title: Therapeutic modulation of cerebral microhemorrhage in a mouse model of cerebral amyloid angiopathy.
abstract: OBJECTIVE
  The aging brain demonstrates frequent MRI and pathological evidence of cerebral microbleeds, which are often associated with cerebral amyloid angiopathy. To develop new therapeutic strategies for this disorder, we studied cerebral microhemorrhage in a well-characterized mouse model of cerebral amyloid angiopathy.
  
  
  METHODS
  Tg2576 mice were studied at ages ranging from 2 to 21 months. Spontaneous and induced microscopic bleeding was analyzed with and without a passive anti-amyloid immunization regimen and dietary supplementation of ischemic stroke prevention medication dipyridamole.
  
  
  RESULTS
  Areas of microhemorrhage were easily demonstrated and were significantly more prominent in the oldest mice and in animals treated with anti-amyloid immunotherapy. Dipyridamole supplementation in the diet generated plasma levels >790 ng/mL within the range seen clinically. Dipyridamole treatment did not worsen frequency and size of cerebral microscopic bleeding.
  
  
  CONCLUSIONS
  The Tg2576 mouse is a useful model to study progression and modification of spontaneous and immunotherapy-induced cerebral microhemorrhage. Absence of microhemorrhage worsening with dipyridamole treatment suggests a potential therapeutic role of this agent when ischemic and microhemorrhagic lesions coexist.
authors: Department of Neurology, University of California Irvine, Irvine, CA, USA. mfisher@uci.edu
authors: Mark
authors: M
authors: Fisher
authors: Vitaly
authors: V
authors: Vasilevko
authors: Giselle F
authors: GF
authors: Passos
authors: Christopher
authors: C
authors: Ventura
authors: Daniel
authors: D
authors: Quiring
authors: David H
authors: DH
authors: Cribbs
mesh_terms: D000818:Animals; D016657:Cerebral Amyloid Angiopathy / Q000276:immunology / Q000628:therapy*; D002543:Cerebral Hemorrhage / Q000276:immunology / Q000628:therapy*; D004176:Dipyridamole / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008833:Microcirculation / Q000187:drug effects / Q000276:immunology
chemical_list: D004176:Dipyridamole