Angiogenesis and Blood-Brain Barrier Permeability in Vascular Remodeling after Stroke.
Angiogenesis and Blood-Brain Barrier Permeability in Vascular Remodeling after Stroke.
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DOI：
10.2174/1570159x18666200720173316
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发表时间：
2020
影响因子：
5.3
通讯作者：
Torbey MT
中科院分区：
文献类型：
--
作者：
Yang Y;Torbey MT
血管生成，即新血管的生长，是一种自然防御机制，有助于在缺血性中风后恢复受影响脑组织的氧气和营养供应。通过刺激血管生长，血管生成可能稳定脑血流，从而促进神经元存活、脑可塑性和神经恢复。然而，卒中后治疗性血管生成面临挑战：新血管生成诱导的血管通透性高于正常，促进血管生成的治疗可能会加剧卒中患者的预后。治疗方法的发展需要阐明疾病的确切细胞和分子基础。中枢神经系统的微环境动态平衡是其正常功能所必需的，由血脑屏障(BBB)维持。紧密连接蛋白(TJP)形成血管内皮细胞(ECs)之间的紧密连接，在调节血脑屏障通透性方面起着关键作用。我们证明，卒中后，由于内皮细胞中缺乏主要的TJP，梗死区周围血管新生血管具有异常高的血脑屏障通透性。因此，促进新血管中TJ的形成和BBB的完整性，再加上快速的血管生成，将为促进卒中的康复提供一种有前途的、更安全的治疗策略。周细胞是血管屏障发生过程中的中枢神经血管联合成分，对血脑屏障的完整性至关重要。我们发现，周细胞在卒中诱导的血管生成和新生血管中的TJ形成中也起着关键作用。基于这些发现，本文重点介绍了BBB功能的调节方面，并描述了TJ形成的细胞和分子特点，重点阐述了周细胞在卒中后血管生成过程中对BBB完整性的作用。
Angiogenesis, the growth of new blood vessels, is a natural defense mechanism helping to restore oxygen and nutrient supply to the affected brain tissue following an ischemic stroke. By stimulating vessel growth, angiogenesis may stabilize brain perfusion, thereby promoting neuronal survival, brain plasticity, and neurologic recovery. However, therapeutic angiogenesis after stroke faces challenges: new angiogenesis-induced vessels have a higher than normal permeability, and treatment to promote angiogenesis may exacerbate outcomes in stroke patients. The development of therapies requires elucidation of the precise cellular and molecular basis of the disease. Microenvironment homeostasis of the central nervous system is essential for its normal function and is maintained by the blood-brain barrier (BBB). Tight junction proteins (TJP) form the tight junction (TJ) between vascular endothelial cells (ECs) and play a key role in regulating the BBB permeability. We demonstrated that after stroke, new angiogenesis-induced vessels in peri-infarct areas have abnormally high BBB permeability due to a lack of major TJPs in ECs. Therefore, promoting TJ formation and BBB integrity in the new vessels coupled with speedy angiogenesis will provide a promising and safer treatment strategy for improving recovery from stroke. Pericyte is a central neurovascular unite component in vascular barriergenesis and are vital to BBB integrity. We found that pericytes also play a key role in stroke-induced angiogenesis and TJ formation in the newly formed vessels. Based on these findings, in this article, we focus on regulation aspects of the BBB functions and describe cellular and molecular special features of TJ formation with an emphasis on role of pericytes in BBB integrity during angiogenesis after stroke.