TY  - JOUR
AU  - Montagne, Axel
AU  - Nikolakopoulou, Angeliki M
AU  - Zhao, Zhen
AU  - Sagare, Abhay P
AU  - Si, Gabriel
AU  - Lazic, Divna
AU  - Barnes, Samuel R
AU  - Daianu, Madelaine
AU  - Ramanathan, Anita
AU  - Go, Ariel
AU  - Lawson, Erica J
AU  - Wang, Yaoming
AU  - Mack, William J
AU  - Thompson, Paul M
AU  - Schneider, Julie A
AU  - Varkey, Jobin
AU  - Langen, Ralf
AU  - Mullins, Eric
AU  - Jacobs, Russell E
AU  - Zlokovic, Berislav V
PY  - 2018
UR  - http://www.nature.com/doifinder/10.1038/nm.4482
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5840035
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3012
AB  - 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.
T2  - Nature Medicine
T2  - Nature Medicine
T1  - Pericyte degeneration causes white matter dysfunction in the mouse central nervous system.
IS  - 3
VL  - 24
DO  - 10.1038/nm.4482
SP  - 326
EP  - 337
ER  - 

@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"
}

Montagne, A., Nikolakopoulou, A. M., Zhao, Z., Sagare, A. P., Si, G., Lazic, D., Barnes, S. R., Daianu, M., Ramanathan, A., Go, A., Lawson, E. J., Wang, Y., Mack, W. J., Thompson, P. M., Schneider, J. A., Varkey, J., Langen, R., Mullins, E., Jacobs, R. E.,& Zlokovic, B. V.. (2018). Pericyte degeneration causes white matter dysfunction in the mouse central nervous system.. in Nature Medicine, 24(3), 326-337.
https://doi.org/10.1038/nm.4482

Montagne A, Nikolakopoulou AM, Zhao Z, Sagare AP, Si G, Lazic D, Barnes SR, Daianu M, Ramanathan A, Go A, Lawson EJ, Wang Y, Mack WJ, Thompson PM, Schneider JA, Varkey J, Langen R, Mullins E, Jacobs RE, Zlokovic BV. Pericyte degeneration causes white matter dysfunction in the mouse central nervous system.. in Nature Medicine. 2018;24(3):326-337.
doi:10.1038/nm.4482 .

Montagne, Axel, Nikolakopoulou, Angeliki M, Zhao, Zhen, Sagare, Abhay P, Si, Gabriel, Lazic, Divna, Barnes, Samuel R, Daianu, Madelaine, Ramanathan, Anita, Go, Ariel, Lawson, Erica J, Wang, Yaoming, Mack, William J, Thompson, Paul M, Schneider, Julie A, Varkey, Jobin, Langen, Ralf, Mullins, Eric, Jacobs, Russell E, Zlokovic, Berislav V, "Pericyte degeneration causes white matter dysfunction in the mouse central nervous system." in Nature Medicine, 24, no. 3 (2018):326-337,
https://doi.org/10.1038/nm.4482 . .