title: Monitoring therapeutic effects in experimental stroke by serial USPIO-enhanced MRI.
abstract: OBJECTIVE
  This study sought to evaluate whether the therapeutic effects of an anti-inflammatory drug such as minocycline could be monitored by serial ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI in experimental stroke.
  
  
  METHODS
  Mice received a three-dose minocycline treatment (n = 12) or vehicle (n = 12) after permanent middle cerebral artery occlusion. USPIOs were administered 5 h post-surgery. MRI was performed before, 24 h and 48 h post-USPIO administration. MRI endpoints were the extent of signal abnormalities on R2 maps (=1/T2) and quantitative R2 changes over time (∆R2). Post-mortem brains were prepared either for immunohistology (n = 16) or for iron dosage (n = 8).
  
  
  RESULTS
  As expected, treatment with minocycline significantly reduced infarct size, blood-brain barrier permeability and F4/80 immunostaining for microglia/macrophages. Areas of R2 maps > 35 ms(-1) also appeared significantly decreased in minocycline-treated mice (ANOVA for repeated measures, P = 0.017). There was a fair correlation between these areas and the amount of iron in the brain (R(2) = 0.69, P = 0.010), but no significant difference in ∆R2 was found between the two groups.
  
  
  CONCLUSIONS
  This study showed that the extent of signal abnormalities on R2 maps can be used as a surrogate marker to detect minocycline effects in a murine experimental model of stroke.
authors: UMR CNRS 5520 CREATIS, Hopital Louis Pradel, Université de Lyon, Lyon 1, 28 avenue du Doyen LEPINE, 69677, Bron, France.
authors: Marilena
authors: M
authors: Marinescu
authors: Fabien
authors: F
authors: Chauveau
authors: Anne
authors: A
authors: Durand
authors: Adrien
authors: A
authors: Riou
authors: Tae-Hee
authors: TH
authors: Cho
authors: Anne
authors: A
authors: Dencausse
authors: Sébastien
authors: S
authors: Ballet
authors: Norbert
authors: N
authors: Nighoghossian
authors: Yves
authors: Y
authors: Berthezène
authors: Marlène
authors: M
authors: Wiart
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003287:Contrast Media; D003911:Dextrans; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology*; D020521:Stroke / Q000188:drug therapy*
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10; D008911:Minocycline