title: C1-Inhibitor protects from focal brain trauma in a cortical cryolesion mice model by reducing thrombo-inflammation.
abstract: Traumatic brain injury (TBI) induces a strong inflammatory response which includes blood-brain barrier damage, edema formation and infiltration of different immune cell subsets. More recently, microvascular thrombosis has been identified as another pathophysiological feature of TBI. The contact-kinin system represents an interface between inflammatory and thrombotic circuits and is activated in different neurological diseases. C1-Inhibitor counteracts activation of the contact-kinin system at multiple levels. We investigated the therapeutic potential of C1-Inhibitor in a model of TBI. Male and female C57BL/6 mice were subjected to cortical cryolesion and treated with C1-Inhibitor after 1 h. Lesion volumes were assessed between day 1 and day 5 and blood-brain barrier damage, thrombus formation as well as the local inflammatory response were determined post TBI. Treatment of male mice with 15.0 IU C1-Inhibitor, but not 7.5 IU, 1 h after cryolesion reduced lesion volumes by ~75% on day 1. This protective effect was preserved in female mice and at later stages of trauma. Mechanistically, C1-Inhibitor stabilized the blood-brain barrier and decreased the invasion of immune cells into the brain parenchyma. Moreover, C1-Inhibitor had strong antithrombotic effects. C1-Inhibitor represents a multifaceted anti-inflammatory and antithrombotic compound that prevents traumatic neurodegeneration in clinically meaningful settings.
authors.affiliation: Department of Neurology, University Hospital Würzburg Würzburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Albert-Weissenberger
authors.affiliation: Department of Neurology, University Hospital Würzburg Würzburg, Germany.
authors.forename: Stine
authors.initials: S
authors.lastname: Mencl
authors.affiliation: Department of Neurology, University Hospital Würzburg Würzburg, Germany.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Schuhmann
authors.affiliation: Department of Neurosurgery, University Hospital Würzburg Würzburg, Germany.
authors.forename: Irmak
authors.initials: I
authors.lastname: Salur
authors.affiliation: Department of Neurology, University Hospital Würzburg Würzburg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Göb
authors.affiliation: Department of Neurology, University Hospital Würzburg Würzburg, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Langhauser
authors.affiliation: Department of Neurology, University Hospital Würzburg Würzburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hopp
authors.affiliation: Department of Neurosurgery, University Hospital Würzburg Würzburg, Germany.
authors.forename: Nelli
authors.initials: N
authors.lastname: Hennig
authors.affiliation: Department of Neurology, University of Münster Münster, Germany ; Institute of Physiology I - Neuropathophysiology, University of Münster Münster, Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.affiliation: CSL Behring GmbH Marburg, Germany.
authors.forename: Marc W
authors.initials: MW
authors.lastname: Nolte
authors.affiliation: Department of Neurosurgery, University Hospital Würzburg Würzburg, Germany.
authors.forename: Anna-Leena
authors.initials: AL
authors.lastname: Sirén
authors.affiliation: Department of Neurology, University Hospital Würzburg Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
keywords: C1-inhibitor; blood-brain barrier; contact-kinin system; edema; inflammation; thrombosis; traumatic brain injury