TY  - JOUR
A1  - Israel, Ina
A1  - Ohsiek, Andrea
A1  - Al-Momani, Ehab
A1  - Albert-Weissenberger, Christiane
A1  - Stetter, Christian
A1  - Mencl, Stine
A1  - Buck, Andreas K.
A1  - Kleinschnitz, Christoph
A1  - Samnick, Samuel
A1  - Sirén, Anna-Leena
T1  - Combined [\(^{18}\)F]DPA-714 micro-positron emission tomography and autoradiography imaging of microglia activation after closed head injury in mice
JF  - Journal of Neuroinflammation
N2  - 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.
KW  - neuroinflammation
KW  - TBI
KW  - immunohistochemistry
KW  - weight drop
KW  - PET
KW  - diffuse
KW  - focal
KW  - TSPO
KW  - autoradiography
KW  - IBA-1
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146606
VL  - 13
IS  - 140
ER  - 
TY  - JOUR
A1  - Göbel, Kerstin
A1  - Pankratz, Susann
A1  - Asaridou, Chloi-Magdalini
A1  - Herrmann, Alexander M.
A1  - Bittner, Stefan
A1  - Merker, Monika
A1  - Ruck, Tobias
A1  - Glumm, Sarah
A1  - Langhauser, Friederike
A1  - Kraft, Peter
A1  - Krug, Thorsten F.
A1  - Breuer, Johanna
A1  - Herold, Martin
A1  - Gross, Catharina C.
A1  - Beckmann, Denise
A1  - Korb-Pap, Adelheid
A1  - Schuhmann, Michael K.
A1  - Kuerten, Stefanie
A1  - Mitroulis, Ioannis
A1  - Ruppert, Clemens
A1  - Nolte, Marc W.
A1  - Panousis, Con
A1  - Klotz, Luisa
A1  - Kehrel, Beate
A1  - Korn, Thomas
A1  - Langer, Harald F.
A1  - Pap, Thomas
A1  - Nieswandt, Bernhard
A1  - Wiendl, Heinz
A1  - Chavakis, Triantafyllos
A1  - Kleinschnitz, Christoph
A1  - Meuth, Sven G.
T1  - Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells
JF  - Nature Communications
N2  - Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders.
KW  - blood coagulation
KW  - factor XII
KW  - neuroinflammation
KW  - dendric cells
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165503
VL  - 7
IS  - 11626
ER  -