Multiple Sclerosis: Glial Cell Diversity in Time and Space

Glia, Год журнала: 2024, Номер unknown

Опубликована: Дек. 24, 2024

ABSTRACT Multiple sclerosis (MS) is the most prevalent human inflammatory disease of central nervous system with demyelination and glial scar formation as pathological hallmarks. Glial cells are key drivers lesion progression in MS roles both tissue damage repair depending on surrounding microenvironment functional state individual subtype. In this review, we describe recent developments context cell diversity summarizing findings respect to maladaptive functions related disease‐associated subtypes. A particular focus spatial temporal dynamics including subtypes microglia, oligodendrocytes, astrocytes. We contextualize high‐dimensional suggesting that dynamically change epigenomic, transcriptomic, metabolic features across inflamed rim during lesions. summary, detailed knowledge spatially restricted subtype critical for a better understanding pathology its pathogenesis well development novel therapies targeting specific types.

Язык: Английский

CCL17/CCR4 Axis Promotes Hematoma Clearance via ERK/AP1/SRA‐Mediated Microglial Polarization After Intracerebral Hemorrhage

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(2)

Опубликована: Фев. 1, 2025

Our previous studies demonstrated that CCL17 and its receptor CCR4 play crucial roles in neuroinflammation microglial activation following intracerebral hemorrhage (ICH). However, the specific mechanisms by which CCL17/CCR4 axis regulates polarization hematoma clearance remain unclear. This study investigates how signaling pathway modulates phenotype transition enhances resolution after ICH, building upon our earlier findings showing CCR4's involvement neuroinflammatory responses. Using CRISPR-mediated disruption overexpression approaches a mouse ICH model, we examined neurological outcomes, inflammatory responses, volumes. We further evaluated therapeutic potential of recombinant administration. The downstream ERK pathway's role CCL17/CCR4-mediated function was investigated through pharmacological inhibition. knockout exacerbated deficits, increased neuroinflammation, enlarged hematomas. In contrast, enhancing expression or administering improved functional recovery provided neuroprotection. Mechanistically, activated ERK/AP1/SRA pathway, promoting anti-inflammatory, phagocytic polarization, evidenced CD206 SRA expression. inhibition reversed these protective effects. extend work revealing pathway-mediated polarization. mechanism represents promising target for treatment.

Язык: Английский

Combined Ionizing Radiation Exposure Improves Behavioral Symptoms and Modulates Brain Innate Immune System Activity in the Tau P301S Mice Line

Biochemistry (Moscow), Год журнала: 2025, Номер 90(3), С. 400 - 412

Опубликована: Март 1, 2025

Язык: Английский