High Resolution Multiplex Confocal Imaging of the Neurovascular Unit in Health and Experimental Ischemic Stroke.
High Resolution Multiplex Confocal Imaging of the Neurovascular Unit in Health and Experimental Ischemic Stroke.
复制标题
在健康和实验性缺血性中风中神经血管单元的高分辨率多重共聚焦成像。
作者：
神经血管单位（NVU）是建立血脑屏障（BBB）并协调与神经元功能相关的脑血流的解剖学细胞群。在大脑灰质中，NVU的细胞成分包括内皮细胞和相关的周细胞、星形胶质细胞、神经元和小胶质细胞。NVU功能障碍是影响CNS的疾病的常见特征，例如缺血性中风。对这些NVU变化的高水平评价需要使用成像模式，这些成像模式可以使疾病条件下的各种细胞类型可视化。在这项研究中，我们应用我们的共聚焦显微镜策略，使用市售的标记试剂，第一次，同时调查健康和缺血脑组织中内皮细胞，血管基底层，周细胞，小胶质细胞，星形胶质细胞和/或星形胶质细胞端足，和神经突之间的关联。这使我们能够在单个共聚焦图像中展示缺血诱导的星形胶质细胞活化、神经突丢失和小胶质细胞向血管迁移。此外，我们的标记混合物能够精确定量神经突和星形胶质细胞反应性的变化，从而显示健康和患病脑组织中不同NVU细胞成分之间的关系。应用我们的成像方法同时可视化多种NVU细胞类型提供了对NVU功能和病理学的更好理解，这是一种最先进的进步，将有助于开发更有效的治疗策略，用于表现出神经血管功能障碍的CNS疾病，如缺血性中风。
The neurovascular unit (NVU) is an anatomical group of cells that establishes the blood–brain barrier (BBB) and coordinates cerebral blood flow in association with neuronal function. In cerebral gray matter, cellular constituents of the NVU include endothelial cells and associated pericytes, astrocytes, neurons, and microglia. Dysfunction of the NVU is a common feature of diseases that affect the CNS, such as ischemic stroke. High-level evaluation of these NVU changes requires the use of imaging modalities that can enable the visualization of various cell types under disease conditions. In this study, we applied our confocal microscopy strategy using commercially available labeling reagents to, for the first time, simultaneously investigate associations between endothelial cells, the vascular basal lamina, pericytes, microglia, astrocytes and/or astrocyte end-feet, and neurites in both healthy and ischemic brain tissue. This allowed us to demonstrate ischemia-induced astrocyte activation, neurite loss, and microglial migration toward blood vessels in a single confocal image. Furthermore, our labeling cocktail enabled a precise quantification of changes in neurites and astrocyte reactivity, thereby showing the relationship between different NVU cellular constituents in healthy and diseased brain tissue. The application of our imaging approach for the simultaneous visualization of multiple NVU cell types provides an enhanced understanding of NVU function and pathology, a state-of-the-art advancement that will facilitate the development of more effective treatment strategies for diseases of the CNS that exhibit neurovascular dysfunction, such as ischemic stroke.
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影响因子：
3.2
作者：
ACARIN, L;VELA, JM;CASTELLANO, B
通讯作者：
CASTELLANO, B
影响因子：
6.3
作者：
Bonney, Stephanie K.;Sullivan, Liam T.;Cherry, Timothy J.;Daneman, Richard;Shih, Andy Y.
通讯作者：
Shih, Andy Y.
DOI：
10.1007/978-1-4939-9658-2_12
发表时间：
2019-01-01
期刊：
MICROGLIA: METHODS AND PROTOCOLS
影响因子：
--
作者：
Brawek, Bianca;del Moral, Maria Olmedillas;Garaschuk, Olga
通讯作者：
Garaschuk, Olga
缺乏周细胞会导致内皮增生和异常血管形态发生。
影响因子：
7.8
作者：
Hellstrom, M;Gerhardt, H;Kalen, M;Li, X;Eriksson, U;Wolburg, H;Betsholtz, C
通讯作者：
Betsholtz, C
影响因子：
5.6
作者：
Battistella R;Kritsilis M;Matuskova H;Haswell D;Cheng AX;Meissner A;Nedergaard M;Lundgaard I
通讯作者：
Lundgaard I