Microglia, the resident immune cells of the central nervous system, are intimately involved in the brain’s most basic processes, from pruning neural synapses during development to preventing excessive neuronal activity throughout life. Studies have reported both helpful and harmful roles for microglia at the blood-brain barrier (BBB) in the context of disease. However, less is known about microglia-endothelial cell interactions in the healthy brain. To investigate the role of microglia at a healthy BBB, we used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia and analyzed the BBB ultrastructure, permeability, and transcriptome. Interestingly, we found that, despite their direct contact with endothelial cells, microglia are not necessary for the maintenance of BBB structure, function, or gene expression in the healthy brain. However, we found that PLX5622 treatment alters brain endothelial cholesterol metabolism. This effect was independent from microglial depletion, suggesting that PLX5622 has off-target effects on brain vasculature.

中文翻译：

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小胶质细胞对于维持健康中的血脑屏障特性不是必需的，但PLX5622会改变脑内皮胆固醇代谢


小胶质细胞是中枢神经系统的常驻免疫细胞，密切参与大脑最基本的过程，从发育过程中修剪神经突触到防止一生中的过度神经元活动。研究报告了小胶质细胞在疾病背景下在血脑屏障 （BBB） 的作用既有益又有害。然而，对健康大脑中小胶质细胞-内皮细胞的相互作用知之甚少。为了研究小胶质细胞在健康 BBB 中的作用，我们使用集落刺激因子 1 受体 （CSF1R） 抑制剂PLX5622来耗竭小胶质细胞并分析 BBB 超微结构、通透性和转录组。有趣的是，我们发现，尽管小胶质细胞与内皮细胞直接接触，但它们对于维持健康大脑中 BBB 结构、功能或基因表达并不是必需的。然而，我们发现PLX5622治疗会改变脑内皮胆固醇代谢。这种效应与小胶质细胞耗竭无关，表明PLX5622对脑血管系统具有脱靶效应。