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@ARTICLE{Walsh:894652,
      author       = {Walsh, Jessica and Tozer, Dan J and Sari, Hasan and Hong,
                      Young T and Drazyk, Anna and Williams, Guy and Shah, N Jon
                      and O’Brien, John T and Aigbirhio, Franklin I and
                      Rosenberg, Gary and Fryer, Tim D and Markus, Hugh S},
      title        = {{M}icroglial activation and blood–brain barrier
                      permeability in cerebral small vessel disease},
      journal      = {Brain},
      volume       = {144},
      number       = {5},
      issn         = {1460-2156},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {FZJ-2021-03337},
      pages        = {1361 - 1371},
      year         = {2021},
      abstract     = {Cerebral small vessel disease (SVD) is a major cause of
                      stroke and dementia. The underlying pathogenesis is poorly
                      understood, but both neuroinflammation and increased
                      blood–brain barrier permeability have been hypothesized to
                      play a role, and preclinical studies suggest the two
                      processes may be linked. We used PET magnetic resonance to
                      simultaneously measure microglial activation using the
                      translocator protein radioligand 11C-PK11195, and
                      blood–brain barrier permeability using dynamic contrast
                      enhanced MRI. A case control design was used with two
                      disease groups with sporadic SVD (n = 20), monogenic SVD
                      (cerebral autosomal dominant arteriopathy with subcortical
                      infarcts and leukoencephalopathy, CADASIL), and normal
                      controls (n = 20) were studied. Hotspots of increased
                      glial activation and blood–brain barrier permeability were
                      identified as values greater than the 95th percentile of the
                      distribution in controls. In sporadic SVD there was an
                      increase in the volume of hotspots of both 11C-PK11195
                      binding (P = 0.003) and blood–brain barrier
                      permeability (P = 0.007) in the normal appearing white
                      matter, in addition to increased mean blood–brain barrier
                      permeability (P < 0.001). In CADASIL no increase in
                      blood–brain barrier permeability was detected; there was a
                      non-significant trend to increased 11C-PK11195 binding
                      (P = 0.073). Hotspots of 11C-PK11195 binding and
                      blood–brain barrier permeability were not spatially
                      related. A panel of 93 blood biomarkers relating to
                      cardiovascular disease, inflammation and endothelial
                      activation were measured in each participant; principal
                      component analysis was performed and the first component
                      related to blood–brain barrier permeability and microglial
                      activation. Within the sporadic SVD group both hotspot and
                      mean volume blood–brain barrier permeability values in the
                      normal appearing white matter were associated with dimension
                      1 (β  =  0.829, P = 0.017, and β  =  0.976,
                      P = 0.003, respectively). There was no association with
                      11C-PK11195 binding. No associations with blood markers were
                      found in the CADASIL group. In conclusion, in sporadic SVD
                      both microglial activation and increased blood–brain
                      barrier permeability occur, but these are spatially distinct
                      processes. No evidence of increased blood–brain barrier
                      permeability was found in CADASIL.},
      cin          = {INM-4 / INM-11 / JARA-BRAIN},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-4-20090406 / I:(DE-Juel1)INM-11-20170113 /
                      I:(DE-Juel1)VDB1046},
      pnm          = {5253 - Neuroimaging (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5253},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34000009},
      UT           = {WOS:000769928100024},
      doi          = {10.1093/brain/awab003},
      url          = {https://juser.fz-juelich.de/record/894652},
}