@article{WagenhaeuserRickertSommeretal.2022,
  author    = {Wagenh{\"a}user, Laura and Rickert, Vanessa and Sommer, Claudia and Wanner, Christoph and Nordbeck, Peter and Rost, Simone and {\"U}{\c{c}}eyler, Nurcan},
  title     = {X-chromosomal inactivation patterns in women with Fabry disease},
  series = {Molecular Genetics \& Genomic Medicine},
  volume    = {10},
  journal   = {Molecular Genetics \& Genomic Medicine},
  number    = {9},
  doi       = {10.1002/mgg3.2029},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312795},
  year      = {2022},
  abstract  = {Background Although Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene (GLA), women may develop severe symptoms. We investigated X-chromosomal inactivation patterns (XCI) as a potential determinant of symptom severity in FD women. Patients and Methods We included 95 women with mutations in GLA (n = 18 with variants of unknown pathogenicity) and 50 related men, and collected mouth epithelial cells, venous blood, and skin fibroblasts for XCI analysis using the methylation status of the androgen receptor gene. The mutated X-chromosome was identified by comparison of samples from relatives. Patients underwent genotype categorization and deep clinical phenotyping of symptom severity. Results 43/95 (45\%) women carried mutations categorized as classic. The XCI pattern was skewed (i.e., ≥75:25\% distribution) in 6/87 (7\%) mouth epithelial cell samples, 31/88 (35\%) blood samples, and 9/27 (33\%) skin fibroblast samples. Clinical phenotype, α-galactosidase A (GAL) activity, and lyso-Gb3 levels did not show intergroup differences when stratified for X-chromosomal skewing and activity status of the mutated X-chromosome. Conclusions X-inactivation patterns alone do not reliably reflect the clinical phenotype of women with FD when investigated in biomaterial not directly affected by FD. However, while XCI patterns may vary between tissues, blood frequently shows skewing of XCI patterns.},
  language  = {en}
}
@article{KraftDrechslerGunrebenetal.2014,
  author    = {Kraft, Peter and Drechsler, Christiane and Gunreben, Ignaz and Nieswandt, Bernhard and Stoll, Guido and Heuschmann, Peter Ulrich and Kleinschnitz, Christoph},
  title     = {Von Willebrand Factor Regulation in Patients with Acute and Chronic Cerebrovascular Disease: A Pilot, Case-Control Study},
  series = {PLoS ONE},
  volume    = {9},
  journal   = {PLoS ONE},
  number    = {6},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0099851},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119588},
  pages     = {e99851},
  year      = {2014},
  abstract  = {Background and Purpose In animal models, von Willebrand factor (VWF) is involved in thrombus formation and propagation of ischemic stroke. However, the pathophysiological relevance of this molecule in humans, and its potential use as a biomarker for the risk and severity of ischemic stroke remains unclear. This study had two aims: to identify predictors of altered VWF levels and to examine whether VWF levels differ between acute cerebrovascular events and chronic cerebrovascular disease (CCD). Methods A case-control study was undertaken between 2010 and 2013 at our University clinic. In total, 116 patients with acute ischemic stroke (AIS) or transitory ischemic attack (TIA), 117 patients with CCD, and 104 healthy volunteers (HV) were included. Blood was taken at days 0, 1, and 3 in patients with AIS or TIA, and once in CCD patients and HV. VWF serum levels were measured and correlated with demographic and clinical parameters by multivariate linear regression and ANOVA. Results Patients with CCD (158±46\%) had significantly higher VWF levels than HV (113±36\%, P<0.001), but lower levels than AIS/TIA patients (200±95\%, P<0.001). Age, sex, and stroke severity influenced VWF levels (P<0.05). Conclusions VWF levels differed across disease subtypes and patient characteristics. Our study confirms increased VWF levels as a risk factor for cerebrovascular disease and, moreover, suggests that it may represent a potential biomarker for stroke severity, warranting further investigation.},
  language  = {en}
}
@article{CapetianMuellerVolkmannetal.2020,
  author    = {Capetian, Philipp and M{\"u}ller, Lorenz and Volkmann, Jens and Heckmann, Manfred and Erg{\"u}n, S{\"u}leyman and Wagner, Nicole},
  title     = {Visualizing the synaptic and cellular ultrastructure in neurons differentiated from human induced neural stem cells - an optimized protocol},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {5},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21051708},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236053},
  year      = {2020},
  abstract  = {The size of the synaptic subcomponents falls below the limits of visible light microscopy. Despite new developments in advanced microscopy techniques, the resolution of transmission electron microscopy (TEM) remains unsurpassed. The requirements of tissue preservation are very high, and human post mortem material often does not offer adequate quality. However, new reprogramming techniques that generate human neurons in vitro provide samples that can easily fulfill these requirements. The objective of this study was to identify the culture technique with the best ultrastructural preservation in combination with the best embedding and contrasting technique for visualizing neuronal elements. Two induced neural stem cell lines derived from healthy control subjects underwent differentiation either adherent on glass coverslips, embedded in a droplet of highly concentrated Matrigel, or as a compact neurosphere. Afterward, they were fixed using a combination of glutaraldehyde (GA) and paraformaldehyde (PFA) followed by three approaches (standard stain, Ruthenium red stain, high contrast en-bloc stain) using different combinations of membrane enhancing and contrasting steps before ultrathin sectioning and imaging by TEM. The compact free-floating neurospheres exhibited the best ultrastructural preservation. High-contrast en-bloc stain offered particularly sharp staining of membrane structures and the highest quality visualization of neuronal structures. In conclusion, compact neurospheres growing under free-floating conditions in combination with a high contrast en-bloc staining protocol, offer the optimal preservation and contrast with a particular focus on visualizing membrane structures as required for analyzing synaptic structures.},
  language  = {en}
}
@article{IpWischhusen2023,
  author    = {Ip, Chi Wang and Wischhusen, J{\"o}rg},
  title     = {Versatile guardians: regenerative regulatory T cells in Parkinson's disease rodent models},
  series = {Signal Transduction and Targeted Therapy},
  volume    = {8},
  journal   = {Signal Transduction and Targeted Therapy},
  doi       = {10.1038/s41392-023-01681-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357674},
  year      = {2023},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{KrajkaNaujockPaulyetal.2021,
  author    = {Krajka, Victor and Naujock, Maximilian and Pauly, Martje G. and Stengel, Felix and Meier, Britta and Stanslowsky, Nancy and Klein, Christine and Seibler, Philip and Wegner, Florian and Capetian, Philipp},
  title     = {Ventral Telencephalic Patterning Protocols for Induced Pluripotent Stem Cells},
  series = {Frontiers in Cell and Developmental Biology},
  volume    = {9},
  journal   = {Frontiers in Cell and Developmental Biology},
  issn      = {2296-634X},
  doi       = {10.3389/fcell.2021.716249},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244607},
  year      = {2021},
  abstract  = {The differentiation of human induced pluripotent stem cells (hiPSCs) into specific cell types for disease modeling and restorative therapies is a key research agenda and offers the possibility to obtain patient-specific cells of interest for a wide range of diseases. Basal forebrain cholinergic neurons (BFCNs) play a particular role in the pathophysiology of Alzheimer's dementia and isolated dystonias. In this work, various directed differentiation protocols based on monolayer neural induction were tested for their effectiveness in promoting a ventral telencephalic phenotype and generating BFCN. Ventralizing factors [i.e., purmorphamine and Sonic hedgehog (SHH)] were applied at different time points, time intervals, and concentrations. In addition, caudal identity was prevented by the use of a small molecule XAV-939 that inhibits the Wnt-pathway. After patterning, gene expression profiles were analyzed by quantitative PCR (qPCR). Rostro-ventral patterning is most effective when initiated simultaneously with neural induction. The most promising combination of patterning factors was 0.5 μM of purmorphamine and 1 μM of XAV-939, which induces the highest expression of transcription factors specific for the medial ganglionic eminence, the source of GABAergic inter- and cholinergic neurons in the telencephalon. Upon maturation of cells, the immune phenotype, as well as electrophysiological properties were investigated showing the presence of marker proteins specific for BFCN (choline acetyltransferase, ISL1, p75, and NKX2.1) and GABAergic neurons. Moreover, a considerable fraction of measured cells displayed mature electrophysiological properties. Synaptic boutons containing the vesicular acetylcholine transporter (VACHT) could be observed in the vicinity of the cells. This work will help to generate basal forebrain interneurons from hiPSCs, providing a promising platform for modeling neurological diseases, such as Alzheimer's disease or Dystonia.},
  language  = {en}
}
@article{HaarmannVollmuthKollikowskietal.2023,
  author    = {Haarmann, Axel and Vollmuth, Christoph and Kollikowski, Alexander M. and Heuschmann, Peter U. and Pham, Mirko and Stoll, Guido and Neugebauer, Hermann and Schuhmann, Michael K.},
  title     = {Vasoactive soluble endoglin: a novel biomarker indicative of reperfusion after cerebral large-vessel occlusion},
  series = {Cells},
  volume    = {12},
  journal   = {Cells},
  number    = {2},
  issn      = {2073-4409},
  doi       = {10.3390/cells12020288},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304995},
  year      = {2023},
  abstract  = {Now that mechanical thrombectomy has substantially improved outcomes after large-vessel occlusion stroke in up to every second patient, futile reperfusion wherein successful recanalization is not followed by a favorable outcome is moving into focus. Unfortunately, blood-based biomarkers, which identify critical stages of hemodynamically compromised yet reperfused tissue, are lacking. We recently reported that hypoxia induces the expression of endoglin, a TGF-β co-receptor, in human brain endothelium in vitro. Subsequent reoxygenation resulted in shedding. Our cell model suggests that soluble endoglin compromises the brain endothelial barrier function. To evaluate soluble endoglin as a potential biomarker of reperfusion (-injury) we analyzed its concentration in 148 blood samples of patients with acute stroke due to large-vessel occlusion. In line with our in vitro data, systemic soluble endoglin concentrations were significantly higher in patients with successful recanalization, whereas hypoxia alone did not induce local endoglin shedding, as analyzed by intra-arterial samples from hypoxic vasculature. In patients with reperfusion, higher concentrations of soluble endoglin additionally indicated larger infarct volumes at admission. In summary, we give translational evidence that the sequence of hypoxia and subsequent reoxygenation triggers the release of vasoactive soluble endoglin in large-vessel occlusion stroke and can serve as a biomarker for severe ischemia with ensuing recanalization/reperfusion.},
  language  = {en}
}
@article{KunzePhamRaslanetal.2012,
  author    = {Kunze, Ekkehard and Pham, Mirko and Raslan, Furat and Stetter, Christian and Lee, Jin-Yul and Solymosi, Laszlo and Ernestus, Ralf-Ingo and Hamilton Vince, Giles and Westermaier, Thomas},
  title     = {Value of Perfusion CT, Transcranial Doppler Sonography and Neurological Examination to detect delayed Vasospasm after aneurysmal Subarachnoid Hemorrhage [Research Article]},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76241},
  year      = {2012},
  abstract  = {Background If detected in time, delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) may be treated by balloon angioplasty or chemical vasospasmolysis in order to enhance cerebral blood flow (CBF) and protect the brain from ischemic damage. This study was conceived to compare the diagnostic accuracy of detailed neurological examination, Transcranial Doppler Sonography (TCD), and Perfusion-CT (PCT) to detect angiographic vasospasm. Methods The sensitivity, specificity, positive and negative predictive values of delayed ischemic neurological deterioration (DIND), pathological findings on PCT- maps, and accelerations of the mean flow velocity (MVF) were calculated. Results The accuracy of DIND to predict angiographic vasospasm was 0.88. An acceleration of MFV in TCD (>140 cm/s) had an accuracy of 0.64, positive PCT-findings of 0.69 with a higher sensitivity, and negative predictive value than TCD. Interpretation Neurological assessment at close intervals is the most sensitive and specific parameter for cerebral vasospasm. PCT has a higher accuracy, sensitivity and negative predictive value than TCD. If detailed neurological evaluation is possible, it should be the leading parameter in the management and treatment decisions. If patients are not amenable to detailed neurological examination, PCT at regular intervals is a helpful tool to diagnose secondary vasospasm after aneurysmal SAH.},
  subject      = {Medizin},
  language  = {en}
}
@article{FrankeBieberStolletal.2021,
  author    = {Franke, Maximilian and Bieber, Michael and Stoll, Guido and Schuhmann, Michael Klaus},
  title     = {Validity and Efficacy of Methods to Define Blood Brain Barrier Integrity in Experimental Ischemic Strokes: A Comparison of Albumin Western Blot, IgG Western Blot and Albumin Immunofluorescence},
  series = {Methods and Protocols},
  volume    = {4},
  journal   = {Methods and Protocols},
  number    = {1},
  issn      = {2409-9279},
  doi       = {10.3390/mps4010023},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234214},
  year      = {2021},
  abstract  = {The clinical and preclinical research of ischemic strokes (IS) is becoming increasingly comprehensive, especially with the emerging evidence of complex thrombotic and inflammatory interactions. Within these, the blood brain barrier (BBB) plays an important role in regulating the cellular interactions at the vascular interface and is therefore the object of many IS-related questions. Consequently, valid, economic and responsible methods to define BBB integrity are necessary. Therefore, we compared the three ex-vivo setups albumin Western blot (WB), IgG WB and albumin intensity measurement (AIM) with regard to validity as well as temporal and economic efficacy. While the informative value of the three methods correlated significantly, the efficacy of the IgG WB dominated.},
  language  = {en}
}
@article{SilwedelHuettenSpeeretal.2023,
  author    = {Silwedel, Christine and H{\"u}tten, Matthias C. and Speer, Christian P. and H{\"a}rtel, Christoph and Haarmann, Axel and Henrich, Birgit and Tijssen, Maud P. M. and Alnakhli, Abdullah Ahmed and Spiller, Owen B. and Schlegel, Nicolas and Seidenspinner, Silvia and Kramer, Boris W. and Glaser, Kirsten},
  title     = {Ureaplasma-driven neonatal neuroinflammation: novel insights from an ovine model},
  series = {Cellular and Molecular Neurobiology},
  volume    = {43},
  journal   = {Cellular and Molecular Neurobiology},
  number    = {2},
  doi       = {10.1007/s10571-022-01213-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324285},
  pages     = {785-795},
  year      = {2023},
  abstract  = {Ureaplasma species (spp.) are considered commensals of the adult genitourinary tract, but have been associated with chorioamnionitis, preterm birth, and invasive infections in neonates, including meningitis. Data on mechanisms involved in Ureaplasma-driven neuroinflammation are scarce. The present study addressed brain inflammatory responses in preterm lambs exposed to Ureaplasma parvum (UP) in utero. 7 days after intra-amniotic injection of UP (n = 10) or saline (n = 11), lambs were surgically delivered at gestational day 128-129. Expression of inflammatory markers was assessed in different brain regions using qRT-PCR and in cerebrospinal fluid (CSF) by multiplex immunoassay. CSF was analyzed for UP presence using ureB-based real-time PCR, and MRI scans documented cerebral white matter area and cortical folding. Cerebral tissue levels of atypical chemokine receptor (ACKR) 3, caspases 1-like, 2, 7, and C-X-C chemokine receptor (CXCR) 4 mRNA, as well as CSF interleukin-8 protein concentrations were significantly increased in UP-exposed lambs. UP presence in CSF was confirmed in one animal. Cortical folding and white matter area did not differ among groups. The present study confirms a role of caspases and the transmembrane receptors ACKR3 and CXCR4 in Ureaplasma-driven neuroinflammation. Enhanced caspase 1-like, 2, and 7 expression may reflect cell death. Increased ACKR3 and CXCR4 expression has been associated with inflammatory central nervous system (CNS) diseases and impaired blood-brain barrier function. According to these data and previous in vitro findings from our group, we speculate that Ureaplasma-induced caspase and receptor responses affect CNS barrier properties and thus facilitate neuroinflammation.},
  language  = {en}
}
@article{SilwedelSpeerHaarmannetal.2019,
  author    = {Silwedel, Christine and Speer, Christian P. and Haarmann, Axel and Fehrholz, Markus and Claus, Heike and Schlegel, Nicolas and Glaser, Kirsten},
  title     = {Ureaplasma species modulate cytokine and chemokine responses in human brain microvascular endothelial cells},
  series = {International Journal of Molecular Science},
  volume    = {20},
  journal   = {International Journal of Molecular Science},
  number    = {14},
  issn      = {1422-0067},
  doi       = {10.3390/ijms20143583},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201848},
  year      = {2019},
  abstract  = {Ureaplasma species are common colonizers of the adult genitourinary tract and often considered as low-virulence commensals. Intraamniotic Ureaplasma infections, however, facilitate chorioamnionitis and preterm birth, and cases of Ureaplasma-induced neonatal sepsis, pneumonia, and meningitis raise a growing awareness of their clinical relevance. In vitro studies are scarce but demonstrate distinct Ureaplasma-driven impacts on immune mechanisms. The current study addressed cytokine and chemokine responses upon exposure of native or lipopolysaccharide (LPS) co-stimulated human brain microvascular endothelial cells (HBMEC) to Ureaplasma urealyticum or U. parvum, using qRT-PCR, RNA sequencing, multi-analyte immunoassay, and flow cytometry. Ureaplasma exposure in native HBMEC reduced monocyte chemoattractant protein (MCP)-3 mRNA expression (p < 0.01, vs. broth). In co-stimulated HBMEC, Ureaplasma spp. attenuated LPS-evoked mRNA responses for C-X-C chemokine ligand 5, MCP-1, and MCP-3 (p < 0.05, vs. LPS) and mitigated LPS-driven interleukin (IL)-1α protein secretion, as well as IL-8 mRNA and protein responses (p < 0.05). Furthermore, Ureaplasma isolates increased C-X-C chemokine receptor 4 mRNA levels in native and LPS co-stimulated HBMEC (p < 0.05). The presented results may imply immunomodulatory capacities of Ureaplasma spp. which may ultimately promote chronic colonization and long-term neuroinflammation.},
  language  = {en}
}
@article{ContarinoSmitvandenDooletal.2016,
  author    = {Contarino, Maria Fiorella and Smit, Marenka and van den Dool, Joost and Volkmann, Jens and Tijssen, Marina A. J.},
  title     = {Unmet Needs in the Management of Cervical Dystonia},
  series = {Frontiers in Neurology},
  volume    = {7},
  journal   = {Frontiers in Neurology},
  number    = {165},
  doi       = {10.3389/fneur.2016.00165},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165225},
  year      = {2016},
  abstract  = {Cervical dystonia (CD) is a movement disorder which affects daily living of many patients. In clinical practice, several unmet treatment needs remain open. This article focuses on the four main aspects of treatment. We describe existing and emerging treatment approaches for CD, including botulinum toxin injections, surgical therapy, management of non-motor symptoms, and rehabilitation strategies. The unsolved issues regarding each of these treatments are identified and discussed, and possible future approaches and research lines are proposed.},
  language  = {en}
}
@article{GabrielJirůHillmannKraftetal.2020,
  author    = {Gabriel, Katharina M. A. and J{\´i}rů-Hillmann, Steffi and Kraft, Peter and Selig, Udo and R{\"u}cker, Victoria and M{\"u}hler, Johannes and D{\"o}tter, Klaus and Keidel, Matthias and Soda, Hassan and Rascher, Alexandra and Schneider, Rolf and Pfau, Mathias and Hoffmann, Roy and Stenzel, Joachim and Benghebrid, Mohamed and Goebel, Tobias and Doerck, Sebastian and Kramer, Daniela and Haeusler, Karl Georg and Volkmann, Jens and Heuschmann, Peter U. and Fluri, Felix},
  title     = {Two years' experience of implementing a comprehensive telemedical stroke network comprising in mainly rural region: the Transregional Network for Stroke Intervention with Telemedicine (TRANSIT-Stroke)},
  series = {BMC Neurology},
  volume    = {20},
  journal   = {BMC Neurology},
  doi       = {10.1186/s12883-020-01676-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229214},
  year      = {2020},
  abstract  = {Background Telemedicine improves the quality of acute stroke care in rural regions with limited access to specialized stroke care. We report the first 2 years' experience of implementing a comprehensive telemedical stroke network comprising all levels of stroke care in a defined region. Methods The TRANSIT-Stroke network covers a mainly rural region in north-western Bavaria (Germany). All hospitals providing acute stroke care in this region participate in TRANSIT-Stroke, including four hospitals with a supra-regional certified stroke unit (SU) care (level III), three of those providing teleconsultation to two hospitals with a regional certified SU (level II) and five hospitals without specialized SU care (level I). For a two-year-period (01/2015 to 12/2016), data of eight of these hospitals were available; 13 evidence-based quality indicators (QIs) related to processes during hospitalisation were evaluated quarterly and compared according to predefined target values between level-I- and level-II/III-hospitals. Results Overall, 7881 patients were included (mean age 74.6 years +/- 12.8; 48.4\% female). In level-II/III-hospitals adherence of all QIs to predefined targets was high ab initio. In level-I-hospitals, three patterns of QI-development were observed: a) high adherence ab initio (31\%), mainly in secondary stroke prevention; b) improvement over time (44\%), predominantly related to stroke specific diagnosis and in-hospital organization; c) no clear time trends (25\%). Overall, 10 out of 13 QIs reached predefined target values of quality of care at the end of the observation period. Conclusion The implementation of the comprehensive TRANSIT-Stroke network resulted in an improvement of quality of care in level-I-hospitals.},
  language  = {en}
}
@article{EhlingBittnerBobaketal.2010,
  author    = {Ehling, P. and Bittner, S. and Bobak, N. and Schwarz, T. and Wiendl, H. and Budde, T. and Kleinschnitz, Christoph and Meuth, S. G.},
  title     = {Two pore domain potassium channels in cerebral ischemia: a focus on K2p9.1 (TASK3, KCNK9)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68129},
  year      = {2010},
  abstract  = {BACKGROUND: Recently, members of the two-pore domain potassium channel family (K2P channels) could be shown to be involved in mechanisms contributing to neuronal damage after cerebral ischemia. K2P3.1-/- animals showed larger infarct volumes and a worse functional outcome following experimentally induced ischemic stroke. Here, we question the role of the closely related K2P channel K2P9.1. METHODS: We combine electrophysiological recordings in brain-slice preparations of wildtype and K2P9.1-/- mice with an in vivo model of cerebral ischemia (transient middle cerebral artery occlusion (tMCAO)) to depict a functional impact of K2P9.1 in stroke formation. RESULTS: Patch-clamp recordings reveal that currents mediated through K2P9.1 can be obtained in slice preparations of the dorsal lateral geniculate nucleus (dLGN) as a model of central nervous relay neurons. Current characteristics are indicative of K2P9.1 as they display an increase upon removal of extracellular divalent cations, an outward rectification and a reversal potential close to the potassium equilibrium potential. Lowering extracellular pH values from 7.35 to 6.0 showed comparable current reductions in neurons from wildtype and K2P9.1-/- mice (68.31 +/- 9.80\% and 69.92 +/- 11.65\%, respectively). These results could be translated in an in vivo model of cerebral ischemia where infarct volumes and functional outcomes showed a none significant tendency towards smaller infarct volumes in K2P9.1-/- animals compared to wildtype mice 24 hours after 60 min of tMCAO induction (60.50 +/- 17.31 mm3 and 47.10 +/- 19.26 mm3, respectively). CONCLUSIONS: Together with findings from earlier studies on K2P2.1-/- and K2P3.1-/- mice, the results of the present study on K2P9.1-/- mice indicate a differential contribution of K2P channel subtypes to the diverse and complex in vivo effects in rodent models of cerebral ischemia.},
  subject      = {Kaliumkanal},
  language  = {en}
}
@article{PozziPalmisanoReichetal.2022,
  author    = {Pozzi, Nicol{\´o} G. and Palmisano, Chiara and Reich, Martin M. and Capetian, Philip and Pacchetti, Claudio and Volkmann, Jens and Isaias, Ioannis U.},
  title     = {Troubleshooting gait disturbances in Parkinson's disease with deep brain stimulation},
  series = {Frontiers in Human Neuroscience},
  volume    = {16},
  journal   = {Frontiers in Human Neuroscience},
  issn      = {1662-5161},
  doi       = {10.3389/fnhum.2022.806513},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-274007},
  year      = {2022},
  abstract  = {Deep brain stimulation (DBS) of the subthalamic nucleus or the globus pallidus is an established treatment for Parkinson's disease (PD) that yields a marked and lasting improvement of motor symptoms. Yet, DBS benefit on gait disturbances in PD is still debated and can be a source of dissatisfaction and poor quality of life. Gait disturbances in PD encompass a variety of clinical manifestations and rely on different pathophysiological bases. While gait disturbances arising years after DBS surgery can be related to disease progression, early impairment of gait may be secondary to treatable causes and benefits from DBS reprogramming. In this review, we tackle the issue of gait disturbances in PD patients with DBS by discussing their neurophysiological basis, providing a detailed clinical characterization, and proposing a pragmatic programming approach to support their management.},
  language  = {en}
}
@article{CruccuPennisiAntoninietal.2014,
  author    = {Cruccu, Giorgio and Pennisi, Elena M. and Antonini, Giovanni and Biasiotta, Antonella and Di Stefano, Giulia and La Cesa, Silvia and Leone, Caterina and Raffa, Salvatore and Sommer, Claudia and Truini, Andrea},
  title     = {Trigeminal isolated sensory neuropathy (TISN) and FOSMN syndrome: despite a dissimilar disease course do they share common pathophysiological mechanisms?},
  series = {BMC Neurology},
  volume    = {14},
  journal   = {BMC Neurology},
  issn      = {1471-2377},
  doi       = {10.1186/s12883-014-0248-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114249},
  year      = {2014},
  abstract  = {Background: Patients presenting with bilateral trigeminal hypoesthesia may go on to have trigeminal isolated sensory neuropathy, a benign, purely trigeminal neuropathy, or facial-onset sensory motor neuronopathy (FOSMN), a malignant life-threatening condition. No diagnostic criteria can yet differentiate the two conditions at their onset. Nor is it clear whether the two diseases are distinct entities or share common pathophysiological mechanisms. Methods: Seeking pathophysiological and diagnostic information to distinguish these two conditions at their onset, in this neurophysiological and morphometric study we neurophysiologically assessed function in myelinated and unmyelinated fibres and histologically examined supraorbital nerve biopsy specimens with optic and electron microscopy in 13 consecutive patients with recent onset trigeminal hypoesthesia and pain. Results: The disease course distinctly differed in the 13 patients. During a mean 10 year follow-up whereas in eight patients the disease remained relatively stable, in the other five it progressed to possibly life-threatening motor disturbances and extra-trigeminal spread. From two to six years elapsed between the first sensory symptoms and the onset of motor disorders. In patients with trigeminal isolated sensory neuropathy (TISN) and in those with FOSMN neurophysiological and histological examination documented a neuronopathy manifesting with trigeminal nerve damage selectively affecting myelinated fibres, but sparing the Ia-fibre-mediated proprioceptive reflex. Conclusions: Although no clinical diagnostic criteria can distinguish the two conditions at onset, neurophysiological and nerve-biopsy findings specify that in both disorders trigeminal nerve damage manifests as a dissociated neuronopathy affecting myelinated and sparing unmyelinated fibres, thus suggesting similar pathophysiological mechanisms.},
  language  = {en}
}
@article{GesslerLehmannBoeseletal.2021,
  author    = {Gessler, Florian and Lehmann, Felix and B{\"o}sel, Julian and Fuhrer, Hannah and Neugebauer, Hermann and Wartenberg, Katja E. and Wolf, Stefan and Bernstock, Joshua D. and Niesen, Wolf-Dirk and Schuss, Patrick},
  title     = {Triage and Allocation of Neurocritical Care Resources During the COVID 19 Pandemic - A National Survey},
  series = {Frontiers in Neurology},
  volume    = {11},
  journal   = {Frontiers in Neurology},
  issn      = {1664-2295},
  doi       = {10.3389/fneur.2020.609227},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221593},
  year      = {2021},
  abstract  = {Objective: In light of the ongoing COVID-19 pandemic and the associated hospitalization of an overwhelming number of ventilator-dependent patients, medical and/or ethical patient triage paradigms have become essential. While guidelines on the allocation of scarce resources do exist, such work within the subdisciplines of intensive care (e.g., neurocritical care) remains limited. Methods: A 16-item questionnaire was developed that sought to explore/quantify the expert opinions of German neurointensivists with regard to triage decisions. The anonymous survey was conducted via a web-based platform and in total, 96 members of the Initiative of German Neurointensive Trial Engagement (IGNITE)-study group were contacted via e-mail. The IGNITE consortium consists of an interdisciplinary panel of specialists with expertise in neuro-critical care (i.e., anesthetists, neurologists and neurosurgeons). Results: Fifty members of the IGNITE consortium responded to the questionnaire; in total the respondents were in charge of more than 500 Neuro ICU beds throughout Germany. Common determinants reported which affected triage decisions included known patient wishes (98\%), the state of health before admission (96\%), SOFA-score (85\%) and patient age (69\%). Interestingly, other principles of allocation, such as a treatment of "youngest first" (61\%) and members of the healthcare sector (50\%) were also noted. While these were the most accepted parameters affecting the triage of patients, a "first-come, first-served" principle appeared to be more accepted than a lottery for the allocation of ICU beds which contradicts much of what has been reported within the literature. The respondents also felt that at least one neurointensivist should serve on any interdisciplinary triage team. Conclusions: The data gathered in the context of this survey reveal the estimation/perception of triage algorithms among neurointensive care specialists facing COVID-19. Further, it is apparent that German neurointensivists strongly feel that they should be involved in any triage decisions at an institutional level given the unique resources needed to treat patients within the Neuro ICU.},
  language  = {en}
}
@article{BaumKojKloetingetal.2021,
  author    = {Baum, Petra and Koj, Severin and Kl{\"o}ting, Nora and Bl{\"u}her, Matthias and Classen, Joseph and Paeschke, Sabine and Gericke, Martin and Toyka, Klaus V. and Nowicki, Marcin and Kosacka, Joanna},
  title     = {Treatment-induced neuropathy in diabetes (TIND) — Developing a disease model in type 1 diabetic rats},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {4},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22041571},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285793},
  year      = {2021},
  abstract  = {Treatment-induced neuropathy in diabetes (TIND) is defined by the occurrence of an acute neuropathy within 8 weeks of an abrupt decrease in glycated hemoglobin-A1c (HbA1c). The underlying pathogenic mechanisms are still incompletely understood with only one mouse model being explored to date. The aim of this study was to further explore the hypothesis that an abrupt insulin-induced fall in HbA1c may be the prime causal factor of developing TIND. BB/OKL (bio breeding/OKL, Ottawa Karlsburg Leipzig) diabetic rats were randomized in three groups, receiving insulin treatment by implanted subcutaneous osmotic insulin pumps for 3 months, as follows: Group one received 2 units per day; group two 1 unit per day: and group three 1 unit per day in the first month, followed by 2 units per day in the last two months. We serially examined blood glucose and HbA1c levels, motor- and sensory/mixed afferent conduction velocities (mNCV and csNCV) and peripheral nerve morphology, including intraepidermal nerve fiber density and numbers of Iba-1 (ionized calcium binding adaptor molecule 1) positive macrophages in the sciatic nerve. Only in BB/OKL rats of group three, with a rapid decrease in HbA1c of more than 2\%, did we find a significant decrease in mNCV in sciatic nerves (81\% of initial values) after three months of treatment as compared to those group three rats with a less marked decrease in HbA1c <2\% (mNCV 106\% of initial values, p ≤ 0.01). A similar trend was observed for sensory/mixed afferent nerve conduction velocities: csNCV were reduced in BB/OKL rats with a rapid decrease in HbA1c >2\% (csNCV 90\% of initial values), compared to those rats with a mild decrease <2\% (csNCV 112\% of initial values, p ≤ 0.01). Moreover, BB/OKL rats of group three with a decrease in HbA1c >2\% showed significantly greater infiltration of macrophages by about 50\% (p ≤ 0.01) and a decreased amount of calcitonin gene related peptide (CGRP) positive nerve fibers as compared to the animals with a milder decrease in HbA1c. We conclude that a mild acute neuropathy with inflammatory components was induced in BB/OKL rats as a consequence of an abrupt decrease in HbA1c caused by high-dose insulin treatment. This experimentally induced neuropathy shares some features with TIND in humans and may be further explored in studies into the pathogenesis and treatment of TIND.},
  language  = {en}
}
@article{BieberFoersterHaefelietal.2021,
  author    = {Bieber, Michael and Foerster, Kathrin I. and Haefeli, Walter E. and Pham, Mirko and Schuhmann, Michael K. and Kraft, Peter},
  title     = {Treatment with edoxaban attenuates acute stroke severity in mice by reducing blood-brain barrier damage and inflammation},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {18},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22189893},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284481},
  year      = {2021},
  abstract  = {Patients with atrial fibrillation and previous ischemic stroke (IS) are at increased risk of cerebrovascular events despite anticoagulation. In these patients, treatment with non-vitamin K oral anticoagulants (NOAC) such as edoxaban reduced the probability and severity of further IS without increasing the risk of major bleeding. However, the detailed protective mechanism of edoxaban has not yet been investigated in a model of ischemia/reperfusion injury. Therefore, in the current study we aimed to assess in a clinically relevant setting whether treatment with edoxaban attenuates stroke severity, and whether edoxaban has an impact on the local cerebral inflammatory response and blood-brain barrier (BBB) function after experimental IS in mice. Focal cerebral ischemia was induced by transient middle cerebral artery occlusion in male mice receiving edoxaban, phenprocoumon or vehicle. Infarct volumes, functional outcome and the occurrence of intracerebral hemorrhage were assessed. BBB damage and the extent of local inflammatory response were determined. Treatment with edoxaban significantly reduced infarct volumes and improved neurological outcome and BBB function on day 1 and attenuated brain tissue inflammation. In summary, our study provides evidence that edoxaban might exert its protective effect in human IS by modulating different key steps of IS pathophysiology, but further studies are warranted.},
  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}
}
@article{WalterReilichThieleetal.2013,
  author    = {Walter, Maggie C. and Reilich, Peter and Thiele, Simone and Schessl, Joachim and Schreiber, Herbert and Reiners, Karlheinz and Kress, Wolfram and M{\"u}ller-Reible, Clemens and Vorgerd, Matthias and Urban, Peter and Schrank, Bertold and Deschauer, Marcus and Schlotter-Weigel, Beate and Kohnen, Ralf and Lochm{\"u}ller, Hans},
  title     = {Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial},
  series = {Orphanet Journal of Rare Diseases},
  volume    = {8},
  journal   = {Orphanet Journal of Rare Diseases},
  number    = {26},
  issn      = {1750-1172},
  doi       = {10.1186/1750-1172-8-26},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125663},
  year      = {2013},
  abstract  = {Background: Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with the most prominent being Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B). Methods: We assessed the one-year-natural course of dysferlinopathy, and the safety and efficacy of deflazacort treatment in a double-blind, placebo-controlled cross-over trial. After one year of natural course without intervention, 25 patients with genetically defined dysferlinopathy were randomized to receive deflazacort and placebo for six months each (1 mg/kg/day in month one, 1 mg/kg every 2nd day during months two to six) in one of two treatment sequences. Results: During one year of natural course, muscle strength declined about 2\% as measured by CIDD (Clinical Investigation of Duchenne Dystrophy) score, and 76 Newton as measured by hand-held dynamometry. Deflazacort did not improve muscle strength. In contrast, there is a trend of worsening muscle strength under deflazacort treatment, which recovers after discontinuation of the study drug. During deflazacort treatment, patients showed a broad spectrum of steroid side effects. Conclusion: Deflazacort is not an effective therapy for dysferlinopathies, and off-label use is not warranted. This is an important finding, since steroid treatment should not be administered in patients with dysferlinopathy, who may be often misdiagnosed as polymyositis.},
  language  = {en}
}