Результаты поиска

The Yin and Yang of cell cycle progression and differentiation in the oligodendroglial lineage.

In white matter disorders such as leukodystrophies (LD), periventricular leucomalacia (PVL), or multiple sclerosis (MS), the hypomyelination or the remyelination failure by oligodendrocyte progenitor cells involves errors in the sequence of events that normally occur during development when progenitors proliferate, migrate through the white matter, contact the axon, and differentiate into myelin-forming oligodendrocytes. Multiple mechanisms underlie the eventual progressive deterioration that typifies the natural history of developmental demyelination in LD and PVL and of adult-onset demyelina…

Near-nerve potential in lepromatous leprosy.

In leprosy, sensory action potentials (SAPs) may be normal in spite of clinical sensory loss. This may result from the early involvement of small nerve fibers, which have potentials that are not detected in routine studies. To evaluate this possibility, we used a near-nerve recording technique that records potentials from nerve fibers as small as 4-6 microm in diameter. We hypothesized that this technique might increase the sensitivity of nerve conduction studies in detecting leprosy neuropathy. We found the technique to be useful for recording conduction abnormalities in recently diagnosed pa

Morphometric analysis of the sural nerve in experimental dorsal rhizotomy in rats.

To investigate the histological changes in the sural nerve by the damage to the centrally projected axon (CPA), we examined light-microscopic findings after dorsal rhizotomy. The L4-6 dorsal roots were cut unilaterally near the entry zone, with minimal laminectomy, in 27 anesthetized 8- to 10-week-old Sprague-Dawley rats. Animals were killed 1, 2, 4 and 8 weeks and 6 months after surgery, and morphometric results from the sural nerves on the side of the rhizotomy were compared with those from the unaffected side. There were no significant differences in total number, density, frequency distrib

The taiep rat: a myelin mutant with an associated oligodendrocyte microtubular defect.

This report describes a new inherited disorder of myelination in the rat, named taiep, in which failure of normal myelination of the CNS and … yelin throughout the CNS, with evidence suggesting either persistent hypomyelination or attempts at remyelination of affected axons. It is proposed that the microtubular defect in oligodendrocytes results in a disruption of the normal myelination process in certain areas of the CNS of this mutant, and eventually leads to failure of maintenance of the myelin she …

Myelin phagocytosis by peritoneal macrophages in organ cultures of mouse peripheral nerve. A new model for studying myelin phagocytosis in vitro.

Organ cultures of degenerating nerve fascicles were exposed to cultured macrophages obtained by peritoneal lavage. Invasion of the nerve fascicle by phagocytes was shown by prelabeling with carbon and with electron microscopy. There was massive active phagocytosis of degenerating myelin sheaths. The invading phagocytic cell population was identified as Fc receptor-positive, Mac-1-positive macrophages by immunocytochemistry. The Schwann cell population persisted without significant myelin phagocytosis. The vitality of the Schwann cell population was shown by subsequent reimplantation of the org

Critical Role of Astrocyte NAD+ Glycohydrolase in Myelin Injury and Regeneration.

Western-style diets cause disruptions in myelinating cells and astrocytes within the mouse CNS. Increased CD38 expression is present in the … cerebellar organotypic slice cultures subject to LL-demyelination, saturated fat impaired signs of remyelination effects that were mitigated by concomitant 78c treatment. Significantly, oral 78c increased counts of oligodendrocytes and remyelinated axons after focal LL-induced spinal cord demyelination. Using a RiboTag approach, we identified a unique in vivo …

Degenerative and regenerative changes in the trochlear nerve of goldfish.

The features of unlesioned and lesioned trochlear nerves of goldfish have been examined electron microscopically. Lesioned nerves were studied between 1 and 107 days after cutting or crushing the nerve. Unlesioned nerves contained, on average, 77 myelinated axons and 19 unmyelinated axons. The latter were found in 1-2 fascicles per nerve. A basal lamina surrounded each myelinated axon and fascicle of unmyelinated axons. The numbers of myelinated axons, fascicles of unmyelinated axons and basal laminae varied by less than 5% over the intraorbital extramuscular segment of the nerve. Following in

Optochemogenetic Stimulation of Transplanted iPS-NPCs Enhances Neuronal Repair and Functional Recovery after Ischemic Stroke.

Cell transplantation therapy provides a regenerative strategy for neural repair. We tested the hypothesis that selective excitation of transplanted induced pluripotent stem cell-derived neural progenitor cells (iPS-NPCs) could recapitulate an activity-enriched microenvironment that confers regenerative benefits for the treatment of stroke. Mouse iPS-NPCs were transduced with a novel optochemogenetics fusion protein, luminopsin 3 (LMO3), which consisted of a bioluminescent luciferase, Gaussia luciferase, and an opsin, Volvox Channelrhodopsin 1. These LMO3-iPS-NPCs can be activated by either pho

A novel eye-movement impairment in multiple sclerosis indicating widespread cortical damage.

In multiple sclerosis, remyelination trials have yet to deliver success like that achieved for relapse rates with disease course modifying treatment trials. The challenge is to have a clinical, functional outcome measure. Currently, there are none that have been validated, other than visual evoked potentials in optic neuritis. Like vision, quick eye movements (saccades) are heavily dependent on myelination. We proposed that it is possible to extrapolate from demyelination of the medial longitudinal fasciculus in the brainstem to quantitative assessment of cortical networks governing saccadic e…

Puerarin Attenuates White Matter Injury and Blood-Brain Barrier Disruption After Intracerebral Hemorrhagic Stroke via cGAS-STING Axis.

White matter injury (WMI) and blood-brain barrier (BBB) disruption contribute to neurological and cognitive deficits in intracerebral hemorr … entally: puerarin suppressed cGAS-STING activation, reduced oligodendrocyte apoptosis, and promoted remyelination. These results provide new insights into ICH pathogenesis and support puerarin as a potential therapeutic agent for BBB disruption and WMI.

Osteopontin in the Central Nervous System: Roles in Development, Injury, Neurodegeneration, and Neuro-Oncology.

Osteopontin (OPN), encoded by the SPP1/Spp1 gene, is increasingly recognized as an extracellular matrix-associated immunoregulatory molecule … e sustained or ectopic OPN activity may contribute to synaptic injury, persistent glial reactivity, remyelination failure, and immunosuppressive tumor progression. In this review, we summarize the molecular basis of SPP1/Spp1 expression and OPN protein signaling, with emphasis on isoforms, proteolytic processing, receptor usage, and secreted versus intracellula …

Regenerative potential of von Hippel-Lindau tumor suppressor protein.

The von Hippel-Lindau (VHL) protein, traditionally known for oxygen sensing via HIF-1α degradation, is now recognized as a multifunctional r … various somatic stem cells, while the Daam2-VHL-Nedd4 axis supports oligodendrocyte maturation and remyelination. Translational studies in models of Parkinson's disease and spinal cord injury demonstrate that VHL-based strategies can achieve significant functional recovery. Understanding the context-dependent dynamics of VHL signaling is crucial for advancing …

Improved Motor Neuron Preservation and Axonal Recovery Following Experimental Sciatic Nerve Repair With Heterologous Fibrin Biopolymer.

Peripheral nerve injuries severely impair motor function. Although neurorrhaphy is the gold-standard treatment, recovery is often incomplete … at HFB acts as a bioactive modulator, preserving central glial homeostasis and enhancing peripheral remyelination and reinnervation, representing a promising adjuvant to overcome the limitations of conventional suture.

Dynamic phosphorylation of Fascin-1 orchestrates microglial phagocytosis and neurological recovery after spinal cord injury.

The persistence of myelin debris after spinal cord injury (SCI) constitutes a formidable barrier to axonal regeneration, remyelination, and functional recovery by initiating inflammatory cascades. Microglia, known for their superior phagocytic and degradative capabilities, are crucial in clearing myelin debris. Yet, the molecular mechanisms governing their function remain elusive. Our previous research has identified a sustained upregulation of Fascin-1, an actin-binding protein essential for phagocytosis, in Cx3cr1+ microglia after SCI. Here, we reveal that ablation of microglial Fascin-1 exa…

3D printing of Y-27632 enhanced elastic hydrogel conduits for peripheral nerve repair.

Nerve guide conduits provide an advanced tool for peripheral nerve repair, but their efficacy remains limited due to suboptimal axon regener … ge nerve defects. At 16 weeks post-surgery, this conduit efficiently promotes axon regeneration and remyelination, facilitates muscle re-innervation, and enhances functional recovery in a 12 mm nerve defect model. These findings implicate that elastic hydrogel conduits with Y-27632 release would provide a promising therapeutic strategy for long-gap peripheral n …

Crocin facilitates peripheral nerve regeneration through modulation of the STAT3/Bcl-2/Beclin-1 signaling axis-mediated autophagic pathway.

Peripheral nerve injury (PNI) is notoriously difficult to repair due to impaired axonal regeneration and dysregulated inflammatory microenvironments. This study demonstrates that crocin facilitates peripheral nerve regeneration by modulating the STAT3/Bcl-2/Beclin-1 signaling axis, enhancing autophagy while suppressing NLRP3 inflammasome-mediated pyroptosis. In a rat model of sciatic nerve crush injury, crocin treatment improved axonal regrowth and ultrastructural remyelination, as evidenced by upregulated expression of β3-Tubulin, neurofilament-200 (NF200), and myelin basic protein (MBP), alo…

Каротеноиды как нейрозащитные агенты в множестве склерозов: пути, механизмы и клинические перспективы.

Множественный склероз (MS) — хроническое аутоиммунное и нейродегенеративное расстройство, воздействующее на центральную нервную систему (CNS), характеризующееся обезвоживанием и нейро-воспалительной реакцией, окислительным стрессом и регулированием иммунной дизакции. Во всем мире растет частота распространения MS, что свидетельствует о необходимости новых терапевтических агентов против его сложной патофизиологии. Каротеноиды, натуральные пигменты с сильным антиоксидантом, антивоспалительным, иммунодуляторным и нейрозащитным оборудованием были признаны перспективными кандидатами на предмет пора

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune andneurodegenerative disorder affecting the central nervous system (CNS), characterized by d … activity and reduces neuroinflammation and protecting oligodendrocytes necessary for the process of remyelination. Moreover, the role of phytochemicals in maintaining blood-brain barrier integrity and modulating gene expression provides evidence for their therapeutic potential.

Сенсорность клеток в глиальных клетках: последствия для множественного склероза.

Старение является наиболее распространенным фактором риска для развития заболевания множественным склерозом (MS). Клеточная сенсация, необратимое состояние остановки клеточного цикла, является основным фактором старения и, как было установлено, накапливается преждевременно в нейродегенеративных заболеваниях, включая болезнь Альцгеймера и Паркинсона. В последнее время внимание привлекает клеточная сенсация в центральной нервной системе пациентов MS, при этом ряд исследований свидетельствуют о том, что демиелинация вызывает клеточную сенесценцию с общими признаками p16INK4A и p21 выражения, окис

Совпадение в аннотации оригинала
Aging is the most common risk factor for Multiple Sclerosis (MS) disease progression. Cellular senescence, the irreversible state of cell cy … the functional effects of senescence on glial cells, and the impact of removing senescent cells on remyelination and MS. This emerging field holds promise for opening new avenues of treatment for MS patients.

The Cuprizone Mouse Model: A Comparative Study of Cuprizone Formulations from Different Manufacturers.

The Cuprizone mouse model is widely used in studies on de- and remyelination. In the hands of different experimenters, the Cuprizone concentrations that lead to comparable levels of demyelination differ considerably. The reasons for this variability are unknown. In this study, we tested whether different Cuprizone formulations from different vendors and manufacturers influenced Cuprizone-induced histopathological hallmarks. We intoxicated male C57BL/6 mice with six Cuprizone powders that differed in their manufacturer, vendor, and purity. After five weeks, we analyzed the body weight changes o…

Schwann cell-specific RhoA knockout accelerates peripheral nerve regeneration via promoting Schwann cell dedifferentiation.

Our previous studies indicated that RhoA knockdown or inhibition could alleviate the proliferation, migration, and differentiation of Schwann cells. However, the role of RhoA in Schwann cells during nerve injury and repair is still unknown. Herein, we developed two lines of Schwann cells conditional RhoA knockout (cKO) mice by breeding RhoAflox / flox mice with PlpCre -ERT2 or DhhCre mice. Our results indicate that RhoA cKO in Schwann cells accelerates axonal regrowth and remyelination after sciatic nerve injury, which enhances the recovery of nerve conduction and hindlimb gait, and alleviates…