Identification of Serum Biomarkers for Blast‐induced Traumatic Brain Injuries: Low vs. High‐intensity Exposure in a Rat Model

Background/Aim: Traumatic brain injury (TBI), particularly from blast exposures, is a growing global health concern due to increasing international conflicts and terrorist attacks. Blast exposure involves whole-body impact; however, the specific effects on the brain remain inadequately defined. This study aimed to identify serum-based protein biomarkers that could serve as non-invasive indicators for early detection and prediction of long-term outcomes of blast-induced TBI (bTBI), and to assess other organ-specific responses. Focus was given to proteins associated with inflammation, mitochondrial dysfunction, and brain-specific injury. Materials and Methods: Adult male Sprague Dawley rats were exposed to repeated blast waves at either 10 pounds per square inch (PSI) or 20 PSI, while sham animals underwent identical procedures without blast exposure (n=8 per group). Serum samples were collected on day 0 (pre-injury) and day 28 (post-injury/sham). Protein levels were quantified using high-throughput western blotting and Meso Scale Discovery (MSD) multiplex assays. Key proteins analyzed included hypoxia-inducible factor 1-alpha (HIF-1α), glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF), C-peptide, fibroblast growth factor 21 (FGF-21), ghrelin, and glucagon-like peptide 1 (GLP-1). Results: Significant elevations in serum HIF-1α (p=0.017) and GFAP (p=0.011) were observed at day 28 following 20 PSI blast, indicating hypoxic stress and astrocyte activation. Levels of FGF-21 (p<0.035), ghrelin (p<0.05), and BDNF (p<0.05) were also significantly altered, whereas C-peptide and GLP-1 showed no significant changes (p>0.05). Conclusion: Serum HIF-1α, GFAP, and BDNF may serve as brain-specific biomarkers, while FGF-21 and ghrelin represent potential systemic markers for differentiating blast intensity and guiding therapeutic development.