title: Blood coagulation factor XII--a neglected player in stroke pathophysiology.
abstract: Ischemic stroke is a devastating disease which, in most cases, is caused by thrombotic occlusion of brain arteries. The molecular mechanisms involved in microvascular thrombus formation during focal cerebral ischemia are not well understood. As a consequence, the current antithrombotic drugs used to treat acute stroke or prevent stroke recurrence either show limited efficacy or put patients at risk for serious bleeding complications. The serine protease blood coagulation factor XII (FXII) initiates the intrinsic pathway of coagulation which, together with the extrinsic pathway, culminates in the formation of fibrin. A physiological function of FXII in clot formation and hemostasis in vivo has been questioned for more than 50 years. This was mainly due to the fact that hereditary FXII deficiency does not induce any bleeding phenotype in humans. However, recent studies in transgenic mice challenged this concept by demonstrating that FXII deficiency prevents pathological thrombus formation, but does not affect regular hemostasis. These findings entailed investigations in relevant disease models of thromboembolism including ischemic stroke. The present review summarizes the pathophysiological role of FXII in experimental cerebral ischemia and highlights novel therapeutic strategies based on FXII inhibition.
authors: Department of Neuroradiology, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany. mirko.pham@med.uni-heidelberg.de
authors: Mirko
authors: M
authors: Pham
authors: Guido
authors: G
authors: Stoll
authors: Bernhard
authors: B
authors: Nieswandt
authors: Martin
authors: M
authors: Bendszus
authors: Christoph
authors: C
authors: Kleinschnitz
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D004195:Disease Models, Animal; D005174:Factor XII / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011859:Radiography; D020521:Stroke / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology*; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology
chemical_list: D005174:Factor XII; D005337:Fibrin