Microglial activation and blood-brain barrier permeability in cerebral small vessel disease.
Microglial activation and blood-brain barrier permeability in cerebral small vessel disease.
复制标题
DOI：
10.1093/brain/awab003
复制
发表时间：
2021-06-22
期刊：
影响因子：
--
通讯作者：
Markus HS
中科院分区：
文献类型：
--
作者：
Walsh J;Tozer DJ;Sari H;Hong YT;Drazyk A;Williams G;Shah NJ;O'Brien JT;Aigbirhio FI;Rosenberg G;Fryer TD;Markus HS
参见Edison（doi：）对这篇文章的科学评论。使用先进的脑成像技术，沃尔什等人提供了脑小血管疾病患者神经炎症和血脑屏障通透性增加的证据。这两个过程都可以作为潜在的治疗靶点。脑小血管病（SVD）是中风和痴呆的主要原因。其潜在的发病机制知之甚少，但神经炎症和血脑屏障通透性增加已被假设发挥作用，临床前研究表明这两个过程可能是相关的。我们使用PET磁共振，同时测量小胶质细胞激活使用转运蛋白放射性配体11 C-PK 11195，和血脑屏障通透性使用动态对比增强MRI。采用病例对照设计，对散发性SVD（n = 20）、单基因SVD（伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病，CADASIL）和正常对照组（n = 20）进行了研究。胶质细胞活化和血脑屏障通透性增加的热点被确定为大于对照组分布的第95百分位数的值。在散发性SVD中，除了平均血脑屏障通透性增加（P < 0.001）外，正常外观的白色物质中11 C-PK 11195结合（P = 0.003）和血脑屏障通透性（P = 0.007）的热点体积也增加。在CADASIL中，未检测到血脑屏障通透性增加; 11 C-PK 11195结合增加的趋势不显著（P = 0.073）。11 C-PK 11195结合和血脑屏障通透性的热点在空间上不相关。在每位参与者中测量了一组93种与心血管疾病，炎症和内皮活化相关的血液生物标志物;进行了主成分分析，第一个成分与血脑屏障通透性和小胶质细胞活化相关。在散发性SVD组中，正常外观白色物质中的热点和平均体积血脑屏障通透性值均与维度1相关（分别为β = 0.829，P = 0.017和β = 0.976，P = 0.003）。与11 C-PK 11195结合无关。在CADASIL组中未发现与血液标志物相关。总之，在散发性SVD中，小胶质细胞活化和血脑屏障通透性增加都发生，但这些是空间上不同的过程。在CADASIL中未发现血脑屏障通透性增加的证据。
See Edison (doi:) for a scientific commentary on this article. Using advanced brain imaging techniques, Walsh et al. provide evidence of both neuroinflammation and increased blood-brain barrier permeability in patients with cerebral small vessel disease. Both processes could serve as potential therapeutic targets. Cerebral small vessel disease (SVD) is a major cause of stroke and dementia. The underlying pathogenesis is poorly understood, but both neuroinflammation and increased blood–brain barrier permeability have been hypothesized to play a role, and preclinical studies suggest the two processes may be linked. We used PET magnetic resonance to simultaneously measure microglial activation using the translocator protein radioligand 11C-PK11195, and blood–brain barrier permeability using dynamic contrast enhanced MRI. A case control design was used with two disease groups with sporadic SVD (n = 20), monogenic SVD (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, CADASIL), and normal controls (n = 20) were studied. Hotspots of increased glial activation and blood–brain barrier permeability were identified as values greater than the 95th percentile of the distribution in controls. In sporadic SVD there was an increase in the volume of hotspots of both 11C-PK11195 binding (P = 0.003) and blood–brain barrier permeability (P = 0.007) in the normal appearing white matter, in addition to increased mean blood–brain barrier permeability (P < 0.001). In CADASIL no increase in blood–brain barrier permeability was detected; there was a non-significant trend to increased 11C-PK11195 binding (P = 0.073). Hotspots of 11C-PK11195 binding and blood–brain barrier permeability were not spatially related. A panel of 93 blood biomarkers relating to cardiovascular disease, inflammation and endothelial activation were measured in each participant; principal component analysis was performed and the first component related to blood–brain barrier permeability and microglial activation. Within the sporadic SVD group both hotspot and mean volume blood–brain barrier permeability values in the normal appearing white matter were associated with dimension 1 (β = 0.829, P = 0.017, and β = 0.976, P = 0.003, respectively). There was no association with 11C-PK11195 binding. No associations with blood markers were found in the CADASIL group. In conclusion, in sporadic SVD both microglial activation and increased blood–brain barrier permeability occur, but these are spatially distinct processes. No evidence of increased blood–brain barrier permeability was found in CADASIL.
登录
查看更多内容
影响因子：
3.3
作者：
Taheri S;Gasparovic C;Shah NJ;Rosenberg GA
通讯作者：
Rosenberg GA
影响因子：
6.1
作者：
Edison, Paul;Archer, Hilary A.;Brooks, David J.
通讯作者：
Brooks, David J.
影响因子：
10.6
作者：
Burgos, Ninon;Cardoso, M. Jorge;Ourselin, Sebastien
通讯作者：
Ourselin, Sebastien
影响因子：
14.5
作者：
Duering, Marco;Csanadi, Endy;Dichgans, Martin
通讯作者：
Dichgans, Martin
影响因子：
3.7
作者：
Lawrence AJ;Patel B;Morris RG;MacKinnon AD;Rich PM;Barrick TR;Markus HS
通讯作者：
Markus HS