Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury. Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues. These proteins initiate inflammatory dysfunction, such as neurogenic heterotopic ossification. This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies. Accordingly, a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues. Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis. The relationships among brain-derived extracellular vesicles, fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo. Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo. The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury.

脑源性细胞外囊泡通过运输病原体以引发继发性损伤，参与创伤性脑损伤后的器官间通讯。封装在脑源性细胞外囊泡中的炎症小体相关蛋白可以穿过血脑屏障到达远端组织。这些蛋白质引发炎症功能障碍，例如神经源性异位骨化。由于其相对未知的发病机制和缺乏有效的预防干预策略，这种复发性疾病使患者非常虚弱。因此，开发了由创伤性脑损伤和跟腱切开术联合诱导的神经源性异位骨化的大鼠模型来解决这两个问题。受伤肌腱的组织学检查显示异位钙化和成纤维细胞焦亡并存。在体外和体内进一步研究了脑源性细胞外囊泡、成纤维细胞焦亡和异位钙化之间的关系。静脉注射焦亡抑制剂 Ac-YVAD-cmk 可逆转体内神经源性异位骨化的发展。目前的工作强调了脑源性细胞外囊泡在神经源性异位骨化发病机制中的作用，并为预防创伤性脑损伤后神经源性异位骨化提供了潜在的策略。