@article{AsterRomanosWalitzaetal.2022,
  author    = {Aster, Hans-Christoph and Romanos, Marcel and Walitza, Susanne and Gerlach, Manfred and M{\"u}hlberger, Andreas and Rizzo, Albert and Andreatta, Marta and Hasenauer, Natalie and Hartrampf, Philipp E. and Nerlich, Kai and Reiners, Christoph and Lorenz, Reinhard and Buck, Andreas K. and Deserno, Lorenz},
  title     = {Responsivity of the striatal dopamine system to methylphenidate — A within-subject I-123-β-CIT-SPECT study in male children and adolescents with attention-deficit/hyperactivity disorder},
  series = {Frontiers in Psychiatry},
  volume    = {13},
  journal   = {Frontiers in Psychiatry},
  issn      = {1664-0640},
  doi       = {10.3389/fpsyt.2022.804730},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270862},
  year      = {2022},
  abstract  = {Background: Methylphenidate (MPH) is the first-line pharmacological treatment of attention-deficit/hyperactivity disorder (ADHD). MPH binds to the dopamine (DA) transporter (DAT), which has high density in the striatum. Assessments of the striatal dopamine transporter by single positron emission computed tomography (SPECT) in childhood and adolescent patients are rare but can provide insight on how the effects of MPH affect DAT availability. The aim of our within-subject study was to investigate the effect of MPH on DAT availability and how responsivity to MPH in DAT availability is linked to clinical symptoms and cognitive functioning. Methods Thirteen adolescent male patients (9-16 years) with a diagnosis of ADHD according to the DSM-IV and long-term stimulant medication (for at least 6 months) with MPH were assessed twice within 7 days using SPECT after application of I-123-β-CIT to examine DAT binding potential (DAT BP). SPECT measures took place in an on- and off-MPH status balanced for order across participants. A virtual reality continuous performance test was performed at each time point. Further clinical symptoms were assessed for baseline off-MPH. Results On-MPH status was associated with a highly significant change (-29.9\%) of striatal DAT BP as compared to off-MPH (t = -4.12, p = 0.002). A more pronounced change in striatal DAT BP was associated with higher off-MPH attentional and externalizing symptom ratings (Pearson r = 0.68, p = 0.01). Striatal DAT BP off-MPH, but not on-MPH, was associated with higher symptom ratings (Pearson r = 0.56, p = 0.04). Conclusion Our findings corroborate previous reports from mainly adult samples that MPH changes striatal DAT BP availability and suggest higher off-MPH DAT BP, likely reflecting low baseline DA levels, as a marker of symptom severity.},
  language  = {en}
}
@article{AsterEvdokimovBraunetal.2022,
  author    = {Aster, Hans-Christoph and Evdokimov, Dimitar and Braun, Alexandra and {\"U}{\c{c}}eyler, Nurcan and Kampf, Thomas and Pham, Mirko and Homola, Gy{\"o}rgy A. and Sommer, Claudia},
  title     = {CNS imaging characteristics in fibromyalgia patients with and without peripheral nerve involvement},
  series = {Scientific Reports},
  volume    = {12},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-022-10489-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300562},
  year      = {2022},
  abstract  = {We tested the hypothesis that reduced skin innervation in fibromyalgia syndrome is associated with specific CNS changes. This prospective case-control study included 43 women diagnosed with fibromyalgia syndrome and 40 healthy controls. We further compared the fibromyalgia subgroups with reduced (n = 21) and normal (n = 22) skin innervation. Brains were analysed for cortical volume, for white matter integrity, and for functional connectivity. Compared to controls, cortical thickness was decreased in regions of the frontal, temporal and parietal cortex in the fibromyalgia group as a whole, and decreased in the bilateral pericalcarine cortices in the fibromyalgia subgroup with reduced skin innervation. Diffusion tensor imaging revealed a significant increase in fractional anisotropy in the corona radiata, the corpus callosum, cingulum and fornix in patients with fibromyalgia compared to healthy controls and decreased FA in parts of the internal capsule and thalamic radiation in the subgroup with reduced skin innervation. Using resting-state fMRI, the fibromyalgia group as a whole showed functional hypoconnectivity between the right midfrontal gyrus and the posterior cerebellum and the right crus cerebellum, respectively. The subgroup with reduced skin innervation showed hyperconnectivity between the inferior frontal gyrus, the angular gyrus and the posterior parietal gyrus. Our results suggest that the subgroup of fibromyalgia patients with pronounced pathology in the peripheral nervous system shows alterations in morphology, structural and functional connectivity also at the level of the encephalon. We propose considering these subgroups when conducting clinical trials.},
  language  = {en}
}
@phdthesis{Aster2023,
  author    = {Aster, Hans-Christoph},
  title     = {Characterization of subgroups in fibromyalgia syndrome},
  doi       = {10.25972/OPUS-31304},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313049},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {The present cumulative dissertation summarizes three clinical studies, which examine subgroups of patients within the fibromyalgia syndrome (FMS). FMS entails chronic pain and associated symptoms, and its pathophysiology is incompletely understood (1). Previous studies show that there is a subgroup of patients with FMS with objective histological pathology of the small nerve fibers of the peripheral nervous system (PNS). Another subgroup of FMS patients does not show any signs of pathological changes of the small nerve fibers. The aim of this dissertation was to compare FMS patients with healthy controls, and these two FMS subgroups for differences in the central nervous system (CNS) in order to explore possible interactions between PNS and the CNS. Regarding the CNS, differences of FMS patients with healthy controls have already been found in studies with small sample sizes, but no subgroups have yet been identified. Another aim of this thesis was to test whether the subgroups show a different response to different classes of pain medication. The methods used in this thesis are structural and functional magnetic resonance imaging (MRI), magnetic resonance diffusion imaging and magnetic resonance spectroscopy. For the evaluation of clinical symptoms, we used standardized questionnaires. The subgroups with and without pathologies of the PNS were determined by skin biopsies of the right thigh and lower leg based on the intraepidermal nerve fiber density (IENFD) of the small nerve fibers. 1) In the first MRI study, 43 female patients with the diagnosis of FMS and 40 healthy control subjects, matched in age and body mass index, were examined with different MRI sequences. Cortical thickness was investigated by structural T1 imaging, white matter integrity by diffusion tensor imaging and functional connectivity within neuronal networks by functional resting state MRI. Compared to the controls, FMS patients had a lower cortical volume in bilateral frontotemporoparietal regions and the left insula, but a higher cortical volume in the left pericalcarine cortex. Compared to the subgroup without PNS pathology, the subgroup with PNS pathology had lower cortical volume in both pericalcarine cortices. Diffusion tensor imaging revealed an increased fractional anisotropy (FA) of FMS patients in corticospinal pathways such as the corona radiata, but also in regions of the limbic systems such as the fornix and cingulum. Subgroup comparison again revealed lower mean FA values of the posterior thalamic radiation and the posterior limb of the left internal capsule in the subgroup with PNS pathology. In the functional connectivity analysis FMS patients, compared to controls, showed a hypoconnectivity between the right median frontal gyrus and the posterior cerebellum and the right crus cerebellum, respectively. In the subgroup comparisons, the subgroup with PNS pathology showed a hyperconnectivity between both inferior frontal gyri, the right posterior parietal cortex and the right angular gyrus. In summary, these results show that differences in brain morphology and functional connectivity exist between FMS patients with and without PNS pathology. These differences were not associated with symptom duration or severity and, in some cases, have not yet been described in the context of FMS. The differences in brain morphology and connectivity between subgroups could also lead to a differential response to treatment with centrally acting drugs. Further imaging studies with FMS patients should take into account this heterogeneity of FMS patient cohorts. 2) Following the results from the first MRI study, drug therapies of FMS patients and their treatment response were compared between PNS subgroups. As there is no licensed drug for FMS in Europe, the German S3 guideline recommends amitriptyline, duloxetine and pregabalin for temporary use. In order to examine the current drug use in FMS patients in Germany on a cross-sectional basis, 156 patients with FMS were systematically interviewed. The drugs most frequently used to treat pain in FMS were non-steroidal anti-inflammatory drugs (NSAIDs) (28.9\%), metamizole (15.4\%) and amitriptyline (8.8\%). Pain relief assessed by patients on a numerical rating scale from 0-10 averaged 2.2 points for NSAIDs, 2.0 for metamizole and 1.5 for amitriptyline. Drugs that were discontinued for lack of efficacy and not for side effects were acetaminophen (100\%), flupirtine (91.7\%), selective serotonin reuptake inhibitors (81.8\%), NSAIDs (83.7\%) and weak opioids (74.1\%). Patients were divided into subgroups with and without PNS pathology as determined by skin biopsies. We found no differences in drug use and effect between the subgroups. Taken together, these results show that many FMS patients take medication that is not in accordance with the guidelines. The reduction of symptoms was best achieved with metamizole and NSAIDs. Further longitudinal studies on medication in FMS are necessary to obtain clearer treatment recommendations. 3) Derived from previous pharmacological and imaging studies (with smaller case numbers), there is a hypothesis in the FMS literature that hyperreactivity of the insular cortex may have an impact on FMS. The hyperreactivity seems to be due to an increased concentration of the excitatory neurotransmitter glutamate in the insular cortex of FMS patients. The hypothesis is supported by magnetic resonance spectroscopy studies with small number of cases, as well as results from pharmacological studies with glutamate-inhibiting medication. Studies from animal models have also shown that an artificially induced increase in glutamate in the insular cortex can lead to reduced skin innervation. Therefore, the aim of this study was to compare glutamate and GABA concentrations in the insular cortex of FMS patients with those of healthy controls using magnetic resonance imaging. There was no significant difference of both neurotransmitters between the groups. In addition, there was no correlation between the neurotransmitter concentrations and the severity of clinical symptoms. There were also no differences in neurotransmitter concentrations between the subgroups with and without PNS pathology. In conclusion, our study could not show any evidence of a correlation of glutamate and GABA concentrations with the symptoms of FMS or the pathogenesis of subgroups with PNS pathologies.},
  subject      = {Fibromyalgie},
  language  = {en}
}
@article{AsterEvdokimovBraunetal.2022,
  author    = {Aster, H-C and Evdokimov, D. and Braun, A. and {\"U}{\c{c}}eyler, N. and Sommer, C.},
  title     = {Analgesic Medication in Fibromyalgia Patients: A Cross-Sectional Study},
  series = {Pain Research and Management},
  volume    = {2022},
  journal   = {Pain Research and Management},
  doi       = {10.1155/2022/1217717},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300578},
  year      = {2022},
  abstract  = {There is no approved drug for fibromyalgia syndrome (FMS) in Europe. In the German S3 guideline, amitriptyline, duloxetine, and pregabalin are recommended for temporary use. The aim of this study was to cross-sectionally investigate the current practice of medication in FMS patients in Germany. We systematically interviewed 156 patients with FMS, while they were participating in a larger study. The patients had been stratified into subgroups with and without a decrease in intraepidermal nerve fiber density. The drugs most commonly used to treat FMS pain were nonsteroidal anti-inflammatory drugs (NSAIDs) (41.0\% of all patients), metamizole (22.4\%), and amitriptyline (12.8\%). The most frequent analgesic treatment regimen was "on demand" (53.9\%), during pain attacks, while 35.1\% of the drugs were administered daily and the remaining in other regimens. Median pain relief as self-rated by the patients on a numerical rating scale (0-10) was 2 points for NSAIDS, 2 for metamizole, and 1 for amitriptyline. Drugs that were discontinued due to lack of efficacy rather than side effects were acetaminophen, flupirtine, and selective serotonin reuptake inhibitors. Reduction in pain severity was best achieved by NSAIDs and metamizole. Our hypothesis that a decrease in intraepidermal nerve fiber density might represent a neuropathic subtype of FMS, which would be associated with better effectiveness of drugs targeting neuropathic pain, could not be confirmed in this cohort. Many FMS patients take "on-demand" medication that is not in line with current guidelines. More randomized clinical trials are needed to assess drug effects in FMS subgroups.},
  language  = {en}
}
@article{AppeltshauserMessingerStarzetal.2022,
  author    = {Appeltshauser, Luise and Messinger, Julia and Starz, Katharina and Heinrich, David and Brunder, Anna-Michelle and Stengel, Helena and Fiebig, Bianca and Ayzenberg, Ilya and Birklein, Frank and Dresel, Christian and Dorst, Johannes and Dvorak, Florian and Grimm, Alexander and Joerk, Alexander and Leypoldt, Frank and M{\"a}urer, Mathias and Merl, Patrick and Michels, Sebastian and Pitarokoili, Kalliopi and Rosenfeldt, Mathias and Sperfeld, Anne-Dorte and Weihrauch, Marc and Welte, Gabriel Simon and Sommer, Claudia and Doppler, Kathrin},
  title     = {Diabetes Mellitus Is a Possible Risk Factor for Nodo-paranodopathy With Antiparanodal Autoantibodies},
  series = {Neurology: Neuroimmunology \& Neuroinflammation},
  volume    = {9},
  journal   = {Neurology: Neuroimmunology \& Neuroinflammation},
  number    = {3},
  doi       = {10.1212/NXI.0000000000001163},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300551},
  year      = {2022},
  abstract  = {Background and Objectives Nodo-paranodopathies are peripheral neuropathies with dysfunction of the node of Ranvier. Affected patients who are seropositive for antibodies against adhesion molecules like contactin-1 and neurofascin show distinct clinical features and a disruption of the paranodal complex. An axoglial dysjunction is also a characteristic finding of diabetic neuropathy. Here, we aim to investigate a possible association of antibody-mediated nodo-paranodopathy and diabetes mellitus (DM). Methods We retrospectively analyzed clinical data of 227 patients with chronic inflammatory demyelinating polyradiculoneuropathy and Guillain-Barr{\´e} syndrome from multiple centers in Germany who had undergone diagnostic testing for antiparanodal antibodies targeting neurofascin-155, pan-neurofascin, contactin-1-associated protein 1, and contactin-1. To study possible direct pathogenic effects of antiparanodal antibodies, we performed immunofluorescence binding assays on human pancreatic tissue sections. Results The frequency of DM was 33.3\% in seropositive patients and thus higher compared with seronegative patients (14.1\%, OR = 3.04, 95\% CI = 1.31-6.80). The relative risk of DM in seropositive patients was 3.4-fold higher compared with the general German population. Seropositive patients with DM most frequently harbored anti-contactin-1 antibodies and had higher antibody titers than seropositive patients without DM. The diagnosis of DM preceded the onset of neuropathy in seropositive patients. No immunoreactivity of antiparanodal antibodies against pancreatic tissue was detected. Discussion We report an association of nodo-paranodopathy and DM. Our results suggest that DM may be a potential risk factor for predisposing to developing nodo-paranodopathy and argue against DM being induced by the autoantibodies. Our findings set the basis for further research investigating underlying immunopathogenetic connections.},
  language  = {en}
}
@article{AppeltshauserBrunderHeiniusetal.2020,
  author    = {Appeltshauser, Luise and Brunder, Anna-Michelle and Heinius, Annika and K{\"o}rtv{\´e}lyessy, Peter and Wandinger, Klaus-Peter and Junker, Ralf and Villmann, Carmen and Sommer, Claudia and Leypoldt, Frank and Doppler, Kathrin},
  title     = {Antiparanodal antibodies and IgG subclasses in acute autoimmune neuropathy},
  series = {Neurology: Neuroimmunology \& Neuroinflammation},
  volume    = {7},
  journal   = {Neurology: Neuroimmunology \& Neuroinflammation},
  number    = {5},
  doi       = {10.1212/NXI.0000000000000817},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230079},
  year      = {2020},
  abstract  = {Objective To determine whether IgG subclasses of antiparanodal autoantibodies are related to disease course and treatment response in acute- to subacute-onset neuropathies, we retrospectively screened 161 baseline serum/CSF samples and 66 follow-up serum/CSF samples. Methods We used ELISA and immunofluorescence assays to detect antiparanodal IgG and their subclasses and titers in serum/CSF of patients with Guillain-Barre syndrome (GBS), recurrent GBS (R-GBS), Miller-Fisher syndrome, and acute- to subacute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP). We evaluated clinical data retrospectively. Results We detected antiparanodal autoantibodies with a prevalence of 4.3\% (7/161), more often in A-CIDP (4/23, 17.4\%) compared with GBS (3/114, 2.6\%). Longitudinal subclass analysis in the patients with GBS revealed IgG2/3 autoantibodies against Caspr-1 and against anti-contactin-1/Caspr-1, which disappeared at remission. At disease onset, patients with A-CIDP had IgG2/3 anti-Caspr-1 and anti-contactin-1/Caspr-1 or IgG4 anti-contactin-1 antibodies, IgG3 being associated with good response to IV immunoglobulins (IVIg). In the chronic phase of disease, IgG subclass of one patient with A-CIDP switched from IgG3 to IgG4. Conclusion Our data (1) confirm and extend previous observations that antiparanodal IgG2/3 but not IgG4 antibodies can occur in acute-onset neuropathies manifesting as monophasic GBS, (2) suggest association of IgG3 to a favorable response to IVIg, and (3) lend support to the hypothesis that in some patients, an IgG subclass switch from IgG3 to IgG4 may be the correlate of a secondary progressive or relapsing course following a GBS-like onset.},
  language  = {en}
}
@article{AndreskaLueningschroerWolfetal.2023,
  author    = {Andreska, Thomas and L{\"u}ningschr{\"o}r, Patrick and Wolf, Daniel and McFleder, Rhonda L. and Ayon-Olivas, Maurilyn and Rattka, Marta and Drechsler, Christine and Perschin, Veronika and Blum, Robert and Aufmkolk, Sarah and Granado, Noelia and Moratalla, Rosario and Sauer, Markus and Monoranu, Camelia and Volkmann, Jens and Ip, Chi Wang and Stigloher, Christian and Sendtner, Michael},
  title     = {DRD1 signaling modulates TrkB turnover and BDNF sensitivity in direct pathway striatal medium spiny neurons},
  series = {Cell Reports},
  volume    = {42},
  journal   = {Cell Reports},
  number    = {6},
  doi       = {10.1016/j.celrep.2023.112575},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349932},
  year      = {2023},
  abstract  = {Highlights • Dopamine receptor-1 activation induces TrkB cell-surface expression in striatal neurons • Dopaminergic deficits cause TrkB accumulation and clustering in the ER • TrkB clusters colocalize with cargo receptor SORCS-2 in direct pathway striatal neurons • Intracellular TrkB clusters fail to fuse with lysosomes after dopamine depletion Summary Disturbed motor control is a hallmark of Parkinson's disease (PD). Cortico-striatal synapses play a central role in motor learning and adaption, and brain-derived neurotrophic factor (BDNF) from cortico-striatal afferents modulates their plasticity via TrkB in striatal medium spiny projection neurons (SPNs). We studied the role of dopamine in modulating the sensitivity of direct pathway SPNs (dSPNs) to BDNF in cultures of fluorescence-activated cell sorting (FACS)-enriched D1-expressing SPNs and 6-hydroxydopamine (6-OHDA)-treated rats. DRD1 activation causes enhanced TrkB translocation to the cell surface and increased sensitivity for BDNF. In contrast, dopamine depletion in cultured dSPN neurons, 6-OHDA-treated rats, and postmortem brain of patients with PD reduces BDNF responsiveness and causes formation of intracellular TrkB clusters. These clusters associate with sortilin related VPS10 domain containing receptor 2 (SORCS-2) in multivesicular-like structures, which apparently protects them from lysosomal degradation. Thus, impaired TrkB processing might contribute to disturbed motor function in PD.},
  language  = {en}
}
@phdthesis{Andreska2021,
  author    = {Andreska, Thomas},
  title     = {Effects of dopamine on BDNF / TrkB mediated signaling and plasticity on cortico-striatal synapses},
  doi       = {10.25972/OPUS-17431},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-174317},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Progressive loss of voluntary movement control is the central symptom of Parkinson's disease (PD). Even today, we are not yet able to cure PD. This is mainly due to a lack of understanding the mechanisms of movement control, network activity and plasticity in motor circuits, in particular between the cerebral cortex and the striatum. Brain-derived neurotrophic factor (BDNF) has emerged as one of the most important factors for the development and survival of neurons, as well as for synaptic plasticity. It is thus an important target for the development of new therapeutic strategies against neurodegenerative diseases. Together with its receptor, the Tropomyosin receptor kinase B (TrkB), it is critically involved in development and function of the striatum. Nevertheless, little is known about the localization of BDNF within presynaptic terminals in the striatum, as well as the types of neurons that produce BDNF in the cerebral cortex. Furthermore, the influence of midbrain derived dopamine on the control of BDNF / TrkB interaction in striatal medium spiny neurons (MSNs) remains elusive so far. Dopamine, however, appears to play an important role, as its absence leads to drastic changes in striatal synaptic plasticity. This suggests that dopamine could regulate synaptic activity in the striatum via modulation of BDNF / TrkB function. To answer these questions, we have developed a sensitive and reliable protocol for the immunohistochemical detection of endogenous BDNF. We find that the majority of striatal BDNF is provided by glutamatergic, cortex derived afferents and not dopaminergic inputs from the midbrain. In fact, we found BDNF in cell bodies of neurons in layers II-III and V of the primary and secondary motor cortex as well as layer V of the somatosensory cortex. These are the brain areas that send dense projections to the dorsolateral striatum for control of voluntary movement. Furthermore, we could show that these projection neurons significantly downregulate the expression of BDNF during the juvenile development of mice between 3 and 12 weeks. In parallel, we found a modulatory effect of dopamine on the translocation of TrkB to the cell surface in postsynaptic striatal Medium Spiny Neurons (MSNs). In MSNs of the direct pathway (dMSNs), which express dopamine receptor 1 (DRD1), we observed the formation of TrkB aggregates in the 6-hydroxydopamine (6-OHDA) model of PD. This suggests that DRD1 activity controls TrkB surface expression in these neurons. In contrast, we found that DRD2 activation has opposite effects in MSNs of the indirect pathway (iMSNs). Activation of DRD2 promotes a rapid decrease in TrkB surface expression which was reversible and depended on cAMP. In parallel, stimulation of DRD2 led to induction of phospho-TrkB (pTrkB). This effect was significantly slower than the effect on TrkB surface expression and indicates that TrkB is transactivated by DRD2. Together, our data provide evidence that dopamine triggers dual modes of plasticity on striatal MSNs by acting on TrkB surface expression in DRD1 and DRD2 expressing MSNs. This surface expression of the receptor is crucial for the binding of BDNF, which is released from corticostriatal afferents. This leads to the induction of TrkB-mediated downstream signal transduction cascades and long-term potentiation (LTP). Therefore, the dopamine-mediated translocation of TrkB could be a mediator that modulates the balance between dopaminergic and glutamatergic signaling to allow synaptic plasticity in a spatiotemporal manner. This information and the fact that TrkB is segregated to persistent aggregates in PD could help to improve our understanding of voluntary movement control and to develop new therapeutic strategies beyond those focusing on dopaminergic supply.},
  subject      = {Brain-derived neurotrophic factor},
  language  = {en}
}
@article{AlbertWeissenbergerVarrallyayRaslanetal.2012,
  author    = {Albert-Weißenberger, Christiane and V{\´a}rrallyay, Csan{\´a}d and Raslan, Furat and Kleinschnitz, Christoph and Sir{\´e}n, Anna-Leena},
  title     = {An experimental protocol for mimicking pathomechanisms of traumatic brain injury in mice},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75368},
  year      = {2012},
  abstract  = {Traumatic brain injury (TBI) is a result of an outside force causing immediate mechanical disruption of brain tissue and delayed pathogenic events. In order to examine injury processes associated with TBI, a number of rodent models to induce brain trauma have been described. However, none of these models covers the entire spectrum of events that might occur in TBI. Here we provide a thorough methodological description of a straightforward closed head weight drop mouse model to assess brain injuries close to the clinical conditions of human TBI.},
  subject      = {Medizin},
  language  = {en}
}
@article{AlbertWeissenbergerStetterMeuthetal.2012,
  author    = {Albert-Weissenberger, Christiane and Stetter, Christian and Meuth, Sven G. and G{\"o}bel, Kerstin and Bader, Michael and Sir{\´e}n, Anna-Leena and Kleinschnitz, Christoph},
  title     = {Blocking of Bradykinin Receptor B1 Protects from Focal Closed Head Injury in Mice by Reducing Axonal Damage and Astroglia Activation},
  series = {Journal of Cerebral Blood Flow and Metabolism},
  volume    = {32},
  journal   = {Journal of Cerebral Blood Flow and Metabolism},
  number    = {9},
  doi       = {10.1038/jcbfm.2012.62},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125903},
  pages     = {1747-1756},
  year      = {2012},
  abstract  = {The two bradykinin receptors B1R and B2R are central components of the kallikrein-kinin system with different expression kinetics and binding characteristics. Activation of these receptors by kinins triggers inflammatory responses in the target organ and in most situations enhances tissue damage. We could recently show that blocking of B1R, but not B2R, protects from cortical cryolesion by reducing inflammation and edema formation. In the present study, we investigated the role of B1R and B2R in a closed head model of focal traumatic brain injury (TBI; weight drop). Increased expression of B1R in the injured hemispheres of wild-type mice was restricted to the later stages after brain trauma, i.e. day 7 (P<0.05), whereas no significant induction could be observed for the B2R (P>0.05). Mice lacking the B1R, but not the B2R, showed less functional deficits on day 3 (P<0.001) and day 7 (P<0.001) compared with controls. Pharmacological blocking of B1R in wild-type mice had similar effects. Reduced axonal injury and astroglia activation could be identified as underlying mechanisms, while inhibition of B1R had only little influence on the local inflammatory response in this model. Inhibition of B1R may become a novel strategy to counteract trauma-induced neurodegeneration.},
  language  = {en}
}
@article{AlbertWeissenbergerMenclSchuhmannetal.2014,
  author    = {Albert-Weissenberger, Christiane and Mencl, Stine and Schuhmann, Michael K. and Salur, Irmak and G{\"o}b, Eva and Langhauser, Friederike and Hopp, Sarah and Hennig, Nelli and Meuth, Sven G. and Nolte, Marc W. and Sir{\´e}n, Anna-Leena and Kleinschnitz, Christoph},
  title     = {C1-Inhibitor protects from focal brain trauma in a cortical cryolesion mice model by reducing thrombo-inflammation},
  series = {Frontiers in Cellular Neuroscience},
  volume    = {8},
  journal   = {Frontiers in Cellular Neuroscience},
  issn      = {1662-5102},
  doi       = {10.3389/fncel.2014.00269},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119263},
  pages     = {269},
  year      = {2014},
  abstract  = {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.},
  language  = {en}
}
@article{AlbertWeissenbergerMenclHoppetal.2014,
  author    = {Albert-Weissenberger, Christiane and Mencl, Stine and Hopp, Sarah and Kleinschnitz, Christoph and Siren, Anna-Leena},
  title     = {Role of the kallikrein-kinin system in traumatic brain injury},
  series = {Frontiers in Cellular Neuroscience},
  volume    = {8},
  journal   = {Frontiers in Cellular Neuroscience},
  issn      = {1662-5102},
  doi       = {10.3389/fncel.2014.00345},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118226},
  pages     = {345},
  year      = {2014},
  abstract  = {Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Despite improvements in acute intensive care, there are currently no specific therapies to ameliorate the effects of TBI. Successful therapeutic strategies for TBI should target multiple pathophysiologic mechanisms that occur at different stages of brain injury. The kallikrein-kinin system is a promising therapeutic target for TBI as it mediates key pathologic events of traumatic brain damage, such as edema formation, inflammation, and thrombosis. Selective and specific kinin receptor antagonists and inhibitors of plasma kallikrein and coagulation factor XII have been developed, and have already shown therapeutic efficacy in animal models of stroke and TBI. However, conflicting preclinical evaluation, as well as limited and inconclusive data from clinical trials in TBI, suggests that caution should be taken before transferring observations made in animals to humans. This review summarizes current evidence on the pathologic significance of the kallikrein-kinin system during TBI in animal models and, where available, the experimental findings are compared with human data.},
  language  = {en}
}
@article{AblinFitzcharlesBuskilaetal.2013,
  author    = {Ablin, Jacob and Fitzcharles, Mary-Ann and Buskila, Dan and Shir, Yoram and Sommer, Claudia and H{\"a}user, Winfried},
  title     = {Treatment of Fibromyalgia Syndrome: Recommendations of Recent Evidence-Based Interdisciplinary Guidelines with Special Emphasis on Complementary and Alternative Therapies},
  series = {Evidence-Bayed Complementary and Alternative Medicine},
  journal   = {Evidence-Bayed Complementary and Alternative Medicine},
  issn      = {1741-427X},
  doi       = {10.1155/2013/485272},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122235},
  pages     = {485272},
  year      = {2013},
  abstract  = {Objective. Current evidence indicates that there is no single ideal treatment for fibromyalgia syndrome (FMS). First choice treatment options remain debatable, especially concerning the importance of complementary and alternative medicine (CAM) treatments. Methods. Three evidence-based interdisciplinary guidelines on FMS in Canada, Germany, and Israel were compared for their first choice and CAM-recommendations. Results. All three guidelines emphasized a patient-tailored approach according to the key symptoms. Aerobic exercise, cognitive behavioral therapy, and multicomponent therapy were first choice treatments. The guidelines differed in the grade of recommendation for drug treatment. Anticonvulsants (gabapentin, pregabalin) and serotonin noradrenaline reuptake inhibitors (duloxetine, milnacipran) were strongly recommended by the Canadian and the Israeli guidelines. These drugs received only a weak recommendation by the German guideline. In consideration of CAM-treatments, acupuncture, hypnosis/guided imagery, and Tai Chi were recommended by the German and Israeli guidelines. The Canadian guidelines did not recommend any CAM therapy. Discussion. Recent evidence-based interdisciplinary guidelines concur on the importance of treatment tailored to the individual patient and further emphasize the need of self-management strategies (exercise, and psychological techniques).},
  language  = {en}
}