TY  - JOUR
AU  - Nikolakopoulou, Angeliki M.
AU  - Montagne, Axel
AU  - Kisler, Kassandra
AU  - Dai, Zhonghua
AU  - Wang, Yaoming
AU  - Huuskonen, Mikko T.
AU  - Sagare, Abhay P.
AU  - Lazić, Divna
AU  - Sweeney, Melanie D.
AU  - Kong, Pan
AU  - Wang, Min
AU  - Owens, Nelly Chuqui
AU  - Lawson, Erica J.
AU  - Xie, Xiaochun
AU  - Zhao, Zhen
AU  - Zloković, Berislav V.
PY  - 2019
UR  - http://www.nature.com/articles/s41593-019-0434-z
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3388
AB  - Pericytes are positioned between brain capillary endothelial cells, astrocytes and neurons. They degenerate in multiple neurological disorders. However, their role in the pathogenesis of these disorders remains debatable. Here we generate an inducible pericyte-specific Cre line and cross pericyte-specific Cre mice with iDTR mice carrying Cre-dependent human diphtheria toxin receptor. After pericyte ablation with diphtheria toxin, mice showed acute blood-brain barrier breakdown, severe loss of blood flow, and a rapid neuron loss that was associated with loss of pericyte-derived pleiotrophin (PTN), a neurotrophic growth factor. Intracerebroventricular PTN infusions prevented neuron loss in pericyte-ablated mice despite persistent circulatory changes. Silencing of pericyte-derived Ptn rendered neurons vulnerable to ischemic and excitotoxic injury. Our data demonstrate a rapid neurodegeneration cascade that links pericyte loss to acute circulatory collapse and loss of PTN neurotrophic support. These findings may have implications for the pathogenesis and treatment of neurological disorders that are associated with pericyte loss and/or neurovascular dysfunction.
T2  - Nature Neuroscience
T1  - Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss.
IS  - 7
VL  - 22
DO  - 10.1038/s41593-019-0434-z
SP  - 1089
EP  - 1098
ER  - 

@article{
author = "Nikolakopoulou, Angeliki M. and Montagne, Axel and Kisler, Kassandra and Dai, Zhonghua and Wang, Yaoming and Huuskonen, Mikko T. and Sagare, Abhay P. and Lazić, Divna and Sweeney, Melanie D. and Kong, Pan and Wang, Min and Owens, Nelly Chuqui and Lawson, Erica J. and Xie, Xiaochun and Zhao, Zhen and Zloković, Berislav V.",
year = "2019",
abstract = "Pericytes are positioned between brain capillary endothelial cells, astrocytes and neurons. They degenerate in multiple neurological disorders. However, their role in the pathogenesis of these disorders remains debatable. Here we generate an inducible pericyte-specific Cre line and cross pericyte-specific Cre mice with iDTR mice carrying Cre-dependent human diphtheria toxin receptor. After pericyte ablation with diphtheria toxin, mice showed acute blood-brain barrier breakdown, severe loss of blood flow, and a rapid neuron loss that was associated with loss of pericyte-derived pleiotrophin (PTN), a neurotrophic growth factor. Intracerebroventricular PTN infusions prevented neuron loss in pericyte-ablated mice despite persistent circulatory changes. Silencing of pericyte-derived Ptn rendered neurons vulnerable to ischemic and excitotoxic injury. Our data demonstrate a rapid neurodegeneration cascade that links pericyte loss to acute circulatory collapse and loss of PTN neurotrophic support. These findings may have implications for the pathogenesis and treatment of neurological disorders that are associated with pericyte loss and/or neurovascular dysfunction.",
journal = "Nature Neuroscience",
title = "Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss.",
number = "7",
volume = "22",
doi = "10.1038/s41593-019-0434-z",
pages = "1089-1098"
}

Nikolakopoulou, A. M., Montagne, A., Kisler, K., Dai, Z., Wang, Y., Huuskonen, M. T., Sagare, A. P., Lazić, D., Sweeney, M. D., Kong, P., Wang, M., Owens, N. C., Lawson, E. J., Xie, X., Zhao, Z.,& Zloković, B. V.. (2019). Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss.. in Nature Neuroscience, 22(7), 1089-1098.
https://doi.org/10.1038/s41593-019-0434-z

Nikolakopoulou AM, Montagne A, Kisler K, Dai Z, Wang Y, Huuskonen MT, Sagare AP, Lazić D, Sweeney MD, Kong P, Wang M, Owens NC, Lawson EJ, Xie X, Zhao Z, Zloković BV. Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss.. in Nature Neuroscience. 2019;22(7):1089-1098.
doi:10.1038/s41593-019-0434-z .

Nikolakopoulou, Angeliki M., Montagne, Axel, Kisler, Kassandra, Dai, Zhonghua, Wang, Yaoming, Huuskonen, Mikko T., Sagare, Abhay P., Lazić, Divna, Sweeney, Melanie D., Kong, Pan, Wang, Min, Owens, Nelly Chuqui, Lawson, Erica J., Xie, Xiaochun, Zhao, Zhen, Zloković, Berislav V., "Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss." in Nature Neuroscience, 22, no. 7 (2019):1089-1098,
https://doi.org/10.1038/s41593-019-0434-z . .

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 . .