Abstract
A previous study reported that relatively high-dose cilostazol (0.3%) promoted the drainage of cerebrovascular amyloid-β (Aβ) protein in Aβ Precursor Protein (APP) transgenic mice overexpressing vasculotropic Aβ. We investigated whether lower-dose cilostazol can decrease micro-hemorrhages and Aβ 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 Aβ-positive vessels × severity of amyloid burden of Aβ-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.
Highlights
Sporadic cerebral amyloid angiopathy (CAA) is characterized by the progressive deposition of amyloid-β (Aβ) protein in the walls of small- to medium-sized arteries, arterioles, and capillaries in the cerebral cortex and overlying leptomeninges [1,2]
In a CAA mice model (Tg-SwDI mice), cilostazol improved cognitive performance, which may be associated with reduced Aβ deposition by cilostazol (0.3% cilostazol) [12]
We sought to determine whether lower-dose cilostazol could reduce the incidence of cerebralhemorrhages or cerebrovascular Aβ depositions using different transgenic mice as a CAA model
Summary
Sporadic cerebral amyloid angiopathy (CAA) is characterized by the progressive deposition of amyloid-β (Aβ) protein in the walls of small- to medium-sized arteries, arterioles, and capillaries in the cerebral cortex and overlying leptomeninges [1,2]. A selective inhibitor of PDE III, cilostazol, has multiple effects on the vasculature including vasodilatation, antioxidation, anti-inflammation, the regulation of smooth muscle cell, and an increase in cerebral hemodynamics, pulse duration time, and arterial elasticity with the maintenance of microvascular integrity [9]. In a CAA mice model (Tg-SwDI mice), cilostazol improved cognitive performance, which may be associated with reduced Aβ deposition by cilostazol (0.3% cilostazol) [12] It is unknown whether the safety and efficacy of cilostazol could be replicated in different settings (i.e., drug dose or experimental transgenic mice). We sought to determine whether lower-dose cilostazol could reduce the incidence of cerebral (micro-)hemorrhages or cerebrovascular Aβ depositions using different transgenic mice as a CAA model
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