Department of Advanced Spectroscopy and Imaging, Centre of Biomedical Research (CBMR), SGPGI Campus, Raebareli Road, Lucknow, India.
Experimental Animal Facility, SGPGIMS, Raebareli Road, Lucknow, India.
J Mol Neurosci. 2023 Oct;73(9-10):843-852. doi: 10.1007/s12031-023-02162-7. Epub 2023 Oct 6.
Mild traumatic brain injury (mTBI) and repetitive mTBI (RmTBI) are silent epidemics, and so far, there is no objective diagnosis. The severity of the injury is solely based on the Glasgow Coma Score (GCS) scale. Most patients suffer from one or more behavioral abnormalities, such as headache, amnesia, cognitive decline, disturbed sleep pattern, anxiety, depression, and vision abnormalities. Additionally, most neuroimaging modalities are insensitive to capture structural and functional alterations in the brain, leading to inefficient patient management. Metabolomics is one of the established omics technologies to identify metabolic alterations, mostly in biofluids. NMR-based metabolomics provides quantitative metabolic information with non-destructive and minimal sample preparation. We employed whole-blood NMR analysis to identify metabolic markers using a high-field NMR spectrometer (800 MHz). Our approach involves chemical-free sample pretreatment and minimal sample preparation to obtain a robust whole-blood metabolic profile from a rat model of concussion. A single head injury was given to the mTBI group, and three head injuries to the RmTBI group. We found significant alterations in blood metabolites in both mTBI and RmTBI groups compared with the control, such as alanine, branched amino acid (BAA), adenosine diphosphate/adenosine try phosphate (ADP/ATP), creatine, glucose, pyruvate, and glycerphosphocholine (GPC). Choline was significantly altered only in the mTBI group and formate in the RmTBI group compared with the control. These metabolites corroborate previous findings in clinical and preclinical cohorts. Comprehensive whole-blood metabolomics can provide a robust metabolic marker for more accurate diagnosis and treatment intervention for a disease population.
轻度创伤性脑损伤（mTBI）和重复性 mTBI（RmTBI）是无声的流行病，到目前为止，还没有客观的诊断方法。损伤的严重程度仅基于格拉斯哥昏迷评分（GCS）量表。大多数患者患有一种或多种行为异常，如头痛、健忘、认知能力下降、睡眠模式紊乱、焦虑、抑郁和视力异常。此外，大多数神经影像学模式对捕捉大脑的结构和功能改变不敏感，导致患者管理效率低下。代谢组学是识别代谢改变的成熟组学技术之一，主要在生物流体中进行。基于 NMR 的代谢组学提供定量代谢信息，具有非破坏性和最小的样品制备。我们使用高场 NMR 光谱仪（800 MHz）对全血 NMR 分析进行了研究，以确定代谢标志物。我们的方法涉及无化学样品预处理和最小的样品制备，以从脑震荡大鼠模型中获得稳健的全血代谢谱。mTBI 组给予单次头部损伤，RmTBI 组给予三次头部损伤。与对照组相比，我们在 mTBI 和 RmTBI 组中均发现了血液代谢物的显著改变，如丙氨酸、支链氨基酸（BAA）、二磷酸腺苷/三磷酸腺苷（ADP/ATP）、肌酸、葡萄糖、丙酮酸和甘油磷酸胆碱（GPC）。与对照组相比，胆碱仅在 mTBI 组中显著改变，而在 RmTBI 组中仅改变甲酸盐。这些代谢物与临床和临床前队列中的先前发现一致。综合全血代谢组学可以为更准确的诊断和治疗干预提供强大的代谢标志物，以治疗疾病人群。
