Molecular pathways linking traumatic brain injury to cardiovascular dysfunction: therapeutic potential of physical exercise

Traumatic brain injury (TBI) affects millions globally and increasingly associates with cardiovascular disease risk through mechanisms involving autonomic nervous system dysfunction, neuroinflammation, oxidative stress, and hypothalamic-pituitary axis disruption. However, the precise molecular pathways remain incompletely understood. This review synthesizes current evidence on TBI-induced cardiovascular dysfunction and explores physical exercise as a therapeutic intervention. We conducted a comprehensive literature narrative review of experimental and clinical studies investigating cardiovascular complications following TBI and exercise-based interventions. TBI triggers a cascade of molecular events leading to autonomic imbalance, chronic inflammation, and oxidative damage that collectively increase cardiovascular risk. Physical exercise emerges as a promising intervention through its capacity to modulate inflammatory processes, restore autonomic balance, and enhance synaptic plasticity. However, optimal timing, intensity, and duration of exercise protocols remain undefined. Understanding heart-brain communication pathways post-TBI is crucial for developing targeted interventions. Physical exercise shows therapeutic potential, but standardized protocols are needed to optimize cardiovascular outcomes in TBI patients.