What is the structure and physiology of the Blood-Brain Barrier (BBB)?

From the Guidelines

The blood-brain barrier (BBB) is a highly selective semipermeable border that separates the circulating blood from the brain and extracellular fluid in the central nervous system, comprising astrocytes, pericytes, and endothelial cells that form a selective diffusion barrier with transmembrane efflux pumps. The BBB's structure includes specialized endothelial cells that line cerebral capillaries, connected by tight junctions that restrict the passage of substances from the bloodstream to the brain, as well as pericytes, a basement membrane, and astrocytic end-feet that surround the capillaries, collectively forming the neurovascular unit 1.

Key Components of the BBB

• Specialized endothelial cells
• Tight junctions
• Pericytes
• Basement membrane
• Astrocytic end-feet

The BBB functions to maintain brain homeostasis by regulating ion balance, preventing harmful substances from entering brain tissue, and protecting the brain from fluctuations in plasma composition 1. It allows selective transport of essential nutrients through specific transport systems, including carrier-mediated transport for glucose and amino acids, receptor-mediated transcytosis for larger molecules like insulin and transferrin, and ATP-binding cassette transporters that actively pump out potentially harmful substances 1.

Physiological Functions of the BBB

• Regulating ion balance
• Preventing harmful substances from entering brain tissue
• Protecting the brain from fluctuations in plasma composition
• Selective transport of essential nutrients

The integrity of the BBB can be compromised in conditions like stroke, traumatic brain injury, multiple sclerosis, and certain infections, leading to neuroinflammation and potential neurological damage 1. The BBB's selective permeability explains why many medications cannot effectively reach the brain, requiring special formulations or delivery methods for CNS-targeting drugs. Recent studies have highlighted the importance of assessing BBB leakage in clinical research studies, particularly in the context of cerebral small vessel disease 1.

From the Research

Structure of the Blood-Brain Barrier (BBB)

• The BBB is formed by an interdependent network of brain capillary endothelial cells, perivascular cells (astrocytes and pericytes), and the basement membrane 2, 3, 4, 5.
• The main physical barrier is found in the CNS endothelial cell, and depends on continuous complexes of tight junctions combined with reduced vesicular transport 3, 4, 5.
• The BBB is characterized by a specialized assortment of molecular specializations, providing the basis for tightening, transport, and immune response functionality 2.

Physiology of the Blood-Brain Barrier (BBB)

• The BBB protects the vertebrate central nervous system from harmful blood-borne, endogenous, and exogenous substances to ensure proper neuronal function 2, 5.
• The BBB regulates the transport of substances across the barrier, with a functional polarity existing between the luminal and abluminal membrane surfaces of the BMVEC 5.
• The Wnt/β-catenin pathway is crucial for inducing and maintaining endothelial barrier function, and requires intact neurovascular unit (NVU) for proper functionality 2.
• Pericytes play a critical role in regulating BBB-specific gene expression patterns in endothelial cells and inducing polarization of astrocyte end-feet surrounding CNS blood vessels 3.

Cellular Components of the Blood-Brain Barrier (BBB)

• Endothelial cells: form the main physical barrier of the BBB and are responsible for regulating the transport of substances across the barrier 3, 4, 5.
• Pericytes: regulate BBB-specific gene expression patterns in endothelial cells and induce polarization of astrocyte end-feet surrounding CNS blood vessels 3.
• Astrocytes: interact with endothelial cells and pericytes to maintain the proper function of the BBB 2, 3, 4, 5.
• Neurons: interact with the NVU to regulate the proper function of the BBB 2, 5.
• Microglia: interact with the NVU to regulate the proper function of the BBB 2.

Regulation and Dysfunction of the Blood-Brain Barrier (BBB)

• The BBB is regulated by various factors, including tight junctions, enzymes, and transport systems 4, 5.
• Alterations in junction assembly and function can significantly affect BBB properties, particularly barrier permeability 4.
• BBB breakdown or alterations in transport systems can play an important role in the pathogenesis of many CNS diseases 5.
• Proinflammatory substances and specific disease-associated proteins can mediate BBB dysfunction 5.