Structure

The blood–brain barrier consists quite simply of the walls of the small brain vessels, which are structured differently here than in the rest of the body. The endothelial cells play an important role. These are the cells that form the walls of the tiny blood vessels in the brain.

These so-called capillary vessels have – in contrast to larger vessels in the circulatory system – only a single-layer wall. While the walls of larger vessels consist of three layers (two layers of connective tissue and in the middle a layer of muscle to regulate the diameter), small capillaries only have the innermost layer – the endothelial layer. These endothelial cells lie on a so-called basal lamina (a thin layer of proteins) and surround the vessel in a ring shape.

In the rest of the body, i.e. outside the brain, the endothelium of the blood vessels is not completely sealed. Small gaps remain between the endothelial cells. In this way, water and dissolved substances and, for example, nutrients from the blood can enter the surrounding tissue.

Inside the brain, however, the endothelial cells of the vessels form a virtually gapless wall. The individual endothelial cells are very closely connected to each other via so-called tight junctions. This endothelial layer can therefore not be penetrated so easily – except by fat-soluble substances that can diffuse through the cell membrane because the membrane itself consists of fat, or by active transport mechanisms such as pumps or channels.

Embedded in the brain tissue, the capillaries are surrounded by astrocytes. Astrocytes are the most important type of cells in the brain besides nerve cells (neurons). Among other things, they are responsible for feeding the neurons. Their extensions are also part of the blood-brain barrier.

Permeability

Nutrients such as sugar (glucose) or electrolytes such as sodium and potassium are actively transported through the endothelium by pumps or transporters, while water can cross the blood-brain barrier through certain channels (aquaporins). Certain hormones – especially stress and sex hormones – can diffuse through the blood-brain barrier and influence the brain. Fat-soluble gases such as oxygen and carbon dioxide can also cross the endothelial layer without special aids.

So can other fat-soluble substances such as alcohol, nicotine and heroin. In this way the addictive substances can work in the brain. So the more a drug is soluble in fat, the stronger is its CNS mobility.

These drugs include psychotropic drugs, anaesthetics, sleeping pills and sedatives. Antibiotics, on the other hand, are manufactured with a low fat solubility (i.e. good water solubility instead) because they are neurotoxic. Substances that are potentially dangerous for the brain are stopped by the blood-brain barrier.

However, there are exceptions. Bacteria and viruses that trigger meningitis, i.e. meningitis, or the human immunodeficiency virus (HIV) cannot be stopped by the barrier. Other substances that are actually needed in the CNS, but which are also unable to overcome the barrier, have to be produced anew within the brain.

One example of such a substance is cholesterol. The astrocytes produce cholesterol themselves, as it is essential for the production of myelin sheaths of the neurons (myelin sheaths, in turn, are an indispensable coating of the nerve cells). Another important point is metastasizing tumor cells.

In particular, the cells of bronchial carcinomas (lung cancer), breast carcinomas (breast cancer) and malignant melanomas (skin cancer) spread hematogenously (i.e. via the blood) into the brain, despite the blood-brain barrier, where metastases, i.e. secondary tumours can form. Here, the barrier poses a problem because it makes it harder for chemotherapy drugs to reach the metastases. In addition, the permeability of the blood-brain barrier can be altered by tumour diseases, brain infarcts, inflammatory processes or rare genetic diseases (e.g. deficits in the above-mentioned channels). As a result, substances that should actually be filtered can enter the cerebrospinal fluid, or nutrients such as glucose, which the brain actually needs, can no longer reach it.