Amelioration of Cognitive and Behavioral Deficits after Traumatic Brain Injury in Coagulation Factor XII Deficient Mice

International Journal of Molecular Sciences

Michael Bieber¹  Christoph Kleinschnitz¹  Christian Stetter²  Christiane Albert-Weißenberger²  Sarah Hopp-Krämer²  Anna-Leena Sirén²  Simon Lopez-Caperuchipi² 

[1] Department of Neurology, University Hospital of Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany;Department of Neurosurgery, University Hospital of Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany;

关键词: closed head injury;    contact-kinin system;    object recognition memory;    IntelliCage;    Crespi effect;    stress;   

DOI  :  10.3390/ijms22094855

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown