Neuroplasticity after traumatic brain injury: mechanisms and clinical implications

Traumatic brain injury (TBI) remains a leading cause of death and long-term neurological disability worldwide. Functional recovery after TBI depends largely on neuroplasticity, the brain's capacity for structural and functional reorganisation. While advances in acute neurocritical care have improved survival, optimising long-term outcomes requires a clearer understanding of how surgical, rehabilitative, pharmacological, neuromodulatory, and computational strategies influence plastic mechanisms across recovery phases.

To synthesise current experimental and clinical evidence on the mechanisms and temporal dynamics of neuroplasticity following traumatic brain injury and to evaluate how neuroimaging and biomarkers, rehabilitation, neuromodulation, pharmacological therapies, surgical interventions, and emerging artificial intelligence-based approaches may inform or modulate functional recovery.

This narrative review integrates experimental and clinical literature addressing cellular and molecular mechanisms of plasticity, neuroimaging and electrophysiological biomarkers, rehabilitation-induced network reorganisation, neuromodulation techniques, pharmacological modulators, surgical timing, and emerging artificial intelligence (AI)-driven precision approaches in TBI care.

Neuroplasticity evolves across acute, subacute, and chronic phases. Early mitigation of secondary injury preserves neural substrates necessary for adaptive reorganisation. Rehabilitation promotes experience-dependent plasticity through task-specific training and network-level recalibration. Neuromodulatory approaches, including non-invasive brain stimulation and vagus nerve stimulation, may enhance circuit responsiveness to therapy. Pharmacological agents targeting neurotrophic and inflammatory pathways show translational promise but require further validation. Advanced neuroimaging, biomarker profiling, and AI-based models improve prognostication and recovery stratification, supporting personalised, phase-specific interventions.

Optimising TBI recovery requires coordinated, multimodal, and temporally informed strategies integrating acute stabilisation with plasticity-targeted rehabilitation and neuromodulation. Biomarker-guided precision care and computational modelling offer opportunities to shift from reactive management toward proactive orchestration of neuroplastic recovery.