Beyond Pathology: Perivascular Spaces as Dynamic Players in Neurodevelopment and Brain Health

Perivascular spaces (PVS) have historically been viewed as radiological markers of aging and cerebrovascular pathology. However, this narrow perspective overlooks accumulating evidence that PVS likely undergo dynamic, prolonged maturation across the lifespan and may play an essential role in healthy brain development. This Viewpoint article challenges the prevailing paradigm by positioning PVS not as passive anatomical structures or mere disease indicators, but as active participants in postnatal neurodevelopment whose morphology and function evolve to meet the metabolic and waste clearance demands of the maturing brain. We integrate evidence from advanced neuroimaging, developmental neuroscience, and neurobiology studies to highlight that PVS structure and fluid dynamics may be coupled with several neurodevelopmental processes, impacted by early experiences, and mature through adolescence to facilitate healthy brain development and cognitive functioning. We advocate for longitudinal, lifespan approaches to PVS research, because understanding normative PVS development is paramount for interpreting pathological changes. This developmental reframing highlights new opportunities for early identification of at-risk individuals and preventive interventions targeting the brain's waste clearance system during sensitive developmental windows.