BACKGROUND AND PURPOSE: 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.
BACKGROUND AND PURPOSE: 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:Tg2576mice 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 Tg2576mouse 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: Y W Chen; M E Gurol; J Rosand; A Viswanathan; S M Rakich; T R Groover; S M Greenberg; E E Smith Journal: Neurology Date: 2006-07-11 Impact factor: 9.910
Authors: Byung Hee Han; Meng-Liang Zhou; Fadi Abousaleh; Robert P Brendza; Hans H Dietrich; Jessica Koenigsknecht-Talboo; John R Cirrito; Eric Milner; David M Holtzman; Gregory J Zipfel Journal: J Neurosci Date: 2008-12-10 Impact factor: 6.167
Authors: M W Vernooij; A van der Lugt; M A Ikram; P A Wielopolski; W J Niessen; A Hofman; G P Krestin; M M B Breteler Journal: Neurology Date: 2008-04-01 Impact factor: 9.910
Authors: Anne F Wiegman; Irene B Meier; Nicole Schupf; Jennifer J Manly; Vanessa A Guzman; Atul Narkhede; Yaakov Stern; Sergi Martinez-Ramirez; Anand Viswanathan; José A Luchsinger; Steven M Greenberg; Richard Mayeux; Adam M Brickman Journal: J Neurol Sci Date: 2014-07-18 Impact factor: 3.181