Deficiency of von Willebrand factor protects mice from ischemic stroke

Importance of T Lymphocytes in Brain Injury, Immunodeficiency, and Recovery after Cerebral Ischemia

“…The net impact of the accumulated platelets in the postischemic microcirculation remains unclear; however, inhibition of platelet tethering and adhesion to vascular endothelial cells (the early phases of platelet activation) has produced reductions in cerebral infarct volume (Elvers et al, 2010;Kleinschnitz et al, 2007Kleinschnitz et al, , 2009Zhao et al, 2009). Furthermore, inhibition of early platelet adhesion and activation maintains cerebral blood flow during reperfusion (Pham et al, 2011).…”

Relevant role of von Willebrand factor in neutrophil recruitment in a mouse sepsis model involving cecal ligation and puncture

“…Although the functional regulation of VWF has recently been proven beneficial in various diseases, [3][4][5][6]15 VWF-dependent inflammatory responses should be carefully considered in the context of these clinical applications.…”

“…Shogo Kasuda, 1 Hideto Matsui,2 Shiro Ono, 2 Yasunori Matsunari, 2 Kenji Nishio, 3 Midori Shima, 4 Katsuhiko Hatake, 1 …”

“…1,2 From the standpoint of the human defense system, VWF could, therefore, be a key protein serving as a functional link between inflammation and thrombosis. 2 Indeed, recent mouse model studies demonstrated that proper functional regulation of VWF-dependent inflammatory responses by ADAMTS13 considerably suppressed disease progression in patients with brain stroke 3,4 or myocardial infarction. 5,6 However, the precise mechanisms and roles of VWF in inflammation remain poorly understood thus far.…”

High VWF, low ADAMTS13 puts women at risk

“…3 In humans, qualitative or quantitative abnormalities of the VWF protein cause the VWF disease, an inherited common bleeding disorder, whereas lack of functional AD-AMTS13 results in thrombotic thrombocytopenic purpura, which is characterized by the formation of thrombi in arterioles and capillaries. 3,4 Studies in mice demonstrated that lack of VWF was highly protective in a model of ischemic stroke and improved the neurologic outcome, 5,6 whereas ADAMTS13 deficiency aggravated the neurologic damage. 6,7 Interestingly, these studies also revealed that alterations in the VWF-ADAMTS13 system not only affected thrombotic activity but also modulated immune cell recruitment to the affected brain territory, indicating that GPIb-VWF interactions contribute to inflammatory responses in this setting by yet undefined mechanisms and lead to the concept of stroke being a "thrombo-inflammatory" disease.…”