TY - THES A1 - Salur, Irmak T1 - Therapie des Hirnschadens nach Neurotrauma mit dem humanen C1-Inhibitor Berinert T1 - Therapy of brain damage after experimental traumatic brain injury with the human C1 inhibitor Berinert N2 - Bei einem SHT handelt es sich um eine mechanische Schädigung des Hirngewebes, verursacht durch eine Gewalteinwirkung auf den Kopf. Diese initiale Schädigung des Hirngewebes weitet sich nachfolgend aus. Wirksame Therapien, um diese sekundären Pathomechanismen zu inhibieren, gibt es nicht. Sofern das SHT überlebt wird, ist es eine der häufigsten Ursachen für bleibende Behinderungen. Wichtige Pathomechanismen, welche zur Ausweitung der Hirnschädigung beitragen, sind das posttraumatische Hirnödem und Entzündungsreaktionen. Beides wird durch die Aktivierung des so-genannten Kallikrein-Kinin-Systems begünstigt. In der vorliegenden Arbeit wurde dieses System 1 Stunde nach experimentellem SHT durch die Applikation des C1-Inhibitors gehemmt und am nachfolgenden Tag die Auswirkungen bewertet. Die Ergebnisse zeigen, dass diese Behandlung nach der Hirnverletzung zu einer Reduktion des Hirnödems und der Entzündungsreaktion führt. Die Bildung von Thromben in den Hirngefäßen ist geringer als in Kontrolltieren, vermutlich da der C1-Inhibitor auch die intrinsische Gerinnungs-kaskade hemmt. Insgesamt führt die Behandlung zu kleineren Hirnläsionen als in entsprechenden Kontrolltieren. Hiermit stellt der C1-Inhibitor ein potenzieller Therapieansatz bei SHT dar. Jedoch bleibt es offen, inwiefern sich diese Ergebnisse auf das menschliche SHT übertragen lassen. N2 - Traumatic brain injury is a mechanical disruption of brain tissue caused by a violent effect on the head. This initial damage to the brain tissue subsequently expands. There are no effective therapies to inhibit these secondary pathomechanisms. The brain injury is one of the major causes of death and disability. Posttraumatic cerebral edema and inflammatory reactions are important pathomechanisms that contribute to the expansion of brain damage. Both are enhanced by the activation of the kallikrein-kinin system. In the present study, this system was inhibited 1 hour after experimental brain injury by the application of the C1 inhibitor and the effects were evaluated on the following day. The results show that this treatment leads to a reduction of brain edema and inflammatory response after brain injury. The formation of microthrombi in the brain vessels is less than in control animals, presumably because the C1 inhibitor also inhibits the intrinsic coagulation cascade. Overall, the treatment leads to smaller brain lesions than in control animals. The C1 inhibitor thus represents a potential therapeutic target for traumatic brain injury. However, it remains unclear how these results can be transferred to human brain injury. KW - Schädel-Hirn-Trauma KW - C1-Inhibitor Berinert KW - Schädel-Hirn-Trauma KW - Kontakt-Kinin-System Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173759 ER - 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 -