Abstract: Blood–brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes. This review systematically analyzes the current understanding of the bidirectional relationship between blood– brain barrier disruption and neuroinflammation in traumatic brain injury, along with emerging combination therapeutic strategies. Literature review indicates that blood–brain barrier disruption and neuroinflammatory responses are key pathological features following traumatic brain injury. In the acute phase after traumatic brain injury, the pathological characteristics include primary blood– brain barrier disruption and the activation of inflammatory cascades. In the subacute phase, the pathological features are characterized by repair mechanisms and inflammatory modulation. In the chronic phase, the pathological features show persistent low-grade inflammation and incomplete recovery of the blood–brain barrier. Various physiological changes, such as structural alterations of the blood–brain barrier, inflammatory cascades, and extracellular matrix remodeling, interact with each other and are influenced by genetic, age, sex, and environmental factors. The dynamic balance between blood–brain barrier permeability and neuroinflammation is regulated by hormones, particularly sex hormones and stress-related hormones. Additionally, the role of gastrointestinal hormones is receiving increasing attention. Current treatment strategies for traumatic brain injury include various methods such as conventional drug combinations, multimodality neuromonitoring, hyperbaric oxygen therapy, and non-invasive brain stimulation. Artificial intelligence also shows potential in treatment decision-making and personalized therapy. Emerging sequential combination strategies and precision medicine approaches can help improve treatment outcomes; however, challenges remain, such as inadequate research on the mechanisms of the chronic phase traumatic brain injury and difficulties with technology integration. Future research on traumatic brain injury should focus on personalized treatment strategies, the standardization of techniques, costeffectiveness evaluations, and addressing the needs of patients with comorbidities. A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.

Key words: artificial intelligence, biomarkers, blood–brain barrier, combination therapy, drug delivery, exosomes, focused ultrasound, hyperbaric oxygen therapy, inflammation, nanocarriers, neurodegeneration, personalized medicine, stem cells, therapeutic hypothermia, traumatic brain injury