TY  - JOUR
A1  - Albert-Weißenberger, Christiane
A1  - Várrallyay, Csanád
A1  - Raslan, Furat
A1  - Kleinschnitz, Christoph
A1  - Sirén, Anna-Leena
T1  - An experimental protocol for mimicking pathomechanisms of traumatic brain injury in mice
N2  - Traumatic brain injury (TBI) is a result of an outside force causing immediate mechanical disruption of brain tissue and delayed pathogenic events. In order to examine injury processes associated with TBI, a number of rodent models to induce brain trauma have been described. However, none of these models covers the entire spectrum of events that might occur in TBI. Here we provide a thorough methodological description of a straightforward closed head weight drop mouse model to assess brain injuries close to the clinical conditions of human TBI.
KW  - Medizin
KW  - closed head injury
KW  - traumatic brain injury
KW  - neurobehavioural deficits
KW  - astrocyte
KW  - microglia
KW  - neurons
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75368
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  - 
TY  - JOUR
A1  - Albert-Weissenberger, Christiane
A1  - Mencl, Stine
A1  - Hopp, Sarah
A1  - Kleinschnitz, Christoph
A1  - Siren, Anna-Leena
T1  - Role of the kallikrein-kinin system in traumatic brain injury
JF  - Frontiers in Cellular Neuroscience
N2  - Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Despite improvements in acute intensive care, there are currently no specific therapies to ameliorate the effects of TBI. Successful therapeutic strategies for TBI should target multiple pathophysiologic mechanisms that occur at different stages of brain injury. The kallikrein-kinin system is a promising therapeutic target for TBI as it mediates key pathologic events of traumatic brain damage, such as edema formation, inflammation, and thrombosis. Selective and specific kinin receptor antagonists and inhibitors of plasma kallikrein and coagulation factor XII have been developed, and have already shown therapeutic efficacy in animal models of stroke and TBI. However, conflicting preclinical evaluation, as well as limited and inconclusive data from clinical trials in TBI, suggests that caution should be taken before transferring observations made in animals to humans. This review summarizes current evidence on the pathologic significance of the kallikrein-kinin system during TBI in animal models and, where available, the experimental findings are compared with human data.
KW  - bradykinin
KW  - factor XII
KW  - kallikrein–kinin system
KW  - kinin receptor
KW  - traumatic brain injury
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-118226
SN  - 1662-5102
VL  - 8
ER  -