Blood-Brain Barrier Leakage Is Increased in Parkinson's Disease.
Blood-Brain Barrier Leakage Is Increased in Parkinson's Disease.
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DOI：
10.3389/fphys.2020.593026
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发表时间：
2020
影响因子：
4
通讯作者：
Parkes LM
中科院分区：
文献类型：
--
作者：
Al-Bachari S;Naish JH;Parker GJM;Emsley HCA;Parkes LM
血脑屏障（BBB）的破坏已经在帕金森病（PD）的动物模型中被注意到，并形成了神经变性的血管假说的基础，但缺乏临床研究。确定与脑血管疾病相比，PD患者血脑屏障完整性的改变。动态对比增强磁共振图像采集自49例PD患者、15例脑血管疾病对照受试者[对照阳性（CP）]和31例健康对照受试者[对照阴性（CN）]，所有组的年龄均匹配。使用Patlak分析产生造影剂穿过BBB的转移系数（Ktranss）和血浆体积（vp）的定量图。采用基于体素的分析以及与PD病理生理学相关的区域评估Ktranss和vp的差异。此外，从T2加权液体衰减反转恢复（FLAIR）图像获得了白色病变（WML）的体积。使用基于体素的分析，发现PD组的Ktranss高于CN组，反映了BBB渗漏较高;差异在后部白色物质区域最为突出。感兴趣区域分析证实PD患者的Ktranss显著高于CN患者，这主要是由于黑质、外观正常的白色物质、WML和后皮质的差异所致。与CN相比，PD中的WML体积显著更高。PD和CP的Ktranss值和WML体积相似，表明尽管心血管危险因素较低，但脑血管疾病的负担相似。这些结果表明PD中的BBB破坏。
Blood–brain barrier (BBB) disruption has been noted in animal models of Parkinson’s disease (PD) and forms the basis of the vascular hypothesis of neurodegeneration, yet clinical studies are lacking. To determine alterations in BBB integrity in PD, with comparison to cerebrovascular disease. Dynamic contrast enhanced magnetic resonance images were collected from 49 PD patients, 15 control subjects with cerebrovascular disease [control positive (CP)] and 31 healthy control subjects [control negative (CN)], with all groups matched for age. Quantitative maps of the contrast agent transfer coefficient across the BBB (Ktrans) and plasma volume (vp) were produced using Patlak analysis. Differences in Ktrans and vp were assessed with voxel-based analysis as well as in regions associated with PD pathophysiology. In addition, the volume of white matter lesions (WMLs) was obtained from T2-weighted fluid attenuation inversion recovery (FLAIR) images. Higher Ktrans, reflecting higher BBB leakage, was found in the PD group than in the CN group using voxel-based analysis; differences were most prominent in the posterior white matter regions. Region of interest analysis confirmed Ktrans to be significantly higher in PD than in CN, predominantly driven by differences in the substantia nigra, normal-appearing white matter, WML and the posterior cortex. WML volume was significantly higher in PD compared to CN. Ktrans values and WML volume were similar in PD and CP, suggesting a similar burden of cerebrovascular disease despite lower cardiovascular risk factors. These results show BBB disruption in PD.
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