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Neutrophils in Mouse and Human Ischemic Stroke

AuthorsPérez-de-Puig, Isabel ; Miró-Mur, Francesc; Ferrer-Ferrer, Maura; Gelpi, Ellen; Pedragosa, Jordi; Justicia, Carles ; Urra, Xabier; Chamorro, Ángel; Planas, Anna M.
Issue Date22-Oct-2014
CitationIX Simposi de Neurobiologia Experimental (2014)
AbstractNeutrophils are rapidly recruited to the sites of infection as part of the innate immune response against invading pathogens. However, neutrophils also respond to sterile inflammation and release of their toxic cargo can damage the tissues. Stroke triggers a strong inflammatory reaction but the location and role of neutrophils in the ischemic brain is still a matter of controversy. Here we investigated neutrophil trafficking to the brain in murine models of permanent middle cerebral artery occlusion and fatal cases of human ischemic stroke. Flow cytometry analyses of mouse brain cells revealed progressive neutrophil accumulation peaking at 24 hours. Confocal microscopy showed neutrophils trapped in capillaries and adhered to post-capillary venules. In addition, during ischemia neutrophils progressively left the circulation at the leptomeninges, reached the surface of the ischemic cortex and the Virchow-Robin spaces of perforating cortical vessels where they accumulated. After 24 hours of sustained ischemia, perivascular neutrophils gained access to the cortical parenchyma across the basement membranes. At this time, some neutrophils presented signs of NET formation by showing citrullination of histone-3, chromatin decondensation, and/or projection of DNA and histones out of the cells. Neutrophil extravasation at the leptomeninges, accumulation in perivascular spaces, and presence in the parenchyma was confirmed in postmortem human stroke brain tissue. We concluded that the leptomeninges are gateways for neutrophil access to perivascular spaces of cortical brain vessels and that long-lasting ischemia is needed for neutrophil activation compromising the integrity of the basement membranes and allowing their infiltration to the cortical brain parenchyma¡
DescriptionComunicación presentada en el IX Simposi de Neurobiologia Experimental, celebrado los días 22 y 23 de octubre de 2014 en Barcelona y organizado por la Societat Catalana de Biologia del Institut d'Estudis Catalans
Appears in Collections:(IIBB) Comunicaciones congresos
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