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Nano-Immunomodulators for Directing Macrophage Fate to Enhance Peripheral Nerve Repair: Advances, Challenges, and Translational Perspectives.

Peripheral nerve injury remains a major clinical challenge due to inefficient axonal regeneration and limited therapeutic options. As central regulators of the repair process, macrophages dynamically transition from a pro-inflammatory to a pro-regenerative phenotype, coordinating debris clearance, axonal regrowth, remyelination, and functional restoration. However, disruptions in macrophage polarization-particularly in aging or chronic injury contexts-compromise regenerative outcomes. Here, we present a comprehensive overview of nano-immunomodulatory strategies designed to precisely direct mac…

Diosgenin enhances transplanted human oligodendrocyte precursor cell-mediated myelination in preterm white matter injury by inhibiting matrix metalloproteinase-9-driven TGF-β/Smad2/3 signaling.

Preterm white matter injury (PWMI) is a major cause of long-term motor and cognitive disability, and there are no therapies that directly pr … both transplanted hOPCs and endogenous OPCs into myelinating oligodendrocytes, thereby accelerating remyelination and improving neurological function. Mechanistic investigations reveal that diosgenin inhibits MMP-9/2 activity. This suppression blunts TGFβ-Smad2/3 signaling in microglia and OPCs, which in turn mitigates microglia activation and upregulates myeli …

Therapeutic reactivation of hippocampal progenitors reverse cognition decline in mice with progressive brain demyelination.

Chronic brain demyelination and neurodegeneration are hallmarks of progressive multiple sclerosis (MS) that underlie cognitive impairments. … and foster hippocampal repair by supporting neurogenesis, neuronal complexity, synaptogenesis, and remyelination that reverse memory impairments. Compared with Siponimod, a current disease modifying therapy for SPMS, NRG-1 achieved greater and multifaceted reparative effects, highlighting its potential as a regenerative therapy for progressive MS.

Transcriptional profiles of mouse oligodendrocyte precursor cells across the lifespan.

Oligodendrocyte progenitor cells (OPCs) are highly dynamic, widely distributed glial cells of the central nervous system responsible for generating myelinating oligodendrocytes throughout life. However, the rates of OPC proliferation and differentiation decline dramatically with aging, which may impair homeostasis, remyelination and adaptive myelination during learning. To determine how aging influences OPCs, we generated a transgenic mouse line (Matn4-mEGFP) and performed single-cell RNA sequencing, providing enhanced resolution of transcriptional changes during key transitions from quiescenc…

Glial-mediated pathogenesis and intervention strategies in neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing autoimmune disease primarily characterized by anti-aquaporin-4 immunoglobulin … roglia further exacerbate inflammation and tissue injury, while oligodendrocyte dysfunction impairs remyelination. This review summarizes the region-specific distribution and pathological functions of glial cells in NMOSD and highlights their contributions to both lesion formation and repair processes. We also discuss current and emerging therapeutic strategies …

Role of Oligodendrocyte Lineage Cells in White Matter Injury.

This chapter provides a comprehensive review of white matter injuries, with a particular focus on oligodendrocyte lineage cell-mediated mech … neration. Therapeutics that target oligodendrocyte lineage cells are warranted due to their role in remyelination, immunomodulation, circuit remodeling, and maintenance of vasculature. Thus, emerging diagnostic techniques can help in assessing the extent of oligodendrocyte lineage cell-related pathology, while regenerative treatments, including cell transplanta …

A Conjugation Delivery System of Macrophages and Platelet Pharmacytes Promotes Regeneration After Spinal Cord Injury.

Mitochondrial dysfunction occurs in macrophages with efferocytosis defects, which hinders recovery from tissue injury. Targeting intercellul … ury model, impaired efferocytosis is reversed by M-P-NP@PPARγ, resulting in neural regeneration and remyelination and ultimately promoting motor function recovery. In summary, this work has developed a strategy combining mitochondria and gene delivery to restore macrophage efferocytosis postinjury by regulating energy and lipid metabolism.

ZEB2: a multifunctional regulator of neural injury repair.

Nerve injury is a pathological condition characterized by damage or necrosis of nerve cells in injured areas due to trauma, infection, ische … tion, and regulatory network of ZEB2 and then elucidates its pivotal roles in glial scar formation, remyelination, and epithelial-to-mesenchymal transition (EMT) for neural injury repair. Furthermore, it provides a comprehensive summary of advances about ZEB2's regulatory role in peripheral nerve injury, spinal cord injury, hemorrhagic brain injury, and Mowat-W …

Химиотерапия вызывает множество склерозовых нейропатологий, которые могут быть спасены клобетозом.

Химиотерапия имеет важное значение для лечения рака, но часто сопровождается неблагоприятными последствиями, особенно для темозоломида (TMZ) - переднего химиотерапии для глиомы. Несмотря на наблюдавшиеся клинические неврологические аномалии, связанные с ТМЗ, механизмы, лежащие в основе нарушений нервной системы ТМЗ, по-прежнему плохо понимаются, а эффективные меры вмешательства отсутствуют. Здесь мы продемонстрировали, что химиотерапия TMZ вызвала нейродегенерацию, которая воспроизвела патологические особенности множественного склероза, включая демиелинацию, нейрофламмацию и аксонное дегенерац

Совпадение в аннотации оригинала
Chemotherapy is essential for cancer management yet frequently accompanied with adverse effects, particularly for temozolomide (TMZ), a fron … ice by suppressing TMZ-induced AMPK activation and attenuating neuroinflammation, thereby promoting remyelination. Our findings reveal the previously underappreciated neural toxicities associated with TMZ chemotherapy and highlight the therapeutic efficacy of clobetasol in mitigating chemotherapy-induced neural impairment, providing a strategy to enhance the li …

Обзор множественных склерозов: Неустранение сложностей патогенеза, прогресса, механизмов и терапевтических инноваций.

Множественный склероз (MS) — хроническое, подстрекательское демиелионирующее расстройство центральной нервной системы (CNS), направленное на миелионированные аксоны. Патогенез MS влечет за собой сложное генетическое, экологическое и иммунологическое взаимодействие. Регулирование иммунной реакции, т.е. автореактивные T & B-Cells и инфильтрация макрофага в CNS, приводит к воспалению, обезвоживанию и нейродегенерации. Инфекционное развитие НР варьируется между отдельными лицами, которые переходят от одной из форм повторного образования к вторичному прогрессивному НР (СПМС). В ходе исследований бы

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disorder of the central nervous system (CNS) targeting myelinated axons. Pa … se rates and control disease progression. Advancements in research, neuroprotective strategies, and remyelination strategies hold promising results in reversing CNS damage. Various mice models are being adopted for testing new entities in MS research.

Microglia influence immune responses and restrict neurologic disease in response to central nervous system infection by a neurotropic murine coronavirus.

Intracranial (i.c.) inoculation of susceptible mice with a glial-tropic strain of mouse hepatitis virus (JHMV), a murine coronavirus, result … ol of JHMV replication within the CNS while restricting the severity of demyelination and enhancing remyelination. This review will highlight our current understanding of the molecular and cellular mechanisms by which microglia aid in host defense, limit neurologic disease, and promote repair following CNS infection by a neurotropic murine coronavirus.

Neuregulin-1 reverses anxiety-like behavior and social behavior deficits induced by unilateral micro-injection of CoCl2 into the ventral hippocampus (vHPC).

Neuregulin-1 (NRG1) is an epidermal growth factor family member with essential roles in the developing and adult nervous systems. In recent years, establishing evidence has collectively suggested that NRG1 is a new modulator of central nervous system (CNS) injury and disease, with multifaceted roles in neuroprotection, remyelination, neuroinflammation, and other repair mechanisms. NRG1 signaling exerts its effects via the tyrosine kinase receptors ErbB2-ErbB4. The NRG1/ErbB network in CNS pathology and repair has evolved, primarily in recent years. In the present study, we demonstrated that a …

Qki is an essential regulator of microglial phagocytosis in demyelination.

The mechanism underpinning the regulation of microglial phagocytosis in demyelinating diseases is unclear. Here, we showed that the Quaking … n unresolved myelin debris that impaired axon integrity, oligodendrocyte maturation, and subsequent remyelination. Thus, our results demonstrate that Qki is an essential regulator of microglia's phagocytic activity under demyelinating conditions.

Aberrant DNA methylation profile exacerbates inflammation and neurodegeneration in multiple sclerosis patients.

Multiple sclerosis (MS) is an autoimmune and demyelinating disease of the central nervous system characterised by incoordination, sensory lo … iological processes, including blood-brain barrier breakdown, inflammatory response, demyelination, remyelination failure and neurodegeneration. In this study, we also accurately summarised a list of environmental factors involved in the MS pathogenesis and its clinical course. A literature search was conducted using MEDLINE through PubMED and Scopus. In conclu …

Increased TRPV4 expression in non-myelinating Schwann cells is associated with demyelination after sciatic nerve injury.

Transient receptor potential vanilloid 4 (TRPV4) is a non-selective calcium-permeable cation channel that is widely expressed and activated … ion of TRPV4 expression impaired the demyelinating process after nerve injury, resulting in delayed remyelination and functional recovery of sciatic nerves. These results suggest that local activation of TRPV4 could be an attractive pharmacological target for therapeutic intervention after peripheral nerve injury.

Promoting Neurite Growth and Schwann Cell Migration by the Harnessing Decellularized Nerve Matrix onto Nanofibrous Guidance.

Synergistic intercellular interactions have been widely acknowledged in tuning functional cell behaviors in vivo, and these interactions hav … larized nerve matrix promoted the ability of SCs to wrap around bundled neurites, triggering axonal remyelination toward nerve fiber functionalization.

Ellen Grass Memorial Lecture: Clinical Neurophysiology in the Treatment of Disease.

Clinical neurophysiology has a long-standing history and value in the diagnosis of neurologic diseases. Because of their unique ability to a … cus. Visual evoked potentials have been shown to be a biomarker for assessment of demyelination and remyelination associated with treatment of multiple sclerosis. Various EMG techniques can be used to independently assess improvement or otherwise of many neuromuscular diseases. The use of these techniques in the treatment of various neurologic disorders is the …

Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain.

Detailed characterization of the cell types in the human brain requires scalable experimental approaches to examine multiple aspects of the … sis for the study of complex processes in the brain, such as genetic programs that coordinate adult remyelination. We also mapped disease-associated risk variants to specific cellular populations, which provided insights into normal and pathogenic cellular processes in the human brain. This integrative multi-omics approach permits more detailed single-cell inte …

Stromal Cell-Derived Factor-1α Plays a Crucial Role Based on Neuroprotective Role in Neonatal Brain Injury in Rats.

Owing to progress in perinatal medicine, the survival of preterm newborns has markedly increased. However, the incidence of cerebral palsy h … t was unimproved by SDF-1α treatment. SDF-1α reduced intracranial inflammation and induced cerebral remyelination, as indicated by the immunohistochemistry results. These data suggest that SDF-1α specifically influences spatial perception abilities in neonatal HI encephalopathy.

Schwann cell spectrins modulate peripheral nerve myelination.

During peripheral nerve development, Schwann cells ensheathe axons and form myelin to enable rapid and efficient action potential propagatio … e myelination in vitro. Silencing expression of these spectrins inhibited myelination in vitro, and remyelination in vivo. Furthermore, myelination was disrupted in motor nerves of zebrafish lacking αII spectrin. Finally, we demonstrate that loss of spectrin significantly reduces both F-actin in the Schwann cell cytoskeleton and the Nectin-like protein, Necl4, …