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A validated quantitative method for the assessment of neuroprotective barrier impairment in neurodegenerative disease models
Journal of Neurochemistry ( IF 4.7 ) Pub Date : 2020-07-06 , DOI: 10.1111/jnc.15119
Vinod Kumar 1 , John D Lee 1 , Elizabeth J Coulson 1, 2 , Trent M Woodruff 1, 2
Affiliation  

The blood–brain barrier (BBB) and blood–spinal cord barrier (BSCB) are highly specialized structures that limit molecule entry from the blood and maintain homeostasis within the central nervous system (CNS). BBB and BSCB breakdown are associated with multiple neurodegenerative diseases. Given the key role of neuroprotective barrier impairment in neurodegeneration, it is important to identify an effective quantitative method to assess barrier integrity in animal models. In this study, we developed and validated a quantitative method for assessing BBB and BSCB integrity using sodium fluorescein, a compound that outperformed other fluorescent dyes. We demonstrated using this method that multiple CNS regions progressively increase in permeability in models of Huntington’s disease and amyotrophic lateral sclerosis, whereas biphasic disruption occurred in a mouse model of Alzheimer’s disease with disease progression. Collectively, we report a quantitative fluorometric marker with validated reproducible experimental methods that allows the effective assessment of BBB and BSCB integrity in animal models. This method could be useful to further the understanding of the contribution of these neuroprotective barriers to neurodegeneration processes.

中文翻译:

一种用于评估神经退行性疾病模型中神经保护屏障损伤的经过验证的定量方法

血脑屏障 (BBB) 和血-脊髓屏障 (BSCB) 是高度特化的结构,可限制分子从血液进入并维持中枢神经系统 (CNS) 内的稳态。BBB 和 BSCB 分解与多种神经退行性疾病有关。鉴于神经保护屏障损伤在神经变性中的关键作用,确定一种有效的定量方法来评估动物模型中的屏障完整性非常重要。在这项研究中,我们开发并验证了一种使用荧光素钠评估 BBB 和 BSCB 完整性的定量方法,荧光素钠是一种优于其他荧光染料的化合物。我们使用这种方法证明了亨廷顿病和肌萎缩侧索硬化模型中多个 CNS 区域的渗透性逐渐增加,而双相破坏发生在阿尔茨海默病的小鼠模型中,随着疾病的进展。总的来说,我们报告了一种具有经过验证的可重复实验方法的定量荧光标记,可以有效评估动物模型中的 BBB 和 BSCB 完整性。这种方法可能有助于进一步了解这些神经保护屏障对神经变性过程的贡献。
更新日期:2020-07-06
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