TY  - JOUR
A1  - Stetter, Christian
A1  - Lopez-Caperuchipi, Simon
A1  - Hopp-Krämer, Sarah
A1  - Bieber, Michael
A1  - Kleinschnitz, Christoph
A1  - Sirén, Anna-Leena
A1  - Albert-Weißenberger, Christiane
T1  - Amelioration of cognitive and behavioral deficits after traumatic brain injury in coagulation factor XII deficient mice
JF  - International Journal of Molecular Sciences
N2  - Based on recent findings that show that depletion of factor XII (FXII) leads to better posttraumatic neurological recovery, we studied the effect of FXII-deficiency on post-traumatic cognitive and behavioral outcomes in female and male mice. In agreement with our previous findings, neurological deficits on day 7 after weight-drop traumatic brain injury (TBI) were significantly reduced in FXII\(^{−/−}\) mice compared to wild type (WT) mice. Also, glycoprotein Ib (GPIb)-positive platelet aggregates were more frequent in brain microvasculature of WT than FXII\(^{−/−}\) mice 3 months after TBI. Six weeks after TBI, memory for novel object was significantly reduced in both female and male WT but not in FXII\(^{−/−}\) mice compared to sham-operated mice. In the setting of automated home-cage monitoring of socially housed mice in IntelliCages, female WT mice but not FXII\(^{−/−}\) mice showed decreased exploration and reacted negatively to reward extinction one month after TBI. Since neuroendocrine stress after TBI might contribute to trauma-induced cognitive dysfunction and negative emotional contrast reactions, we measured peripheral corticosterone levels and the ration of heart, lung, and spleen weight to bodyweight. Three months after TBI, plasma corticosterone levels were significantly suppressed in both female and male WT but not in FXII\(^{−/−}\) mice, while the relative heart weight increased in males but not in females of both phenotypes when compared to sham-operated mice. Our results indicate that FXII deficiency is associated with efficient post-traumatic behavioral and neuroendocrine recovery.
KW  - closed head injury
KW  - contact-kinin system
KW  - object recognition memory
KW  - IntelliCage
KW  - Crespi effect
KW  - stress
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284959
SN  - 1422-0067
VL  - 22
IS  - 9
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  -