Prognostic relevance of changes of proteomics in patients after traumatic brain injury (TBI)

Status:

completed 07/2023

Aims:

Severe traumatic brain injury (sTBI) is one of the most devastating causes of morbidity, mortality and incapacity-to-work for the working population. Due to its poor prognosis, which leads to high medical efforts and interventions, it is a relevant source of costs for accident insurances. So far, well-established biomarkers are missing to assess patients´ outcome with regard to secondary brain damages such as hypoxia, ischemia or malignant brain edema. The goal of the present study was to discover prognostic biomarkers in sTBI specific cerebrospinal fluid (CSF), blood and brain tissue that can identify the risk of occurrence of secondary brain damage and to identify patients with poor prognosis and to correlate these biomarkers with clinical well established methods such as neuromonitoring and electrophysiology.

Activities/Methods:

Within the first week after sTBI, CSF and blood samples from 32 sTBI patients were collected on days 0, 3 and 6, as well as brain tissue in case operation was necessary due to brain haematoma. On a daily basis, routine parameters (laboratory and ventilation parameters, as well as neuromonitoring) were documented. Furthermore, CSF samples of 18 healthy control patients were collected at one time point. By terms of quantitative mass spectrometric methods, proteomic profiles of the collected samples were performed in the Medical Proteome-Center (MPC). Afterwards bioinformatics and statistical methods were used to evaluate the proteomic data with regard to the other parameters. First, the differences between patients and controls and the temporal course of proteins within the sTBI samples were analyzed. Then, the proteomic changes were correlated with clinical parameters such as the intracranial pressure (ICP), the cerebral perfusion pressure (CPP), electrophysiology data and the early (at discharge) and late (6 months post trauma) clinical outcome.

Results:

32 sTBI patients and 18 control patients were included in the present study. In total, CSF samples were collected in 27 patients (day 0), in 30 patients (day 3) and in 23 patients (day 6).

Furthermore, brain samples were collected from 19 TBI patients during an operation for a cerebral hemorrhage. The remaining 13 TBI patients only received external ventricular drainage surgery to measure the ICP and, if necessary, therapy if pathological ICP values occurred. In comparison to control patients, 438 proteins on day 0, 382 proteins on day 3 and 350 proteins on day 6 were significant differently regulated in sTBI samples. Upregulated proteins were specifically associated with the GO-Terms "Response to stress" und "Regulation of complement activation". Furthermore, 265 proteins were significant differently regulated over the observation time in the sTBI samples.

No correlation was found between the proteomic profiles and both SSEP/FAEP-data and the early clinical patient outcome. 3 proteins correlated with the ICP when grouped into the following values: ICP ≤18 mmHg (physiological range) and ICP>18 mmHg (pathological increased range): UCH-L1, YWHAG and NPTXR.

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