, enhancing the restoration of the original pattern of myelination. …

Remyelination-oriented clemastine treatment attenuates neuropathies of optic nerve and retina in glaucoma.

As one of the top causes of blindness worldwide, glaucoma leads to diverse optic neuropathies such as degeneration of retinal ganglion cells … es were attenuated via promoting oligodendrocyte precursor cell (OPC) differentiation and enhancing remyelination. Taken together, our results reveal the timeline of the optic neuropathies in glaucoma and highlight the potential role of oligodendroglial lineage cells playing in its treatment. Clemastine may be used in future clinical applications for demyelinat …

Multiple sclerosis risk gene Mertk is required for microglial activation and subsequent remyelination.

In multiple sclerosis (MS) and other neurological diseases, the failure to repair demyelinated lesions contributes to axonal damage and clinical disability. Here, we provide evidence that Mertk, a gene highly expressed by microglia that alters MS risk, is required for efficient remyelination. Compared to wild-type (WT) mice, Mertk-knockout (KO) mice show impaired clearance of myelin debris and remyelination following demyelination. Using single-cell RNA sequencing, we characterize Mertk-influenced responses to cuprizone-mediated demyelination and remyelination across different cell types. Mert…

Quercetin improves hypoxia-ischemia induced cognitive deficits via promoting remyelination in neonatal rat.

Myelination failure is associated with perinatal cerebral hypoxia-ischemia (PHI) induced brain injury in premature infants. How to efficiently promote remyelination is crucial for improving cognitive deficits caused by brain injury. Here, we demonstrated that quercetin (Que), a kind of flavonoids, significantly improved cognitive deficits and the behavior of PHI-rat in Morris water maze and open field tasks. After administration of Que to PHI-rat, the number of neogenetic Olig2⁺ oligodendrocyte progenitor cells (OPCs) was evidently increased in the subventricular zone. Additionally, in corpus …

Imaging the peripheral benzodiazepine receptor response in central nervous system demyelination and remyelination.

We used a rodent model of cuprizone-induced demyelination to examine the peripheral benzodiazepine receptor (PBR) response during remyelination. C57BL/6J mice were fed a 0.2% cuprizone-containing or control diet for 3 weeks and then removed to allow for remyelination. Quantitative autoradiography of 3H-(R)-PK11195 binding to PBR in the corpus callosum showed increased levels at 3 weeks of demyelination and gradually decreased as a function of remyelination. PBR levels were associated with the degree of remyelination and activation of microglia and astrocytes. However, the temporal pattern sugg…

Spontaneous CNS remyelination in beta 2 microglobulin-deficient mice following virus-induced demyelination.

Animal models with selective genetic immunodeficiencies are useful tools to identify pathogenic mechanisms of disease. Resistant (C57BL/6F 129/J) (H-2b) mice are rendered susceptible to Theiler's murine encephalomyelitis virus-induced demyelination by genetic disruption of the beta 2 microglobulin gene [beta 2 m(-l-)]. The absence of beta 2 m prevents the expression of major histocompatibility complex class I molecules and normal levels of functional CD8+ T cells. We tested whether genetic depletion of beta 2 m would permit CNS remyelination after chronic demyelination induced by the Daniel's …

Induction of oligodendrocyte proliferation and remyelination after chronic demyelination. Relevance to multiple sclerosis.

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Inhibitors of Myelination and Remyelination, Bone Morphogenetic Proteins, are Upregulated in Human Neurological Disease.

During demyelinating disease such as multiple sclerosis and stroke, myelin is destroyed and along with it, the oligodendrocytes that synthesize the myelin. Thus, recovery is limited due to both interruptions in neuronal transmission as well as lack of support for neurons. Although oligodendrocyte progenitor cells remain abundant in the central nervous system, they rarely mature and form new functional myelin in the diseased CNS. In cell culture and in experimental models of demyelinating disease, inhibitory signaling factors decrease myelination and remyelination. One of the most potent of the…

Nudging oligodendrocyte intrinsic signaling to remyelinate and repair: Estrogen receptor ligand effects.

Demyelination in multiple sclerosis (MS) leads to significant, progressive axonal and neuronal degeneration. Currently existing immunosuppre … chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS by stimulating endogenous remyelination. Recently, we found that the more potent, selective ERβ agonist indazole-chloride (Ind-Cl) improves clinical disease and motor performance. Importantly, electrophysiological measures revealed improved corpus callosal conduction and reduced axon refr …

The p38α mitogen-activated protein kinase is a key regulator of myelination and remyelination in the CNS.

The p38α mitogen-activated protein kinase (MAPK) is one of the serine/threonine kinases regulating a variety of biological processes, includ … ator of OL differentiation and myelination. Unexpectedly, we observed an opposite effect of p38α on remyelination in the cuprizone-induced demyelination model. The p38α CKO mice exhibited better remyelination capability compared with p38α fl/fl mice following demyelination. The opposing roles of p38α in myelination and remyelination could be due to a strong ant …

Long-term impact of neonatal inflammation on demyelination and remyelination in the central nervous system.

Perinatal inflammation causes immediate changes of the blood-brain barrier (BBB) and thus may have different consequences in adult life incl … oval in the corpus callosum, which was paralleled by reduced numbers of activated microglia. During remyelination, postnatal LPS treatment enhanced early remyelination with a concomitant increase of mature oligodendrocytes. Furthermore, the postnatal LPS challenge impacts the phenotype of microglia since an elevated mRNA expression of microglia related genes su …

Effects of acute and repeated exposure to lipopolysaccharide on cytokine and corticosterone production during remyelination.

Chronic exposure to the copper-chelating agent, cuprizone (CPZ), is an increasingly popular model for producing demyelination. More importantly, cessation of cuprizone exposure allows for full remyelination, which represents a window of opportunity for determining the influence of environmental factors on regenerative processes. In the present study, CPZ-treated animals were assessed for functional status of systemic and central cytokine responsiveness to LPS, as well as assessment for signs of body weight changes. Exposure of male C57BL/6J mice to 5 weeks of 0.2% CPZ in the diet was optimal i…

Human monoclonal antibodies reactive to oligodendrocytes promote remyelination in a model of multiple sclerosis.

Promoting remyelination, a major goal of an effective treatment for demyelinating diseases, has the potential to protect vulnerable axons, increase conduction velocity, and improve neurologic deficits. Strategies to promote remyelination have focused on transplanting oligodendrocytes (OLs) or recruiting endogenous myelinating cells with trophic factors. Ig-based therapies, routinely used to treat a variety of neurological and autoimmune diseases, underlie our approach to enhance remyelination. We isolated two human mAbs directed against OL surface antigens that promoted significant remyelinati…

Promotion of remyelination by polyclonal immunoglobulin in Theiler's virus-induced demyelination and in multiple sclerosis.

Spontaneous remyelination occurs in experimental models of demyelination and in patients with multiple sclerosis, although to a limited extent. This enables the search for factors that promote remyelination. Using the Theiler's virus model of central nervous system demyelination, promotion of remyelination was observed after passive transfer of CNS-specific antiserum and transfer of CNS-specific purified immunoglobulin. Mouse polyclonal immunoglobulin from normal non-syngeneic mice, comparable with the human immunoglobulin preparation, also promotes CNS remyelination in the Theiler's virus mod…

Glial cells in the rat optic nerve and some thoughts on remyelination in the mammalian CNS.

Studies on the rat optic nerve in the past 5 years have produced two surprises. First, they demonstrated that there are two biochemically, developmentally and functionally distinct types of astrocytes in the optic nerve, and probably in white matter tracts throughout the CNS: one seems to be responsible for inducing endothelial cells to form the blood-brain barrier while the other seems to service nodes of Ranvier. Second, they showed that oligodendrocytes and type-2 astrocytes develop from a common bipotential (O-2A) progenitor cell that seems to migrate into the developing optic nerve, and m

Neurorestorative properties of ibogaine: linking multi-receptor affinities to remyelination and metabolic restoration.

Ibogaine is a psychedelic alkaloid without an approved indication. Observational clinical research shows linkages between single administration of ibogaine and relief of symptoms of neuropsychiatric conditions including substance use disorder, multiple sclerosis (MS), and traumatic brain injury. Ibogaine has multi-receptor actions, but the neurobiological mechanisms underlying such putative effects are unknown. Here we review and discuss the relevant literature, focusing on remyelination and metabolic restoration. We provide evidence that ibogaine upregulates markers of myelination following o…

Aurkb deficiency disrupts microglial development, homeostasis and hinders remyelination following cuprizone-induced demyelination.

Microglia are crucial for phagocytic clearance of myelin debris, which hinders remyelination and leads to neurological decline during aging and in multiple sclerosis (MS). However, the molecular mechanism enabling microglia to expand and function effectively in remyelination remains elusive. Here, we identified that mitotic kinase Aurkb was upregulated in microglia during early development and in MS. Neonatal deletion of Aurkb disrupted cell density, morphology, and proliferation, which is attributed to stalled mitosis. Inducible Aurkb ablation in adulthood led to microglial dystrophy and disr…