Measuring Biomarkers in Various Biological Compartments after TBI

描述(申请人提供)：创伤性脑损伤(TBI)在美国是导致死亡和慢性残疾的主要原因。直接医疗费用(每年约600亿美元！)、收入损失和长期支持的组合是令人震惊的。早期诊断和循证治疗是改善脑外伤后预后的关键，减少直接和间接成本，更重要的是减少人类痛苦。这项建议解决了通过对脑微透析液、脑脊液和血液样本进行蛋白质组学分析来改善早期诊断的问题，这些分析与临床数据和长期结果有关。脑微透析(CMD)是一种微创技术，它可以采集脑细胞外液(BECF)，并提供有关神经密集型单位中脑损伤正在进行的代谢变化的重要信息。血清和/或脑脊液中蛋白质生物标志物水平的变化可以很容易地确定，并可以指示由损伤引发的特定病理变化。不同生物间隔中蛋白质生物标志物变化之间的确切关系目前尚不清楚。作为与瑞典斯德哥尔摩卡罗林斯卡大学医院正在进行的合作的一部分，我们每隔6至12小时收集17名脑外伤患者的bECF、脑脊液和血液样本，直到受伤后7天。本研究的目的是通过蛋白质组学分析，识别和比较三种生物体液中神经元和神经胶质细胞特异性生物标志物的变化模式。我们的理论基础是，如果我们建立损伤诱导的bECF、CSF和血清中蛋白质生物标志物变化之间的关系，我们可以提高脑脊液和血清中检测到的变化的诊断价值。

DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is a major cause of death and chronic disability in the US. The combinations of direct medical expense (~60 BILLION USD annually!), lost income and long-term support are staggering. Early diagnosis and evidence-based treatments are critical to improve outcome after TBI reducing direct and indirect costs and importantly human suffering. This proposal addresses the issue of improving early diagnosis through proteomics analysis of brain microdialysates, CSF and blood samples in relation to clinical data and long-term outcome. Cerebral microdialysis (cMD) is a minimally invasive technique that samples the brain extracellular fluid (bECF) and provides vital information about ongoing metabolic changes in TBI in neurointensive units. Changes in the serum and/or CSF levels of protein biomarkers can be easily determined and can indicate specific pathological changes triggered by the injury. The exact relationship between changes in protein biomarkers in the different biological compartments are currently unknown. As part of an ongoing collaborative effort with the Karolinska University Hospital, Stockholm, Sweden we have collected bECF, CSF and blood samples at every 6 to 12 hrs from 17 TBI patients up to 7 days post- injury. The objective of this proposal is to identify and compare the pattern of changes of neuron and glia specific biomarkers through proteomics analysis among the three bio fluids. Our rationale is that if we establish the relationship between the injury-induced changes in protein biomarkers in the bECF, CSF and serum, we can improve the diagnostic value of changes measured in CSF and serum.