Quantitative Analysis of GFAP and CD68 Immunohistochemical Expressions in Fatal Traumatic Brain Injury Cases

Traumatic brain injury (TBI) remains a leading cause of morbidity and mortality worldwide, particularly affecting individuals under 45 years of age. Fatal TBI cases necessitate detailed neuropathological assessment to determine the extent and timing of injury. Immunohistochemical markers, specifically glial fibrillary acidic protein (GFAP) and cluster of differentiation 68 (CD68), provide objective evidence of astrocytic activation and microglial response. This comprehensive systematic review synthesized quantitative findings from 23 primary sources examining GFAP and CD68 as biomarkers in fatal TBI. GFAP demonstrates robust diagnostic utility with FDA-approved blood tests, sensitivity exceeding 95% for detecting intracranial lesions, and well-characterized temporal profiles (peaking within 20-24 hours post-injury). CD68 reflects microglial activation with delayed but sustained elevation (peak at 3-7 days post-injury). The combined assessment of GFAP and CD68 enhances diagnostic accuracy, particularly in challenging forensic cases with advanced decomposition. However, significant limitations remain, including specificity challenges (both markers can be elevated in other neuropathological conditions), methodological variability across institutions, and the lack of standardized protocols. Future research should prioritize protocol standardization, specificity enhancement through multi-biomarker panels, large-scale prospective validation studies, integration of advanced technologies (single-cell transcriptomics, artificial intelligence), and translation of findings into forensic practice guidelines.