Goli Mona, Sanni Akeem, Gautam Sakshi, Mallah Khalil, Hubbard W Brad, Reslan Mohammad, Haidar Muhammad Ali, Halabi Karim, Walker Joseph, Mondello Stefania, Kobeissy Firas, Mechref Yehia
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas, USA.
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA.
Neurotrauma Rep. 2025 Jun 16;6(1):525-538. doi: 10.1089/neur.2025.0054. eCollection 2025.
Traumatic brain injury (TBI) represents a significant cause of injury-related deaths and disabilities. Repeated exposure to mechanical impact can lead to metabolic and ionic imbalance, which can cause oxidative stress and worsen the cellular dysfunction initiated by the initial mild TBI (mTBI). Currently, no FDA-approved drug targets repeated mTBI (rmTBI) and its potential sequelae. Mitoquinone (MitoQ) is a mitochondrion-targeted drug that has proven beneficial in different brain-related diseases. We have previously demonstrated the neurotherapeutic effects of MitoQ at a 30-day chronic time point in a similar rmTBI mouse model, where we observed decreased neuroinflammation, enhanced behavioral outcomes, and diminished oxidation. Recently, alterations in glycans have been shown to modulate key roles in the nervous system. Their relevance has been recognized in several neurodegenerative disorders, including TBI, which indicated injury severity and pathobiology. In this study, we aimed to assess brain glycome profiles post MitoQ treatment in experimental rmTBI using liquid chromatography-tandem mass spectrometry. Our findings indicate that there is a correlation between the HexNAcHexDeoxyHex glycan profile and MitoQ administration at the acute phase, the levels of HexNAcHex glycan in the subacute phase of MitoQ treatment, and the HexNAcHex glycan profile at the chronic time point phase of MitoQ treatment. These data suggest that these three glycan profiles can be considered molecular signatures for MitoQ-associated neurotherapy. However, further research is required to validate and establish that these three glycan profiles are accurate and sensitive markers associated with TBI neuroprotection.
创伤性脑损伤（TBI）是损伤相关死亡和残疾的一个重要原因。反复暴露于机械冲击可导致代谢和离子失衡，进而引发氧化应激，并使最初的轻度创伤性脑损伤（mTBI）所引发的细胞功能障碍恶化。目前，尚无经美国食品药品监督管理局（FDA）批准的药物可针对反复发生的轻度创伤性脑损伤（rmTBI）及其潜在后遗症。米托醌（MitoQ）是一种靶向线粒体的药物，已被证明在不同的脑部相关疾病中具有益处。我们之前在一个类似的rmTBI小鼠模型中，于30天的慢性时间点证明了MitoQ的神经治疗作用，在该模型中我们观察到神经炎症减轻、行为结果改善以及氧化作用减弱。最近，已表明聚糖的改变在神经系统中发挥关键作用。它们的相关性已在包括TBI在内的几种神经退行性疾病中得到认可，这表明了损伤的严重程度和病理生物学特征。在本研究中，我们旨在使用液相色谱 - 串联质谱法评估实验性rmTBI经MitoQ治疗后脑聚糖谱。我们的研究结果表明，己糖胺己糖脱氧己糖聚糖谱与急性期MitoQ给药之间、MitoQ治疗亚急性期己糖胺己糖聚糖水平以及MitoQ治疗慢性时间点阶段的己糖胺己糖聚糖谱之间存在相关性。这些数据表明，这三种聚糖谱可被视为与MitoQ相关神经治疗的分子特征。然而，需要进一步的研究来验证并确定这三种聚糖谱是与TBI神经保护相关的准确且敏感的标志物。
