@article{IsraelOhsiekAlMomanietal.2016,
  author    = {Israel, Ina and Ohsiek, Andrea and Al-Momani, Ehab and Albert-Weissenberger, Christiane and Stetter, Christian and Mencl, Stine and Buck, Andreas K. and Kleinschnitz, Christoph and Samnick, Samuel and Sir{\´e}n, Anna-Leena},
  title     = {Combined [\(^{18}\)F]DPA-714 micro-positron emission tomography and autoradiography imaging of microglia activation after closed head injury in mice},
  series = {Journal of Neuroinflammation},
  volume    = {13},
  journal   = {Journal of Neuroinflammation},
  number    = {140},
  doi       = {10.1186/s12974-016-0604-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146606},
  year      = {2016},
  abstract  = {Background Traumatic brain injury (TBI) is a major cause of death and disability. Neuroinflammation contributes to acute damage after TBI and modulates long-term evolution of degenerative and regenerative responses to injury. The aim of the present study was to evaluate the relationship of microglia activation to trauma severity, brain energy metabolism, and cellular reactions to injury in a mouse closed head injury model using combined in vivo PET imaging, ex vivo autoradiography, and immunohistochemistry. Methods A weight-drop closed head injury model was used to produce a mixed diffuse and focal TBI or a purely diffuse mild TBI (mTBI) in C57BL6 mice. Lesion severity was determined by evaluating histological damage and functional outcome using a standardized neuroscore (NSS), gliosis, and axonal injury by immunohistochemistry. Repeated intra-individual in vivo μPET imaging with the specific 18-kDa translocator protein (TSPO) radioligand [\(^{18}\)F]DPA-714 was performed on day 1, 7, and 16 and [\(^{18}\)F]FDG-μPET imaging for energy metabolism on days 2-5 after trauma using freshly synthesized radiotracers. Immediately after [\(^{18}\)F]DPA-714-μPET imaging on days 7 and 16, cellular identity of the [\(^{18}\)F]DPA-714 uptake was confirmed by exposing freshly cut cryosections to film autoradiography and successive immunostaining with antibodies against the microglia/macrophage marker IBA-1. Results Functional outcome correlated with focal brain lesions, gliosis, and axonal injury. [\(^{18}\)F]DPA-714-μPET showed increased radiotracer uptake in focal brain lesions on days 7 and 16 after TBI and correlated with reduced cerebral [\(^{18}\)F]FDG uptake on days 2-5, with functional outcome and number of IBA-1 positive cells on day 7. In autoradiography, [\(^{18}\)F]DPA-714 uptake co-localized with areas of IBA1-positive staining and correlated strongly with both NSS and the number of IBA1-positive cells, gliosis, and axonal injury. After mTBI, numbers of IBA-1 positive cells with microglial morphology increased in both brain hemispheres; however, uptake of [\(^{18}\)F]DPA-714 was not increased in autoradiography or in μPET imaging. Conclusions [\(^{18}\)F]DPA-714 uptake in μPET/autoradiography correlates with trauma severity, brain metabolic deficits, and microglia activation after closed head TBI.},
  language  = {en}
}
@article{StetterLopezCaperuchipiHoppKraemeretal.2021,
  author    = {Stetter, Christian and Lopez-Caperuchipi, Simon and Hopp-Kr{\"a}mer, Sarah and Bieber, Michael and Kleinschnitz, Christoph and Sir{\´e}n, Anna-Leena and Albert-Weißenberger, Christiane},
  title     = {Amelioration of cognitive and behavioral deficits after traumatic brain injury in coagulation factor XII deficient mice},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {9},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22094855},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284959},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}