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Title: CNS-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage
Author: Pedragosa Ollé, Jordi
Salas Perdomo, Angélica María
Gallizioli, Mattia
Cugota, Roger
Miró Mur, Francesc
Briansó, Ferran
Justicia Mercader, Carles
Pérez Asensio, Fernando
Márquez-Kisinousky, Leonardo
Urra, Xabier
Gieryng, Anna
Kaminska, Bozena
Chamorro Sánchez, Ángel
Planas Obradors, Anna Maria
Keywords: Cervell
Isquèmia cerebral
Expressió gènica
Cerebral ischemia
Gene expression
Issue Date: 9-Aug-2018
Publisher: BioMed Central
Abstract: The central nervous system (CNS) contains several types of immune cells located in specific anatomic compartments. Macrophages reside at the CNS borders surrounding the brain vessels, in leptomeningeal spaces and the choroid plexus, where they interact with the vasculature and play immunological surveillance and scavenging functions. We investigated the phenotypic changes and role of these macrophages in response to acute ischemic stroke. Given that CD163 expression is a hallmark of perivascular and meningeal macrophages in the rat and human brain, we isolated CD163+ brain macrophages by fluorescence activated cell sorting. We obtained CD163+ cells from control rats and 16 h following transient middle cerebral artery occlusion, after verifying that infiltration of CD163+ peripheral myeloid cells is negligible at this acute time point. Transcriptome analysis of the sorted CD163+ cells identified ischemia-induced upregulation of the hypoxia inducible factor-1 pathway and induction of genes encoding for extracellular matrix components and leukocyte chemoattractants, amongst others. Using a cell depletion strategy, we found that CNS border-associated macrophages participate in granulocyte recruitment, promote the expression of vascular endothelial growth factor (VEGF), increase the permeability of pial and cortical blood vessels, and contribute to neurological dysfunction in the acute phase of ischemia/reperfusion. We detected VEGF expression surrounding blood vessels and in some CD163+ perivascular macrophages in the brain tissue of ischemic stroke patients deceased one day after stroke onset. These findings show ischemia-induced reprogramming of the gene expression profile of CD163+ macrophages that has a rapid impact on leukocyte chemotaxis and blood-brain barrier integrity, and promotes neurological impairment in the acute phase of stroke.
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It is part of: Acta Neuropathologica Communications, 2018, vol. 6, num. 1, p. 76-95
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ISSN: 2051-5960
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Medicina)

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