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Proteomic differences between focal and diffuse traumatic brain injury in human brain tissue

机译:人脑组织局灶性和弥漫性外伤性脑损伤之间的蛋白质组学差异

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摘要

The early molecular response to severe traumatic brain injury (TBI) was evaluated using biopsies of structurally normal-appearing cortex, obtained at location for intracranial pressure (ICP) monitoring, from 16 severe TBI patients. Mass spectrometry (MS; label free and stable isotope dimethyl labeling) quantitation proteomics showed a strikingly different molecular pattern in TBI in comparison to cortical biopsies from 11 idiopathic normal pressure hydrocephalus patients. Diffuse TBI showed increased expression of peptides related to neurodegeneration (Tau and Fascin, p < 0.05), reduced expression related to antioxidant defense (Glutathione S-transferase Mu 3, Peroxiredoxin-6, Thioredoxin-dependent peroxide reductase; p < 0.05) and increased expression of potential biomarkers (e.g. Neurogranin, Fatty acid-binding protein, heart p < 0.05) compared to focal TBI. Proteomics of human brain biopsies displayed considerable molecular heterogeneity among the different TBI subtypes with consequences for the pathophysiology and development of targeted treatments for TBI.
机译:使用16例重度TBI患者在颅内压(ICP)监测部位获得的结构正常的皮层活检,评估了对重度颅脑损伤(TBI)的早期分子反应。质谱(MS;无标记且稳定的同位素二甲基标记)定量蛋白质组学与来自11名特发性常压脑积水患者的皮质活检相比,在TBI中显示出截然不同的分子模式。弥漫性TBI显示与神经变性相关的肽表达增加(Tau和Fascin,p <0.05),与抗氧化防御相关的表达减少(谷胱甘肽S-转移酶Mu 3,Peroxiredoxin-6,硫氧还蛋白依赖性过氧化物还原酶; p <0.05)和增加与局灶性TBI相比,潜在生物标志物(例如,神经颗粒蛋白,脂肪酸结合蛋白,心脏p <0.05)的表达。人脑活检的蛋白质组学在不同的TBI亚型之间显示出相当大的分子异质性,对TBI的病理生理和靶向治疗的发展产生了影响。

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