Blood-Brain Barrier Dysfunction after Traumatic Brain Injury: Molecular Pathways and Clinical Evidence -A Systematic Review
DOI:
https://doi.org/10.68041/jmmhr.v1i2/06Keywords:
Blood-Brain Barrier, Brain Injuries, Traumatic, Cerebrospinal Fluid, Magnetic Resonance Imaging, NeuroinflammationAbstract
Objective: The blood–brain barrier (BBB) is an important component of the secondary injury mechanism in traumatic brain injury (TBI), associated with changes in BBB permeability, neuroinflammation, impaired protein clearance, and neurological deterioration. This systematic review aimed to synthesize clinical evidence on BBB dysfunction and associated molecular pathways following TBI. Data Sources: This review was conducted following PRISMA 2020 guidelines. PubMed, Scopus, Web of Science, and Google Scholar were searched from January 2019 to February 2026. Study Selection: Studies having BBB disruption or molecular mechanisms associated with BBB in human TBI using imaging, serum or plasma, CSF, or cerebral microdialysis methods were selected. Data Extraction: Two reviewers independently extracted data. QUADAS-2, adapted PROBAST, QUIPS, and adapted JBI tools were used to assess risk of bias. The GRADE approach was used to assess certainty of evidence. Data Synthesis: Fifteen studies met the inclusion criteria. Studies demonstrated the presence of BBB or blood–CSF barrier disruption by DCE-MRI, gadolinium leakage, permeability mapping, and meningeal enhancement. Biomarker studies found links between TBI and neurofilament light chain, GFAP, UCH-L1, S100B, NSE, inflammatory cytokines and chemokines, MMPs, and microdialysis proteins. These markers were correlated with injury severity, CT abnormalities, post-concussion symptoms, axonal injury, cerebral blood flow changes, and functional outcomes. The risk of bias was mostly moderate. Certainty of evidence was low to moderate. Conclusion: BBB dysfunction following TBI is associated with altered permeability, neuroaxonal damage, inflammation, proteinase activity, and impaired protein clearance. Larger standardized studies are needed to validate BBB biomarkers and clarify underlying molecular pathways.
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