title: Platelet secretion is crucial to prevent bleeding in the ischemic brain but not in the inflamed skin or lung in mice.
abstract: Platelets maintain hemostasis after injury, but also during inflammation. Recent studies have shown that platelets prevent inflammatory bleeding through (hem) immunoreceptor tyrosine-based activation motif-dependent mechanisms irrespective of aggregation during skin and lung inflammation. Although the exact mechanisms underlying this process remain unknown, it was speculated that mediators released from platelet granules might be involved. Maintaining cerebral hemostasis during stroke treatment is of high clinical relevance because hemorrhage may aggravate the disease state and increase mortality. Although it was shown that platelets help maintain hemostasis in the ischemic brain, their exact contribution remains ill defined. Here we show thatUnc13d-/-/Nbeal2-/-mice, which lack platelet α- and dense-granule secretion, show no signs of hemorrhage in models of skin or lung inflammation. In stark contrast, lack of platelet granule release resulted in impaired hemostasis in the ischemic brain after transient middle cerebral artery occlusion leading to increased intracranial hemorrhage and mortality. Our results reveal for the first time that platelet granule constituents are essential for maintenance of hemostasis during thrombo-inflammatory brain infarction but not experimental inflammation of the skin or lung, thereby uncovering vascular bed-specific differences in the prevention of inflammatory bleeding.
authors.affiliation: Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, and.
authors.forename: Carsten
authors.identifier: 0000-0003-3740-8635
authors.initials: C
authors.lastname: Deppermann
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, and.
authors.forename: Julia
authors.initials: J
authors.lastname: Volz
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Schuhmann
authors.affiliation: Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, and.
authors.forename: Sarah
authors.initials: S
authors.lastname: Beck
authors.affiliation: Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, and.
authors.forename: Karen
authors.initials: K
authors.lastname: Wolf
authors.affiliation: Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, and.
authors.forename: David
authors.identifier: 0000-0003-1059-9865
authors.initials: D
authors.lastname: Stegner
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Stoll
authors.affiliation: Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, and.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002545:Brain Ischemia / Q000097:blood / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000097:blood / Q000517:prevention & control*; D006470:Hemorrhage / Q000473:pathology; D006487:Hemostasis; D020244:Infarction, Middle Cerebral Artery; D007249:Inflammation / Q000097:blood / Q000473:pathology; D008168:Lung / Q000473:pathology; D051379:Mice; D022142:Secretory Vesicles / Q000502:physiology; D012867:Skin / Q000473:pathology