Sahebi Keivan, Foroozand Hassan, Amirsoleymani Mobina, Eslamzadeh Saghi, Negahdaripour Manica, Tajbakhsh Amir, Rahimi Jaberi Abbas, Savardashtaki Amir
Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
Cell Death Discov. 2024 Jul 11;10(1):321. doi: 10.1038/s41420-024-02049-5.
Stroke stands as a predominant cause of mortality and morbidity worldwide, and there is a pressing need for effective therapies to improve outcomes and enhance the quality of life for stroke survivors. In this line, effective efferocytosis, the clearance of apoptotic cells, plays a crucial role in neuroprotection and immunoregulation. This process involves specialized phagocytes known as "professional phagocytes" and consists of four steps: "Find-Me," "Eat-Me," engulfment/digestion, and anti-inflammatory responses. Impaired efferocytosis can lead to secondary necrosis and inflammation, resulting in adverse outcomes following brain pathologies. Enhancing efferocytosis presents a potential avenue for improving post-stroke recovery. Several therapeutic targets have been identified, including osteopontin, cysteinyl leukotriene 2 receptor, the µ opioid receptor antagonist β-funaltrexamine, and PPARγ and RXR agonists. Ferroptosis, defined as iron-dependent cell death, is now emerging as a novel target to attenuate post-stroke tissue damage and neuronal loss. Additionally, several biomarkers, most importantly CD163, may serve as potential biomarkers and therapeutic targets for acute ischemic stroke, aiding in stroke diagnosis and prognosis. Non-pharmacological approaches involve physical rehabilitation, hypoxia, and hypothermia. Mitochondrial dysfunction is now recognized as a major contributor to the poor outcomes of brain stroke, and medications targeting mitochondria may exhibit beneficial effects. These strategies aim to polarize efferocytes toward an anti-inflammatory phenotype, limit the ingestion of distressed but viable neurons, and stimulate efferocytosis in the late phase of stroke to enhance post-stroke recovery. These findings highlight promising directions for future research and development of effective stroke recovery therapies.
中风是全球范围内导致死亡和发病的主要原因，迫切需要有效的治疗方法来改善中风幸存者的预后并提高其生活质量。在这方面，有效的胞葬作用，即凋亡细胞的清除，在神经保护和免疫调节中起着关键作用。这个过程涉及被称为“专业吞噬细胞”的特殊吞噬细胞，包括四个步骤：“找到我”、“吃掉我”、吞噬/消化和抗炎反应。胞葬作用受损会导致继发性坏死和炎症，从而在脑部病变后产生不良后果。增强胞葬作用为改善中风后的恢复提供了一条潜在途径。已经确定了几个治疗靶点，包括骨桥蛋白、半胱氨酰白三烯2受体、μ阿片受体拮抗剂β-芬太尼酰吗啉，以及过氧化物酶体增殖物激活受体γ（PPARγ）和视黄酸X受体（RXR）激动剂。铁死亡，定义为铁依赖性细胞死亡，现在正成为减轻中风后组织损伤和神经元损失的一个新靶点。此外，几种生物标志物，最重要的是CD163，可能作为急性缺血性中风的潜在生物标志物和治疗靶点，有助于中风的诊断和预后。非药物方法包括物理康复、缺氧和低温。线粒体功能障碍现在被认为是脑中风不良预后的主要原因，针对线粒体的药物可能会显示出有益的效果。这些策略旨在使吞噬细胞向抗炎表型极化，限制对受损但仍存活的神经元的摄取，并在中风后期刺激胞葬作用以增强中风后的恢复。这些发现突出了未来有效中风恢复治疗研发的有前景的方向。
