Early Blood-Brain Barrier Disruption in Ischemic Stroke Initiates Multifocally Around Capillaries/Venules

Stroke; a Journal of Cerebral Circulation
Angelika HoffmannMirko Pham

Abstract

Detection and localization of the early phase of blood-brain barrier disruption (BBBD) in vivo during cerebral ischemia/reperfusion injury remain a major challenge but may be a relevant outcome parameter in stroke. We studied early BBBD in mice after transient middle cerebral artery occlusion by multimodal, high-field (9.4T) in vivo magnetic resonance imaging, including the contrast agent gadofluorineM as an albumin-binding tracer. GadofluorineM contrast-enhanced magnetic resonance imaging was performed to determine BBBD at 2, 6, and 24 hours after reperfusion. BBBD was confirmed and localized along the microvascular tree by using fluorescent gadofluorineM and immunofluorescence stainings (cluster of differentiation 31, ephrin type-B receptor 4, alpha smooth muscle actin, ionized calcium binding adaptor molecule 1). GadofluorineM contrast-enhanced magnetic resonance imaging revealed a multifocal spatial distribution of early BBBD and its close association with the microvasculature at a resolution of 40 μm. GadofluorineM leakage was closely associated with ephrin type-B receptor 4-positive but not alpha smooth muscle actin-positive vessels. The multifocal pattern of early BBBD (already at 2 hours after reperfusion) thus occurred...Continue Reading

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Citations

Feb 27, 2020·Advanced Healthcare Materials·Shantanu PradhanJohn H Slater
Mar 4, 2020·Stroke; a Journal of Cerebral Circulation·Minkyung Kang, Yao Yao
Jul 22, 2020·Journal of Cellular Physiology·Kitti ThiankhawSiripron C Chattipakorn
Oct 20, 2018·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Gina HadleyAlastair M Buchan
Sep 3, 2019·Frontiers in Cellular Neuroscience·Goutam Kumar TantiBernhard Hemmer
Jul 16, 2020·The International Journal of Biochemistry & Cell Biology·Zeinab Y MotaweJerome W Breslin
May 1, 2021·International Journal of Molecular Sciences·Sweilem B Al RihaniVeronique Michaud
Aug 3, 2021·Frontiers in Immunology·Dianhui ZhangZhen-Ni Guo
Sep 14, 2021·Journal of the American Heart Association·Susmita BhattaraiManikandan Panchatcharam

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