THE BLOOD BRAIN BARRIER
INTRODUCTION
The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system, thus protecting the brain from harmful or unwanted substances in the blood. The blood–brain barrier is formed by endothelial cells of the capillary wall, astrocyte end-feet ensheathing the capillary, and pericytes embedded in the capillary basement membrane. This system allows the passage of some small molecules by passive diffusion, as well as the selective and active transport of various nutrients, ions, organic anions, and macromolecules such as glucose and amino acids that are crucial to neural function.
STRUCTURE
The BBB results from the selectivity of the tight junctions between the endothelial cells of brain capillaries, restricting the passage of solutes. At the interface between blood and the brain, endothelial cells are adjoined continuously by these tight junctions, which are composed of smaller subunits of transmembrane proteins, such as occludin, claudins (such as Claudin-5), junctional adhesion molecule (such as JAM-A).Each of these tight junction proteins is stabilized to the endothelial cell membrane by another protein complex that includes scaffolding proteins such as tight junction protein 1 (ZO1) and associated proteins.
The BBB is composed of endothelial cells restricting passage of substances from the blood more selectively than endothelial cells of capillaries elsewhere in the body. Astrocyte cell projections called astrocytic feet (also known as "glia limitans") surround the endothelial cells of the BBB, providing biochemical support to those cells.
WHY DO WE NEED IT?
The purpose of the blood–brain barrier is to protect against circulating toxins or pathogens that could cause brain infections, while at the same time allowing vital nutrients to reach the brain. Its other function is to help maintain relatively constant levels of hormones, nutrients and water in the brain – fluctuations in which could disrupt the finely tuned environment.
So what happens if the blood–brain barrier is damaged or somehow compromised?
One common way this occurs is through bacterial infection, as in meningococcal disease. Meningococcal bacteria can bind to the endothelial wall, causing tight junctions to open slightly. As a result, the blood–brain barrier becomes more porous, allowing bacteria and other toxins to infect the brain tissue, which can lead to inflammation and sometimes death.
It’s also thought the blood–brain barrier’s function can decrease in other conditions. In multiple sclerosis, for example, a defective blood–brain barrier allows white blood cells to infiltrate the brain and attack the functions that send messages from one brain cell (neuron) to another. This causes problems with how neurons signal to each other.
THERAPEUTICS AND BLOOD BRAIN BARRIER
Nanotechnology is under preliminary research for its potential to facilitate the transfer of drugs across the BBB. Capillary endothelial cells and associated pericytes may be abnormal in tumors and the blood–brain barrier may not always be intact in brain tumors. Other factors, such as astrocytes, may contribute to the resistance of brain tumors to therapy using nanoparticles. Fat soluble molecules less than 400 daltons in mass can freely diffuse past the BBB through lipid mediated passive diffusion.
Neurotherapeutic design involves an understanding of neuroimmunology at the BBB and throughout the brain. A better understanding of the BBB and microbe entry mechanisms, along with new insights into the brain’s complex immune system, will ultimately aid in the development of effective neurotherapeutics.
REFERENCES
Assessed and Endorsed by the MedReport Medical Review Board
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