Long-term Effect of Telmisartan on Alzheimer’s Amyloid Genesis in SHR-SR After tMCAO

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• 作者：Tomoko Kurata ; Violeta Lukic ; Miki Kozuki ; Daisuke Wada…
• 关键词：Alzheimer’s disease ; Amyloid β ; Metabolic syndrome ; Spontaneously hypertensive rat ; Telmisartan ; Transient middle cerebral artery occlusion
• 刊名：Translational Stroke Research
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：6
• 期：2
• 页码：107-115
• 全文大小：12,499 KB
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• 刊物主题：Neurosciences; Neurology; Cardiology; Neurosurgery; Vascular Surgery;
• 出版者：Springer US
• ISSN：1868-601X

文摘

Telmisartan is expected to reduce not only the level of blood pressure but also neuroinflammation and neurotoxicity via pleiotrophic effects as a metabo-sartan. We examined the effects of telmisartan on Alzheimer’s disease (AD) pathology in spontaneously hypertensive rat stroke resistant (SHR-SR) after transient middle cerebral artery occlusion (tMCAO) by giving either telmisartan at 0 (vehicle), 0.3?mg/kg/day (low dose, with no reduction of blood pressure), or 3?mg/kg/day (high dose, with a significant reduction of blood pressure) p.o. from 3?months (M) of age, and performed immunohistological analysis at 6, 12, and 18?M of age. The numbers of amyloid β (Aβ)-positive neurons in the cerebral cortex and hippocampus and senile plaque (SP) in the ipsilateral cerebral cortex progressively increased with age until 18?M in the SHR-SR after tMCAO. On the other hand, low-dose telmisartan significantly reduced the number of Aβ-positive neuron as well as SP at 6, 12, and 18?M. High-dose telmisartan showed further reductions of the above AD pathology. The present study suggests that telmisartan reduced both intracellular Aβ and extracellular SP accumulations after tMCAO in SHR-SR, with a further improvement by combined BP lowering. Such a strong effect of telmisartan could provide a preventative approach for AD in post-stroke patients with hypertension.