Manrui Li, Xu Yang, Liu Jinyuan, Zhang Xiao, Yuan Ruixuan, Sun Yuwen, Sun Yihan, Yang Qiuyun, Liao Miao, Lv Meili, Hu Xin, Chen Xiameng, Liang Weibo
Department of Forensic Genetics, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Sichuan, 610000, Chengdu, China.
Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan, 637000, China.
Cell Mol Life Sci. 2025 Feb 22;82(1):87. doi: 10.1007/s00018-025-05601-3.
Traumatic brain injury (TBI) is a significant global health issue, characterized by high rates of morbidity and mortality, along with substantial economic strains on healthcare systems. This study explores the potential of Aminophylline (AMP), a medication traditionally used for cardiovascular conditions and bronchiectasis, to enhance TBI outcomes by protecting against neuronal damage. Our findings indicate that AMP treatment significantly reduces neuronal ferroptosis in the cortex, leading to less tissue damage and notable improvements in cognitive and motor functions in mice subjected to controlled cortical impact (CCI). Additionally, we found that TBI resulted in decreased expression of miR-128-3p, a reduction that was further strengthened by AMP treatment. Gain-of-function experiments showed that overexpressing miR-128-3p increases neuronal ferroptosis by targeting Slc7a11, indicating how AMP mitigates cognitive and motor impairments in CCI mice. This study highlights the potential of AMP in treating TBI through the miR-128-3p/Slc7a11 pathway, marking the first report of its protective effects against ferroptosis in TBI.
创伤性脑损伤（TBI）是一个重大的全球健康问题，其特点是发病率和死亡率高，同时给医疗系统带来巨大经济压力。本研究探讨了传统上用于心血管疾病和支气管扩张症的药物氨茶碱（AMP）通过防止神经元损伤来改善TBI预后的潜力。我们的研究结果表明，AMP治疗可显著降低皮质中的神经元铁死亡，减少组织损伤，并使遭受控制性皮质撞击（CCI）的小鼠的认知和运动功能得到显著改善。此外，我们发现TBI导致miR-128-3p表达降低，而AMP治疗进一步加剧了这种降低。功能获得实验表明，过表达miR-128-3p通过靶向Slc7a11增加神经元铁死亡，这表明AMP如何减轻CCI小鼠的认知和运动障碍。本研究强调了AMP通过miR-128-3p/Slc7a11途径治疗TBI的潜力，这是其对TBI中铁死亡保护作用的首次报道。
