Proteomic-based identification of injury-specific patterns of biomarkers in rotational and penetrating TBI

Background: Traumatic Brain Injury (TBI) biomarkers would be highly valuable in the diagnosis of various forms of TBI and also in evaluation and treatment of TBI patients and may even provide prediction of outcome of the future impairments of the patients. Here we use proteomics to investigate the temporal changes of chosen proteins in serum and brain in 2 different animal TBI models. Methods: The first model is a controlled penetration of 2 mm thick needle shaped object, which is accelerated with a bullet from air gun or a pendulum, pen-TBI. In the second model where we produce diffuse axonal injury, the animal is subjected to high-speed sagittal rotation acceleration, rot-TBI. The rats were sacrificed 1 day, 3 days and 14 days post injury. We used 30rats, 15rats in each model, 5 rats for each timepoint where 2 of these where sham, these results were compared with values from normal rats. The FC (FC) and HC (HC) were extracted in addition to serum samples. The tissue extractions were analyzed with reverse capture antibody based proteomics for N-cadherin, S-100B, Tau, NSE, NF200, TNF-a, MBP, BDNF, C3, C9, C5b9, Results: In brain significant changes could be seen in N-cadherin in HC in pen-TBI on day 1, BDNF showed a peak in rot-TBI on day 1 while in pen-TBI the peak was after 14 days. C3 increased significantly in the HC of rot-TBI at day 1. C9 increased significantly in rot-TBI both in FC and HC on day 3 and day1 and 3 respectively. C5b9 had its peak in HC in rot-TBI on day 1 but in pen-TBI at day14. N-cadherin in serum of rot-TBI showed a significant increase in day 1 and 14 with a nadir at day3. The pattern was different in pen-TBI where there was an increase at all timepoint with increase overtime. Tau in serum was significantly increased uniformly at all time points in both models. TNF-a was also increased at all timepoints but in rot-TBI it decreased by day 14. S-100B showed no significant change in rot-TBI while in pen-TBI it was significantly increased at all timepoints. NSE in rot-TBI had a peak at day 1 and declined but in pen-TBI there was a nadir at day 3 and the peak was reached by day14. Similar pattern was seen in NF200. MBP was increased at all timepoints with a peak at day 3 in both models. C3 was increased at all timepoints but in pen-TBI it had a peak in day 3. C9 in rot-TBI increased significantly at day 3 and 14 while in pen-TBI it increased from day1 till day 14. C5b9 was significantly increased at all timepoints in both models however in rot-TBI it increased overtime while in pen-TBI it had a peak on day 14. Conclusion: To the best of our knowledge these are the first results showing TBI – type specific changes in different proteins that can be considered as future biomarkers