TY  - JOUR
A1  - Raslan, Furat
A1  - Albert-Weißenberger, Christiane
A1  - Ernestus, Ralf-Ingo
A1  - Kleinschnitz, Christoph
A1  - Sirén, Anna-Leena
T1  - Focal brain trauma in the cryogenic lesion model in mice
N2  - The method to induce unilateral cryogenic lesions was first described in 1958 by Klatzo. We describe here an adaptation of this model that allows reliable measurement of lesion volume and vasogenic edema by 2, 3, 5-triphenyltetrazolium chloride-staining and Evans blue extravasation in mice. A copper or aluminium cylinder with a tip diameter of 2.5 mm is cooled with liquid nitrogen and placed on the exposed skull bone over the parietal cortex (coordinates from bregma: 1.5 mm posterior, 1.5 mm lateral). The tip diameter and the contact time between the tip and the parietal skull determine the extent of cryolesion. Due to an early damage of the blood brain barrier, the cryogenic cortical injury is characterized by vasogenic edema, marked brain swelling, and inflammation. The lesion grows during the first 24 hours, a process involving complex interactions between endothelial cells, immune cells, cerebral blood flow, and the intracranial pressure. These contribute substantially to the damage from the initial injury. The major advantage of the cryogenic lesion model is the circumscribed and highly reproducible lesion size and location.
KW  - Medizin
KW  - Experimental brain trauma
KW  - Cryolesion
KW  - Secondary traumatic brain damage
KW  - Mice
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75419
ER  - 
TY  - JOUR
A1  - Hopp, Sarah
A1  - Albert-Weissenberger, Christiane
A1  - Mencl, Stine
A1  - Bieber, Michael
A1  - Schuhmann, Michael K.
A1  - Stetter, Christian
A1  - Nieswandt, Bernhard
A1  - Schmidt, Peter M.
A1  - Monoranu, Camelia-Maria
A1  - Alafuzoff, Irina
A1  - Marklund, Niklas
A1  - Nolte, Marc W.
A1  - Sirén, Anna-Leena
A1  - Kleinschnitz, Christoph
T1  - Targeting coagulation factor XII as a novel therapeutic option in brain trauma
JF  - Annals of Neurology
N2  - Objective: 
Traumatic brain injury is a major global public health problem for which specific therapeutic interventions are lacking. There is, therefore, a pressing need to identify innovative pathomechanism-based effective therapies for this condition. Thrombus formation in the cerebral microcirculation has been proposed to contribute to secondary brain damage by causing pericontusional ischemia, but previous studies have failed to harness this finding for therapeutic use. The aim of this study was to obtain preclinical evidence supporting the hypothesis that targeting factor XII prevents thrombus formation and has a beneficial effect on outcome after traumatic brain injury. 

Methods: 
We investigated the impact of genetic deficiency of factor XII and acute inhibition of activated factor XII with a single bolus injection of recombinant human albumin-fused infestin-4 (rHA-Infestin-4) on trauma-induced microvascular thrombus formation and the subsequent outcome in 2 mouse models of traumatic brain injury. 

Results: 
Our study showed that both genetic deficiency of factor XII and an inhibition of activated factor XII in mice minimize trauma-induced microvascular thrombus formation and improve outcome, as reflected by better motor function, reduced brain lesion volume, and diminished neurodegeneration. Administration of human factor XII in factor XII-deficient mice fully restored injury-induced microvascular thrombus formation and brain damage. 

Interpretation: 
The robust protective effect of rHA-Infestin-4 points to a novel treatment option that can decrease ischemic injury after traumatic brain injury without increasing bleeding tendencies.
KW  - Molecular-weight heparin
KW  - Thrombus formation
KW  - Cerebral-ischemia
KW  - in-vivo
KW  - Intravascular coagulation
KW  - Hemodynamic depression
KW  - Head-injury
KW  - Rats
KW  - Model
KW  - Mice
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188800
VL  - 79
IS  - 6
ER  -