The Stroke-Induced Blood-Brain Barrier Disruption: Current Progress of Inspection Technique, Mechanism, and Therapeutic Target.
The Stroke-Induced Blood-Brain Barrier Disruption: Current Progress of Inspection Technique, Mechanism, and Therapeutic Target.
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DOI：
10.2174/1570159x18666200528143301
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发表时间：
2020
影响因子：
5.3
通讯作者：
Zhang JH
中科院分区：
文献类型：
--
作者：
Okada T;Suzuki H;Travis ZD;Zhang JH
中风是世界范围内导致死亡和发病的主要原因之一。血脑屏障(BBB)是脑内微血管的一种特有结构。在正常生理条件下，血脑屏障起到阻止有害物质进入中枢神经系统内脑实质的作用。然而，中风刺激会导致血脑屏障的破坏，导致细胞毒性物质的涌入，血管源性脑水肿和出血性转化。因此，血脑屏障中断是一个主要的并发症，为了改善中风的临床结果，需要解决这个问题。在本文中，我们首先讨论了血脑屏障的结构和功能。接下来，我们讨论了在体外和体内研究血脑屏障破裂的技术进展，以及临床环境中的生物标记物和成像技术。最后，我们重点介绍了卒中诱导的神经炎症和内皮细胞凋亡过程导致血脑屏障破坏的机制，以及保护卒中后血脑屏障完整性的潜在治疗靶点。卒中引起的组织损伤产生的次生产物使小胶质细胞和巨噬细胞等髓系细胞转变为促炎表型，继而通过神经炎症和内皮细胞的凋亡进一步破坏血脑屏障。相反，这些髓样细胞也被极化为抗炎表型，修复受损的血脑屏障。因此，诱导髓系细胞抗炎表型的治疗策略可能会保护血脑屏障，从而改善中风患者的临床预后。
Stroke is one of the leading causes of mortality and morbidity worldwide. The blood-brain barrier (BBB) is a characteristic structure of microvessel within the brain. Under normal physiological conditions, the BBB plays a role in the prevention of harmful substances entering into the brain parenchyma within the central nervous system. However, stroke stimuli induce the breakdown of BBB leading to the influx of cytotoxic substances, vasogenic brain edema, and hemorrhagic transformation. Therefore, BBB disruption is a major complication, which needs to be addressed in order to improve clinical outcomes in stroke. In this review, we first discuss the structure and function of the BBB. Next, we discuss the progress of the techniques utilized to study BBB breakdown in in-vitro and in-vivo studies, along with biomarkers and imaging techniques in clinical settings. Lastly, we highlight the mechanisms of stroke-induced neuroinflammation and apoptotic process of endothelial cells causing BBB breakdown, and the potential therapeutic targets to protect BBB integrity after stroke. Secondary products arising from stroke-induced tissue damage provide transformation of myeloid cells such as microglia and macrophages to pro-inflammatory phenotype followed by further BBB disruption via neuroinflammation and apoptosis of endothelial cells. In contrast, these myeloid cells are also polarized to anti-inflammatory phenotype, repairing compromised BBB. Therefore, therapeutic strategies to induce anti-inflammatory phenotypes of the myeloid cells may protect BBB in order to improve clinical outcomes of stroke patients.