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Imaging progenitor cell differentiation during central nervous system remyelination using an MRI gene reporter.

Demyelination, the loss of the myelin sheath from around otherwise intact axons, occurs in several diseases, most notably multiple sclerosis (MS). Demyelinated axons that are not remyelinated are vulnerable to irreversible degeneration and therefore therapies that enhance remyelination have been sought. However, there remains a paucity of suitable outcome measures to assess their efficacy. Magnetic Resonance Imaging (MRI) is a non-invasive imaging modality that is used both preclinically and clinically for the assessment of anatomy and tissue function. Here we describe an MRI technique for fol…

Inhomogeneous Magnetization Transfer (ihMT) imaging in the acute cuprizone mouse model of demyelination/remyelination.

BACKGROUND: To investigate the association of ihMT (inhom signals with the demyelination and remyelination phases of the acute cuprizone mouse model in comparison with histology, and to assess the extent of tissue damage and repair from MRI data. METHODS: Acute demyelination by feeding 0.2% cuprizone for five weeks, followed by a four-week remyelination period was applied on genetically modified plp-GFP mice. Animals were scanned at different time points of the demyelination and remyelination phases of the cuprizone model using a multimodal MRI protocol, including ihMT T1D-filters, MPF (Macro…

Remyelination in neuromyelitis optica spectrum disorder is promoted by edaravone through mTORC1 signaling activation.

Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory autoimmune disease of the central nervous system that is manifested … Drug Administration (FDA), as a promoter of OPC differentiation into mature OLs. Edaravone enhanced remyelination in organotypic slice cultures and in mice, even when edaravone was administered following NMO-IgG-induced demyelination, and ameliorated motor impairment in a systemic mouse model of NMOSD. The results of mechanistic studies in NMO-IgG-treated mice …

Extracorporeal shockwave therapy enhances peripheral nerve remyelination and gait function in a crush model.

BACKGROUND: Conservative treatment, such as electrical stimulation and steroid injection, have been employed in an attempt to improve symptoms after peripheral nerve injury, without significant success. Although non-invasive and safe extracorporeal shockwave therapy (ESWT) can be a practical alternative, the therapeutic effects of ESWT on peripheral nerve remyelination has not been established. OBJECTIVES: To investigate the effects of ESWT on peripheral nerve remyelination and gait function for 5 weeks in a sciatic nerve crush model. MATERIAL AND METHODS: In total, we divided 97 rats into 5…

Berberine enhances L1 expression and axonal remyelination in rats after brachial plexus root avulsion.

BACKGROUND AND PURPOSE: Enhanced remyelination of the regenerated axons results in functional re-innervation and improved functional motor recovery after brachial plexus root avulsion (BPRA). The neural cell adhesion molecule L1 (L1CAM, L1) regulates myelination and promotes regeneration after acute injury in the nervous system. Berberine (BBR) can exert neuroprotective roles against the lesion. Herein, we investigated whether berberine (BBR) can affect the expression of L1 and enhance the axonal remyelination in rats following BPRA. METHODS: The surgical procedures were performed to build th…

The interleukin-4/PPARγ signaling axis promotes oligodendrocyte differentiation and remyelination after brain injury.

The repair of white matter damage is of paramount importance for functional recovery after brain injuries. Here, we report that interleukin-4 (IL-4) promotes oligodendrocyte regeneration and remyelination. IL-4 receptor expression was detected in a variety of glial cells after ischemic brain injury, including oligodendrocyte lineage cells. IL-4 deficiency in knockout mice resulted in greater deterioration of white matter over 14 d after stroke. Consistent with these findings, intranasal delivery of IL-4 nanoparticles after stroke improved white matter integrity and attenuated long-term sensori…

Tanshinone IIA attenuates demyelination and promotes remyelination in A. cantonensis-infected BALB/c mice.

BACKGROUND: Angiostrongylus cantonensis infection can cause demyelination in the central nervous system, and there is no effective treatment. METHODS: We used dexamethasone, Tanshinone IIA (TSIIA) and Cryptotanshinone(Two traditional Chinese medicine monomers) in combination with albendazole (AB, a standard anti-helminthic compound) to observe their therapeutic effect on demyelination in A. cantonensis-infected mice. Luxol fast blue staining and electron microscope of myelin sheath, Oligodendrocyte (OL) number and myelin basic protein (MBP) expression in brain was detected in above groups. R

Дорога к ремилинизации в множестве склерозов: прорывы, проблемы и соображения для будущего экспериментального дизайна.

Несмотря на значительные успехи в лечении множественных склерозов (МС), накопление инвалидности, независимо от рецидива, по-прежнему является серьезной проблемой. Хроническое обезвоживание является одним из ключевых факторов нейродегенерации и развития заболеваний, подчеркивая воспоминание как многообещающую терапевтическую стратегию. Коллективные данные, полученные в ходе нескольких клинических испытаний второго этапа, свидетельствуют о том, что воспоминание возможно у пациентов с MS. Вместе с тем в рамках нескольких программ развития наркобизнеса были приняты менее решительные меры, чем ожид

Совпадение в аннотации оригинала
Despite major advances in multiple sclerosis (MS) treatment, disability accumulation independent of relapse activity remains a significant challenge. Chronic demyelination is a key driver of neurodegeneration and disease progression, highlighting remyelination as a promising therapeutic strategy. Collective evidence from several phase II clinical trials now …

Количественный T1 чувствителен к кортикальной ремиилизации при множестве склерозов: посмертное исследование МРТ.

Было продемонстрировано, что ремиилизация корковых повреждений у людей с множественным склерозом (pwMS) является обширной. В этой работе мы стремились оценить, может ли посмертная количественная МРТ (qMRI) помочь в обнаружении этих районов. Мы сняли шесть стационарных целых мозгов умершего PSMS на 3T-MRI с использованием коэффициента переноса магнитизации (MTR, 570 мкм изотроп), миелиновой водной фракции (MWF, 1000 мкм изотроп), количественного Т1 (qT1, 670 мкм изотроп), количественного картирования уязвимости (QSM, 330 мкм изотроп) и радиальной диффузии (RD, 1300 или 1400 мкм изотроп). Иммуно

Совпадение в аннотации оригинала
Remyelination of cortical lesions in people with multiple sclerosis (pwMS) has been shown to be extensive. In this work, we aimed to assess whether postmortem quantitative MRI (qMRI) can help detect those areas. We imaged six fixed whole brains of deceased pwMS by 3T-MRI using magnetization transfer ratio (MTR, 570 μm isotropic), myelin water fraction (MWF, …

Neural stem cells and oligodendrocyte progenitor cells compete for remyelination in the corpus callosum.

A major therapeutic goal in demyelinating diseases, such as Multiple Sclerosis, is to improve remyelination, thereby restoring effective axon conduction and preventing neurodegeneration. In the adult central nervous system (CNS), parenchymal oligodendrocyte progenitor cells (pOPCs) and, to a lesser extent, pre-existing oligodendrocytes (OLs) and oligodendrocytes generated from neural stem cells (NSCs) in the sub-ventricular zone (SVZ) are capable of forming new myelin sheaths. Due to their self-renewal capabilities and the ability of their progeny to migrate widely within the CNS, NSCs represe…

A TCF7L2-responsive suppression of both homeostatic and compensatory remyelination in Huntington disease mice.

Huntington's disease (HD) is characterized by defective oligodendroglial differentiation and white matter disease. Here, we investigate the role of oligodendrocyte progenitor cell (OPC) dysfunction in adult myelin maintenance in HD. We first note a progressive, age-related loss of myelin in both R6/2 and zQ175 HD mice compared with wild-type controls. Adult R6/2 mice then manifest a significant delay in remyelination following cuprizone demyelination. RNA-sequencing and proteomic analysis of callosal white matter and OPCs isolated from both R6/2 and zQ175 mice reveals a systematic downregulati…

The prion protein is not required for peripheral nerve de- and remyelination after crush injury.

The cellular prion protein (PrP) is essential to the long-term maintenance of myelin sheaths in peripheral nerves. PrP activates the adhesio … d peripheral nerve repair processes. Generation of repair Schwann cells, macrophage recruitment and remyelination were similar in PrP-deficient and wild-type mice. We conclude that PrP is dispensable for sciatic nerve de- and remyelination after crush injury. Adgrg6 may sustain its function in peripheral nerve repair independently of its activation by PrP.

Using the Anterior Visual System to Assess Neuroprotection and Remyelination in Multiple Sclerosis Trials.

PURPOSE OF REVIEW: Clinical trials using agents directed at neuroprotection and remyelination in multiple sclerosis (MS) are needed. As optic neuritis (ON) is common in people with MS and the pathology of ON is similar to other MS lesions in the brain, measurements of the anterior visual system are frequently utilized in neuroprotection and remyelination trials. Understanding the strengths and weaknesses of the measurements is vital when interpreting the results of this research. RECENT FINDINGS: Techniques such as visual evoked potentials (VEP) and optical coherence tomography (OCT) are well…

Transection and Crush Models of Nerve Injury to Measure Repair and Remyelination in Peripheral Nerve.

Injury to the peripheral nervous system begins a well-characterized process within both neurons and Schwann cells to allow axonal regrowth, remyelination, and functional repair. Models of peripheral nerve injury have been widely used to study the behavior of Schwann cells, neurons, and other cell types such as macrophages as the events of Wallerian degeneration and regeneration take place. The most commonly used approaches in rodent models to model nerve injury in human patients are sciatic nerve transection and nerve crush, and both have well established time courses of demyelination, immune …

[Effect of cerebrolysin on remyelination processes in multiple sclerosis patients in stage of relapse regression].

AIM: To evaluate the efficacy and safety of Cerebrolysin (EVER Neuro Pharma GmbH, Austria) in the treatment of patients with multiple sclero … n the intrathecal inflammation in MS. CONCLUSION: Cerebrolysin positive role in the stimulation of remyelination process in MS has been confirmed by CNE and the selected treatment regimen has demonstrated its safety. Effect of the drug appear to be due to its composition: so according to a group of authors found that investigated the drug contained fragments o …

Significance of remyelination by neural stem/progenitor cells transplanted into the injured spinal cord.

Previous reports of functional recovery from spinal cord injury (SCI) in rodents and monkeys after the delayed transplantation of neural stem/progenitor cells (NS/PCs) have raised hopes that stem cell therapy could be used to treat SCI in humans. More research is needed, however, to understand the mechanism of functional recovery. Oligodendrocytes derived from grafted NS/PCs remyelinate spared axons in the injured spinal cord. Here, we studied the extent of this remyelination's contribution to functional recovery following contusive SCI in mice. To isolate the effect of remyelination from othe…

Demyelination and remyelination in anatomically distinct regions of the corpus callosum following cuprizone intoxication.

Multiple sclerosis is a chronic demyelinating disease of the central nervous system. Spontaneous remyelination during early disease stages is thought to preserve and partially restore function. However, this process ceases in later stages despite the presence of pre-oligodendrocytes. Cuprizone-induced demyelination is a useful model with which to study the remyelination process. Previous studies have demonstrated heterogeneities in demyelination in individual animals. Here we investigated regional differences in demyelination and remyelination within the corpus callosum. C57BL/6 mice were fed …

Cell-based remyelinating therapies in multiple sclerosis: evidence from experimental studies.

PURPOSE OF REVIEW: Spontaneous remyelination occurs in the central nervous system of patients with multiple sclerosis. However, this process is not robust enough to promote a functional and stable recovery of the myelin architecture. The development of cell-based therapies, aimed at promoting multifocal remyelination, is therefore foreseen. RECENT FINDINGS: Several experimental cell-based strategies aimed at replacing damaged myelin-forming cells have been developed in the last few years. However, most of these therapeutic approaches - although consistently able to form new myelin sheaths at …

Remyelination of the demyelinated CNS: the case for and against transplantation of central, peripheral and olfactory glia.

Although originally developed as a research tool for studying glial-glial and glial-axonal interactions, the technique of transplanting glial cell into the central nervous system has more recently been employed as a potential means for repairing persistent demyelination in clinical disease. It has now been clearly established using various experimental models that oligodendrocyte lineage cells, Schwann cells and olfactory ensheathing cells can all produce new myelin sheaths around demyelinated or amyelinated axons following transplantation. However, this property alone does not necessarily mea

Remyelination and its association with increased oxygen extraction fraction in acute multiple sclerosis lesions.

The study investigates the relationship between longitudinal changes in oxygen extraction fraction (OEF) and remyelination in acute multiple sclerosis (MS) lesions. Twenty-two MS patients with 68 new gadolinium-enhancing lesions underwent MRI scans at baseline, 3 months, and 12 months. OEF was quantified using QQ, an integrative model combining quantitative susceptibility mapping (QSM) and quantitative blood oxygen level-dependent (qBOLD), while myelin content was measured by myelin water fraction using FAST-T2 imaging. A linear mixed-effect model assessed longitudinal changes in OEF and MWF a…