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@ARTICLE{Liu:863043,
      author       = {Liu, Jingjin and Nolte, Kay and Brook, Gary and
                      Liebenstund, Lisa and Weinandy, Agnieszka and Höllig, Anke
                      and Veldeman, Michael and Willuweit, Antje and Langen,
                      Karl-Josef and Rossaint, Rolf and Coburn, Mark},
      title        = {{P}ost-stroke treatment with argon attenuated brain injury,
                      reduced brain inflammation and enhanced {M}2
                      microglia/macrophage polarization: a randomized controlled
                      animal study},
      journal      = {Critical care},
      volume       = {23},
      number       = {1},
      issn         = {1364-8535},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {FZJ-2019-03165},
      pages        = {198},
      year         = {2019},
      abstract     = {BackgroundIn recent years, argon has been shown to exert
                      neuroprotective effects in an array of models. However, the
                      mechanisms by which argon exerts its neuroprotective
                      characteristics remain unclear. Accumulating evidence imply
                      that argon may exert neuroprotective effects via modulating
                      the activation and polarization of microglia/macrophages
                      after ischemic stroke. In the present study, we analyzed the
                      underlying neuroprotective effects of delayed argon
                      application until 7 days after reperfusion and explored the
                      potential mechanisms.MethodsTwenty-one male Wistar rats
                      underwent transient middle cerebral artery occlusion or sham
                      surgery randomly for 2 h using the endoluminal thread
                      model. Three hours after transient middle cerebral artery
                      occlusion induction and 1 h after reperfusion, animals
                      received either $50\%$ vol $Argon/50\%$ vol O2 or $50\%$ vol
                      $N2/50\%$ vol O2 for 1 h. The primary outcome was the
                      6-point neuroscore from 24 h to d7 after reperfusion.
                      Histological analyses including infarct volume, survival of
                      neurons (NeuN) at the ischemic boundary zone, white matter
                      integrity (Luxol Fast Blue), microglia/macrophage activation
                      (Iba1), and polarization (Iba1/Arginase1 double staining) on
                      d7 were conducted as well. Sample size calculation was
                      performed using nQuery Advisor + nTerim 4.0. Independent t
                      test, one-way ANOVA and repeated measures ANOVA were
                      performed, respectively, for statistical analysis (SPSS
                      23.0).ResultsThe 6-point neuroscore from 24 h to d7 after
                      reperfusion showed that tMCAO Ar group displayed
                      significantly improved neurological performance compared to
                      tMCAO N2 group (p = 0.026). The relative numbers of
                      NeuN-positive cells in the ROIs of tMCAO Ar group
                      significantly increased compared to tMCAO N2 group
                      (p = 0.010 for cortex and p = 0.011 for subcortex).
                      Argon significantly suppressed the microglia/macrophage
                      activation as revealed by Iba1 staining (p = 0.0076) and
                      promoted the M2 microglia/macrophage polarization as
                      revealed by Iba1/Arginase 1 double staining
                      (p = 0.000095).ConclusionsArgon administration with a
                      3 h delay after stroke onset and 1 h after reperfusion
                      significantly alleviated neurological deficit within the
                      first week and preserved the neurons at the ischemic
                      boundary zone 7 days after stroke. Moreover, argon reduced
                      the excessive microglia/macrophage activation and promoted
                      the switch of microglia/macrophage polarization towards the
                      anti-inflammatory M2 phenotype. Studies making efforts to
                      further elucidate the protective mechanisms and to benefit
                      the translational application are of great value.},
      cin          = {INM-4},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-4-20090406},
      pnm          = {573 - Neuroimaging (POF3-573)},
      pid          = {G:(DE-HGF)POF3-573},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31159847},
      UT           = {WOS:000470127200001},
      doi          = {10.1186/s13054-019-2493-7},
      url          = {https://juser.fz-juelich.de/record/863043},
}