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Int J Mol Sci ; 21(7)2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32225099

RESUMO

A previous study reported that relatively high-dose cilostazol (0.3%) promoted the drainage of cerebrovascular amyloid-ß (Aß) protein in Aß Precursor Protein (APP) transgenic mice overexpressing vasculotropic Aß. We investigated whether lower-dose cilostazol can decrease micro-hemorrhages and Aß deposition in the brain using APP transgenic mice. At baseline, 14-month-old female Tg2576 mice were randomly assigned to a control group (vehicle), aspirin group (0.01% aspirin), or cilostazol group (0.01% cilostazol). The severity of cerebral micro-hemorrhages (i.e., number), area of senile plaque, and severity of vascular amyloid burden (quantified with cerebral amyloid angiopathy (CAA) score (=number of Aß-positive vessels × severity of amyloid burden of Aß-positive vessels) were evaluated in the brain of mice aged 15 and 21-23 months. At 15 months, no differences were shown in each pathological change among the three groups. At 21-23 months, there were no differences in the severity of cerebral micro-hemorrhages or area of senile plaque among the three groups. However, the CAA score was significantly lower in the cilostazol compared to the control group (p = 0.046, Mann-Whitney U test), although no difference was seen between the control and aspirin group. Our study showed that lower-dose cilostazol could reduce the vascular amyloid burden without increasing cerebral micro-hemorrhages in APP transgenic mice.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Angiopatia Amiloide Cerebral/tratamento farmacológico , Cilostazol/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Inibidores da Fosfodiesterase 3/uso terapêutico , Animais , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Encéfalo/patologia , Cilostazol/administração & dosagem , Feminino , Camundongos , Fármacos Neuroprotetores/administração & dosagem , Inibidores da Fosfodiesterase 3/administração & dosagem
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