Mavroudis Ioannis, Balmus Ioana-Miruna, Ciobica Alin, Nicoara Mircea Nicusor, Luca Alina Costina, Palade Dragos Octavian
Department of Neurology, Leeds Teaching Hospitals, NHS Trust, Leeds LS2 9JT, UK.
Faculty of Medicine, Leeds University, Leeds LS2 9JT, UK.
Life (Basel). 2023 Sep 16;13(9):1924. doi: 10.3390/life13091924.
(1) Background: In this study, we aimed to explore the regulatory mechanism of miR-124-3p microglial exosomes, as they were previously reported to modulate neuroinflammation and promote neuronal repair following traumatic brain injury (TBI). (2) Methods: Studies investigating the impact of microglial exosomal miRNAs, specifically miR-124-3p, on injured neurons and brain microvascular endothelial cells (BMVECs) in the context of TBI were reviewed. (3) Results: Animal models of TBI, in vitro cell culture experiments, RNA sequencing analysis, and functional assays were employed to elucidate the mechanisms underlying the effects of miR-124-3p-loaded exosomes on neuroinflammation and neuronal repair. Anti-inflammatory M2 polarization of microglia, mTOR signaling suppression, and BMVECs-mediated autophagy were reported as the main processes contributing to neuroprotection, reduced blood-brain barrier leakage, and improved neurologic outcomes in animal models of TBI. (4) Conclusions: Microglial exosomes, particularly those carrying miR-124-3p, have emerged as promising candidates for therapeutic interventions in TBI. These exosomes exhibit neuroprotective effects, attenuate neuroinflammation, and promote neuronal repair and plasticity. However, further research is required to fully elucidate the underlying mechanisms and optimize their delivery strategies for effective treatment in human TBI cases.
(1) 背景:在本研究中,我们旨在探索微小RNA-124-3p(miR-124-3p)小胶质细胞外泌体的调控机制,因为先前有报道称其可调节神经炎症并促进创伤性脑损伤(TBI)后的神经元修复。(2) 方法:综述了研究小胶质细胞外泌体微小RNA,特别是miR-124-3p,在TBI背景下对受损神经元和脑微血管内皮细胞(BMVECs)影响的研究。(3) 结果:采用TBI动物模型、体外细胞培养实验、RNA测序分析和功能测定,以阐明装载miR-124-3p的外泌体对神经炎症和神经元修复作用的潜在机制。据报道,小胶质细胞的抗炎M2极化、mTOR信号抑制和BMVECs介导的自噬是TBI动物模型中神经保护、血脑屏障渗漏减少和神经功能改善的主要过程。(4) 结论:小胶质细胞外泌体,特别是携带miR-124-3p的外泌体,已成为TBI治疗干预的有前景的候选者。这些外泌体具有神经保护作用,减轻神经炎症,并促进神经元修复和可塑性。然而,需要进一步研究以充分阐明其潜在机制并优化其递送策略,以便在人类TBI病例中进行有效治疗。