The blood–brain barrier serves as a natural barrier between the central nervous system (CNS) and the bloodstream. It allows only selective transport of substances. Disruption of the blood–brain barrier can lead to severe brain disease.
What is the blood-brain barrier?
The blood–brain barrier demarcates the milieu conditions in the brain and in the bloodstream. Very complex and finely tuned processes take place in the brain, the disruption of which would have incalculable consequences. The blood-brain barrier therefore ensures protection of the CNS from pathogens, toxins, antibodies, leukocytes, from the influence of neurotransmitters in the blood, and from changes in PH levels. At the same time, it is necessary to ensure that the CNS is supplied with the basic nutrients and substances necessary for its function. The same applies to the removal of degradation products of brain metabolism. Therefore, the barrier is not completely hermetic, but selectively permeable. The transport of important substances between the bloodstream and the brain is regulated by passive and active diffusion processes as well as selective chemical processes. Vital molecules, such as water, oxygen, and important nutrients, can pass through the blood-brain barrier without restriction.
Anatomy and structure
The blood-brain barrier is composed of the endothelial cells, pericytes, and astrocytes. The endothelial cells form the innermost wall layer of the capillaries. Among other things, these cells regulate the exchange of substances between tissue and blood. In the blood-brain barrier, the endothelial cells have so-called tight junctions. These are narrow bands of membrane proteins that connect the endothelial cells so tightly that they form a layer impermeable to many substances. Only very small molecules can diffuse through this layer. The exchange of substances between the cell and the intercellular space is thus largely prevented. The pericytes, in turn, are located on the outer wall of the capillaries and are connective tissue cells. They are connected to the endothelial cells via cell-cell channels, the gap junctions. The interaction of both cell types via these channels controls the membrane potential, which is responsible for the selective diffusion of substances. Astrocytes, as so-called spider cells, constitute the majority of glial cells contained in the CNS. They supply the neurons with nutrients via the contacts to the blood vessel. Receptors for neurotransmitters are located in their membrane. They also induce and simultaneously maintain the blood-brain barrier through the membrana limitans glialis perivascularis (a limiting membrane surrounding the blood vessels of the brain).
Function and Tasks
In addition to its protective function for the CNS against harmful influences, the blood-brain barrier also regulates the transport processes between the bloodstream and the brain. Thus, there are various physical and chemical processes that control this transport. Most soluble substances that can cross this barrier at all pass through it by diffusion. Since the blood-brain barrier is tightly sealed by tight junctions, diffusion cannot occur via intercellular clefts as it does in other organs. Via the capillary vessels of the brain, substances can only be passed by transmembrane transport. Free diffusion represents the simplest form of this transport. Small lipophilic molecules can passively diffuse through the cell membranes of epithelia and even through tight junctions. Small polar molecules, such as water, are subject to channel-mediated permeability. Certain channel proteins, aquaporins, mediate the transport of water across the blood-brain barrier and thus simultaneously regulate the water balance of the brain. For large and polar but vital nutrient molecules, such as glucose or many amino acids, there are certain transport molecules that facilitate the diffusion of the corresponding substances. Since no energy is required for these forms of diffusion, they are passive diffusions. However, there are also substances that can only be transported with the use of ATP, i.e. by adding energy. Active transporters are so-called “pumps” that transport the substrates with energy input even against the concentration gradient. Selected molecules also cross the blood-brain barrier with the help of special receptors that are specifically responsible for their transport.
Diseases
Disruption of the blood-brain barrier can lead to various neurologic diseases. Initial diseases, such as diabetes mellitus, inflammation in the brain, or brain tumors, often damage this barrier. Long-term consequences are brain damage. Certain pathogens can cross the blood-brain barrier. These include the HI virus. Some bacteria, such as Escherichia coli, also sometimes overcome the protective mechanisms of the barrier by releasing special toxins. If cells for the body’s own immune defense system overcome the blood-brain barrier, the clinical picture of multiple sclerosis can develop. Studies have shown that neurodegenerative diseases, such as Alzheimer’s, also cause the barrier between the brain and the bloodstream to become permeable. This may be the starting point for the extensive demise of brain cells. A major risk factor for neurological disease is known to be alcohol abuse. Chronic alcohol consumption damages the blood-brain barrier with incalculable consequences. Dysfunction of the barrier favors bacterial infections and autoimmunologically induced inflammatory responses in the brain. Nicotine abuse is also a risk factor with regard to blood-brain barrier damage. Nicotine promotes cardiovascular disease, which in turn has a major impact on brain performance. Smokers have a higher risk of developing bacterial meningitis. Studies have shown that the structure of the blood-brain barrier is altered by nicotine. The tight junction proteins are distributed differently and can no longer fully perform their function. The influence of electromagnetic radiation on the blood-brain barrier is also being discussed. Its negative health effects have been documented for the megahertz to gigahertz range for high energy densities. The high energy density of electromagnetic radiation leads to a measurable heating in the affected tissue. The extent to which heating damages the blood-brain barrier remains to be investigated.
Typical and common brain diseases.
- Dementia
- Creutzfeldt-Jakob disease
- Memory gaps
- Brain hemorrhage
- Meningitis
