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Perivascular space dysfunction in cerebral small vessel disease is related to neuroinflammation
Brain ( IF 10.6 ) Pub Date : 2024-11-07 , DOI: 10.1093/brain/awae357
Hui Hong, Dan Tozer, Yutong Chen, Robin Brown, Audrey Low, Hugh S Markus

Enlarged perivascular spaces are a feature of cerebral small vessel disease, and it has been hypothesized that they may reflect impaired glymphatic drainage. The mechanisms underlying perivascular spaces enlargement are not fully understood, but both increased inflammation and blood brain barrier permeability have been hypothesized to play a role. We investigated the relationship between perivascular spaces and both CNS and peripheral inflammation, as well as blood brain barrier permeability, in cerebral small vessel disease. Fifty-four symptomatic sporadic cerebral small vessel disease patients were studied. perivascular spaces were quantified using both a visual rating scale, and by measurement of perivascular spaces volume, in both the white matter and basal ganglia. PET-MRI was used to simultaneously measure microglial activation using the radioligand 11C-PK11195, and blood brain barrier permeability was acquired using dynamic contrast enhanced MRI. We determined 11C-PK11195 binding and blood brain barrier permeability in the local vicinity of individual perivascular spaces in concentric shells surrounding perivascular spaces. In addition, both mean 11C-PK11195 binding and blood brain barrier permeability in both the white matter and basal ganglia were determined. To assess systemic inflammation a panel of 93 blood biomarkers relating to cardiovascular disease, inflammation and endothelial activation were measured. Within the white matter tissue in closest proximity to perivascular spaces displayed greater 11C-PK11195 binding (p < 0.001), in the vicinity of perivascular spaces. Higher white matter perivascular spaces burden on the visual rating scale was associated with higher white matter 11C-PK11195 binding (rho = 0.469, FDR-p =0.009); values for perivascular spaces volume showed a similar trend. In contrast there were no associations between basal ganglia perivascular spaces burden and 11C-PK11195 binding. No perivascular spaces marker correlated with blood brain barrier permeability. There was no association between perivascular spaces markers and systemic inflammation blood biomarkers. Our findings demonstrate that white matter perivascular spaces are associated with increased 11C-PK11195 binding, consistent with neuroinflammation playing a role in white matter perivascular spaces enlargement. Further longitudinal and intervention studies and required to determine whether the relationship between neuroinflammation with enlarged perivascular spaces is causal.

中文翻译:


脑小血管疾病的血管周围间隙功能障碍与神经炎症有关



血管周围间隙扩大是脑小血管疾病的一个特征,据推测,它们可能反映淋巴引流受损。血管周围间隙扩大的机制尚不完全清楚,但据推测炎症增加和血脑屏障通透性都起了作用。我们研究了脑小血管病中血管周围间隙与 CNS 和外周炎症以及血脑屏障通透性之间的关系。研究了 54 例有症状的散发性脑小血管病患者。使用视觉评定量表和测量白质和基底神经节中的血管周围间隙体积来量化血管周围间隙。PET-MRI 用于使用放射配体 11C-PK11195 同时测量小胶质细胞活化,并使用动态对比增强 MRI 获得血脑屏障通透性。我们确定了血管周围间隙周围同心壳中单个血管周围间隙局部附近的 11C-PK11195 结合和血脑屏障通透性。此外,还确定了白质和基底神经节中 11C-PK11195 结合的平均 11C- 结合和血脑屏障通透性。为了评估全身炎症,测量了一组与心血管疾病、炎症和内皮活化相关的 93 种血液生物标志物。在血管周围间隙附近的白质组织中,显示出更大的 11C-PK11195 结合 (p < 0.001)。视觉评定量表上较高的白质血管周围间隙负荷与较高的白质 11C-PK11195 结合相关 (rho = 0.469,FDR-p =0。009);血管周围间隙体积的值显示出类似的趋势。相比之下,基底神经节、血管周围间隙负荷和 11C-PK11195 结合之间没有关联。没有血管周围间隙标志物与血脑屏障通透性相关。血管周围间隙标志物与全身炎症血液生物标志物之间没有关联。我们的研究结果表明,白质血管周围间隙与 11C-PK11195 结合增加有关,这与神经炎症在白质血管周围间隙扩大中发挥作用一致。进一步的纵向和干预研究,需要确定神经炎症与血管周围间隙扩大之间的关系是否是因果关系。
更新日期:2024-11-07
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