Tumor-associated macrophages as mediators of vascular and cognitive dysfunction in glioblastoma

The blood–brain barrier (BBB) is a dynamic regulatory interface that maintains cerebral homeostasis by tightly controlling molecular exchange between the circulation and the central nervous system. In glioblastoma, this regulatory function becomes progressively compromised through the emergence of a heterogeneous blood–tumor barrier (BTB), characterized by regionally variable permeability and vascular dysfunction that supports tumor growth while limiting therapeutic efficacy. This review examines the molecular mechanisms underlying BBB disruption in glioblastoma, with particular emphasis on the role of tumor-associated macrophages (TAMs) as central drivers of endothelial instability, basement membrane remodeling, and sustained neuroinflammation. Through the secretion of cytokines, proteases, and angiogenic factors, TAMs link immune signaling to pathological vascular remodeling. Beyond molecular and vascular alterations, BBB dysfunction in glioblastoma has significant neuropsychological consequences. Disruption of the neurovascular unit contributes to impairments in attention, memory, and executive function, alongside heightened emotional distress, including anxiety, depression, and reduced quality of life. These findings illustrate a continuum in which cellular pathology translates into functional and psychosocial decline. By integrating molecular, vascular, and cognitive perspectives, this synthesis highlights the need for multidisciplinary neuro-oncological strategies that extend beyond tumor control to include immunomodulation, vascular stabilization, and cognitive and psychological support. Such integrative approaches may improve not only survival but also functional outcomes and patient well-being in glioblastoma.