Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, NIH, Baltimore, United States.
Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, NIH, Baltimore, United States.
Elife. 2020 Aug 17;9:e55827. doi: 10.7554/eLife.55827.
Traumatic brain injury (TBI) is a serious global health problem, many individuals live with TBI-related neurological dysfunction. A lack of biomarkers of TBI has impeded medication development. To identify new potential biomarkers, we time-dependently evaluated mouse brain tissue and neuronally derived plasma extracellular vesicle proteins in a mild model of TBI with parallels to concussive head injury. Mice (CD-1, 30-40 g) received a sham procedure or 30 g weight-drop and were euthanized 8, 24, 48, 72, 96 hr, 7, 14 and 30 days later. We quantified ipsilateral cortical proteins, many of which differed from sham by 8 hours post-mTBI, particularly GAS-1 and VEGF-B were increased while CXCL16 reduced, 23 proteins changed in 4 or more of the time points. Gene ontology pathways mapped from altered proteins over time related to pathological and physiological processes. Validation of proteins identified in this study may provide utility as treatment response biomarkers.
创伤性脑损伤 (TBI) 是一个严重的全球健康问题，许多人患有与 TBI 相关的神经功能障碍。由于缺乏 TBI 的生物标志物，药物研发受到了阻碍。为了确定新的潜在生物标志物，我们在轻度 TBI 模型中对小鼠脑组织和神经元衍生的血浆细胞外囊泡蛋白进行了时间依赖性评估，该模型与冲击性头部损伤相似。小鼠 (CD-1，30-40 克) 接受假手术或 30 克重物坠落，然后在 8、24、48、72、96 小时、7、14 和 30 天后安乐死。我们定量了同侧皮质蛋白，其中许多蛋白在 mTBI 后 8 小时就与假手术组不同，特别是 GAS-1 和 VEGF-B 增加，而 CXCL16 减少，23 种蛋白在 4 个或更多时间点发生变化。随着时间的推移，与病理和生理过程相关的改变蛋白的基因本体途径被映射出来。本研究中鉴定的蛋白质的验证可能为治疗反应生物标志物提供效用。
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