@article{
author = "Montagne, Axel and Nikolakopoulou, Angeliki M and Zhao, Zhen and Sagare, Abhay P and Si, Gabriel and Lazic, Divna and Barnes, Samuel R and Daianu, Madelaine and Ramanathan, Anita and Go, Ariel and Lawson, Erica J and Wang, Yaoming and Mack, William J and Thompson, Paul M and Schneider, Julie A and Varkey, Jobin and Langen, Ralf and Mullins, Eric and Jacobs, Russell E and Zlokovic, Berislav V",
year = "2018",
abstract = "Diffuse white-matter disease associated with small-vessel disease and dementia is prevalent in the elderly. The biological mechanisms, however, remain elusive. Using pericyte-deficient mice, magnetic resonance imaging, viral-based tract-tracing, and behavior and tissue analysis, we found that pericyte degeneration disrupted white-matter microcirculation, resulting in an accumulation of toxic blood-derived fibrin(ogen) deposits and blood-flow reductions, which triggered a loss of myelin, axons and oligodendrocytes. This disrupted brain circuits, leading to white-matter functional deficits before neuronal loss occurs. Fibrinogen and fibrin fibrils initiated autophagy-dependent cell death in oligodendrocyte and pericyte cultures, whereas pharmacological and genetic manipulations of systemic fibrinogen levels in pericyte-deficient, but not control mice, influenced the degree of white-matter fibrin(ogen) deposition, pericyte degeneration, vascular pathology and white-matter changes. Thus, our data indicate that pericytes control white-matter structure and function, which has implications for the pathogenesis and treatment of human white-matter disease associated with small-vessel disease.",
journal = "Nature Medicine, Nature Medicine",
title = "Pericyte degeneration causes white matter dysfunction in the mouse central nervous system.",
number = "3",
volume = "24",
doi = "10.1038/nm.4482",
pages = "326-337"
}