Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000, Odense, Denmark.
Department of Clinical Research, BRIDGE-Brain Research-Inter-Disciplinary Guided Excellence, University of Southern Denmark, 5000, Odense C, Denmark.
Acta Neuropathol. 2019 May;137(5):693-714. doi: 10.1007/s00401-018-1930-z. Epub 2018 Nov 27.
Inflammation is currently considered a prime target for the development of new stroke therapies. In the acute phase of ischemic stroke, microglia are activated and then circulating immune cells invade the peri-infarct and infarct core. Resident and infiltrating cells together orchestrate the post-stroke inflammatory response, communicating with each other and the ischemic neurons, through soluble and membrane-bound signaling molecules, including cytokines. Inflammation can be both detrimental and beneficial at particular stages after a stroke. While it can contribute to expansion of the infarct, it is also responsible for infarct resolution, and influences remodeling and repair. Several pre-clinical and clinical proof-of-concept studies have suggested the effectiveness of pharmacological interventions that target inflammation post-stroke. Experimental evidence shows that targeting certain inflammatory cytokines, such as tumor necrosis factor, interleukin (IL)-1, IL-6, and IL-10, holds promise. However, as these cytokines possess non-redundant protective and immunoregulatory functions, their neutralization or augmentation carries a risk of unwanted side effects, and clinical translation is, therefore, challenging. This review summarizes the cell biology of the post-stroke inflammatory response and discusses pharmacological interventions targeting inflammation in the acute phase after a stroke that may be used alone or in combination with recanalization therapies. Development of next-generation immune therapies should ideally aim at selectively neutralizing pathogenic immune signaling, enhancing tissue preservation, promoting neurological recovery and leaving normal function intact.
炎症目前被认为是开发新的中风治疗方法的主要靶点。在缺血性中风的急性期，小胶质细胞被激活，然后循环免疫细胞浸润到梗死周边区和梗死核心区。驻留细胞和浸润细胞通过可溶性和膜结合信号分子（包括细胞因子）共同协调中风后的炎症反应，相互之间以及与缺血神经元进行通讯。炎症在中风后特定阶段可能既有弊又有利。虽然它可能导致梗死扩大，但它也负责梗死的溶解，并影响重塑和修复。一些临床前和临床概念验证研究表明，针对中风后炎症的药物干预是有效的。实验证据表明，针对某些炎症细胞因子（如肿瘤坏死因子、白细胞介素 (IL)-1、IL-6 和 IL-10）具有一定的潜力。然而，由于这些细胞因子具有非冗余的保护和免疫调节功能，其中和或增强可能会带来不必要的副作用，因此临床转化具有挑战性。本综述总结了中风后炎症反应的细胞生物学，并讨论了针对中风后急性期炎症的药物干预措施，这些措施可单独使用或与再通治疗联合使用。下一代免疫疗法的开发理想情况下应旨在选择性地中和致病免疫信号，增强组织保存，促进神经恢复并保持正常功能。
