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小胶质细胞动力学、血脑屏障形态发生与发育毒性:

Microglial Dynamics, Blood-Brain Barrier Morphogenesis, and Developmental Toxicity: .

作者信息

Naphade Om, Barham Kaitlyn, Spencer Richard, Baker Nancy C, Zurlinden Todd J, Saili Katerine S, Carstens Kelly, Silvin Aymeric, Ginhoux Florent, Knudsen Thomas B

机构信息

Center for Computational Toxicology and Exposure (CCTE), Office of Research and Development (ORD), U.S. Environmental Protection Agency (USEPA), Research Triangle Park, NC 27711.

Oak Ridge Associated Universities, Contractor to USEPA/ORD/CCTE, Research Triangle Park, NC 27711.

出版信息

Curr Opin Toxicol. 2023 Dec 1;36. doi: 10.1016/j.cotox.2023.100419.

Abstract

Morphogenesis of the blood-brain barrier (BBB) is a complex process linked to neovascularization of the embryonic neural tube. This selective transport interface forms between vascular-neural compartments during organogenesis and dysregulation has been linked to neuroinflammation and neurodevelopmental defects. One emerging concept is that microglial cells play a central role in this neurovascular patterning, yet despite an extensive literature base, many gaps still exist in understanding how this resident immunological sentinel cell type interacts with chemical exposure at critical stages of neurodevelopment. The goals of this short review were to: (i) synopsize current understanding of microglial function during BBB morphogenesis; (ii) review potential disruption of microglial function linked to drug/chemical exposure during pregnancy; and (iii) present a working computational model for predictive toxicology of BBB dysmorphogenesis.

摘要

血脑屏障(BBB)的形态发生是一个与胚胎神经管新血管形成相关的复杂过程。这种选择性转运界面在器官发生过程中于血管-神经腔室之间形成,其失调与神经炎症和神经发育缺陷有关。一个新兴的概念是,小胶质细胞在这种神经血管模式形成中起核心作用,然而,尽管有大量的文献基础,但在理解这种常驻免疫哨兵细胞类型在神经发育关键阶段如何与化学暴露相互作用方面,仍存在许多空白。这篇简短综述的目的是:(i)概述目前对BBB形态发生过程中小胶质细胞功能的理解;(ii)综述与孕期药物/化学暴露相关的小胶质细胞功能潜在破坏;(iii)提出一个用于BBB畸形发生预测毒理学的实用计算模型。

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