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A tuned gelatin methacryloyl (GelMA) hydrogel facilitates myelination of dorsal root ganglia neurons in vitro.

Investigating axonal myelination by Schwann cells (SCs) is crucial for understanding mechanisms underlying demyelination and remyelination, which may help gain insights into incurable disorders like neurodegenerative diseases. In this study, a gelatin-based hydrogel, gelatin methacryloyl (GelMA), was optimized to achieve the biocompatibility, porosity, mechanical stability, and degradability needed to provide high cell viability for dorsal root ganglia (DRG) neurons and SCs, and to enable their long-term coculture needed for myelination studies. The results of cell viability, neurite elongatio…

Elezanumab, a clinical stage human monoclonal antibody that selectively targets repulsive guidance molecule A to promote neuroregeneration and neuroprotection in neuronal injury and demyelination models.

Repulsive guidance molecule A (RGMa) is a potent inhibitor of axonal growth and a regulator of neuronal cell death. It is up-regulated follo … experimental autoimmune encephalomyelitis (EAE) model, elezanumab promotes axonal regeneration and remyelination, decreases inflammatory lesion area and improves functional recovery. Finally, in the mouse cuprizone model, elezanumab reduces demyelination, which is consistent with its inhibitory effect on BMP signaling. Taken together, these preclinical data de …

Transplantation of Mesenchymal Stem Cells Overexpressing Fibroblast Growth Factor 21 Facilitates Cognitive Recovery and Enhances Neurogenesis in a Mouse Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a progressive and complex pathological condition that results in multiple adverse consequences, including impaired learning and memory. Transplantation of mesenchymal stem cells (MSCs) has produced limited benefits in experimental TBI models. Fibroblast growth factor 21 (FGF21) is a novel metabolic regulator that has neuroprotective effects, promotes remyelination, enhances angiogenesis, and elongates astrocytic processes. In this study, MSCs were genetically engineered to overexpress FGF21 in order to improve their efficacy in TBI. MSCs overexpressing FGF21 (MS…

RhoA/Rho Kinase Mediates Neuronal Death Through Regulating cPLA2 Activation.

Activation of RhoA/Rho kinase leads to growth cone collapse and neurite retraction. Although RhoA/Rho kinase inhibition has been shown to improve axon regeneration, remyelination and functional recovery, its role in neuronal cell death remains unclear. To determine whether RhoA/Rho kinase played a role in neuronal death after injury, we investigated the relationship between RhoA/Rho kinase and cytosolic phospholipase A2 (cPLA2), a lipase that mediates inflammation and cell death, using an in vitro neuronal death model and an in vivo contusive spinal cord injury model performed at the 10th thor…

White matter injury restoration after stem cell administration in subcortical ischemic stroke.

INTRODUCTION: Despite its high incidence, nerve fiber (axon and myelin) damage after cerebral infarct has not yet been extensively investiga … ed by ADMSC treatment; this is mediated by repair molecular factors implicated in axonal sprouting, remyelination and oligodendrogenesis. These findings are associated with improved functional recovery after stroke.

[A case of malignant thymoma associated with Eaton-Lambert-type neuromuscular transmission block and sensorimotor neuropathy].

The patient is a 73-year-old male. In January 1988, he noticed sensory disturbance and muscular weakness of his extremities. His thymoma was … ed a decrease in the number of myelinated fibers (fiber density 4333/mm2), segmental demyelination, remyelination, and mild axonal change. Thymectomy was performed and pathological examination showed invasive thymoma of predominantly the epithelial type. His muscular weakness and sensory disturbance improved gradually after thymectomy. On the postoperative immu …

Regenerative Medicine Strategies for Spinal Cord Injury: Advances in Stem Cell Therapy.

Spinal cord injuries disrupt the motor, sensory, and autonomic functions routinely carried out by the spinal cord, with injury progressing f … investigated as potential regenerative approaches that may promote repair through neuroprotection, remyelination, and axonal regeneration. Preclinical studies have demonstrated encouraging results in motor and sensory recovery following injury; however, clinical evidence remains limited and variable. Some studies report improvements in motor and sensory functi …

TREM2 Facilitates Myelin Debris Clearance but Exacerbates Chronic Inflammation and Fibrosis After Spinal Cord Injury.

BACKGROUND: The accumulation of myelin debris after spinal cord injury (SCI) inhibits axon regeneration and remyelination. Triggering receptor expressed on myeloid cell 2 (TREM2) is crucial for cellular debris clearance and disease-associated microglia (DAM) activation. However, whether TREM2 mediates these processes after SCI remains unclear. METHODS: A mouse model of spinal cord crush injury was employed. Female TREM2-/- mice were used to delete TREM2, while COG1410 was administered to activate TREM2 in female wild-type mice. Tissue immunostaining and western blotting were performed to anal…

3D-printed PCL scaffold coated with chitosan-hyaluronic acid hydrogel loaded with NGF-overexpressing UiPSC-derived neural crest cells restores erectile function via cavernous nerve regeneration.

This study investigated whether erectile function could be restored by promoting cavernous nerve (CN) regeneration via perineural administra … nd NH demonstrated increased axonal density and upregulated expression of neuronal regeneration and remyelination markers. Furthermore, these groups showed decreased cavernosal apoptosis and preserved endothelial content and smooth muscle/collagen ratio. Across all metrics, Group NH demonstrated the superior therapeutic effect, followed by Groups N and H. Our r …

Isoform-specific roles of QKI-6 and QKI-7 direct Schwann cell lineage progression and enhance peripheral nerve regeneration.

Peripheral nerve injury presents a major therapeutic challenge owing to limited endogenous repair and incomplete functional recovery. Schwan … el, transplantation of QKI-7-overexpressing SCPs or SCs significantly enhanced axonal regeneration, remyelination, and motor recovery compared with unmodified or QKI-6-expressing counterparts. Histological analysis confirmed improved donor cell engraftment, myelin protein expression, and neurotrophin levels in QKI-7-modified grafts. These findings establish a s …

Метформин репурируется в неврологических расстройствах: клинический экспериментальный ландшафт.

КОЛИЧЕСТВО: Неврологические расстройства, такие, как болезнь Альцгеймера (AD) и множественный склероз (MS), предполагают постепенную потерю нервных клеток, а текущее лечение в основном обеспечивает симптоматическое облегчение без остановки развития болезни. Для устранения этого пробела перспективным подходом является перерасчет лекарств. Метформин, широко используемый пероральный антидиабетический препарат, изучается в случае расстройств центральной нервной системы (СНС) в силу его множественных последствий, включая активацию аденосинового монофосфата, активирующего белковую киназу (АМПК), под

Совпадение в аннотации оригинала
BACKGROUND: Neurological disorders such as Alzheimer's disease (AD) and multiple sclerosis (MS) involve progressive nerve cell loss and curr … ine monophosphate-activated protein kinase (AMPK) pathway, supporting neuroprotection and promoting remyelination. PURPOSE: To systematically analyse the current clinical trial landscape of metformin repurposing in CNS disorders. METHODS: Data were collected exclusively from ClinicalTrials.gov. The search focused on neurological, neurodegenerative and neurode …

Investigations of remibrutinib in models pertinent to multiple sclerosis.

Inhibitors of Bruton tyrosine kinase (BTK) are actively being pursued as potential disease-modifying therapies for multiple sclerosis (MS), … t affect oligodendrogenesis in young mice with robust repair capacity, or in middle-aged mice where remyelination is deficient. Across microglia and macrophage cultures of human or murine origin, remibrutinib effectively reduced immune complex-induced TNF-α. Multiplex cytokine analyses showed that this reduction coincided with increased interleukin-10, suggesti …

Microglial dysregulation and spatiotemporal dynamics of inflammation in multiple sclerosis white matter: an integrative transcriptomic analysis.

OBJECTIVE: White matter damage in Multiple Sclerosis (MS) exhibits significant heterogeneity. The cellular and molecular underpinnings of th … aditional polarization models. MS white matter displays significant spatial heterogeneity. Hindered remyelination in the LR may reflect inflammation from sustained microglial activation.

Neuroprotective potential of resveratrol in Parkinson, Huntington, amyotrophic lateral sclerosis, and multiple sclerosis: a comprehensive review.

Resveratrol shows neuroprotective effects in preclinical studies across a number of neurodegenerative illnesses, including Parkinson's disea … odels and dosages varies. The primary mechanism by which resveratrol promotes neuronal survival and remyelination in multiple sclerosis is through SIRT1 activation, which does not directly reduce inflammation. As innovative delivery systems, intranasal nanoparticles and exosomes produced from macrophages have shown improved CNS targeting accuracy. Resveratrol s …

Pro-repair macrophages driven by CGRP rescue white matter integrity following intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) triggers a dynamic immune response involving macrophages, However, the functional heterogeneity o … H, correlating with WM repair and neurological recovery. These macrophages exhibited pro-repair and remyelination gene signatures (e.g., Arg1, Tgm2). Bone marrow-derived myeloid cells, particularly skull-resident populations, served as the primary source of THBS1 + macrophages. CGRP, elevated in meninges and bone marrow post-ICH, drove macrophage polarization t …

Plasmalogens Activate AKT/mTOR Signaling to Attenuate Reactive Oxygen Species Production in Spinal Cord Injury.

BACKGROUND: Plasmalogens, the primary phospholipids in the brain, possess intrinsic antioxidant properties and are crucial components of the … ation-induced damage, contributing to neuroprotection. This study reveals that plasmalogens promote remyelination, reduce axonal degeneration and neuronal apoptosis, and-used here for the first time in spinal cord injury repair- may protect neurons by reducing ROS levels and activating the AKT/mTOR signaling pathway.

TNFR2 signaling in oligodendrocyte precursor cells suppresses their immune-inflammatory function and detrimental microglia activation in CNS demyelinating disease.

Multiple Sclerosis (MS) is a chronic degenerative disease of the central nervous system (CNS) characterized by inflammation, demyelination, and progressive neurodegeneration. These processes, combined with the failure of reparative remyelination initiated by oligodendrocyte precursor cells (OPCs), lead to irreversible neurological impairment. The cytokine tumor necrosis factor (TNF) has been implicated in CNS repair via activation of its cognate receptor TNFR2 in glia. Here, we demonstrate the important role of TNFR2 in regulating OPC function in vivo during demyelinating disease, and that TNF…

Evidence of brain target engagement in Parkinson's disease and multiple sclerosis by the investigational nanomedicine, CNM-Au8, in the REPAIR phase 2 clinical trials.

BACKGROUND: Impaired brain energy metabolism has been observed in many neurodegenerative diseases, including Parkinson's disease (PD) and multiple sclerosis (MS). In both diseases, mitochondrial dysfunction and energetic impairment can lead to neuronal dysfunction and death. CNM-Au8® is a suspension of faceted, clean-surfaced gold nanocrystals that catalytically improves energetic metabolism in CNS cells, supporting neuroprotection and remyelination as demonstrated in multiple independent preclinical models. The objective of the Phase 2 REPAIR-MS and REPAIR-PD clinical trials was to investigat…

Alterations of oligodendrocyte progenitor cells (OPCs) with survival time in humans following high impact brain trauma.

BACKGROUND: As there is a lack of comprehensive literature regarding the molecular environment of the human brain emphasizing on oligodendro … elination performed using LFB-PAS/IHC-MBP, IHC Olig-2 and mRNA expression revealed tendency towards remyelination in both corpus callosum and grey white matter interface. Number of Olig-2 positive cells was significantly higher in sTBI group as compared to control group (P-value: 0.0001). Moreover, mRNA expression studies of Olig-2 showed significant upregulati …

Effects of sulfatide on peripheral nerves in metachromatic leukodystrophy.

OBJECTIVE: To evaluate the longitudinal correlations between sulfatide/lysosulfatide levels and central and peripheral nervous system functi … rhASA treatment may reduce CSF sulfatide levels and enhance sulfatide/lysosulfatide processing and remyelination in peripheral nerves.