期刊论文详细信息
Journal of Neuroinflammation
Platelets and lymphocytes drive progressive penumbral tissue loss during middle cerebral artery occlusion in mice
Michael K. Schuhmann1  Maximilian Franke1  Michael Bieber1  Guido Stoll1  Mirko Pham2  Alexander M. Kollikowski2  Katrin G. Heinze3  David Stegner4  Bernhard Nieswandt4 
[1] Department of Neurology, University Hospital Würzburg, Würzburg, Germany;Department of Neuroradiology, University Hospital Würzburg, Würzburg, Germany;Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany;Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany;Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany;
关键词: Ischemic penumbra;    Glycoprotein receptor Ib;    T-cells;    Ischemic stroke;    Thrombo-inflammation;    middle cerebral artery occlusion;   
DOI  :  10.1186/s12974-021-02095-1
来源: Springer
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【 摘 要 】

BackgroundIn acute ischemic stroke, cessation of blood flow causes immediate tissue necrosis within the center of the ischemic brain region accompanied by functional failure in the surrounding brain tissue designated the penumbra. The penumbra can be salvaged by timely thrombolysis/thrombectomy, the only available acute stroke treatment to date, but is progressively destroyed by the expansion of infarction. The underlying mechanisms of progressive infarction are not fully understood.MethodsTo address mechanisms, mice underwent filament occlusion of the middle cerebral artery (MCAO) for up to 4 h. Infarct development was compared between mice treated with antigen-binding fragments (Fab) against the platelet surface molecules GPIb (p0p/B Fab) or rat immunoglobulin G (IgG) Fab as control treatment. Moreover, Rag1−/− mice lacking T-cells underwent the same procedures. Infarct volumes as well as the local inflammatory response were determined during vessel occlusion.ResultsWe show that blocking of the platelet adhesion receptor, glycoprotein (GP) Ibα in mice, delays cerebral infarct progression already during occlusion and thus before recanalization/reperfusion. This therapeutic effect was accompanied by decreased T-cell infiltration, particularly at the infarct border zone, which during occlusion is supplied by collateral blood flow. Accordingly, mice lacking T-cells were likewise protected from infarct progression under occlusion.ConclusionsProgressive brain infarction can be delayed by blocking detrimental lymphocyte/platelet responses already during occlusion paving the way for ultra-early treatment strategies in hyper-acute stroke before recanalization.

【 授权许可】

CC BY   

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