THE BLOOD–BRAIN BARRIER: STRUCTURE, FUNCTIONS, AND MECHANISMS OF DYSFUNCTION IN CENTRAL NERVOUS SYSTEM DISEASES
Keywords:
Blood-brain barrier, neurovascular unit, endothelial cells, tight junctions, BBB dysfunction, neurodegenerative diseases, CNS drug delivery.Abstract
The blood–brain barrier (BBB) is a specialized neurovascular interface that maintains central nervous system homeostasis by regulating the exchange of substances between the circulation and brain. It is a dynamic component of the neurovascular unit (NVU), comprising brain endothelial cells, tight and adherens junctions, pericytes, astrocytic end-feet, and the extracellular matrix. BBB permeability is determined by passive diffusion, carrier-mediated transport, receptor-mediated transcytosis, and active efflux systems. BBB disruption involves endothelial dysfunction, tight junction degradation, oxidative stress, inflammation, matrix metalloproteinase activation, and NVU dysfunction, contributing to disorders such as ischemic stroke, multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and brain tumors. The BBB also remains a major obstacle to CNS drug delivery. Emerging approaches, including receptor-mediated delivery, nanoparticles, and focused ultrasound, aim to improve drug penetration while preserving barrier integrity.
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