Open Access

Fatima Gimeno-Ferrer, Lisa Teresa Porschen, Frank Matthes, Katrin Gohlsch, Anja Meissner

• Ambient particulate matter (PM), especially fine and ultrafine particles, has emerged as a significant environmental risk factor for neurological disorders, largely through its impact on the blood-brain barrier (BBB) and the neurovascular unit. This review summarizes current evidence on how PM affects BBB integrity, emphasizing the coordinated and cell-specific responses that drive neurovascular dysfunction. Upon systemic or neural translocation, PM induces oxidative stress and inflammation in endothelial cells, disrupting tight junctions (TJs), enhancing permeability, and upregulating adhesion molecules (e.g. ICAM-1 and VCAM-1), which facilitate immune cell infiltration. Pericytes contribute to these processes in a stage-dependent manner, promoting BBB leakage through detachment and inflammation in acute settings while participating in later reparative processes such as angiogenesis and neurogenesis. Astrocytes respond to PM exposure by adopting a reactive phenotype, releasingAmbient particulate matter (PM), especially fine and ultrafine particles, has emerged as a significant environmental risk factor for neurological disorders, largely through its impact on the blood-brain barrier (BBB) and the neurovascular unit. This review summarizes current evidence on how PM affects BBB integrity, emphasizing the coordinated and cell-specific responses that drive neurovascular dysfunction. Upon systemic or neural translocation, PM induces oxidative stress and inflammation in endothelial cells, disrupting tight junctions (TJs), enhancing permeability, and upregulating adhesion molecules (e.g. ICAM-1 and VCAM-1), which facilitate immune cell infiltration. Pericytes contribute to these processes in a stage-dependent manner, promoting BBB leakage through detachment and inflammation in acute settings while participating in later reparative processes such as angiogenesis and neurogenesis. Astrocytes respond to PM exposure by adopting a reactive phenotype, releasing pro-inflammatory cytokines and reactive oxygen species that exacerbate barrier disruption and impair neurovascular coupling. Microglia act as central mediators of neuroinflammation, releasing cytokines that weaken TJs and perpetuate endothelial dysfunction. These mechanisms are further modulated by particle properties and host-related factors including age, metabolic status, and pre-existing comorbidities. The resulting cascade of BBB impairment and neuroinflammation underscores the multifaceted nature of PM-induced neurotoxicity and identifies potential cellular targets for intervention.…