Department of Biomedical Engineering, Southern University of Science and Technology, No. 1088, Xueyuan Avenue, Shenzhen 518055, China.
Institute of Nervous System Diseases, Xuzhou Medical University, No. 84 Huaihai Xi Road, Xuzhou 221002, China.
Sci Adv. 2024 Jan 12;10(2):eadj4260. doi: 10.1126/sciadv.adj4260. Epub 2024 Jan 10.
Posttraumatic neuroinflammation is a key driver of secondary injury after traumatic brain injury (TBI). Pyroptosis, a proinflammatory form of programmed cell death, considerably activates strong neuroinflammation and amplifies the inflammatory response by releasing inflammatory contents. Therefore, treatments targeting pyroptosis may have beneficial effects on the treatment of secondary brain damage after TBI. Here, a cysteine-alanine-glutamine-lysine peptide-modified β-lactoglobulin (β-LG) nanoparticle was constructed to deliver disulfiram (DSF), C-β-LG/DSF, to inhibit pyroptosis and decrease neuroinflammation, thereby preventing TBI-induced secondary injury. In the post-TBI mice model, C-β-LG/DSF selectively targets the injured brain, increases DSF accumulation, and extends the time of the systemic circulation of DSF. C-β-LG/DSF can alleviate brain edema and inflammatory response, inhibit secondary brain injury, promote learning, and improve memory recovery in mice after trauma. Therefore, this study likely provided a potential approach for reducing the secondary spread of TBI.
创伤性脑损伤 (TBI) 后，创伤后神经炎症是继发性损伤的关键驱动因素。细胞焦亡是一种促炎形式的程序性细胞死亡，通过释放炎症内容物，极大地激活强烈的神经炎症并放大炎症反应。因此，针对细胞焦亡的治疗方法可能对 TBI 后继发性脑损伤的治疗具有有益效果。在这里，构建了一种半胱氨酸-丙氨酸-谷氨酰胺-赖氨酸肽修饰的β-乳球蛋白 (β-LG) 纳米颗粒来递送双硫仑 (DSF)，即 C-β-LG/DSF，以抑制细胞焦亡和减少神经炎症，从而防止 TBI 引起的继发性损伤。在 TBI 后小鼠模型中，C-β-LG/DSF 选择性地靶向损伤的大脑，增加 DSF 积累，并延长 DSF 在全身循环中的时间。C-β-LG/DSF 可减轻脑水肿和炎症反应，抑制继发性脑损伤，促进创伤后小鼠的学习和记忆恢复。因此，这项研究可能为减少 TBI 的继发性扩散提供了一种潜在的方法。
