Centre for Inflammatory Diseases, Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.
Immunol Cell Biol. 2021 Oct;99(9):924-935. doi: 10.1111/imcb.12463. Epub 2021 May 27.
Clinical trials involving the blockage of peripheral inflammatory leukocyte recruitment into the brain have puzzlingly led to either no significant improvement in stroke outcome, or even worsened outcomes and increased mortality, prompting a re-evaluation of our understanding into the neuroinflammatory processes after stroke. Whilst traditionally understood as simple effectors of the innate immune system, emerging research in vascular disease biology has redefined the neutrophil as a specialized and highly specific cell type with dynamic functional capacity. Indeed, emerging experimental evidence indicates that neutrophils display diverse roles in the acute stages of ischemic stroke with the ability to elicit both pro-inflammatory and anti-inflammatory effects. Currently, there is some uncertainty as to whether neutrophil diversity is beneficial or harmful in stroke as their interactions with the resident cells of the brain, such as microglia and neurons, would potentially elicit heterogeneous outcomes. Current treatments for patients with stroke aim to remove the vascular blockage and to restore blood flow, but there are currently no drug treatments for managing the loss of functional brain tissue nor restoration of microglial and neuronal damage. If these hypothesized wound-healing functions of neutrophils can be validated in a stroke setting, promoting the recruitment of this type of neutrophils into the injured brain tissue may form a promising therapeutic target for the majority of stroke patients currently without treatment. In this review, we will provide an update on recent research that has explored neutrophil heterogeneity in the neuroinflammatory cascade after ischemic stroke.
临床试验涉及阻断外周炎性白细胞募集到大脑中，但令人费解的是，这要么没有显著改善中风的结果，甚至使结果恶化，死亡率增加，促使我们重新评估中风后神经炎症过程的理解。虽然传统上被理解为先天免疫系统的简单效应物，但血管疾病生物学的新兴研究已经重新定义了中性粒细胞是一种具有动态功能能力的专门化和高度特异的细胞类型。事实上，新兴的实验证据表明，中性粒细胞在缺血性中风的急性阶段表现出多种作用，具有引发促炎和抗炎作用的能力。目前，对于中风患者来说，中性粒细胞的多样性是有益还是有害还存在一些不确定性，因为它们与大脑的常驻细胞（如小胶质细胞和神经元）的相互作用可能会产生不同的结果。目前中风患者的治疗方法旨在清除血管阻塞和恢复血流，但目前还没有药物治疗来管理功能性脑组织的丧失或恢复小胶质细胞和神经元的损伤。如果这些假设的中性粒细胞的伤口愈合功能可以在中风环境中得到验证，那么促进这种类型的中性粒细胞进入受损脑组织可能成为目前大多数没有治疗方法的中风患者的一个有前途的治疗靶点。在这篇综述中，我们将提供最新的研究进展，探讨缺血性中风后神经炎症级联反应中的中性粒细胞异质性。
