Blood-brain barrier breakdown (BBBB)

Blood-brain barrier (BBB) breakdown is a complex pathological process characterized by the loss of structural and functional integrity of the neurovascular unit (NVU), particularly the endothelial tight junctions, basement membrane, and the regulatory roles of pericytes and astrocytes. This disruption allows the influx of neurotoxic blood-derived products, peripheral immune cells, and pathogens into the brain parenchyma, while simultaneously impairing the efflux of metabolic waste products like amyloid-beta. It is a hallmark of numerous central nervous system disorders, including stroke, traumatic brain injury, multiple sclerosis, and neurodegenerative diseases such as Alzheimer's. Pharmacological intervention focuses on either stabilizing the barrier to prevent neuroinflammation—often through the use of glucocorticoids or matrix metalloproteinase inhibitors—or intentionally and transiently increasing permeability to facilitate the delivery of systemic drugs that are otherwise excluded from the brain.

Other names

Blood-brain barrier dysfunctionBBB disruptionIncreased blood-brain barrier permeabilityNeurovascular unit breakdownBBB leakage

Stabilization of endothelial tight junction proteins (claudins, occludins), inhibition of matrix metalloproteinases (MMPs) to prevent basement membrane degradation, suppression of vascular endothelial growth factor (VEGF) signaling to reduce paracellular leakage, and osmotic induction of endothelial cell shrinkage for transient opening.