Dynamic modulation of the blood-brain barrier in the healthy brain

The blood-brain barrier (BBB) performs intricate and dynamic functions that extend far beyond its traditional role as a static protective barrier, playing a pivotal role in maintaining CNS homeostasis. These multifaceted functions are rooted in its specialized architectural and cellular composition. In this Review, we examine the dynamic modulation of BBB function during physiological conditions and the hypothesis that such modulation contributes directly to neural and glial plasticity. We provide an integrated examination of the BBB's diverse cellular components - endothelial cells, pericytes, astrocytes, microglia and vascular smooth muscle cells - across different CNS vascular segments. We discuss how physiological features and states, including circadian rhythms, physical activity, stress and hormonal fluctuations, dynamically alter BBB permeability and signalling, potentially shaping synaptic function, neuronal circuit dynamics and glial responsiveness. Understanding these mechanisms offers new insights into the neurovascular basis of synaptic plasticity and suggests that the BBB may be an under-recognized regulator and modulator of brain adaptability in both health and disease.