Microembolus clearance through angiophagy is an auxiliary mechanism preserving tissue perfusion in the rat brain

Autor: Stephan Huveneers, Theodosia Georgakopoulou, Jan van Bezu, Miesje M. van der Stoel, Helga E. de Vries, Anne Eva van der Wijk, Erik N. T. P. Bakker, Peter L. Hordijk, Jisca Majolée, Ed van Bavel, Bert van het Hof
Přispěvatelé: Physiology, Molecular cell biology and Immunology, ACS - Microcirculation, Amsterdam Neuroscience - Neurovascular Disorders, ACS - Atherosclerosis & ischemic syndromes, Biomedical Engineering and Physics, Graduate School, AII - Inflammatory diseases, Amsterdam Gastroenterology Endocrinology Metabolism, Medical Biochemistry, ANS - Neurovascular Disorders, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Diabetes & metabolism
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: van der Wijk, A E, Georgakopoulou, T, Majolée, J, van Bezu, J S M, van der Stoel, M M, van het Hof, B J, de Vries, H E, Huveneers, S, Hordijk, P L, Bakker, E N T P & van Bavel, E 2020, ' Microembolus clearance through angiophagy is an auxiliary mechanism preserving tissue perfusion in the rat brain ', Acta neuropathologica communications, vol. 8, no. 1, 195 . https://doi.org/10.1186/s40478-020-01071-9
Acta Neuropathologica Communications
Acta neuropathologica communications, 8(1):195. BioMed Central
PubMed Central
NARCIS
DOAJ-Articles
OpenAIRE
Acta Neuropathologica Communications, Vol 8, Iss 1, Pp 1-14 (2020)
ISSN: 2051-5960
Popis: Considering its intolerance to ischemia, it is of critical importance for the brain to efficiently process microvascular occlusions and maintain tissue perfusion. In addition to collateral microvascular flow and enzymatic degradation of emboli, the endothelium has the potential to engulf microparticles and thereby recanalize the vessel, through a process called angiophagy. Here, we set out to study the dynamics of angiophagy in relation to cytoskeletal remodeling in vitro and reperfusion in vivo. We show that polystyrene microspheres and fibrin clots are actively taken up by (brain) endothelial cells in vitro, and chart the dynamics of the actin cytoskeleton during this process using live cell imaging. Whereas microspheres were taken up through the formation of a cup structure by the apical endothelial membrane, fibrin clots were completely engulfed by the cells, marked by dense F-actin accumulation surrounding the clot. Both microspheres and fibrin clots were retained in the endothelial cells. Notably, fibrin clots were not degraded intracellularly. Using an in vivo microembolization rat model, in which microparticles are injected into the common carotid artery, we found that microspheres are transported by the endothelium from the microvasculature into the brain parenchyma. Microembolization with microspheres caused temporal opening of the blood–brain barrier and vascular nonperfusion, followed by microsphere extravasation and restoration of vessel perfusion over time. Taken together, angiophagy is accompanied by active cytoskeletal remodeling of the endothelium, and is an effective mechanism to restore perfusion of the occluded microvasculature in vivo. Electronic supplementary material The online version of this article (10.1186/s40478-020-01071-9) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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