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Exploring the potential for biomarkers to aid forensic diagnosis of traumatic brain injury (TBI) – a systematic literature review and meta-analysis
Background: Traumatic brain injury (TBI) is a prevalent condition worldwide. Understanding its pathophysiology is imperative for clinical diagnosis, treatment, and cause of death determination. Biomarkers could offer potential insight. Proteins involved in neuroinflammation, such as systemic inflamm...
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| Format: | Thesis |
| Language: | English ENG |
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Department of Pathology
2025
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| Summary: | Background: Traumatic brain injury (TBI) is a prevalent condition worldwide. Understanding its pathophysiology is imperative for clinical diagnosis, treatment, and cause of death determination. Biomarkers could offer potential insight. Proteins involved in neuroinflammation, such as systemic inflammatory biomarkers interleukin (IL)-1β, IL-6, and IL-10 and astroglia-associated biomarkers S100 Calcium-Binding Protein B (S100β) and Glial Fibrillary Acidic Protein (GFAP), have been assessed as potential TBI biomarkers. The aim of this review was to evaluate recent articles that investigated these biomarkers in relation to TBI and relate this to a forensic diagnostic context. Methods: This review included 44 peer-reviewed articles from three major literature databases published from 2018 onwards, that investigated either IL-1β, IL-6, IL-10, GFAP, S100β, or a combination thereof, in relation to TBI. Studies conducted in a clinical or forensic setting were included. A meta-analysis was conducted on a subset of these studies. Results: Majority of the biomarkers were elevated in TBI versus control groups. The most promising biomarkers were GFAP and S100β, which in addition to being elevated also correlated with unfavourable outcomes and TBI severity. GFAP alone was increased in TBI patients with positive CT scans. The ILs had inconclusive results due to minimal studies and inconsistent study designs. A wide range of biomarker expression levels were noted across all articles (from 0.01 to 1.5 million pg/mL). The meta-analysis yielded a pooled effect size of 0.97. Discussion: Inconsistencies in results could potentially be explained by heterogenous TBI and control groups, various body specimens, and different immunoassays used. Thus, each biomarker should be investigated systematically whilst keeping other variables consistent to ensure definitive conclusions. Overall, none of the proteins could function as biomarkers of TBI alone. However, the meta-analysis did indicate a moderately significant association between biomarker levels and TBI occurrence. Future studies are needed to corroborate the findings. |
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