Pericyte degeneration causes white matter dysfunction in the mouse central nervous system.
Level 5 - mechanism / opinion, no new human data
Preclinical animal model and in vitro study (also flagged as a retracted publication)
PubMed 29400711 · doi:10.1038/nm.4482
What was done
Investigated the mechanisms of white matter dysfunction using pericyte-deficient mice, magnetic resonance imaging, viral-based tract-tracing, behavioral assessments, and tissue histology. Oligodendrocyte and pericyte cultures were exposed to fibrinogen and fibrin fibrils to study cell death pathways, and systemic fibrinogen levels were manipulated pharmacologically and genetically in pericyte-deficient and control mice.
What was found
The abstract reports directional findings without numerical values or confidence intervals. Pericyte degeneration disrupted white-matter microcirculation, decreased blood flow, and caused accumulation of toxic fibrin(ogen) deposits, leading to loss of myelin, axons, and oligodendrocytes and resulting in circuit disruption before neuronal loss. In cell culture, fibrinogen and fibrin fibrils induced autophagy-dependent cell death. Modulating systemic fibrinogen levels altered the severity of vascular pathology and white-matter changes in pericyte-deficient mice.
Why it matters
It outlines a biological mechanism linking pericyte degeneration and vascular leakage to white-matter pathology in small-vessel disease.
Limits
The study is restricted to rodent and cell-culture models, lacking direct human clinical testing. Sample sizes, quantitative effect sizes, and statistical variance are not reported in the abstract. Additionally, this article is indexed as a retracted publication.
Cited by
- partial Extravasated fibrinogen in the brain is neurotoxic and is internalized by oligodendrocytes, causing them to die via autophagy and promoting white matter disease.
- supports Systemically lowering fibrinogen in mouse models of blood-brain barrier dysfunction reduced brain fibrinogen leakage and partially restored cerebral blood flow and barrier integrity.