title: The Formation of Microthrombi in Parenchymal Microvessels after Traumatic Brain Injury Is Independent of Coagulation Factor XI.
abstract: Microthrombus formation and bleeding worsen the outcome after traumatic brain injury (TBI). The aim of the current study was to characterize these processes in the brain parenchyma after experimental TBI and to determine the involvement of coagulation factor XI (FXI). C57BL/6 mice (n = 101) and FXI-deficient mice (n = 15) were subjected to controlled cortical impact (CCI). Wild-type mice received an inhibitory antibody against FXI (14E11) or control immunoglobulin G 24 h before or 30 or 120 min after CCI. Cerebral microcirculation was visualized in vivo by 2-photon microscopy 2-3 h post-trauma and histopathological outcome was assessed after 24 h. TBI induced hemorrhage and microthrombus formation in the brain parenchyma (p < 0.001). Inhibition of FXI activation or FXI deficiency did not reduce cerebral thrombogenesis, lesion volume, or hemispheric swelling. However, it also did not increase intracranial hemorrhage. Formation of microthrombosis in the brain parenchyma after TBI is independent of the intrinsic coagulation cascade since it was not reduced by inhibition of FXI. However, since targeting FXI has well-established antithrombotic effects in humans and experimental animals, inhibition of FXI could represent a reasonable strategy for the prevention of deep venous thrombosis in immobilized patients with TBI.
authors.affiliation: 1 Department of Neurodegeneration, Royal College of Surgeons in Ireland (RCSI) , Dublin, Ireland .|2 Institute for Stroke and Dementia Research (ISD), University of Munich Medical Center , Munich, Germany .|3 Department of Anesthesiology, University of Munich Medical Center , Munich, Germany .
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Schwarzmaier
authors.affiliation: 1 Department of Neurodegeneration, Royal College of Surgeons in Ireland (RCSI) , Dublin, Ireland .
authors.forename: Ciaran
authors.initials: C
authors.lastname: de Chaumont
authors.affiliation: 1 Department of Neurodegeneration, Royal College of Surgeons in Ireland (RCSI) , Dublin, Ireland .|2 Institute for Stroke and Dementia Research (ISD), University of Munich Medical Center , Munich, Germany .
authors.forename: Matilde
authors.initials: M
authors.lastname: Balbi
authors.affiliation: 2 Institute for Stroke and Dementia Research (ISD), University of Munich Medical Center , Munich, Germany .
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Terpolilli
authors.affiliation: 4 Department of Neurology, University Hospital of Würzburg , Würzburg, Germany .
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.affiliation: 5 Departments of Biomedical Engineering and Medicine, Knight Cardiovascular Institute, Oregon Health and Science University , School of Medicine, Portland, Oregon.
authors.forename: Andras
authors.initials: A
authors.lastname: Gruber
authors.affiliation: 1 Department of Neurodegeneration, Royal College of Surgeons in Ireland (RCSI) , Dublin, Ireland .|2 Institute for Stroke and Dementia Research (ISD), University of Munich Medical Center , Munich, Germany .|6 SyNergy, Munich Cluster for Systems Neurology , Munich, Germany .
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Plesnila
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D000070642:Brain Injuries, Traumatic / Q000150:complications*; D005172:Factor XI / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000473:pathology; D013927:Thrombosis / Q000209:etiology* / Q000378:metabolism*
chemical_list: D005172:Factor XI
keywords: 2-photon microscopy; anticoagulation; in vivo; microthrombi; traumatic brain injury