From the Guidelines
The Blood-Brain Barrier (BBB) is a selective diffusion barrier composed of astrocytes, pericytes, and endothelial cells, which protects the brain by preventing the influx of harmful solutes and disposing of unwanted compounds through transmembrane efflux pumps, such as P-glycoprotein. The BBB's structure and function are crucial in maintaining the brain's stable environment, and its integrity can be compromised by various factors, including chemotherapy-induced oxidative stress and pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) 1. The BBB's mechanism involves the formation of tight junctions between endothelial cells, which prevents most substances from passing through, while specialized transport proteins allow essential nutrients to enter the brain.
The BBB's composition and function can be affected by various factors, including:
- Astrocytes, pericytes, and endothelial cells working together to form a selective barrier
- Transmembrane efflux pumps, such as P-glycoprotein, disposing of unwanted compounds
- Tight junctions between endothelial cells preventing the passage of most substances
- Specialized transport proteins allowing essential nutrients to enter the brain
- The potential disruption of the BBB's integrity by chemotherapy, oxidative stress, and pro-inflammatory cytokines, leading to increased permeability and potential neurotoxicity 1.
The importance of the BBB's function is highlighted by its role in protecting the brain from toxins, pathogens, and fluctuations in blood composition, while also allowing necessary nutrients to reach brain tissue. However, the BBB's selective permeability can also prevent beneficial medications from reaching the brain, presenting challenges in treating brain disorders. Overall, the BBB's mechanism is complex and crucial for maintaining the brain's stable environment, and its integrity should be carefully considered in various medical contexts, including chemotherapy and the treatment of brain disorders 1.
From the Research
Mechanism of the Blood-Brain Barrier (BBB)
The Blood-Brain Barrier (BBB) is a highly selective and semi-permeable barrier that separates the circulating blood from the brain and central nervous system (CNS) 2, 3, 4. The main physical barrier is found in the CNS endothelial cell, and depends on continuous complexes of tight junctions combined with reduced vesicular transport 2.
Components of the BBB
The BBB consists of:
- Endothelial cells of CNS vessels
- Pericytes
- Astrocytes
- Neurons
- Microglia, together forming the neurovascular unit (NVU) 4, 5
- Extracellular matrix 2
Function of the BBB
The BBB regulates the transport of:
- Ions
- Nutrients
- Metabolites to help maintain proper brain function 5
- Essential nutrients, hormones, and signaling molecules between the bloodstream and the CNS 6 The BBB also protects the brain from:
- Harmful blood-borne, endogenous and exogenous substances 4
- Potentially harmful substances and pathogens 6
Regulation of the BBB
The BBB is regulated by:
- The Wnt/β-catenin pathway, which induces and maintains endothelial barrier function 4
- Pericytes, which regulate BBB-specific gene expression patterns in endothelial cells and induce polarization of astrocyte end-feet surrounding CNS blood vessels 2
- Insulin signaling, which modifies BBB permeability by regulating the expression of tight junction proteins, angiogenesis, and vascular remodeling 6