[Mechanisms and intervention strategies by which neuropsychological stress promotes central nervous system tumor recurrence through blood

Tumor recurrence is a major cause of treatment failure in central nervous system (CNS) tumors, although its underlying mechanisms have not yet been fully elucidated. Recent studies have suggested that neuropsychological stress may activate the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal-medullary system, thereby inducing the release of glucocorticoids, catecholamines, and inflammatory mediators. These processes may contribute to structural damage to the neurovascular unit, resulting in structural disruption of the blood-brain barrier (BBB) and increased BBB permeability. Increased BBB permeability not only provides a route for tumor-cell invasion but also facilitates infiltration of immunosuppressive cells into the brain parenchyma and the passage of proinflammatory cytokines across the BBB. These changes may remodel the tumor microenvironment (TME) and reactivate dormant tumor cells, thereby forming a potential regulatory axis that drives the recurrence of CNS tumors. This review systematically summarizes the potential regulatory axis of "neuropsychological stress-BBB dysfunction-TME remodeling-CNS tumor recurrence", elucidates the molecular mechanisms underlying neuropsychological stress-mediated BBB injury, and discusses how BBB abnormalities regulate the CNS TME and tumor-cell dormancy. Potential strategies, including BBB-targeted vascular normalization, localized and reversible BBB opening, active trans-BBB drug delivery, and psychological interventions, are also discussed. These insights may provide a theoretical basis and new perspectives for the prevention and management of CNS tumor recurrence.