Meningeal Mast Cells as Key Effectors of Stroke Pathology
Meningeal Mast Cells as Key Effectors of Stroke Pathology
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DOI：
10.3389/fncel.2019.00126
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发表时间：
2019-04-03
影响因子：
5.3
通讯作者：
Steinberg, Gary K.
中科院分区：
文献类型：
--
作者：
Arac, Ahmet;Grimbaldeston, Michele A.;Steinberg, Gary K.
中风是美国成人残疾的主要原因。由于中风后炎症是中风后损伤和恢复的关键决定因素，因此了解中风后免疫系统和大脑之间的相互作用对治疗干预大有希望。这种相互作用的一个未被充分研究但很重要的方面是围绕大脑的脑膜的作用。所有的血管在进入脑实质之前都穿过脑膜间隙，使得脑膜理想地定位成作为下面的脑实质的免疫守门人。新出现的证据表明，驻留在脑膜中的免疫细胞的活动对于执行这种守门人功能至关重要。肥大细胞（MC），最为人所知的促炎效应细胞，是脑膜中长期驻留的免疫细胞之一。在这里，我们讨论了最近的研究结果，在文献中的作用，位于脑膜空间和中风病理的MC。本文综述了小鼠模型的最新进展，以研究MC及其衍生产物在体内的作用，以及使用这些小鼠模型的重要性。我们研究了脑膜在大脑和免疫相互作用中发挥关键作用的概念，重新评估了中风病理学关键效应器的观点，并讨论了治疗开发的机遇和挑战。
Stroke is the leading cause of adult disability in the United States. Because post-stroke inflammation is a critical determinant of damage and recovery after stroke, understanding the interplay between the immune system and the brain after stroke holds much promise for therapeutic intervention. An understudied, but important aspect of this interplay is the role of meninges that surround the brain. All blood vessels travel through the meningeal space before entering the brain parenchyma, making the meninges ideally located to act as an immune gatekeeper for the underlying parenchyma. Emerging evidence suggests that the actions of immune cells resident in the meninges are essential for executing this gatekeeper function. Mast cells (MCs), best known as proinflammatory effector cells, are one of the long-term resident immune cells in the meninges. Here, we discuss recent findings in the literature regarding the role of MCs located in the meningeal space and stroke pathology. We review the latest advances in mouse models to investigate the roles of MCs and MC-derived products in vivo, and the importance of using these mouse models. We examine the concept of the meninges playing a critical role in brain and immune interactions, reevaluate the perspectives on the key effectors of stroke pathology, and discuss the opportunities and challenges for therapeutic development.