Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, United States; Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China.
Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, United States; Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, AZ, United States.
Neurosci Lett. 2020 Sep 14;735:135160. doi: 10.1016/j.neulet.2020.135160. Epub 2020 Jun 16.
Endothelial sphingosine-1-phosphate receptors are emerging as relevant therapeutic targets during acute ischemic stroke (AIS). Physiologically, the cerebrovascular endothelium plays a vital role in maintaining barrier integrity and cerebrovascular homeostasis. During a cerebral ischemic event, products from parenchymal cell death are released and trigger vascular endothelial dysfunction and vascular inflammation leading to barrier integrity disruption. Endothelial dysfunction, inflammation, and a breach in barrier property play a significant role in contributing to a vicious cycle which promotes brain edema formation and exacerbates neuronal injury post stroke. Data from experimental stroke models and clinical trials suggest that selective sphingosine-1-phosphate receptor type 1 (S1PR1) modulation improves endothelial health and function and, as a result, contributes to improved neurological outcome post ischemic injury. This review highlights the impact of sphingosine-1-phosphate (S1P)/S1PR1 signaling involved in blood brain barrier (BBB) integrity and cerebrovascular inflammation following AIS. We focus on the beneficial actions of S1PR1 signaling during ischemic injury including barrier protection to lessen brain edema formation and reduction in the development and progression of vascular inflammation by attenuating endothelial cell activation resulting in reduced neurovascular inflammation. Potential gaps and future directions related to the role of S1PR during AIS are also discussed.
内皮鞘氨醇-1-磷酸受体在急性缺血性脑卒中（AIS）期间成为相关的治疗靶点。从生理学上讲，脑血管内皮在维持血脑屏障完整性和脑血管稳态方面起着至关重要的作用。在脑缺血事件中，实质细胞死亡产物释放并触发血管内皮功能障碍和血管炎症，导致屏障完整性破坏。内皮功能障碍、炎症和屏障特性的破坏在促进脑水肿形成和加重卒中后神经元损伤的恶性循环中起着重要作用。来自实验性中风模型和临床试验的数据表明，选择性鞘氨醇-1-磷酸受体 1（S1PR1）调节可改善内皮细胞的健康和功能，从而有助于改善缺血性损伤后的神经功能预后。这篇综述强调了在 AIS 后血脑屏障（BBB）完整性和脑血管炎症中涉及的鞘氨醇-1-磷酸（S1P）/S1PR1 信号的影响。我们重点介绍了 S1PR1 信号在缺血性损伤中的有益作用，包括通过减轻内皮细胞激活来减轻脑水肿形成和减少血管炎症的发展和进展，从而保护屏障。还讨论了与 S1PR 在 AIS 中的作用相关的潜在差距和未来方向。
