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Mechanism of Efferocytosis in Determining Ischaemic Stroke Resolution—Diving into Microglia/Macrophage Functions and Therapeutic Modality

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Abstract

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.

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Funding

This research was supported by the National Natural Science Foundation of China (No. 82204663) and the Natural Science Foundation of Shandong Province (No. ZR2022QH058).

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  1. Department of Pathophysiology, School of Basic Medicine, Institute of Neuroregeneration & Neurorehabilitation, Qingdao University, No. 308 Ningxia Road, Qingdao, China

    Xiao-Di Xie, Shan-Shan Dong, Ru-Juan Liu, Liu-Liu Shi & Ting Zhu

  2. Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China

    Shan-Shan Dong & Ru-Juan Liu

  3. Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, China

    Liu-Liu Shi

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Literature retrieval and manuscript writing: XDX; figure preparation: XDX, SSD, RJL; manuscript revision: SSD, LLS; review supervision: TZ. All authors approved the final version of the manuscript.

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Xie, XD., Dong, SS., Liu, RJ. et al. Mechanism of Efferocytosis in Determining Ischaemic Stroke Resolution—Diving into Microglia/Macrophage Functions and Therapeutic Modality. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04060-4

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