@article{KamaliRajendranStadelmannetal.2021,
  author    = {Kamali, Salar and Rajendran, Ranjithkumar and Stadelmann, Christine and Karnati, Srikanth and Rajendran, Vinothkumar and Giraldo-Velasquez, Mario and Berghoff, Martin},
  title     = {Oligodendrocyte-specific deletion of FGFR2 ameliorates MOG\(_{35-55}\)-induced EAE through ERK and Akt signalling},
  series = {Brain Pathology},
  volume    = {31},
  journal   = {Brain Pathology},
  doi       = {10.1111/bpa.12916},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224354},
  pages     = {297 -- 311},
  year      = {2021},
  abstract  = {Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in demyelinating pathologies including multiple sclerosis (MS). In our recent study, oligodendrocyte-specific deletion of FGFR1 resulted in a milder disease course, less inflammation, reduced myelin and axon damage in EAE. The objective of this study was to elucidate the role of oligodendroglial FGFR2 in MOG\(_{35-55}\)-induced EAE. Oligodendrocyte-specific knockout of FGFR2 (Fgfr2\(^{ind-/-}\)) was achieved by application of tamoxifen; EAE was induced using the MOG\(_{35-55}\) peptide. EAE symptoms were monitored over 62 days. Spinal cord tissue was analysed by histology, immunohistochemistry and western blot. Fgfr2\(^{ind-/-}\) mice revealed a milder disease course, less myelin damage and enhanced axonal density. The number of oligodendrocytes was not affected in demyelinated areas. However, protein expression of FGFR2, FGF2 and FGF9 was downregulated in Fgfr2\(^{ind-/-}\) mice. FGF/FGFR dependent signalling proteins were differentially regulated; pAkt was upregulated and pERK was downregulated in Fgfr2\(^{ind-/-}\) mice. The number of CD3(+) T cells, Mac3(+) cells and B220(+) B cells was less in demyelinated lesions of Fgfr2\(^{ind-/-}\) mice. Furthermore, expression of IL-1β, TNF-α and CD200 was less in Fgfr2\(^{ind-/-}\) mice than controls. Fgfr2ind-/- mice showed an upregulation of PLP and downregulation of the remyelination inhibitors SEMA3A and TGF-β expression. These data suggest that cell-specific deletion of FGFR2 in oligodendrocytes has anti-inflammatory and neuroprotective effects accompanied by changes in FGF/FGFR dependent signalling, inflammatory cytokines and expression of remyelination inhibitors. Thus, FGFRs in oligodendrocytes may represent potential targets for the treatment of inflammatory and demyelinating diseases including MS.},
  language  = {en}
}
@article{VogelsangEichlerHuntemannetal.2021,
  author    = {Vogelsang, Anna and Eichler, Susann and Huntemann, Niklas and Masanneck, Lars and B{\"o}hnlein, Hannes and Sch{\"u}ngel, Lisa and Willison, Alice and Loser, Karin and Nieswandt, Bernhard and Kehrel, Beate E. and Zarbock, Alexander and G{\"o}bel, Kerstin and Meuth, Sven G.},
  title     = {Platelet inhibition by low-dose acetylsalicylic acid reduces neuroinflammation in an animal model of multiple sclerosis},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {18},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22189915},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284535},
  year      = {2021},
  abstract  = {Aside from the established immune-mediated etiology of multiple sclerosis (MS), compelling evidence implicates platelets as important players in disease pathogenesis. Specifically, numerous studies have highlighted that activated platelets promote the central nervous system (CNS)-directed adaptive immune response early in the disease course. Platelets, therefore, present a novel opportunity for modulating the neuroinflammatory process that characterizes MS. We hypothesized that the well-known antiplatelet agent acetylsalicylic acid (ASA) could inhibit neuroinflammation by affecting platelets if applied at low-dose and investigated its effect during experimental autoimmune encephalomyelitis (EAE) as a model to study MS. We found that oral administration of low-dose ASA alleviates symptoms of EAE accompanied by reduced inflammatory infiltrates and less extensive demyelination. Remarkably, the percentage of CNS-infiltrated CD4\(^+\) T cells, the major drivers of neuroinflammation, was decreased to 40.98 ± 3.28\% in ASA-treated mice compared to 56.11 ± 1.46\% in control animals at the disease maximum as revealed by flow cytometry. More interestingly, plasma levels of thromboxane A\(_2\) were decreased, while concentrations of platelet factor 4 and glycoprotein VI were not affected by low-dose ASA treatment. Overall, we demonstrate that low-dose ASA could ameliorate the platelet-dependent neuroinflammatory response in vivo, thus indicating a potential treatment approach for MS.},
  language  = {en}
}