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.

Public Health Relevance

Traumatic brain injury (TBI) affects 1.7 MILLION Americans EVERY year and it is a major cause of death and chronic disability. Direct medical costs and indirect costs, lost productivity due to TBI did cost ~76 BILLION USD in 2000. Extended rehabilitation and support of TBI survivors multiply this amount. Favorable outcome after TBI is critically dependent on precise, early classification and diagnosis of the injury so targeted evidence-based therapies can be developed and applied. The objective of the proposed work is to improve the early diagnostic process through determining the relationship between protein biomarkers measured in blood and CSF and cerebral microdialysates.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Small Research Grants (R03)
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Acute Neural Injury and Epilepsy Study Section (ANIE)
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Bellgowan, Patrick S F
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Henry M. Jackson Fdn for the Adv Mil/Med
United States
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