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Macrophages counteract demyelination in a mouse model of globoid cell leukodystrophy.

Whether microglia and macrophages are beneficial or harmful in many neurological disorders, including demyelinating diseases such as multipl … y higher in twi+op mice than in twi mice at 45 d old. The difference appeared to be due to impaired remyelination in twi+op mice rather than accelerated demyelination. Quantitative reverse transcription PCR and immunohistochemical studies revealed that the recruitment of oligodendrocyte progenitor cells in response to demyelination was compromised in twi+op mic …

Cell therapy for multiple sclerosis.

The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic plasticity, by which neural precursors can replace damaged oligodendrocytes and myelin, and also effectiv…

Dominant-negative beta1 integrin mice have region-specific myelin defects accompanied by alterations in MAPK activity.

Recent studies have demonstrated the importance of beta1 integrin in oligodendrocyte maturation in vitro. Similar studies in vivo have been … In contrast, the corpus callosum from these mice did not show similar myelin defects. To assess if remyelination would be affected in the corpus callosum, mice were subjected to a cuprizone-induced demyelination. Interestingly, the dominant-negative mice recovered from this insult in a manner similar to the wild type littermates. Axons within the corpus callos …

Sequestrum-like appearance of a multiple sclerosis brain lesion on serial magnetic resonance images.

Using serial magnetic resonance imaging, we monitored an unique lesion of the brain in a 15-year-old girl with clinically definite and laboratory-supported remitting-relapsing multiple sclerosis. During initial phases of the disease course, cystic necrosis around the plaque was observed. Later, remyelination of the central core of the lesion was speculated, as similarities in signal intensity between the core and the normal appearing white matter were partially recovered both on the T1- and the T2-weighted images.

Hemifacial spasm: early postoperative normalization of blink reflex latency.

Electrophysiological improvement in the blink reflex latency after neurovascular decompression of the facial nerve in patients with hemifacial spasm is believed to be related to remyelination and occurs 2-8 months after surgery. We report a patient with hemifacial spasms for 3 years, in whom the increased blink reflex latency returned to normal within a week after surgery. This suggests that compression without demyelination may be responsible for increased blink reflex latency in some of the patients with hemifacial spasms.

Терапия на основе ствола клеток для лечения заболеваний центральной нервной системы: клинические доказательства, терапевтические ниши и границы письменного перевода.

Проблемы, связанные с демиелином центральной нервной системы, существенно различаются в плане патобологии, обратимости и способности к восстановлению тканей. Лекарства, направленные на изменение болезней, могут подавлять подстрекательскую активность при множественном склерозе (MS) и расстройстве спектра нейромиелита (NMOSD), но они не заменяют потерянных олигодендроцитов или надежно установленных нейроаксональных травм. Поэтому стратегии, основанные на использовании стволовых клеток, направлены на достижение различных терапевтических целей, включая восстановление иммунной системы, иммунодуляци

Совпадение в аннотации оригинала
Central nervous system demyelinating disorders differ substantially in pathobiology, reversibility, and capacity for tissue repair. Disease- … ing immune reconstitution, paracrine immunomodulation and neuroprotection, direct cell replacement, remyelination, and correction of defined genetic defects. Autologous hematopoietic stem cell transplantation (AHSCT) currently has the most mature clinical evidence, particularly for carefully selected patients with highly active relapsing MS despite high-efficac …

Нацеливание на α7-никотиновый ацетилхолиновый рецептор при множественном склерозе: последствия для иммуномодуляции и нейрозащиты.

Множественный склероз (MS) — хроническое иммунное расстройство, характеризующееся демиелинацией, аксонной дегенерацией и прогрессивной неврологической инвалидностью. Текущие методы лечения с целью изменения заболеваний (ДМТ) неадекватно решают проблемы нейродегенерации и отказа от ремиелинирования, особенно в прогрессивных СМ. α7-никотиновый ацетилхолиновый рецептор (α7-nAChR), являющийся ключевым посредником в холинергическом антивоспалительном пути, стал многообещающей терапевтической целью, которая соединяет иммуномодуляцию и нейрозащиту. Этот обзор синтезирует текущие данные о биологии, ра

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic immune-mediated disorder characterized by demyelination, axonal degeneration, and progressive neurological disability. Current disease-modifying therapies (DMTs) inadequately address neurodegeneration and remyelination failure, particularly in progressive MS. The α7-nicotinic acetylcholine receptor (α7-nAChR), a key media…

Characterization of brain microstructural changes in children with infantile vitamin B12 deficiency using diffusion tensor imaging.

BACKGROUND AND OBJECTIVE: Infantile Vitamin B12 deficiency commonly called Infantile tremor syndrome (ITS) is a neurocutaneous disorder prim … nd normalized homocysteine levels. DTI revealed increased FA and reduced MD, RD, and AD, indicating remyelination and axonal recovery. Corpus callosum, corona radiata, and internal capsule showed maximal improvement, aligning with recovery remyelination. Grey matter areas, including the thalamus and pre-central gyrus, also demonstrated recovery. Developmental s …

ACY1215 Exerts Anti-inflammatory Effects by Inhibition of NF-κB and STAT3 Signaling Pathway to Repair Spinal Cord Injury.

Spinal cord injury (SCI), a public health problem caused by mechanical injury, leads to secondary excessive inflammatory reactions and long-term damage to neurological function. ACY1215 is a highly selective histone deacetylase 6 (HDAC6) inhibitor and reportedly has anti-inflammatory effects; however, its regulatory role in SCI has not been studied. The purpose of this study was to explore the role of ACY1215 in preventing inflammation, inhibiting astrogliosis, enhancing remyelination and preserving axons after spinal cord injury and further exploring the possible cellular signaling pathways i…

Perilipin-2 mediates ferroptosis in oligodendrocyte progenitor cells and myelin injury after ischemic stroke.

JOURNAL/nrgr/04.03/01300535-202507000-00024/figure1/v/2024-09-09T124005Z/r/image-tiff Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination. Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe nerve damage. Ferroptosis is an iron-dependent form of regulated cell death caused by membrane rupture induced by lipid peroxidation, and plays an important role in the pathological process of ischemic stroke. However, there are few studies on oligodendrocyte progenitor cell ferroptosis. We analy…

OTULIN of exosomes derived from Schwann cells promotes peripheral nerve injury repair by regulating macrophage polarization via deubiquitination of ERBB2.

A significant public health burden is peripheral nerve damage (PNI), which is frequently brought on by trauma. Macrophages were essential to the effective regeneration of nerves and restoration of function. It is still not entirely understood how macrophages and Schwann cells interact after damage during remyelination. Here, we established an inflammatory model in bone marrow-derived macrophages (BMDMs) and a rat sciatic nerve damage model to investigate the possible relationship between lipopolysaccharides (LPS)-induced exosomes derived from Schwann cells (LPS SCs-Exos) and peripheral nerve r…

Differential effects of integrase strand transfer inhibitors, elvitegravir and raltegravir, on oligodendrocyte maturation: A role for the integrated stress response.

Regardless of adherence to combined antiretroviral therapy, white matter and myelin pathologies persist in patients with HIV-associated neur … no effect. Following cuprizone demyelination, administration of elvitegravir to adult mice reduced remyelination compared with control animals. Elvitegravir treatment activated the integrated stress response in oligodendrocytes in vitro, an effect which was completely blocked by pretreatment with the integrated stress response inhibitor Trans-ISRIB, preventing …

Anti-mouse CX3CR1 Antibody Alleviates Cognitive Impairment, Neuronal Loss and Myelin Deficits in an Animal Model of Brain Ischemia.

White matter lesions are common when global cerebral ischemia (GCI) occurs in the elderly, and cause damage to neurological and psychological functions. Remyelination often fails because of the limited recruitment of oligodendrocyte progenitor cells (OPCs) to the demyelinated site or the inefficient differentiation of OPCs to mature oligodendrocytes (OLs). The activation of microglia, the most important immune cells in the central nervous system, and subsequent inflammation have been implicated in myelination repair disorder. Little is known about the role of the Fractalkine/CX3CR1 signaling p…

miR-219 attenuates demyelination in cuprizone-induced demyelinated mice by regulating monocarboxylate transporter 1.

Remyelination is limited in patients with multiple sclerosis (MS) due to the difficulties in recruiting proliferating oligodendrocyte precursors (OPCs), the inhibition of OPC differentiation and/or maturation, and/or failure in the generation of the myelin sheath. In vitro studies have revealed that miR-219 is necessary for OPC differentiation and monocarboxylate transporter 1 (MCT1) plays a vital role in oligodendrocyte maturation and myelin synthesis. Herein, we hypothesized that miR-219 might promote oligodendrocyte differentiation and attenuate demyelination in a cuprizone (CPZ)-induced de…

Cuprizone demyelination induces a unique inflammatory response in the subventricular zone.

BACKGROUND: Cuprizone leads to demyelination of the corpus callosum (CC) and activates progenitor cells in the adjacent subventricular zone (SVZ), a stem cell niche which contributes to remyelination. The healthy SVZ contains semi-activated microglia and constitutively expresses the pro-inflammatory molecule galectin-3 (Gal-3) suggesting the niche uniquely regulates inflammation. METHODS: We studied the inflammatory response to cuprizone in the SVZ and CC in Gal-3 knockout mice using immunohistochemistry and with the in vitro neurosphere assay. RESULTS: Cuprizone caused loss of myelin basic …

Small Molecule Agonists of Cell Adhesion Molecule L1 Mimic L1 Functions In Vivo.

Lack of permissive mechanisms and abundance of inhibitory molecules in the lesioned central nervous system of adult mammals contribute to th … an L1-dependent manner. In a femoral nerve injury mouse model, enhanced functional regeneration and remyelination after application of the L1 agonists were observed. In a spinal cord injury mouse model, L1 agonists improved recovery of motor functions, being paralleled by enhanced remyelination, neuronal survival, and monoaminergic innervation, reduced astrogli …

MicroRNAs modulate Schwann cell response to nerve injury by reinforcing transcriptional silencing of dedifferentiation-related genes.

In the peripheral nervous system, Schwann cells (SCs) surrounding damaged axons undergo an injury response that is driven by an intricate tr … of SC dedifferentiation/proliferation and thereby re-enforce the transcriptional program driving SC remyelination. SCs deficient in miRNAs manifested a delay in the transition between the distinct differentiation states required to support peripheral nerve regeneration. Among the miRNAs expressed in adult mouse SCs, miR-34a and miR-140 were identified as functi …

Superparamagnetic iron oxide-labeled Schwann cells and olfactory ensheathing cells can be traced in vivo by magnetic resonance imaging and retain functional properties after transplantation into the CNS.

Schwann cell (SC) and olfactory ensheathing cell (OEC) transplantation has been shown experimentally to promote CNS axonal regeneration and remyelination. To advance this technique into a clinical setting it is important to be able to follow the fates of transplanted cells by noninvasive imaging. Previous studies, using complex modification processes to enable uptake of contrast agents, have shown that cells labeled in vitro with paramagnetic contrast agents transplanted into rodent CNS can be visualized using magnetic resonance imaging (MRI). Here we show that SCs and OECs efficiently interna…

Paraparesis following intrathecal chemotherapy.

We studied a case of flaccid paraplegia that immediately followed intrathecal injection of cytosine arabinoside diluted in 1.5% bacteriostatic water (1.5% benzyl alcohol in H2O). The complication was reversed by rinsing the CSF space with saline. Autopsy showed fibrosis and remyelination of lumbosacral nerve roots. In acute and chronic animal experiments, we showed that benzyl alcohol in commercially used concentrations can have a local anesthetic and an irreversible toxic effect on nerve fibers. This provides a sufficient explanation for many cases of paraparesis following intrathecal chemoth…

Axonal degeneration in beriberi neuropathy.

Ultrastructural and teased-fiber studies were carried out on the sural nerves of nine patients with beriberi neuropathy Axonal degeneration was the most prominent feature, and large myelinated fibers were more affected than unmyelinated ones. An unusual change with accumulation of flattened sacs or tubuli was recognized in the axoplasm of myelinated fibers of untreated patients. Active regeneration was extensive in patients receiving vitamin B. Segmental demyelination, remyelination, and early onion bulbs were scarece in patients with a long and relapsing course before treatment.