Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Neurotherapeutics. 2020 Apr;17(2):414-435. doi: 10.1007/s13311-020-00844-3.
The immune response to stroke is an exciting target for future stroke therapies. Stroke is a leading cause of morbidity and mortality worldwide, and clot removal (mechanical or pharmacological) to achieve tissue reperfusion is the only therapy currently approved for patient use. Due to a short therapeutic window and incomplete effectiveness, however, many patients are left with infarcted tissue that stimulates inflammation. Although this is critical to promote repair, it can also damage surrounding healthy brain tissue. In addition, acute immunodepression and subsequent infections are common and are associated with worse patient outcomes. Thus, the acute immune response is a major focus of researchers attempting to identify ways to amplify its benefits and suppress its negative effects to improve short-term recovery of patients. Here we review what is known about this powerful process. This includes the role of brain resident cells such as microglia, peripherally activated cells such as macrophages and neutrophils, and activated endothelium. The role of systemic immune activation and subsequent immunodepression in the days after stroke is also discussed, as is the chronic immune responses and its effects on cognitive function. The biphasic role of inflammation, as well as complex timelines of cell production, differentiation, and trafficking, suggests that the relationship between the acute and chronic phases of stroke recovery is complex. Gaining a more complete understanding of this intricate process by which inflammation is initiated, propagated, and terminated may potentially lead to therapeutics that can treat a larger population of stroke patients than what is currently available. The immune response plays a critical role in patient recovery in both the acute and chronic phases after stroke. In patients, the immune response can be beneficial by promoting repair and recovery, and also detrimental by propagating a pro-inflammatory microenvironment. Thus, it is critical to understand the mechanisms of immune activation following stroke in order to successfully design therapeutics.
中风后的免疫反应是未来中风治疗的一个令人兴奋的靶点。中风是全球发病率和死亡率的主要原因，目前唯一批准用于患者的治疗方法是通过机械或药物手段清除血栓以实现组织再灌注。然而，由于治疗窗口期短且效果不完全，许多患者仍留有受损组织，这会刺激炎症反应。尽管这对于促进修复至关重要，但也会损害周围健康的脑组织。此外，急性免疫抑制和随后的感染很常见，并且与患者预后较差相关。因此，急性免疫反应是研究人员的主要关注点，他们试图寻找方法来放大其益处并抑制其负面影响，以改善患者的短期恢复。本文综述了这一强大过程的已知内容。其中包括脑内固有细胞（如小胶质细胞）、外周激活细胞（如巨噬细胞和中性粒细胞）和激活的内皮细胞的作用。还讨论了中风后几天内系统免疫激活和随后的免疫抑制的作用，以及慢性免疫反应及其对认知功能的影响。炎症的双相作用以及细胞产生、分化和迁移的复杂时间线表明，中风恢复的急性期和慢性期之间的关系很复杂。更全面地了解炎症的起始、传播和终止的复杂过程，可能会为治疗方法提供新的思路，使更多的中风患者受益。免疫反应在中风后急性和慢性阶段对患者的恢复都起着至关重要的作用。在患者中，免疫反应可以通过促进修复和恢复来发挥有益作用，也可以通过促进促炎微环境而产生有害作用。因此，为了成功设计治疗方法，了解中风后免疫激活的机制至关重要。
