Biofluid Proteomics and Biomarkers in Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is an injury to the brain caused by an external mechanical force, affecting millions of people worldwide. The disease course and prognosis are often unpredictable, and it can be challenging to determine an early diagnosis in case of mild injury as well as to accurately phenotype the injury. There is currently no cure for TBI-drugs having failed repeatedly in clinical trials-but an intense effort has been put to identify effective neuroprotective treatment. The detection of novel biomarkers, to understand more of the disease mechanism, facilitates early diagnosis, predicts disease progression, and develops molecularly targeted therapies that would be of high clinical interest. Over the last decade, there has been an increasing effort and initiative toward finding TBI-specific biomarker candidates. One promising strategy has been to use state-of-the-art neuroproteomics approaches to assess clinical biofluids and compare the cerebrospinal fluid (CSF) and blood proteome between TBI and control patients or between different subgroups of TBI. In this chapter, we summarize and discuss the status of biofluid proteomics in TBI, with a particular focus on the latest findings.

Using Serum Amino Acids to Predict Traumatic Brain Injury: A Systematic Approach to Utilize Multiple Biomarkers

“…These brain biomechanical loads initiate a cascade of short-and long-term cellular and sub-cellular biochemical and metabolomic alterations in the brain which cause primary injury and secondary injury that evolves over time [1] and can lead to long-term neurodegeneration [2]. These biochemical and metabolomic alterations first appear in the brain tissue and then, by crossing a number of barriers, manifest in biofluids such as cerebrospinal fluid (CSF), blood, saliva and urine [1][2][3][4][5][6][7][8][9][10][11][12]. Therefore, biofluids contain valuable information about the occurrence and progression of TBI and thus recently have been explored as a source for potential biomarkers to diagnose TBI, as well as to assess its severity, monitor its progression, predict patient outcomes, and determine the effectiveness of therapeutic interventions [1,4,5,[9][10][11][13][14][15][16][17][18][19].…”

Proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients - a pilot study

“…In recent years CMD has been used as part of NCC monitoring and to study biomarkers of various neurological diseases in particular traumatic brain injury (28)(29)(30), gliomas (31,32), ischemic stroke(1), intracerebral hemorrhage (33) and subarachnoid hemorrhage (34,35). CMD sampling for subsequent proteomic biomarker analysis has advantages, such as capture of proteins near the site of origin in the extracellular space, and no effect of dilution as is the case in CSF or plasma (28).…”

A proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients

“…In recent years CMD has been used as part of NCC monitoring and to study biomarkers of various neurological diseases in particular traumatic brain injury (18)(19)(20), gliomas (21,22), ischemic stroke(1), intracerebral hemorrhage(23) and subarachnoid hemorrhage (24,25). CMD sampling for subsequent proteomic biomarker analysis has advantages, such as capture of proteins near the site of origin in the extracellular space, and no effect of dilution as is the case in CSF or plasma (18).…”