Department of Pathophysiology, School of Basic Medicine, Institute of Neuroregeneration & Neurorehabilitation, Qingdao University, No. 308 Ningxia Road, Qingdao, China.
Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.
Mol Neurobiol. 2024 Oct;61(10):7583-7602. doi: 10.1007/s12035-024-04060-4. Epub 2024 Feb 27.
After ischaemic cerebral vascular injury, efferocytosis-a process known as the efficient clearance of apoptotic cells (ACs) by various phagocytes in both physiological and pathological states-is crucial for maintaining central nervous system (CNS) homeostasis and regaining prognosis. The mechanisms of efferocytosis in ischaemic stroke and its influence on preventing inflammation progression from secondary injury were still not fully understood, despite the fact that the fundamental process of efferocytosis has been described in a series of phases, including AC recognition, phagocyte engulfment, and subsequent degradation. The genetic reprogramming of macrophages and brain-resident microglia after an ischaemic stroke has been equated by some researchers to that of the peripheral blood and brain. Based on previous studies, some molecules, such as signal transducer and activator of transcription 6 (STAT6), peroxisome proliferator-activated receptor γ (PPARG), CD300A, and sigma non-opioid intracellular receptor 1 (SIGMAR1), were discovered to be largely associated with aspects of apoptotic cell elimination and accompanying neuroinflammation, such as inflammatory cytokine release, phenotype transformation, and suppressing of antigen presentation. Exacerbated stroke outcomes are brought on by defective efferocytosis and improper modulation of pertinent signalling pathways in blood-borne macrophages and brain microglia, which also results in subsequent tissue inflammatory damage. This review focuses on recent researches which contain a number of recently discovered mechanisms, such as studies on the relationship between benign efferocytosis and the regulation of inflammation in ischaemic stroke, the roles of some risk factors in disease progression, and current immune approaches that aim to promote efferocytosis to treat some autoimmune diseases. Understanding these pathways provides insight into novel pathophysiological processes and fresh characteristics, which can be used to build cerebral ischaemia targeting techniques.
缺血性脑血管损伤后,吞噬作用——即各种吞噬细胞在生理和病理状态下有效清除凋亡细胞 (ACs) 的过程——对于维持中枢神经系统 (CNS) 内稳态和恢复预后至关重要。尽管吞噬作用的基本过程已在一系列阶段中进行了描述,包括 AC 的识别、吞噬细胞的吞噬作用以及随后的降解,但缺血性中风中吞噬作用的机制及其对防止继发性损伤中炎症进展的影响仍未完全了解。一些研究人员将缺血性中风后巨噬细胞和脑驻留小胶质细胞的遗传重编程等同于外周血和大脑的重编程。基于先前的研究,一些分子,如信号转导和转录激活因子 6 (STAT6)、过氧化物酶体增殖物激活受体 γ (PPARG)、CD300A 和 sigma 非阿片类细胞内受体 1 (SIGMAR1),被发现与凋亡细胞清除和伴随的神经炎症密切相关,如炎症细胞因子释放、表型转化和抑制抗原呈递。循环血液中的巨噬细胞和脑小胶质细胞中吞噬作用缺陷和相关信号通路的不当调节会导致中风恶化,并导致随后的组织炎症损伤。本综述重点介绍了最近的研究,其中包含了一些新发现的机制,如研究良性吞噬作用与缺血性中风中炎症调节的关系、一些风险因素在疾病进展中的作用,以及目前旨在促进吞噬作用以治疗一些自身免疫性疾病的免疫方法。了解这些途径为新的病理生理过程和新的特征提供了深入的了解,这些过程和特征可用于构建针对脑缺血的靶向技术。