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@ARTICLE{Vay:851194,
      author       = {Vay, Sabine Ulrike and Flitsch, Lea Jessica and Rabenstein,
                      Monika and Rogall, Rebecca and Blaschke, Stefan and
                      Kleinhaus, Judith and Reinert, Noémie and Bach, Annika and
                      Fink, Gereon Rudolf and Schroeter, Michael and Rueger, Maria
                      Adele},
      title        = {{T}he plasticity of primary microglia and their
                      multifaceted effects on endogenous neural stem cells in
                      vitro and in vivo},
      journal      = {Journal of neuroinflammation},
      volume       = {15},
      number       = {1},
      issn         = {1742-2094},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {FZJ-2018-04894},
      pages        = {226},
      year         = {2018},
      abstract     = {BackgroundMicroglia—the resident immune cells of the
                      brain—are activated after brain lesions, e.g., cerebral
                      ischemia, and polarize towards a classic “M1”
                      pro-inflammatory or an alternative “M2”
                      anti-inflammatory phenotype following characteristic
                      temporo-spatial patterns, contributing either to secondary
                      tissue damage or to regenerative responses. They closely
                      interact with endogenous neural stem cells (NSCs) residing
                      in distinct niches of the adult brain. The current study
                      aimed at elucidating the dynamics of microglia polarization
                      and their differential effects on NSC
                      function.ResultsPrimary rat microglia in vitro were
                      polarized towards a M1 phenotype by LPS, or to a M2
                      phenotype by IL4, while simultaneous exposure to LPS plus
                      IL4 resulted in a hybrid phenotype expressing both M1- and
                      M2-characteristic markers. M2 microglia migrated less but
                      exhibit higher phagocytic activity than M1 microglia.
                      Defined mediators switched microglia from one polarization
                      state to the other, a process more effective when
                      transforming M2 microglia towards M1 than vice versa.
                      Polarized microglia had differential effects on the
                      differentiation potential of NSCs in vitro and in vivo, with
                      M1 microglia promoting astrocytogenesis, while M2 microglia
                      supported neurogenesis. Regardless of their polarization,
                      microglia inhibited NSC proliferation, increased NSC
                      migration, and accelerated NSC
                      differentiation.ConclusionOverall, this study shed light on
                      the complex conditions governing microglia polarization and
                      the effects of differentially polarized microglia on
                      critical functions of NSCs in vitro and in vivo. Refining
                      the understanding of microglia activation and their
                      modulatory effects on NSCs is likely to facilitate the
                      development of innovative therapeutic concepts supporting
                      the innate regenerative capacity of the brain.},
      cin          = {INM-3},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-3-20090406},
      pnm          = {572 - (Dys-)function and Plasticity (POF3-572)},
      pid          = {G:(DE-HGF)POF3-572},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30103769},
      UT           = {WOS:000441501400001},
      doi          = {10.1186/s12974-018-1261-y},
      url          = {https://juser.fz-juelich.de/record/851194},
}