Measuring Biomarkers in Various Biological Compartments after TBI

描述（由申请人提供）：创伤性脑损伤（TBI）是美国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！），损失的收入和长期支助令人震惊。早期诊断和循证治疗对于改善TBI后的结果至关重要，可以减少直接和间接成本，重要的是减少人类痛苦。该提案解决了通过脑微透析液、CSF和血液样本的蛋白质组学分析与临床数据和长期结局相关来改善早期诊断的问题。脑微透析（cMD）是一种微创技术，可对脑细胞外液（bECF）进行采样，并提供有关神经强化单元中TBI持续代谢变化的重要信息。蛋白质生物标志物的血清和/或CSF水平的变化可以容易地确定，并且可以指示由损伤触发的特定病理变化。目前尚不清楚不同生物区室中蛋白质生物标志物变化之间的确切关系。作为与瑞典斯德哥尔摩的卡罗林斯卡大学医院持续合作努力的一部分，我们每6至12小时从17名TBI患者中收集bECF、CSF和血液样本，直至受伤后7天。本提案的目的是通过蛋白质组学分析在三种生物流体中识别和比较神经元和神经胶质特异性生物标志物的变化模式。我们的基本原理是，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CSF和血清中测量的变化的诊断价值。

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.