Blood-brain barrier permeability in Parkinson's disease patients with and without dyskinesia.
Blood-brain barrier permeability in Parkinson's disease patients with and without dyskinesia.
复制标题
有或没有运动障碍的帕金森病患者的血脑屏障通透性。
DOI：
10.1007/s00415-021-10411-1
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发表时间：
2021
影响因子：
6
通讯作者：
Dhawan,Vijay
中科院分区：
文献类型：
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作者：
Fujita,Koji;Peng,Shichun;Ma,Yilong;Tang,ChrisC;Hellman,Matthew;Feigin,Andrew;Eidelberg,David;Dhawan,Vijay
最近对帕金森病（PD）啮齿动物模型的研究提出了血脑屏障（BBB）通透性增加的可能性，通过组织学，放射自显影和正电子发射断层扫描（PET）证实。然而，在人PD患者中，缺乏BBB通透性增加的体内证据。我们研究的假设，左旋多巴治疗增加血脑屏障通透性在人类受试者与PD，特别是在那些左旋多巴诱导的运动障碍（LID）。MethodsWe使用铷-82（82Rb）和PET定量血脑屏障流入体内19例PD患者，包括8例LID，和12个年龄和性别匹配的健康受试者。所有受试者均接受基线82Rb扫描。17例长期接受左旋多巴治疗的患者在静脉输注左旋多巴期间额外重新扫描。通过房室模型或净内流转运，Ki，通过图形方法的内流速率常数，K1不能可靠地估计。然而，Vd，“表观分布体积”的基础上的脑组织和血液中的82 Rb浓度，估计具有良好的稳定性作为一个本地的测量体积distribution.ResultsRb流入脑组织是不可检测的PD患者或没有LID，扫描和关闭药物。除左丘脑外，PD伴或不伴LID患者的区域Vd与健康受试者相比无显著差异。此外，运动障碍和非运动障碍受试者在左旋多巴输注前后的Vd变化也无统计学意义。结论82 Rb PET未显示PD患者血脑屏障通透性的显著变化。
ObjectiveRecent studies on a rodent model of Parkinson’s disease (PD) have raised the possibility of increased blood–brain barrier (BBB) permeability, demonstrated by histology, autoradiography, and positron emission tomography (PET). However, in human PD patients, in vivo evidence of increased BBB permeability is lacking. We examined the hypothesis that levodopa treatment increases BBB permeability in human subjects with PD, particularly in those with levodopa-induced dyskinesia (LID).MethodsWe used rubidium-82 (82Rb) and PET to quantify BBB influx in vivo in 19 PD patients, including eight with LID, and 12 age- and sex-matched healthy subjects. All subjects underwent baseline82Rb scans. Seventeen chronically levodopa-treated patients were additionally rescanned during intravenous levodopa infusion. Influx rate constant,K1, by compartmental modeling or net influx transport,Ki, by graphical approach could not be estimated reliably. However,Vd, the “apparent volume of distribution” based on the82Rb concentration in brain tissue and blood, was estimated with good stability as a local measure of the volume of distribution.ResultsRubidium influx into brain tissue was undetectable in PD patients with or without LID, scanned on and off drug. No significant differences in regionalVdwere observed for PD patients with or without LID relative to healthy subjects, except in left thalamus. Moreover, changes inVdmeasured off- and on-levodopa infusion were also not significant for dyskinetic and non-dyskinetic subjects.Conclusion82Rb PET did not reveal significant changes in BBB permeability in PD patients.