TY  - JOUR
A1  - Üçeyler, Nurcan
A1  - Buchholz, Hans-Georg
A1  - Kewenig, Susanne
A1  - Ament, Stephan-Johann
A1  - Birklein, Frank
A1  - Schreckenberger, Mathias
A1  - Sommer, Claudia
T1  - Cortical Binding Potential of Opioid Receptors in Patients With Fibromyalgia Syndrome and Reduced Systemic Interleukin-4 Levels – A Pilot Study
JF  - Frontiers in Neuroscience
N2  - Objective: We investigated cerebral opioid receptor binding potential in patients with fibromyalgia syndrome (FMS) using positron-emission-tomography (PET) and correlated our results with patients’ systemic interleukin-4 (IL-4) gene expression.
Methods: In this pilot study, seven FMS patients (1 man, 6 women) agreed to participate in experimental PET scans. All patients underwent neurological examination, were investigated with questionnaires for pain, depression, and FMS symptoms. Additionally, blood for IL-4 gene expression analysis was withdrawn at two time points with a median latency of 1.3 years. Patients were investigated in a PET scanner using the opioid receptor ligand F-18-fluoro-ethyl-diprenorphine ([18F]FEDPN) and results were compared with laboratory normative values.
Results: Neurological examination was normal in all FMS patients. Reduced opioid receptor binding was found in mid cingulate cortex compared to healthy controls (p < 0.005). Interestingly, three patients with high systemic IL-4 gene expression had increased opioid receptor binding in the fronto-basal cortex compared to those with low IL-4 gene expression (p < 0.005).
Conclusion: Our data give further evidence for a reduction in cortical opioid receptor availability in FMS patients as another potential central nervous system contributor to pain in FMS.
KW  - fibromyalgia syndrome
KW  - PET
KW  - brain
KW  - opioid
KW  - IL-4
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204457
SN  - 1662-453X
VL  - 14
ER  - 
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  -