The brain is separated from the rest of the body by the blood-brain barrier. How do viruses cross the blood-brain barrier to access the central nervous system? How does the blood brain barrier work?

The blood-brain barrier is a highly selective barrier whose main function is to separate the central nervous system (CNS) from the bloodstream. Its mechanism makes it possible to closely control the exchanges between the blood and the cerebral compartment. The blood-brain barrier therefore isolates the brain from the rest of the body and provides it with a specific environment, different from the internal environment of the rest of the body.

The blood-brain barrier has special filtering properties that allow it to prevent potentially toxic foreign substances from entering the brain and spinal cord.

This hemoencephalic barrier, thanks to its highly selective filter, can allow the passage of water, certain gases and liposoluble molecules by passive diffusion, as well as the selective transport of molecules such as glucose and amino acids which play a role. crucial in neuronal function and prevent entry of potential lipophilic neurotoxins, through an active glycoprotein-mediated transport mechanism.

Astrocytes (help maintain the chemical and electrical environment by providing necessary nutrients to the brain and flushing out their wastes) are essential in creating this barrier.

The blood-brain barrier protects the brain against toxins and messengers that circulate in the blood.

Moreover, this role is double-edged, because it also prevents the entry of molecules for therapeutic purposes.

Some viruses can still pass this barrier either through the blood or by “retrograde axonal” transport. Disorders of the blood-brain barrier are caused by different diseases.

Neurodegenerative diseases

Due to its essential function in maintaining cerebral homeostasis, the blood-brain barrier can also be the start of certain neurological diseases such as neurodegenerative diseases and brain lesions such as Alzheimer’s disease (AD) but which remain very rare. .

Diabetes mellitus

Other diseases, such as diabetes mellitus, also have a bad impact on the maintenance of the blood-brain barrier.

Other pathologies

Other pathologies, on the other hand, interfere with the function of the endothelium from the inside, that is, the entire blood-brain barrier is damaged by actions from the extracellular matrix.

In contrast, a number of brain diseases are manifested by the fact that certain pathogens can cross the blood-brain barrier causing brain infections which are devastating diseases accompanied by high mortality or in survivors of severe neurological sequelae. These include, for example, a variety of pathogenic microorganisms, bacteria, fungi, HI virus, human T-lymphotropic virus 1, West Nile virus and bacteria, such as Neisseria meningitidis or Vibrio cholerae.

In multiple sclerosis, “pathogens” are cells of the body’s immune system that cross the blood-brain barrier.

Metastatic cells successfully cross the blood-brain barrier in some non-brain tumors and can cause metastases in the brain (glioblastoma).

Administering treatments to the brain by crossing the blood-brain barrier is a real journey because it also prevents the access of drugs, especially those with a large molecular structure, to the area that needs to be treated.

Some drugs like Temozolomide, used to fight glioblastoma have the chemical and physical properties that allow it to pass the barrier and reach the tumor.

One of the possibilities explored in an attempt to eliminate this problem is to implement techniques which can mechanically penetrate the blood-brain barrier.

The blood-brain barrier is a significant barrier to treatment, but research is underway.

The first contrast product developed for MRI was gadolinium (Gd) and then Gd-DTPA77, which made it possible to obtain more advanced MRIs for the diagnosis of local lesions of the blood-brain barrier. The Gd-DTPA molecule is very impermeable to cross a healthy blood-brain barrier.

Other imaging mechanisms

The use of “single-photon emission tomography” or “positron emission tomography”.

Defects in the blood brain barrier can also be assessed by diffusion of appropriate contrast media using computed tomography.