Age-related meningeal extracellular matrix remodeling compromises CNS lymphatic function

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Апрель 17, 2025

Abstract Efficient clearance of central nervous system (CNS) waste proteins and appropriate immune surveillance is essential for brain health. These processes are facilitated by lymphatic networks present in the meninges that drain cerebrospinal fluid (CSF). Age-related impairments to meningeal drainage contribute CNS accumulation dysfunction, yet underlying mechanisms remain poorly understood. Here, we identify extracellular matrix (ECM) remodeling aged dura as a key driver CSF deficits, demonstrating peri-lymphatic collagen disrupts function. Exploring immune-derived factors contributing this ECM remodeling, transforming growth factor beta 1 (TGFβ1) major regulator using primary human dural fibroblasts. Using novel mouse model with constitutively active TGFβ receptor (TGFβR1) signaling fibroblasts, show excessive deposition impairs alters immunity. Mechanistically, reveal ECM-associated stiffness junction integrity lymphangiogenesis endothelial cells. findings establish cell fibroblast-mediated critical highlight it potential therapeutic target restoring aging.

Язык: Английский

Redefining CNS immune privilege

Nature reviews. Immunology, Год журнала: 2025, Номер unknown

Опубликована: Май 2, 2025

Язык: Английский

CSF transport at the brain–meningeal border: effects on neurological health and disease

The Lancet Neurology, Год журнала: 2025, Номер 24(6), С. 535 - 547

Опубликована: Май 20, 2025

Язык: Английский