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Peripheral nerve elongation by laser Doppler flowmetry-monitored expansion: an experimental basis for future application in the management of peripheral nerve defects.

Nerve grafting often fails to achieve optimal functional results and is always associated with donor-site morbidity. Peripheral nerve elonga … be secondary to the observed widening of the nodes of Ranvier and altered membrane properties after remyelination. Demyelination and remyelination of whole internodes and axonal degeneration occurred only sporadically. Thus laser Doppler flowmetry-monitored expansion provides a safe method for elongation of intact rabbit sciatic nerve while nerve function and a …

A ligand-mimetic anti-TREM2 agonist antibody elevates soluble TREM2 and ameliorates pathology in mouse models of Alzheimer's disease and multiple sclerosis.

BACKGROUND: Triggering receptor expressed on myeloid cell-2 (TREM2) signaling promotes disease-associated microglia (DAM) and phagocytosis i … beta (Aβ) plaque clearance, microglial state and neuronal health were evaluated in the 5xFAD model. Remyelination and microglial status were assessed in the cuprizone model. RESULTS: Anti-TREM2 antibody 03O05 binds a conformational epitope (M41–W44, L89) within the immunoglobulin-like domain, distal from the cleavage site, activates TREM2 signaling in vitro and …

Emerging therapeutic strategies in multiple sclerosis: a focus on innovative and targeted approaches.

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system marked by damage to myelin and nerve cells. Current trea … T-cell therapy, vaccines targeting Epstein-Barr virus (EBV) and specific antigens, drugs promoting remyelination, monoclonal antibodies, stem cell therapy, sphingosine-1-phosphate receptor modulators, cytokine blockers, gut microbiome interventions, and nanotechnology-based drug delivery. Emerging therapeutic strategies in MS increasingly target mechanisms bey …

Множественная склерозовая патофизиология: всеобъемлющий обзор генетических, экологических и иммунологических факторов.

Множественный склероз (MS) представляет собой сложное хроническое нервное и нейро-дегенеративное расстройство центральной нервной системы. В этом всеобъемлющем обзоре обобщаются факты, свидетельствующие о том, что первостепенная задача в НР заключается в устранении разрыва между противовоспалительной терапией и неэффективными стратегиями нейрозащиты, что требует применения подхода, предусматривающего двойные цели. В этом документе рассматривается важнейшая роль генетической предрасположенности, при этом особое внимание уделяется аллее HLA-DRB1*15:01 и другим не связанным с HLA loci, а также эк

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a complex, chronic neuroinflammatory and neurodegenerative disorder of the central nervous system. This comprehen … lin, as well as the intricate mechanisms of neurodegeneration, axonal damage, and the challenges of remyelination. The review also incorporates emerging insights into the role of the gut microbiome and epigenetic modifications, underscoring the necessity of an integrative model to understand MS pathogenesis. Ultimately, this review provides a foundational under …

Abcd1 deficiency accelerates cuprizone-induced oligodendrocyte loss and axonopathy in a demyelinating mouse model of X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (X-ALD), the most frequent, inherited peroxisomal disease, is caused by mutations in the ABCD1 gene encoding a … he copper chelator cuprizone induces reproducible demyelination in the corpus callosum, followed by remyelination upon cuprizone removal. By immunohistochemical analyses of oligodendrocytes, myelin, axonal damage and microglia activation during de-and remyelination, we found that the mature oligodendrocytes of Abcd1 KO mice are more susceptible to cuprizone-ind …

Disinhibition of Cathepsin C Caused by Cystatin F Deficiency Aggravates the Demyelination in a Cuprizone Model.

Although the precise mechanism underlying initial lesion development in multiple sclerosis (MS) remains unclear, CNS inflammation has long b … n correlated with ongoing demyelination, and the sites of Cys F expression overlapped with areas of remyelination. Cys F induction ceased in chronic demyelination when remyelination capacity was lost, suggesting that Cys F expressed by microglia/macrophages may play an important role in demyelination and/or remyelination. The functional role of Cys F in demyeli …

Cytokine-induced changes in the ability of astrocytes to support migration of oligodendrocyte precursors and axon growth.

Repair of demyelination in the CNS requires that oligodendrocyte precursors (OPs) migrate, divide and then myelinate. Repair of axon damage requires axonal regeneration. Limited remyelination and axon regeneration occurs soon after injury, but usually ceases in a few days. In vivo and in vitro experiments have shown that astrocytic environments are not very permissive for migration of OPs or for axonal re-growth. Yet remyelination and axon sprouting early after injury occurs in association with astrocytes, while later astrocytes can exclude remyelination and prevent axon regeneration. A large …

Efficient myelin repair in the macaque spinal cord by autologous grafts of Schwann cells.

Experimental transplantation in rodent models of CNS demyelination has led to the idea that Schwann cells may be candidates for cell therapy in human myelin diseases. Here we investigated the ability of Schwann cells autografts to generate myelin in the demyelinated monkey spinal cord. We report that monkey Schwann cells derived from adult peripheral nerve biopsies retain, after growth factor expansion and transduction with a lentiviral vector encoding green fluorescent protein, the ability to differentiate in vitro into promyelinating cells. When transplanted in the demyelinated nude mouse sp

Stem cell transplantation and other novel techniques for promoting recovery from spinal cord injury.

A number of potential approaches aim to optimize functional recovery after spinal cord injury. They include minimizing the progression of secondary injury, manipulating the neuroinhibitory environment of the spinal cord, replacing lost tissue with transplanted cells or peripheral nerve grafts, remyelinating denuded axons, and maximizing the intrinsic regenerative potential of endogenous progenitor cells. We review the application of stem cell transplantation to the spinal cord, emphasizing the use of embryonic stem cells for remyelinating damaged axons. We speculate that harnessing the potenti

Pericytes: Unsung heroes in myelin repair after neonatal brain hypoxia.

Preterm infants can face lasting neurodevelopmental challenges due to hypoxia-induced injury of the cerebral white matter. In this issue of Neuron, Ren et al.1 identify microvascular pericytes as unexpected targets for growth hormone signaling, which enhances angiogenesis and remyelination after hypoxic injury in the developing mouse brain.

Sphingosine-1-Phosphate Is a Key Signaling Molecule in Normal Conditions and in Multiple Sclerosis.

Sphingosine-1-phosphate (S1P) is one of the most extensively studied bioactive signaling molecules of sphingolipid metabolism, which plays a … S1P levels, which promotes prevalence of the neuroinflammatory and neurodegenerative processes over remyelination. This review summarizes current data on the structure, metabolism, and intra- and extracellular signaling pathways of S1P, its dual role under physiological conditions and in multiple sclerosis, and analyzes approaches to pharmacological modulation …

Natural flavonoids in multiple sclerosis: molecular insights and emerging therapeutic strategies.

Multiple sclerosis is a chronic immune mediated disease in which current disease modifying therapies reduce inflammatory relapses but incompletely address neurodegeneration and remyelination. Natural flavonoids are pleiotropic polyphenols that can modulate immune and glial signaling, oxidative stress, and mitochondrial function. This review synthesizes evidence from experimental models and human studies on flavonoids relevant to multiple sclerosis, emphasizing mechanisms involving NF-κB, Nrf2, inflammasome signaling, and microglia and macrophage polarization that shape oligodendrocyte precurso…

Повышение эффективности мезенхимальных стволовых клеток, полученных с помощью kloto, в деле дифференциации и созревания олигодендроцитов в модели мыши экспериментального аутоиммунного энцефаломиелита.

Текущая терапия множественных склерозов (MS) оказывает иммуномодулятивное воздействие, но не устраняет непосредственно повреждения центральной нервной системы (СНС). Мезенхимальные стволовые клетки (МСЦ) стали перспективной терапевтической стратегией для MS, поскольку, как было показано, они способствуют ремонту миелина. Согласно сообщениям, генетические модификации КБМ повышают их терапевтическую эффективность в случае нейродегенеративных заболеваний. Цель этого исследования заключалась в изучении терапевтического потенциала MSC, разработанных с помощью секретного клото (s-KL) для усиления ре

Совпадение в аннотации оригинала
Current therapies for multiple sclerosis (MS) exert immunomodulatory effects but do not directly repair central nervous system (CNS) damage. … o investigate the therapeutic potential of MSCs engineered with secreted klotho (s-KL) in enhancing remyelination by mature oligodendrocytes in an experimental autoimmune encephalomyelitis (EAE) model in mice. The results showed that MSCs carrying s-KL alleviated clinical signs and reduced inflammation and demyelination in the CNS more significantly than MSCs. …

Эксосомная совместная доставка супероксидной дисмутазы и хондроитиназы ABC для многократной склерозовой терапии.

Множественный склероз - это аутоиммунное демиелинирующее заболевание, и его эффективное лечение является большой проблемой. Экспериментальный аутоиммунный энцефаломиэлит (EAE) — типичная модель животных для изучения множественных склерозов — характеризуется воспалением, обезвоживанием, глиозом и аксонной потерей. Таким образом, одновременное регулирование нейроинфламмации и воспылания может быть полезной стратегией против ЕАЭ. В данном случае супероксидная дисмутаза (SOD) и хондроитиназа ABC (ChABC) были совместно собраны в экзосомах, с тем чтобы получить загруженные SOD и ChABC экзосомы (SOD/

Совпадение в аннотации оригинала
Multiple sclerosis is an autoimmune demyelinating disease, and its effective treatment is a great challenge. As a typical animal model for studying multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) is characterized by inflammation, demyelination, gliosis and axonal loss. Thus, simultaneous regulation of neuroinflammation and remyelination m…

Development of a Chemical Cocktail That Rescues Mouse Brain Demyelination in a Cuprizone-Induced Model.

Oligodendrocytes are glial cells located in the central nervous system (CNS) that play essential roles in the transmission of nerve signals and in the neuroprotection of myelinated neurons. The dysfunction or loss of oligodendrocytes leads to demyelinating diseases such as multiple sclerosis (MS). To treat demyelinating diseases, the development of a therapy that promotes remyelination is required. In the present study, we established an in vitro method to convert human fibroblasts into induced oligodendrocyte-like cells (iOLCs) in 3 days. The induced cells displayed morphologies and molecular…

miR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS.

A lack of sufficient oligodendrocyte myelination contributes to remyelination failure in demyelinating disorders. miRNAs have been implicated in oligodendrogenesis; however, their functions in myelin regeneration remained elusive. Through developmentally regulated targeted mutagenesis, we demonstrate that miR-219 alleles are critical for CNS myelination and remyelination after injury. Further deletion of miR-338 exacerbates the miR-219 mutant hypomyelination phenotype. Conversely, miR-219 overexpression promotes precocious oligodendrocyte maturation and regeneration processes in transgenic mic…

Artificial axons as a biomimetic 3D myelination platform for the discovery and validation of promyelinating compounds.

Multiple sclerosis (MS), a chronic neurodegenerative disease driven by damage to the protective myelin sheath, is currently incurable. Today, all clinically available treatments modulate the immune-mediated symptoms of the disease but they fail to stop neurodegeneration in many patients. Remyelination, the regenerative process of myelin repair by oligodendrocytes, which is considered a necessary step to protect demyelinated axons and stop neuronal death, is impaired in MS patients. One of the major obstacles to finding effective remyelinating drugs is the lack of biomimetic drug screening plat…

Oral Delivery of Methylthioadenosine to the Brain Employing Solid Lipid Nanoparticles: Pharmacokinetic, Behavioral, and Histopathological Evidences.

The present study aimed to orally deliver methylthioadenosine (MTA) to the brain employing solid lipid nanoparticles (SLNs) for the manageme … nt staining with myelin staining dye luxol fast blue proved the potential of MTA-loaded SLNs in the remyelination of neurons. The pharmacokinetic studies provided the evidences for improved bioavailability and enhanced bioresidence supporting the pharmacodynamic findings. The studies proved that SLN-encapsulated MTA can be substantially delivered to the brain a …

Regeneration of peripheral nerves by bioabsorbable polymer tubes with fibrin gel.

We developed two types of nerve conduits, straight tubes, and bellows tubes, for peripheral nerve regeneration with bioabsorbable polymer me … ties of the bellows tubes were suitably maintained after implantation. At 4 weeks after operations, remyelinations were observed in the regenerated tissue at the location of the middle parts of the tubes filled with fibrin gel whereas no remyelinations in the tubes without fibrin gel. The use of fibrin gel as filling materials within the tubes significantly enh …

Extensive proliferation of peripheral type myelin in necrotic spinal cord lesions of multiple sclerosis.

Peripheral type "remyelination" in the spinal cord was investigated in a 34-year-old woman with relapsing multiple sclerosis (MS) over 7 years following her initial presentation with myelopathy. Confined to the large necrotizing cord lesions involving the gray matter, there was prominent proliferation of peripheral type myelin, measuring up to one-third of the cross-sectional field of the cord. These nerve bundles with peripheral type myelin, which was devoid of glial fibrillary acidic protein immunoreactivity, consisted of relatively monotonous, small-caliber nerve fibers arranged in parallel…