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首页> 外文期刊>Journal of stroke and cerebrovascular diseases: The official journal of National Stroke Association >Twendee X Ameliorates Phosphorylated Tau, alpha-Synuclein and Neurovascular Dysfunction in Alzheimer's Disease Transgenic Mice With Chronic Cerebral Hypoperfusion
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Twendee X Ameliorates Phosphorylated Tau, alpha-Synuclein and Neurovascular Dysfunction in Alzheimer's Disease Transgenic Mice With Chronic Cerebral Hypoperfusion

机译：Twendee X改善了阿尔茨海默病转基因小鼠的磷酸化Tau，α-突触核蛋白和神经血管功能障碍，慢性脑低血量灌注

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Background: The pathological impact of chronic cerebral hypoperfusion (CCH) on Alzheimer's disease (AD) is still poorly understood. In the present study, we investigated the role of CCH on an AD mouse model in phosphorylated tau and alpha-synudein pathology, neurovascular unit, cerebrovascular remodeling, and neurovascular trophic coupling. Moreover, examined protective effect of a new antioxidant Twendee X (TwX). Methods: APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors to gradually decrease the cerebral blood flow. The effects of the administration of TwX were evaluated by immunohistochemical analysis and Immunofluorescent histochemistry. Results: The present study revealed that the expressions of phospho-tau and phospho-alpha-synudein were significantly increased in the APP23 + CCH mice group as compared with wild type and APP23 mice groups (*P < .05 and **P < .01 versus WT; P-# < .05 and (##) P < .01 versus APP23). In addition, CCH significantly exacerbated MMP-9 activation relating to blood-brain barrier destruction (*P < .01 versus WT; (#) P < .05, and (##) P < .01 versus APP23), enhanced neurovascular remodeling, and impaired a neurovascular trophic coupling in the vascular endothelial BDNF expression of the APP23 + CCH group. TwX treatment (20 mg/kg/ day, from 4.5 to 12 months) significantly reduced tau and oc-synudein pathologies, ameliorated neurovascular dysfunction compared with APP23 + CCH group. Conclusions: Our findings indicate that administration of a new antioxidative mixture TwX substantially reduced the above neuropathologic abnormalities, suggesting a potential therapeutic benefit of TwX for AD with CCH.
机译：背景：慢性脑低渗（CCH）对阿尔茨海默病（AD）的病理影响仍然不知识。在本研究中，我们研究了CCH对磷酸化TAU和α-综合征病理，神经血管单位，脑血管改造和神经血管脱蛋白偶联的AD小鼠模型的作用。此外，检查了新的抗氧化捻X（TWX）的保护作用。方法：将APP23小鼠植入双侧常见的颈动脉狭窄，含有Ameroid收缩仪逐渐降低脑血流量。通过免疫组织化学分析和免疫荧光组织化学评估TWX给药的影响。结果：本研究表明，与野生型和APP23小鼠组相比，APP23 + CCH小鼠组中磷酸盐和磷酸α-综合征的表达显着增加（* P <.05和** P <。 01与wt; p-＃<.05和（##）p <.01与app23）。此外，CCH显着加剧了与血脑屏障破坏有关的MMP-9激活（* P <.01与wt;（＃）p <.05，和（##）p <.01与APP23），增强神经血管重塑，并在APP23 + CCH组的血管内皮BDNF表达中损害了神经血管脱蛋白偶联。 TWX治疗（20毫克/千克/天，4.5至12个月）显着降低了TAU和OC-Synucein病理，改善了神经血管功能障碍与APP23 + CCH组相比。结论：我们的研究结果表明，新的抗氧化混合物TWX的给药显着降低了上述神经病理学异常，表明TWX与CCH的潜在治疗益处。

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