Результаты поиска

Beyond Histamine Blockade: Clemastine Fumarate as a Promoter of Myelin Regeneration, Inflammatory Regulation, and Neuroimmune Modulation in CNS Disorders.

Clemastine fumarate, a first-generation H1 antihistamine, has emerged as a promising candidate for drug repurposing in neurodegenerative and neuropsychiatric disorders owing to its ability to cross the blood-brain barrier and interact with multiple central nervous system targets. Experimental studies indicate that clemastine promotes remyelination by stimulating the differentiation of oligodendrocyte precursor cells into mature, myelin-producing oligodendrocytes, thereby restoring myelin integrity and improving axonal function in experimental models. In addition to its remyelinating properties…

Disrupted CXCR2 Signaling in Oligodendroglia Lineage Cells Enhances Myelin Repair in a Viral Model of Multiple Sclerosis.

CXCR2 is a chemokine receptor expressed on oligodendroglia that has been implicated in the pathogenesis of neuroinflammatory demyelinating d … moxifen-treated mice and vehicle-treated controls. Notably, deletion of Cxcr2 resulted in increased remyelination, as assessed by g-ratio (the ratio of the inner axonal diameter to the total outer fiber diameter) calculation, compared to that in vehicle-treated control mice. Collectively, our findings argue that CXCR2 signaling in oligodendroglia is dispensable …

Потенциальное терапевтическое воздействие ибудиластной и ретиновой кислоты на поведенческие и биохимические изменения в мышечном мозге.

Ibudilast (IBD) — новый препарат, выпущенный в качестве лекарства от множественных склерозов (MS). Ретиноиновая кислота (RA), являющаяся метаболитом витамина А, известна своими прорегенеративными и антивоспалительными свойствами, поэтому она была предложена в качестве дополнительного метода лечения для MS. Цель этого исследования заключается в изучении терапевтического воздействия RA и IBD на модели мышей, вызываемые кухонной зоной (CPZ). Seventy-two Швейцарские мыши-альбино (SWR/J) были разделены на two контроль за основными группами (n = 18); нормальная чау и CPZ (n = 54); 0.25% CPZ, смешанн

Совпадение в аннотации оригинала
Ibudilast (IBD) is a new drug that has been released as treatment for multiple sclerosis (MS). Retinoic acid (RA), a metabolite of vitamin A … ixed into chow at demyelination stage (first 5 weeks). The following 4 weeks included two stages of remyelination: early remyelination (2 weeks after CPZ discontinuation) and late remyelination (week 9). In the early stage of remyelination, the CPZ group was divided into four subgroups beside daily treatment intraperitoneal injections CPZ (+ve control- no treat …

Multifaceted response of microglia in the cuprizone model of demyelination.

The cuprizone diet paradigm, which involves selective depletion of oligodendrocytes and subsequent myelin loss, provides an excellent model to study the neuroimmune response to demyelination and remyelination. Microglia, the resident immune cells of the central nervous system, mount a robust response to cuprizone administration. However, the specific triggers and temporal trajectory of microglia activation are not well-defined. Moreover, it is unclear the extent to which microglia respond to cuprizone directly rather than to cuprizone-induced demyelination. In this study, we characterized the …

TLR3 Agonist Poly-IC Induces IL-33 and Promotes Myelin Repair.

BACKGROUND: Impaired remyelination of demyelinated axons is a major cause of neurological disability. In inflammatory demyelinating disease of the central nervous system (CNS), although remyelination does happen, it is often incomplete, resulting in poor clinical recovery. Poly-IC a known TLR3 agonist and IL-33, a cytokine which is induced by poly-IC are known to influence recovery and promote repair in experimental models of CNS demyelination. METHODOLOGY AND PRINCIPAL FINDINGS: We examined the effect of addition of poly-IC and IL-33 on the differentiation and maturation of oligodendrocyte p…

Evidence that nuclear factor IA inhibits repair after white matter injury.

OBJECTIVE: Chronic demyelination can result in axonopathy and is associated with human neurological conditions such as multiple sclerosis (M … (HIE) and MS as well as developmental expression in mice were evaluated. Functional studies during remyelination were performed using a lysolecithin model, coupled with lentiviral misexpression of NFIA. The role of NFIA during oligodendrocyte lineage development was characterized using chick and mouse models and in vitro culture of oligodendrocyte progenitors. …

Обзор метаболизма Олигодендроцита.

Олигодендроциты (ОИ) демонстрируют сложные метаболические взаимодействия, необходимые для нейрональной функции и здоровья CNS. В этой главе анализируется метаболизм ОН, в частности глюкозы, липидов и аминокислотного метаболизма, и их воздействие на синтез, техническое обслуживание и устойчивость CNS. ОН используют глюкозу для получения энергии с помощью гликолиза и пентоза фосфата, поддерживая производство СПС и антиоксидативную защиту. Липидный синтез, включая производство холестерина и финголипида, имеет решающее значение для поддержания целостности миелин и быстрого проведения сигнала. Кром

Совпадение в аннотации оригинала
Oligodendrocytes (OLs) exhibit complex metabolic interactions essential for neuronal function and CNS health. This chapter analyzes the meta … amino acid pathways, such as those involving glutamine and serine, modulate OL differentiation and remyelination. OLs also provide metabolic support to neurons through lactate shuttling and their interactions with astrocytes in the Panglial network, ensuring sustained energy flow. Dysregulation of OL metabolic functions underlies demyelinating diseases, such a …

Axonal and Myelin Neuroprotection by the Peptoid BN201 in Brain Inflammation.

The development of neuroprotective therapies is a sought-after goal. By screening combinatorial chemical libraries using in vitro assays, we … on factor Foxo3 to the cytoplasm. In vivo, BN201 prevents axonal and neuronal loss, and it promotes remyelination in models of multiple sclerosis, chemically induced demyelination, and glaucoma. In summary, we provide a new promising strategy to promote neuroaxonal survival and remyelination, potentially preventing disability in brain diseases.

The Cambridge Centre for Myelin Repair trial Two (CCMR Two): a trial protocol for a phase 2a, randomised, double-blind, placebo-controlled clinical trial of the ability of the combination of metformin and clemastine to promote remyelination in people with relapsing-remitting multiple sclerosis already on disease-modifying therapy.

BACKGROUND: In multiple sclerosis (MS), progressive disability occurs following degeneration of demyelinated axons. A tractable approach to delay, prevent or reverse disability progression is through enhancement of endogenous remyelination. Clinical trials have deployed drugs, such as clemastine, to target the rate-limiting step in this process: differentiation of oligodendrocyte progenitor cells (OPCs). Preclinical research has shown that metformin can reverse an age-associated deficit in the responsiveness of OPCs to pro-differentiation factors. The purpose of the Cambridge Centre for Myelin…

The Biology of Persistent Infection: Inflammation and Demyelination following Murine Coronavirus Infection of the Central Nervous System.

Multiple Sclerosis (MS) is an immune-mediated demyelinating disease of humans. Although causes of MS are enigmatic, underlying elements cont … tion. Recent efforts by our laboratory and others have focused upon strategies capable of enhancing remyelination in response to viral-induced demyelination, both by dampening chronic inflammation and by surgical engraftment of remyelination - competent neural precursor cells.

Emodin Suppresses the RAGE/ROCK1 Pathway to Modulate the Oligodendrocyte Lineage and Ameliorate Demyelination in Vascular Dementia Rats.

BACKGROUND: Vascular dementia (VD), a prevalent cognitive disorder mainly resulting from chronic cerebral hypoperfusion-triggered white matter injury (WMI), takes regulation of oligodendrocyte (OL) lineage and restoration of remyelination as key therapeutic targets, whereas the precise role and mechanism of the natural neuroprotective compound emodin in VD-related demyelination have yet to be elucidated. METHODS: A VD rat model was generated by bilateral common carotid artery occlusion. After 2 weeks of emodin administration, cognitive function, myelination, and OL lineage were evaluated usin…

Оценка МРТ механизмов, лежащих в основе роста и сокращения повреждений при множественном склерозе.

ЦЕЛЬ: Оценка патологических механизмов, способствующих расширению или свертыванию белых веществ (ВМ) и ремиилизации при множественном склерозе (МС). Мы провели оценку 1,613 Повреждения 49 люди с повторной эмиссией MS в CCMR-One Испытание на бексаротене (EudraCT) 2014-003145-99). Мы измерили направление повреждения по отношению к WM трактам, градиентам поверхности и венам. Деформация якоба использовалась для оценки расширения повреждения по сравнению с 6 Месяцы, в то время как для оценки ремиэлизации использовалась визуализация коэффициента передачи магнитизации (MTR). Результаты: 33% Поврежден

Совпадение в аннотации оригинала
OBJECTIVE: To assess the pathological mechanisms contributing to white matter (WM) lesion expansion or contraction and remyelination in multiple sclerosis (MS). METHODS: We assessed 1,613 lesions in 49 people with relapsing-remitting MS in the CCMR-One bexarotene trial (EudraCT 2014-003145-99). We measured lesion orientation relative to WM tracts, surface-i…

Therapeutic effect of oligomeric proanthocyanidin in cuprizone-induced demyelination.

NEW FINDINGS: What is the central question of this study? Oligomeric proanthocyanidin has the capacity to alleviate abnormalities in neurological functioning. However, whether oligomeric proanthocyanidin can reduce the progression of demyelination or promote remyelination in demyelinating diseases remains unknown. What is the main finding and its importance? Oligomeric proanthocyanidin can improve cuprizone-induced demyelination by inhibiting immune cell infiltration, reversing overactivated microglia, decreasing the inflammatory cytokines secreted by inflammatory cells and decreasing the prod…

Microglia P2X4 receptors as pharmacological targets for demyelinating diseases.

Pharmacological activation of the P2X4 receptor expressed by brain microglia may provide a novel avenue to promote remyelination and improve clinical symptoms in experimental autoimmune encephalomyelitis and potentially in multiple sclerosis.

[Promoting myelin repair in disorders such as multiple sclerosis and some types of leukodystrophy: current studies].

Several ways of promoting myelin repair in myelin disorders such as multiple sclerosis and certain types of leukodystrophies are currently being investigated. Numerous studies suggest that it is possible to repair the central nervous system (CNS) by cell transplantation or by enhancing endogenous remyelination. Investigations in animal models indicate that cell therapy results in robust anatomical and functional recovery of acute myelin lesions. These models are also used to explore and validate the role of candidate molecules to stimulate endogenous remyelination by activating the myelin comp…

Effect of treatment with interferon beta-1a on changes in voxel-wise magnetization transfer ratio in normal appearing brain tissue and lesions of patients with relapsing-remitting multiple sclerosis: a 24-week, controlled pilot study.

BACKGROUND: This pilot study investigated changes in remyelinating and demyelinating activity in normal appearing brain tissue (NABT) and lesions, by using voxel-wise magnetization transfer ratio (VW-MTR), in patients with relapsing-remitting multiple sclerosis (RRMS) receiving interferon beta-1a 44 mcg subcutaneously (IFN β-1a SC) three times weekly versus healthy controls (HCs) (NCT01085318). METHODS: Increasing (suggestive of remyelination) and decreasing (suggestive of demyelination) VW-MTR changes in NABT and in T2, T1 and gadolinium (Gd)-enhancing lesion volume were measured over 24 wee…

Therapeutic ultrasound for the treatment of demyelinating diseases.

Demyelinating diseases, such as multiple sclerosis, result from the progressive loss of myelin sheaths in the central and peripheral nervous systems, leading to impaired neural conduction and disability. Current disease-modifying therapies focus on immunosuppression to limit inflammation but fail to restore lost myelin. This lack of regenerative capacity underscores the need for strategies that actively promote remyelination. Recent advances highlight neuromodulation, and in particular low-intensity ultrasound (US), as a promising approach to stimulate both neuronal activity and glial response…

Cell-based experimental strategies for myelin repair in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS), diagnosed at a mean age of 32 years. CN … d in various experimental models of MS, with different results, both in significant improvements in remyelination and the reduction of neuroinflammation and glial activation, or in neuroprotection. All cell types tested have advantages and disadvantages, which makes it difficult to choose a better option for therapeutic application in MS. New strategies combini …

AAV-Based Intracerebral Administration of BDNF Promotes Myelin Repair and Cognitive Improvement After Cuprizone-Induced Demyelination.

Multiple sclerosis (MS) is a chronic neurological disorder involving immune-mediated demyelination and neurodegeneration in the central nervous system (CNS). Current therapies primarily target inflammation, with limited strategies to promote remyelination or neural repair. This study explores the therapeutic potential of Brain-Derived Neurotrophic Factor (BDNF) delivered via an adeno-associated virus (AAV) vector to enhance remyelination and improve cognitive function in a subchronic cuprizone (CPZ)-induced demyelination mouse model. Sixty female C57BL/6 mice were used, with half receiving a 7…

Tetramethylpyrazine promotes axonal remodeling and modulates microglial polarization via JAK2-STAT1/3 and GSK3-NFκB pathways in ischemic stroke.

Ischemic stroke results in demyelination that underlies neurological disfunction. Promoting oligodendrogenesis will rescue the injured axons and accelerate remyelination after stroke. Microglia react to ischemia/hypoxia and polarize to M1/M2 phenotypes influencing myelin injury and repair. Tetramethylpyrazine (TMP) has neuroprotective effects in treating cerebrovascular disorders. This study aims to evaluate whether TMP promotes the renovation of damaged brain tissues especially on remyelination and modulates microglia phenotypes following ischemic stroke. Here magnetic resonance imaging (MRI)…