Measuring Biomarkers in Various Biological Compartments after TBI

TBI 后测量各个生物区室中的生物标志物

• 批准号: 8821954
• 负责人: Denes V. Agoston
• 金额: $ 7.8万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8821954
• 关键词: Address; Affect; American; Antibodies; Biological; Biological Assay; Biological Markers; Blood; Blood specimen; Brain; Caring; Cause of Death; Cerebrospinal Fluid; Cerebrum; Chronic; Classification; Clinical; Clinical Data; Clinical Research; Data; Diagnosis; Diagnostic; Direct Costs; Early Diagnosis; Evidence based treatment; Extracellular Fluid; Facilities and Administrative Costs; Glial Fibrillary Acidic Protein; Human; Income; Injury; Liquid substance; Measures; Medical; Metabolic; Microdialysis; Neuroglia; Neuron-Specific Enolase; Neurons; Outcome; Pathology; Patients; Pattern; Phase; Process; Productivity; Protein Microarray Assay; Proteins; Proteome; Proteomics; Rehabilitation therapy; Resolution; Sampling; Serum; Severities; Specificity; Survivors; Sweden; Techniques; Technology; Testing; Time; Traumatic Brain Injury; University Hospitals; Work; cost; design; disability; evidence base; improved; innovation; insight; minimally invasive; outcome forecast; public health relevance; research study; tau Proteins

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.

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！），收入损失和长期支持的组合令人震惊。在TBI降低直接和间接成本以及重要的是人类苦难之后，早期诊断和基于证据的治疗对于改善结果至关重要。该提案通过蛋白质组学分析脑晶状体，CSF和血液样本与临床数据和长期结局有关改善早期诊断的问题。脑微透析（CMD）是一种微创技术，可对脑外流体（BECF）进行采样，并提供有关神经大量单位中TBI正在进行的代谢变化的重要信息。可以轻松确定蛋白质生物标志物的血清和/或CSF水平的变化，并表明损伤触发的特定病理变化。目前尚不清楚不同生物室中蛋白质生物标志物的变化之间的确切关系。作为与瑞典斯德哥尔摩Karolinska大学医院进行的持续合作努力的一部分，我们每6至12小时收集了BECF，CSF和血液样本，从17名TBI患者到受伤后7天。该建议的目的是通过三种生物液中的蛋白质组学分析来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。我们的理由是，如果我们在BECF，CSF和血清中受伤诱导的蛋白质生物标志物变化之间的关系，则可以提高CSF和血清中测量的变化的诊断价值。