Hu Yue, Zheng Yangmin, Wang Tao, Jiao Liqun, Luo Yumin
1Institute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
3Beijing Geriatric Medical Research Center and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China.
Aging Dis. 2022 Jun 1;13(3):647-654. doi: 10.14336/AD.2021.1121. eCollection 2022 Jun.
Blood brain barrier (BBB) injury is an important factor affecting the prognosis of ischemic stroke. Extensive research on BBB injury has revealed that blood vessels and neural networks are interdependent and interrelated during and after the development of the brain. An array of signaling molecules, known as angioneurins, can affect both blood vessels and neural networks simultaneously. Angioneurins not only regulate the angiogenesis and remodeling process of the vascular system, but also act as neurotrophic and neuroprotective factors, or serve as guide molecules for axons. Vascular endothelial growth factor (VEGF) is a type of angioneurin that is expressed in neurons, astrocytes, macrophages, and vascular endothelial cells in ischemic and hypoxic brain tissues after cerebral ischemia. VEGF can increase and induce the destruction of the endothelial barrier in the early stages of cerebral ischemia. Both the upregulation of endogenous VEGF levels and the use of exogenous VEGF are harmful in the acute stage of stroke. However, the harmful effects of VEGF on vascular integrity are transient. Several studies have shown that VEGF regulates angiogenesis, neurogenesis, neurite growth and brain edema after cerebral ischemia. Therefore, it is crucial to understand the dual role of VEGF in ischemic stroke. The following will focus on the damage caused by VEGF to the BBB in the context of cerebral ischemic stroke, as well as therapeutic studies targeting VEGF.
血脑屏障(BBB)损伤是影响缺血性脑卒中预后的重要因素。对血脑屏障损伤的广泛研究表明,在脑发育过程中和发育后,血管和神经网络相互依存、相互关联。一系列被称为血管神经素的信号分子可同时影响血管和神经网络。血管神经素不仅调节血管系统的血管生成和重塑过程,还作为神经营养和神经保护因子,或作为轴突的导向分子。血管内皮生长因子(VEGF)是一种血管神经素,在脑缺血后的缺血缺氧脑组织中的神经元、星形胶质细胞、巨噬细胞和血管内皮细胞中表达。VEGF可在脑缺血早期增加并诱导内皮屏障的破坏。内源性VEGF水平上调和使用外源性VEGF在脑卒中急性期均有害。然而,VEGF对血管完整性的有害作用是短暂的。多项研究表明,VEGF在脑缺血后调节血管生成、神经发生、神经突生长和脑水肿。因此,了解VEGF在缺血性脑卒中中的双重作用至关重要。以下将重点探讨在脑缺血性脑卒中背景下VEGF对血脑屏障的损伤以及针对VEGF的治疗研究。