Bernardo-Castro Sara, Sousa João André, Brás Ana, Cecília Carla, Rodrigues Bruno, Almendra Luciano, Machado Cristina, Santo Gustavo, Silva Fernando, Ferreira Lino, Santana Isabel, Sargento-Freitas João
Stroke Unit, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal.
Front Neurol. 2020 Dec 9;11:594672. doi: 10.3389/fneur.2020.594672. eCollection 2020.
The blood-brain barrier (BBB) is a dynamic interface responsible for maintaining the central nervous system homeostasis. Its unique characteristics allow protecting the brain from unwanted compounds, but its impairment is involved in a vast number of pathological conditions. Disruption of the BBB and increase in its permeability are key in the development of several neurological diseases and have been extensively studied in stroke. Ischemic stroke is the most prevalent type of stroke and is characterized by a myriad of pathological events triggered by an arterial occlusion that can eventually lead to fatal outcomes such as hemorrhagic transformation (HT). BBB permeability seems to follow a multiphasic pattern throughout the different stroke stages that have been associated with distinct biological substrates. In the hyperacute stage, sudden hypoxia damages the BBB, leading to cytotoxic edema and increased permeability; in the acute stage, the neuroinflammatory response aggravates the BBB injury, leading to higher permeability and a consequent risk of HT that can be motivated by reperfusion therapy; in the subacute stage (1-3 weeks), repair mechanisms take place, especially neoangiogenesis. Immature vessels show leaky BBB, but this permeability has been associated with improved clinical recovery. In the chronic stage (>6 weeks), an increase of BBB restoration factors leads the barrier to start decreasing its permeability. Nonetheless, permeability will persist to some degree several weeks after injury. Understanding the mechanisms behind BBB dysregulation and HT pathophysiology could potentially help guide acute stroke care decisions and the development of new therapeutic targets; however, effective translation into clinical practice is still lacking. In this review, we will address the different pathological and physiological repair mechanisms involved in BBB permeability through the different stages of ischemic stroke and their role in the development of HT and stroke recovery.
血脑屏障（BBB）是一个动态界面，负责维持中枢神经系统的稳态。其独特的特性可保护大脑免受有害化合物的侵害，但其功能受损与大量病理状况有关。血脑屏障的破坏及其通透性增加是几种神经系统疾病发展的关键因素，并且在中风研究中已得到广泛研究。缺血性中风是最常见的中风类型，其特征是由动脉闭塞引发的一系列病理事件，最终可能导致致命后果，如出血性转化（HT）。在整个不同的中风阶段，血脑屏障通透性似乎呈现多相模式，这与不同的生物学底物有关。在超急性期，突然缺氧会损害血脑屏障，导致细胞毒性水肿和通透性增加；在急性期，神经炎症反应会加重血脑屏障损伤，导致更高的通透性以及随之而来的出血性转化风险，这可能是由再灌注治疗引起的；在亚急性期（1 - 3周），修复机制开始起作用，尤其是新生血管形成。不成熟的血管血脑屏障渗漏，但这种通透性与临床恢复改善有关。在慢性期（>6周），血脑屏障恢复因子增加导致屏障开始降低其通透性。尽管如此，损伤后数周通透性仍会在一定程度上持续存在。了解血脑屏障失调和出血性转化病理生理学背后的机制可能有助于指导急性中风护理决策和新治疗靶点的开发；然而，目前仍缺乏有效的临床实践转化。在本综述中，我们将探讨缺血性中风不同阶段血脑屏障通透性所涉及的不同病理和生理修复机制及其在出血性转化和中风恢复发展中的作用。
