Traumatic brain injury (TBI) remains a major global health problem, contributing significantly to morbidity and mortality worldwide. Despite advances in understanding its complex pathophysiology, current therapeutic strategies are insufficient in addressing the long-term cognitive, emotional, and neurological impairments. While the primary mechanical injury is immediate and unavoidable, the secondary phase involves a cascade of biological processes leading to neuroinflammation, blood–brain barrier (BBB) disruption, and systemic immune activation. The heterogeneity of patient responses underscores the urgent need for reliable biomarkers and targeted interventions. Emerging evidence highlights the gut–brain axis as a critical modulator of the secondary phase, with microbiota-derived extracellular vesicles (MEVs) representing a promising avenue for both diagnosis and therapy. MEVs can cross the intestinal barrier and BBB, carrying biomolecules that influence neuronal survival, synaptic plasticity, and inflammatory signaling. These properties make MEVs promising biomarkers for early detection, severity classification, and prognosis in TBI, while also offering therapeutic potential through modulation of neuroinflammation and promotion of neural repair. MEV-based strategies could enable tailored interventions based on the individual’s microbiome profile, immune status, and injury characteristics. The integration of multi-omics with artificial intelligence is expected to fully unlock the diagnostic and therapeutic potential of MEVs. These approaches can identify molecular subtypes, predict outcomes, and facilitate real-time clinical decision-making. By bridging microbiology, neuroscience, and precision medicine, MEVs hold transformative potential to advance TBI diagnosis, monitoring, and treatment. This review also identifies key research gaps and proposes future directions for MEVs in precision diagnostics and gut microbiota-based therapeutics in neurotrauma care.

Background: This study was designed as a dosimetric feasibility analysis to compare hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) using 3D-CRT, IMRT, and VMAT techniques, with particular attention to clinical applicability in resource-limited settings. While 3D-CRT was used as a reference for conventional WBRT, the primary aim was to determine whether IMRT can serve as an effective and accessible alternative to VMAT for HA-WBRT in centers without advanced technology infrastructure. Methods: Fifteen patients undergoing WBRT for symptom relief were planned using 3D-CRT, IMRT, and VMAT on the Elekta Monaco 6.1.4.0 system. Key organs at risk (OARs) such as the optic nerves, chiasm, eyes, and lenses were considered in the treatment planning. Plans were evaluated based on PTV dose distribution, Conformity Index (CI), Homogeneity Index (HI), and OAR dose constraints (RTOG 0933, NRG-CC001). Gamma pass rate analysis (3%/3 mm) was performed for the IMRT and VMAT plans. Results: IMRT and VMAT significantly reduced the hippocampal dose compared to 3D-CRT, with similar PTV coverage and OAR sparing. The mean D_max for the hippocampus was 15.4 Gy for IMRT and 15.5 Gy for VMAT compared to 31.2 Gy for 3D-CRT. The D100% for the hippocampus was 7.5 Gy for IMRT and 7.6 Gy for VMAT, both well below the RTOG 0933 threshold of 9 Gy, while 3D-CRT delivered 30.3 Gy. Additionally, IMRT and VMAT delivered lower doses to the optic nerves and chiasm. QA results showed gamma pass rates above 96% for all plans. This study focused solely on treatment-planning and dosimetric feasibility without evaluating patient outcomes or clinical follow-up. Conclusions: HA-WBRT with IMRT and VMAT significantly reduced the hippocampal dose while maintaining optimal PTV coverage. VMAT is preferred for its balance of efficacy, protection, and treatment time, while IMRT represents a feasible approach for facilities without VMAT, though it requires stricter dose control and longer treatment times.