Background and Purpose
The aging brain demonstrates frequent MRI and pathological evidence of cerebral microbleeds, which are often associated with cerebral amyloid angiopathy. In order to develop new therapeutic strategies for this disorder, we studied cerebral microhemorrhage in a well-characterized mouse model of cerebral amyloid angiopathy.
Tg 2576 mice were studied at ages ranging from 2 to 21 months. Spontaneous and induced microscopic bleeding was analyzed with and without passive anti-amyloid immunization regimen and dietary supplementation of ischemic stroke prevention medication dipyridamole.
Areas of microhemorrhage were easily demonstrated, and were significantly more prominent in oldest mice and in animals treated with anti-amyloid immunotherapy. Dipyridamole supplementation in diet generated plasma levels greater than 790ng/ml, within the range seen clinically. Dipyridamole treatment did not worsen frequency and size of cerebral microscopic bleeding.
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.
Keywords: Alzheimer’s, Amyloid angiopathy, Animal models, Antiplatelet drugs, Basic science, Experimental, Intracerebral hemorrhage, Microcirculation