Integrated application of Raman spectroscopy in traumatic brain injury: A systematic review and clinical perspective

BACKGROUND: This systematic review explores the application of Raman spectroscopy (RS) in traumatic brain injury (TBI) research, emphasizing the need for innovative and efficient diagnostic tools. The development of such techniques aims to alleviate healthcare costs while providing timely assessment of injury severity. METHODS: A systematic literature search for the use of RS in TBI was conducted in PubMed, Scopus, and Web of Science from inception to July 28, 2025, following PRISMA guidelines. We included only original English-language studies (animals and humans) in free full-text format. Risk of bias was assessed using specific tools for both animal and human models. Findings were classified according to the cohorts, and spectroscopic technique alongside their particularities. RESULTS: The initial search found 261 articles, with 26 studies meeting the inclusion criteria. Among them: 15 were animal studies and 11 translational/human-relevant studies. Among animal studies, 3 focused on in-situ monitoring and TBI classification, 2 on blast-induced models, 5 on blood biomarker analysis, 2 on retinal-based point-of-care diagnostics, and 3 on Raman microscopy. The translational research studies aimed to identify and validate TBI biomarkers for developing future diagnostic strategies in human patients. DISCUSSION: RS distinguished injured from control tissue through spectral changes reflecting protein and lipid alterations and differentiated lesion areas by revealing astrogliosis-related reorganization. Instantaneous in-situ RS devices achieved >92% accuracy in severity classification and detected biomarker-related molecular changes. Point-of-care RS platforms using lateral flow strips enabled rapid detection of specific TBI biomarkers (GFAP, NAA, NSE, S100B, UCH-L1), showing performance comparable to ELISA while offering faster, simpler, and cost-efficient testing.