title: Dynamics of neuroinflammation in the macrosphere model of arterio-arterial embolic focal ischemia: an approximation to human stroke patterns.
abstract: BACKGROUND
  Neuroinflammation evolves as a multi-facetted response to focal cerebral ischemia. It involves activation of resident glia cell populations, recruitment of blood-derived leucocytes as well as humoral responses. Among these processes, phagocyte accumulation has been suggested to be a surrogate marker of neuroinflammation. We previously assessed phagocyte accumulation in human stroke by MRI. We hypothesize that phagocyte accumulation in the macrosphere model may resemble the temporal and spatial patterns observed in human stroke.
  
  
  METHODS
  In a rat model of permanent focal ischemia by embolisation of TiO2-spheres we assessed key features of post-ischemic neuroinflammation by the means of histology, immunocytochemistry of glial activation and influx of hematogeneous cells, and quantitative PCR of TNF-α, IL-1, IL-18, and iNOS mRNA.
  
  
  RESULTS
  In the boundary zone of the infarct, a transition of ramified microglia into ameboid phagocytic microglia was accompanied by an up-regulation of MHC class II on the cells after 3 days. By day 7, a hypercellular infiltrate consisting of activated microglia and phagocytic cells formed a thick rim around the ischemic infarct core. Interestingly, in the ischemic core microglia could only be observed at day 7. TNF-α was induced rapidly within hours, IL-1β and iNOS peaked within days, and IL-18 later at around 1 week after ischemia.
  
  
  CONCLUSIONS
  The macrosphere model closely resembles the characteristical dynamics of postischemic inflammation previously observed in human stroke. We therefore suggest that the macrosphere model is highly appropriate for studying the pathophysiology of stroke in a translational approach from rodent to human.
authors.affiliation: Department of Neurology, University Hospital, Cologne, Germany. g.r.fink@fz-juelich.de.
authors.forename: Maureen
authors.initials: M
authors.lastname: Walberer
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rueger
authors.forename: Marie-Lune
authors.initials: ML
authors.lastname: Simard
authors.forename: Beata
authors.initials: B
authors.lastname: Emig
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jander
authors.forename: Gereon R
authors.initials: GR
authors.lastname: Fink
authors.forename: Michael
authors.initials: M
authors.lastname: Schroeter