TY  - JOUR
A1  - Albert-Weissenberger, Christiane
A1  - Mencl, Stine
A1  - Schuhmann, Michael K.
A1  - Salur, Irmak
A1  - Göb, Eva
A1  - Langhauser, Friederike
A1  - Hopp, Sarah
A1  - Hennig, Nelli
A1  - Meuth, Sven G.
A1  - Nolte, Marc W.
A1  - Sirén, Anna-Leena
A1  - Kleinschnitz, Christoph
T1  - C1-Inhibitor protects from focal brain trauma in a cortical cryolesion mice model by reducing thrombo-inflammation
JF  - Frontiers in Cellular Neuroscience
N2  - 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.
KW  - thrombosis
KW  - traumatic brain injury
KW  - C1-inhibitor
KW  - blood-brain barrier
KW  - contact-kinin system
KW  - edema
KW  - inflammation
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119263
SN  - 1662-5102
VL  - 8
ER  -