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脑微血管内皮细胞代谢及其与屏障功能的关系。

Brain microvascular endothelial cell metabolism and its ties to barrier function.

机构信息

Fischell Department of Bioengineering, University of Maryland, College Park, MD, United States.

Fischell Department of Bioengineering, University of Maryland, College Park, MD, United States.

出版信息

Vitam Horm. 2024;126:25-75. doi: 10.1016/bs.vh.2024.05.002. Epub 2024 May 31.

DOI:10.1016/bs.vh.2024.05.002
PMID:39029976
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11756814/
Abstract

Brain microvascular endothelial cells, which lie at the interface between blood and brain, are critical to brain energetics. These cells must precisely balance metabolizing nutrients for their own demands with transporting nutrients into the brain to sustain parenchymal cells. It is essential to understand this integrated metabolism and transport so that we can develop better diagnostics and therapeutics for neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis, and traumatic brain injury. In this chapter, we first describe brain microvascular endothelial cell metabolism and how these cells regulate both blood flow and nutrient transport. We then explain the impact of brain microvascular endothelial cell metabolism on the integrity of the blood-brain barrier, as well as how metabolites produced by the endothelial cells impact other brain cells. We detail some ways that cell metabolism is typically measured experimentally and modeled computationally. Finally, we describe changes in brain microvascular endothelial cell metabolism in aging and neurodegenerative diseases. At the end of the chapter, we highlight areas for future research in brain microvascular endothelial cell metabolism. The goal of this chapter is to underscore the importance of nutrient metabolism and transport at the brain endothelium for cerebral health and neurovascular disease treatment.

摘要

脑微血管内皮细胞位于血液和大脑之间的界面,对大脑的能量代谢至关重要。这些细胞必须精确地平衡代谢营养物质以满足自身需求,同时将营养物质运输到大脑中以维持实质细胞的功能。了解这种整合的代谢和运输对于开发更好的神经退行性疾病(如阿尔茨海默病、多发性硬化症和创伤性脑损伤)的诊断和治疗方法至关重要。在本章中,我们首先描述了脑微血管内皮细胞的代谢,以及这些细胞如何调节血流量和营养物质的运输。然后,我们解释了脑微血管内皮细胞代谢对血脑屏障完整性的影响,以及内皮细胞产生的代谢物如何影响其他脑细胞。我们详细介绍了一些通常用于实验测量和计算建模的细胞代谢方法。最后,我们描述了衰老和神经退行性疾病中脑微血管内皮细胞代谢的变化。在本章的最后,我们强调了未来在脑微血管内皮细胞代谢研究中的重点领域。本章的目的是强调营养物质代谢和运输在大脑内皮中的重要性,以维持大脑健康和治疗神经血管疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/829f/11756814/1af1903962e1/nihms-2045712-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/829f/11756814/708e529c2248/nihms-2045712-f0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/829f/11756814/1586cf03e7f9/nihms-2045712-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/829f/11756814/1af1903962e1/nihms-2045712-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/829f/11756814/708e529c2248/nihms-2045712-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/829f/11756814/5a3ae5444953/nihms-2045712-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/829f/11756814/741c2048957c/nihms-2045712-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/829f/11756814/203cc8cd610c/nihms-2045712-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/829f/11756814/d84fa8e512ce/nihms-2045712-f0005.jpg
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Ketone bodies supplementation restores the barrier function, induces a metabolic switch, and elicits beta-hydroxybutyrate diffusion across a monolayer of iPSC-derived brain microvascular endothelial cells.酮体补充剂恢复了屏障功能,诱导了代谢转换,并使 iPSC 衍生的脑微血管内皮细胞单层中的 β-羟丁酸扩散。
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