Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.
Tianjin Neurological Institute, Key Laboratory of Post Neuro-Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China.
Neurotox Res. 2022 Dec;40(6):2264-2277. doi: 10.1007/s12640-022-00566-8. Epub 2022 Sep 10.
Traumatic brain injury (TBI)-induced neuroinflammation is closely associated with poor outcomes and high mortality in affected patients, with unmet needs for effective clinical interventions. A series of causal and disseminating factors have been identified to cause TBI-induced neuroinflammation. Among these are cellular microvesicles released from injured cerebral cells, endothelial cells, and platelets. In previous studies, we have put forward that cellular microvesicles can be released from injured brains that induce consumptive coagulopathy. Extracellular mitochondria accounted for 55.2% of these microvesicles and induced a redox-dependent platelet procoagulant activity that contributes to traumatic brain injury-induced coagulopathy and inflammation. These lead to the hypothesis that metabolically active extracellular mitochondria contribute to the neuroinflammation in traumatic brain injury, independent of their procoagulant activity. Here, we found that these extracellular mitochondria induced polarization of microglial M1-type pro-inflammatory phenotype, aggravating neuroinflammation, and mediated cerebral edema in a ROS-dependent manner. In addition, the effect of ROS can be alleviated by ROS inhibitor N-ethylmaleimide (NEM) in vitro experiments. These results revealed a novel pro-inflammatory activity of extracellular mitochondria that may contribute to traumatic brain injury-associated neuroinflammation.
创伤性脑损伤（TBI）引起的神经炎症与受影响患者的预后不良和高死亡率密切相关，临床干预措施的需求未得到满足。已经确定了一系列因果和传播因素导致 TBI 引起的神经炎症。其中包括从受伤脑细胞、内皮细胞和血小板释放的细胞微泡。在之前的研究中，我们提出细胞微泡可以从受伤的大脑中释放出来，从而引起消耗性凝血病。这些微泡中 55.2%是由细胞外线粒体组成，并诱导依赖于氧化还原的血小板促凝活性，导致创伤性脑损伤引起的凝血病和炎症。这就提出了一个假设，即代谢活跃的细胞外线粒体独立于其促凝活性，参与创伤性脑损伤的神经炎症。在这里，我们发现这些细胞外线粒体诱导小胶质细胞 M1 型促炎表型的极化，加重神经炎症，并以 ROS 依赖的方式介导脑水肿。此外，ROS 抑制剂 N-乙基马来酰亚胺（NEM）在体外实验中可以减轻 ROS 的作用。这些结果揭示了细胞外线粒体的一种新的促炎活性，可能导致与创伤性脑损伤相关的神经炎症。
