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@ARTICLE{Chen:857901,
      author       = {Chen, Ji and Yan, Ya and Yuan, Fengjuan and Cao, Jianbo and
                      Li, Shanhua and Eickhoff, Simon and Zhang, Jiaxing},
      title        = {{B}rain grey matter volume reduction and anxiety-like
                      behavior in lipopolysaccharide-induced chronic pulmonary
                      inflammation rats: {A} structural {MRI} study with
                      histological validation},
      journal      = {Brain, behavior and immunity},
      volume       = {76},
      issn         = {0889-1591},
      address      = {Orlando, Fla.},
      publisher    = {Academic Press},
      reportid     = {FZJ-2018-06855},
      pages        = {182-197},
      year         = {2019},
      note         = {This work was supported by National Science Foundation of
                      China (Project NOs. 81171324; 81471630; 81472230; 81871519),
                      the European Union’s Horizon 2020 Research and Innovation
                      Programme under Grant Agreement No. 720270 (HBP SGA1) and
                      785907 (HBP SGA2). Ji Chen has received a Ph.D fellowship
                      from the Chinese Scholarship Council.},
      abstract     = {While there have been multiple fMRI studies into the brain
                      functional changes after acutely stimulated peripheral
                      infection, knowledge for the effect of chronic peripheral
                      infection on whole brain morphology is still quite limited.
                      The present study was designed to investigate the brain
                      structural and emotional changes after peripheral local
                      infection initiated chronic systemic inflammation and the
                      relationship between circulating inflammatory markers and
                      brain grey matter. Specifically, in-vivo T2-weighted MRI was
                      performed on rats with lipopolysaccharide (LPS)-induced
                      chronic pulmonary inflammation (CPI) for 4 months and those
                      without. Grey matter volume was quantified using
                      diffeomorphic anatomical registration through exponentiated
                      lie (DARTEL) enhanced voxel-based morphometry followed by
                      between-group comparison. Open field experiment was
                      conducted to test the potential anxiety-like behaviors after
                      CPI, along with the ELISA estimated inflammatory markers
                      were correlated to grey matter volume. Guided by image
                      findings, we undertook a focused histological investigation
                      with immunefluorescence and Nissl staining. A widespread
                      decrease of grey matter volume in CPI-model rats was
                      revealed. 8 of the 12 measured inflammatory markers
                      presented differential neuroanatomical correlation patterns
                      with three of the pro-inflammatory cytokines (IL-1β, IL-6
                      and TNF-α) and CRP being the most notable. Lower grey
                      matter volumes in some of the inflammatory markers related
                      regions (amygdala, CA2 and cingulate cortex) were associated
                      with more-severe anxiety-like behaviors. Furthermore, grey
                      matter volumes in amygdala and CA3 were correlated
                      negatively with the expressions of glial proteins (S100β
                      and Nogo-A), while the grey matter volume in hypo-thalamus
                      was changing positively with neural cell area. Overall, the
                      neuroanatomical association patterns and the histopathology
                      underpinning the MRI observations we demonstrated here would
                      probably serve as one explanation for the cerebral and
                      emotional deficits presented in the patients with CPI, which
                      would furthermore yield new insights into the adverse
                      effects the many other systemic inflammation and
                      inflammatory autoimmune diseases would pose on brain
                      morphology.},
      cin          = {INM-7},
      ddc          = {150},
      cid          = {I:(DE-Juel1)INM-7-20090406},
      pnm          = {572 - (Dys-)function and Plasticity (POF3-572) / HBP SGA1 -
                      Human Brain Project Specific Grant Agreement 1 (720270) /
                      HBP SGA2 - Human Brain Project Specific Grant Agreement 2
                      (785907)},
      pid          = {G:(DE-HGF)POF3-572 / G:(EU-Grant)720270 /
                      G:(EU-Grant)785907},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30472482},
      UT           = {WOS:000458089300020},
      doi          = {10.1016/j.bbi.2018.11.020},
      url          = {https://juser.fz-juelich.de/record/857901},
}