Blood Brain Barrier: Definition, Function, Anatomy, Substance Transport and Associated Diseases

It is a complex structure formed by a layer of endothelial cells of the central nervous system.

These cells selectively allow the entry of molecules necessary for brain function , such as amino acids, oxygen, glucose, and water, while keeping the other elements out.

Function

The blood-brain barrier restricts the passage of substances from the bloodstream to the tissues of the central nervous system.

It provides a highly selective permeability, with much tighter control than in most other tissues in the body over the movement of substances through the endothelium of the capillaries.

It contributes to the formation of the specific neuronal microenvironment and is considered part of the neuroimmune system.

In addition to protecting the brain from potentially harmful molecules and plasma fluctuations, the blood-brain barrier also serves a homeostatic purpose, providing nutrients to the brain (via selective transporters) and helping to remove waste products.

By maintaining a stable environment, the blood-brain barrier helps ensure synaptic transmission.

Anatomy

The blood-brain barrier arises in the blood capillaries of the central nervous system, a unique characteristic of this organ in the human body.

It is made up of endothelial cells that line the inside of each blood vessel.

In the endothelium of brain capillaries, each cell border is intimately attached to an adjacent cell.

This union makes the inner wall of the capillary waterproof.

This structure limits the passage of hydrophilic molecules to the nervous tissue.

The basement membrane of the capillaries is surrounded by specialized cells of the central nervous system, which are also functionally involved, such as the pericytes, the abluminal basal lamina, the perivascular astrocytes, and the microglia.

Pericitos

These are contractile cells arranged around capillaries and their function is to regulate endothelial cell maturation and capillary blood flow.

The lack of function of the pericytes is so severe that it can cause the effectiveness of the blood-brain barrier.

Astrocitos

They are the most abundant glial cells. One of its most important functions is the metabolic and structural support of neurons.

With the final part of their cellular projections, called astrocytic feet, astrocytic feet or glial limiting, the astrocytes cover the outer zone of the capillaries and reinforce the effect of the blood-brain barrier and make a filter between the blood and the neurons.

Transport at the blood-brain barrier

The brain depends on the delivery of key hormones and nutrients, including glucose and various amino acids, from other organs in the body.

The blood-brain barrier helps block harmful substances and microscopic objects, such as toxins, bacteria, and viruses, from entering the brain.

Through an extensive study, scientists discovered that compounds that are very small or fat-soluble, such as antidepressants, anti-anxiety medications, alcohol, cocaine, and many hormones, can pass through the endothelial cells that form a blood brain barrier without a lot of effort.

In contrast, larger molecules, such as glucose or insulin, must be transported by proteins.

These transporter proteins, located on the walls of blood vessels in the brain, selectively hook up and draw desired molecules from the blood to the brain.

Cells within and on either side of the blood-brain barrier are in constant communication about which molecules to let through and when.

For example, if nerve cells in a region of the brain are working particularly hard, they will signal the blood vessels to dilate, allowing the nutrients that the cells carry to travel rapidly from the blood to nerve cells in need.

Diseases

When the blood-brain barrier is broken, as is the case in some brain cancers, brain infections, and other neurological diseases such as: stroke, multiple sclerosis, epilepsy, hypoxia and ischemia, among others, small ruptures to the blood vessels occur.

Viral meningitis is characterized by inflammation of the membranes that surround and protect the brain and spinal cord and compromises the functional integrity of the blood-brain barrier.

Inflammation, caused by an infection or virus, can have a detrimental effect on the integrity of the blood-brain barrier, making it more permeable to infiltration by immune cells.

Ischemic stroke precedes a breakdown in the blood-brain barrier.

Studies suggest that a leaky blood-brain barrier allows too many white blood cells in the brains of people with multiple sclerosis.

With access to the brain, these cells attack myelin, the insulating coating between nerve cells, leading to the devastating symptoms of the disease.

Stress increases the permeability of the blood-brain barrier to macromolecules that circulate in the blood.

While the tight junctions of the blood-brain barrier are responsible for keeping bacteria out of the brain, they also prevent the entry of antibodies and antibiotics; brain infections are therefore quite difficult to improve.

Brain cancers are also difficult to treat with chemotherapeutic agents, which do not normally penetrate the brain and are often transported out of cells by multi-drug transporters.

For example, P-glycoprotein transports drugs out of the target cell, so inhibition of this transporter is of particular interest in reversing multidrug resistance.

The entry of T lymphocytes across the blood-brain barrier in multiple sclerosis causes demyelination.

Disruption of the blood-brain barrier has been associated with numerous neurological disorders, including Alzheimer’s disease and Parkinson’s disease, where the breakdown of the barrier is believed to stimulate disease progression.

The alteration of the blood-brain barrier induces the loss of dopaminergic neurons, which may contribute to the pathogenesis of Parkinson’s disease.

Increased expression of the receptor for advanced β-amyloid peptide (Aβ) glycation end products is observed in neurons, microglia, astrocytes, in Alzheimer’s disease.