New proteins discovered in brain injury

Schematic of overall experimental design for the proteomics analysis.
CSF = cerebrospinal fluid; TBI = traumatic brain injury;
TMT = tandem mass tag labeling. Image: Fig. 1 in the study

A team from Monash University’s Department of Neuroscience in Melbourne, Australia, collaborating with the Monash Proteomics and Metabolomics Facility, has found new proteins affected by brain injury which may represent new biomarkers, or biological indicators, of injury. 

It remains a significant clinical challenge to accurately predict long-term outcomes for a patient who sustains a severe traumatic brain injury.

Biomarkers can provide insight into the severity of the injury as well as the biological processes that are triggered in the injured brain, giving clinicians a greater understanding of the patients' condition, and allowing for personalisation of treatment and care. 

Associate Professor Bridgette Semple, senior author on the study, said, "In this study, we used a state-of-the-art technique to measure the levels of thousands of different proteins in cerebrospinal fluid (the fluid surrounding the brain) in patients who had sustained a severe traumatic brain injury. We identified several new proteins that were increased or decreased over time after injury in these patients compared to uninjured controls.” 

She said that past studies in the field have typically been hypothesis-driven - meaning that they were looking to measure specific molecules of interest. "Instead, we took a broad, data-driven approach, meaning that we analysed ALL the proteins that we could detect in the cerebrospinal fluid of severe brain injured patients. This allowed us to identify new proteins that were affected by brain injury, which provides new avenues for future research." 

The team used a technique called mass spectrometry to measure all the proteins present in the cerebrospinal fluid 'soup', and then compared these to existing databases to identify each of these soup ingredients. Some of the key ingredients were known, confirming past findings of key proteins that are affected by brain injury. But some of the ingredients were newly identified. 

Associate Professor Semple said, "This research aims to better understand what is happening in the brain acutely after a severe brain injury. These exciting findings will direct future research into potential targeting of these proteins for therapy, or measurement of these proteins as predictors of patient outcomes."

The research team has also made the dataset available to the research community, so that others can examine it and gain further insight. 

Reference

Shultz SR, Shah AD, Huang C, Dill LK, Schittenhelm RB, Morganti-Kossmann C, Semple BD. Temporal proteomics of human cerebrospinal fluid after severe traumatic brain injury. Journal of Neuroinflammation. doi: 10.1186/s12974-022-02654-0 https://rdcu.be/c1huL