美国哈佛医学院Chenghua Gu研究团队发现，通过血管和血管周围细胞的分析揭示脑区之间血脑屏障异质性的特征。2024年8月29日，《自然—神经科学》杂志在线发表了这项成果。

研究人员使用单细胞和空间转录组学技术，对比了小鼠的正中隆起（一个具有天然漏血管的脑室旁器官）与皮层。研究人员在内皮细胞（EC）和血管周围细胞（包括星形胶质细胞、周细胞和成纤维细胞）中识别出数百种分子差异。通过电子显微镜和基于水的组织清除方法，研究人员揭示了这些区域内内皮细胞和血管周围细胞的独特解剖特征和相互作用模式。

最后，研究人员识别了候选的区域富集的内皮细胞—血管周围细胞配体-受体对。这些结果表明，内皮细胞的分子特化和独特的内皮细胞—血管周围细胞相互作用共同促成了血脑屏障（BBB）的功能异质性。这一平台可用于研究其他脑区的BBB异质性，并可能促进中枢神经系统区域特异性治疗方法的发展。

据悉，BBB保护大脑并维持神经元稳态。BBB的特性在不同脑区之间可能有所不同，以支持区域功能，但BBB异质性的形成机制尚不清楚。

附：英文原文

Title: Characteristics of blood–brain barrier heterogeneity between brain regions revealed by profiling vascular and perivascular cells

Author: Pfau, Sarah J., Langen, Urs H., Fisher, Theodore M., Prakash, Indumathi, Nagpurwala, Faheem, Lozoya, Ricardo A., Lee, Wei-Chung Allen, Wu, Zhuhao, Gu, Chenghua

Issue&Volume: 2024-08-29

Abstract: The blood–brain barrier (BBB) protects the brain and maintains neuronal homeostasis. BBB properties can vary between brain regions to support regional functions, yet how BBB heterogeneity occurs is poorly understood. Here, we used single-cell and spatial transcriptomics to compare the mouse median eminence, one of the circumventricular organs that has naturally leaky blood vessels, with the cortex. We identified hundreds of molecular differences in endothelial cells (ECs) and perivascular cells, including astrocytes, pericytes and fibroblasts. Using electron microscopy and an aqueous-based tissue-clearing method, we revealed distinct anatomical specializations and interaction patterns of ECs and perivascular cells in these regions. Finally, we identified candidate regionally enriched EC–perivascular cell ligand–receptor pairs. Our results indicate that both molecular specializations in ECs and unique EC–perivascular cell interactions contribute to BBB functional heterogeneity. This platform can be used to investigate BBB heterogeneity in other regions and may facilitate the development of central nervous system region-specific therapeutics.

DOI: 10.1038/s41593-024-01743-y

Source: https://www.nature.com/articles/s41593-024-01743-y