Cheng Jian, Wang Wei, Xia Yiqing, Li Yi, Jia Jia, Xiao Guodong
Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Soochow University, Suzhou, China.
Front Pharmacol. 2023 Aug 2;14:1122527. doi: 10.3389/fphar.2023.1122527. eCollection 2023.
Stroke, including ischemic and hemorrhagic stroke, causes massive cell death in the brain, which is followed by secondary inflammatory injury initiated by disease-associated molecular patterns released from dead cells. Phagocytosis, a cellular process of engulfment and digestion of dead cells, promotes the resolution of inflammation and repair following stroke. However, professional or non-professional phagocytes also phagocytose stressed but viable cells in the brain or excessively phagocytose myelin sheaths or prune synapses, consequently exacerbating brain injury and impairing repair following stroke. Phagocytosis includes the smell, eating and digestion phases. Notably, efficient phagocytosis critically depends on phagocyte capacity to take up dead cells continually due to the limited number of phagocytes vs. dead cells after injury. Moreover, phenotypic polarization of phagocytes occurring after phagocytosis is also essential to the proresolving and prorepair properties of phagocytosis. Much has been learned about the molecular signals and regulatory mechanisms governing the sense and recognition of dead cells by phagocytes during the smell and eating phase following stroke. However, some key areas remain extremely understudied, including the mechanisms involved in digestion regulation, continual phagocytosis and phagocytosis-induced phenotypic switching following stroke. Here, we summarize new discoveries related to the molecular mechanisms and multifaceted effects of phagocytosis on brain injury and repair following stroke and highlight the knowledge gaps in poststroke phagocytosis. We suggest that advancing the understanding of poststroke phagocytosis will help identify more biological targets for stroke treatment.
中风，包括缺血性中风和出血性中风，会导致大脑中大量细胞死亡，随后由死亡细胞释放的疾病相关分子模式引发继发性炎症损伤。吞噬作用是一种吞噬和消化死亡细胞的细胞过程，可促进中风后的炎症消退和修复。然而，专业或非专业吞噬细胞也会吞噬大脑中应激但仍存活的细胞，或过度吞噬髓鞘或修剪突触，从而加剧脑损伤并损害中风后的修复。吞噬作用包括识别、吞噬和消化阶段。值得注意的是，由于损伤后吞噬细胞数量与死亡细胞数量有限，高效的吞噬作用关键取决于吞噬细胞持续摄取死亡细胞的能力。此外，吞噬作用后发生的吞噬细胞表型极化对于吞噬作用的促消退和促修复特性也至关重要。在中风后的识别和吞噬阶段，关于吞噬细胞识别死亡细胞的分子信号和调节机制已经有了很多了解。然而，一些关键领域仍研究极少，包括中风后消化调节、持续吞噬作用和吞噬作用诱导的表型转换所涉及的机制。在这里，我们总结了与吞噬作用对中风后脑损伤和修复的分子机制及多方面影响相关的新发现，并强调了中风后吞噬作用方面的知识空白。我们认为，加深对中风后吞噬作用的理解将有助于确定更多中风治疗的生物学靶点。
