Lee Wei Ling Amelia, Michael-Titus Adina T, Shah Divyen K
Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Dev Neurosci. 2017;39(1-4):49-58. doi: 10.1159/000467392. Epub 2017 Apr 22.
This review aims to highlight a possible relationship between hypoxic-ischaemic encephalopathy (HIE) and the disruption of the blood-brain barrier (BBB). Inflammatory reactions perpetuate a large proportion of cerebral injury. The extent of injury noted in HIE is not only determined by the biochemical cascades that trigger the apoptosis-necrosis continuum of cell death in the brain parenchyma, but also by the breaching of the BBB by pro-inflammatory factors. We examine the changes that contribute to the breakdown of the BBB that occur during HIE at a macroscopic, cellular, and molecular level. The BBB is a permeability barrier which separates a large majority of brain areas from the systemic circulation. The concept of a physiological BBB is based at the anatomical level on the neurovascular unit (NVU). The NVU consists of various cellular components that jointly regulate the exchanges that occur at the interface between the systemic circulation and the brain parenchyma. There is increased understanding of the contribution of the components of the NVU, e.g., astrocytes and pericytes, to the maintenance of this physiological barrier. We also explore the development of therapeutic options in HIE, such as harnessing the transport systems in the BBB, to enable the delivery of large molecules with molecular Trojan horse technology, and the reinforcement of the physical barrier with cell-based therapy which utilizes endothelial progenitor cells and stem cells.
本综述旨在强调缺氧缺血性脑病（HIE）与血脑屏障（BBB）破坏之间可能存在的关系。炎症反应使大部分脑损伤持续存在。HIE中所观察到的损伤程度不仅取决于触发脑实质细胞凋亡 - 坏死连续过程的生化级联反应，还取决于促炎因子对血脑屏障的破坏。我们在宏观、细胞和分子水平上研究了HIE期间导致血脑屏障破坏的各种变化。血脑屏障是一种通透性屏障，将大部分脑区与体循环分隔开。生理性血脑屏障的概念在解剖学层面基于神经血管单元（NVU）。神经血管单元由多种细胞成分组成，它们共同调节体循环与脑实质之间界面处发生的物质交换。人们对神经血管单元的成分（如星形胶质细胞和周细胞）在维持这种生理屏障中的作用有了更多的了解。我们还探讨了HIE治疗方案的发展，例如利用血脑屏障中的转运系统，通过分子特洛伊木马技术实现大分子的递送，以及利用内皮祖细胞和干细胞的细胞疗法加强物理屏障。
