Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Repair and Regeneration in Central Nervous System, Tianjin, China; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China; Graduate School, Tianjin Medical University, Tianjin, China.
Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Repair and Regeneration in Central Nervous System, Tianjin, China; Department of Urology, Tianjin Medical University General Hospital, Tianjin, China.
Brain Res. 2023 Aug 1;1812:148383. doi: 10.1016/j.brainres.2023.148383. Epub 2023 May 4.
Traumatic brain injury (TBI) is an important reason of neurological damage and has high morbidity and mortality rates. The secondary damage caused by TBI leads to a poor clinical prognosis. According to the literature, TBI leads to ferrous iron aggregation at the site of trauma and may be a key factor in secondary injury. Deferoxamine (DFO), which is an iron chelator, has been shown to inhibit neuron degeneration; however, the role of DFO in TBI is unclear. The purpose of this study was to explore whether DFO can ameliorate TBI by inhibiting ferroptosis and neuroinflammation. Here, our findings suggest that DFO can reduce the accumulation of iron, lipid peroxides, and reactive oxygen species (ROS) and modulate the expression of ferroptosis-related indicators. Moreover, DFO may reduce NLRP3 activation via the ROS/NF-κB pathway, modulate microglial polarization, reduce neutrophil and macrophage infiltration, and inhibit the release of inflammatory factors after TBI. Additionally, DFO may reduce the activation of neurotoxic responsive astrocytes. Finally, we demonstrated that DFO can protect motor memory function, reduce edema and improve peripheral blood perfusion at the site of trauma in mice with TBI, as shown by behavioral experiments such as the Morris water maze test, cortical blood perfusion assessment and animal MRI. In conclusion, DFO ameliorates TBI by reducing iron accumulation to alleviate ferroptosis and neuroinflammation, and these findings provide a new therapeutic perspective for TBI.
创伤性脑损伤（TBI）是神经损伤的一个重要原因，具有较高的发病率和死亡率。TBI 引起的继发性损伤导致临床预后较差。根据文献报道，TBI 导致创伤部位亚铁离子聚集，这可能是继发性损伤的一个关键因素。去铁胺（DFO）是一种铁螯合剂，已被证明能抑制神经元变性；然而，DFO 在 TBI 中的作用尚不清楚。本研究旨在探讨 DFO 是否能通过抑制铁死亡和神经炎症来改善 TBI。在这里，我们的研究结果表明，DFO 可以减少铁、脂质过氧化物和活性氧（ROS）的积累，并调节铁死亡相关指标的表达。此外，DFO 可能通过 ROS/NF-κB 通路减少 NLRP3 的激活，调节小胶质细胞极化，减少中性粒细胞和巨噬细胞浸润，并抑制 TBI 后炎症因子的释放。此外，DFO 还可以减少神经毒性反应性星形胶质细胞的激活。最后，我们通过 Morris 水迷宫测试、皮质血流评估和动物 MRI 等行为实验表明，DFO 可以保护运动记忆功能，减少 TBI 小鼠创伤部位的水肿和改善周围血液灌注。综上所述，DFO 通过减少铁积累来减轻铁死亡和神经炎症，从而改善 TBI，这些发现为 TBI 提供了新的治疗视角。
