What can cross the blood brain barrier?

Scientists explain the increasing number of diseases by dysfunction of the blood brain barrier (BBB). Pathological permeability of BBB develops with almost all types of central nervous system pathology. On the other hand, to ensure the penetration of certain drugs into the brain overcoming the BBB becomes a primary target.

Methods which allow to purposefully overcome the protective barrier between the circulatory bed and cerebral structures can provide an significant impetus to the treatment of many diseases. The brain vessels are lined by endothelial cells from the inside (like all blood vessels in the body). However, endotheliocytes which make up the neurovascular unit of the cerebrum are more closely related to each other than in the rest of the vascular bed. This interaction of cells provides a barrier function and prevents the free movement of fluids, macromolecules and ions. This explains why some drugs cannot penetrate from the blood into the brain tissue. Interference with this barrier was considered bad. Over time, this view has changed, since the BBB turned out to be a very active structure. The cells on both sides of the barrier are in constant contact and mutually influence each other. For example, leukocytes have long been considered too large cells to enter the BBB. In fact, leukocytes overcome this barrier and carry out “immunological surveillance.” Scientists were able to track how individual cells move from the bloodstream through the capillary wall (through the same layer of endothelial cells, which until recently was literally considered impenetrable).

One of the hypotheses by which scientists are trying to explain the contraction of neurodegenerative diseases is the dysfunction of microglial cells. For example, impairment of the BBB leads to the development of multiocular sclerosis. In this case, the immune cells in large numbers migrate to the brain tissue and trigger the synthesis of antibodies that attack myelin. As a result, the myelin sheath of axons is destroyed. The pathological permeability of the BBB also plays a role in the occurrence and progress of epilepsy. It has long been known that epileptic attacks are associated with a disturbance of the integrity of the BBB. However, until recently it was believed that this is a consequence of epilepsy attacks and not the cause. But this view has changed with new research results. Also, scientists are studying the interconnection of the BBB with Alzheimer's disease. For example, scientists were able to identify two BBB proteins that probably play a role in the development of this disease. One of these proteins (PAGE) mediates the penetration of beta-amyloid molecules from the blood into the brain tissue. The second protein (LRP1) transports them in the opposite direction.

Amyloid plaques characteristic of the disease are formed if the balance in the activity of these proteins is disturbed.There is the opposite problem in addition to the problem of restoring the integrity of the BBB. This problem is the ability to redirect drugs through the barrier between the bloodstream and the cerebrum.

There are three conditions for solving this problem. The BBB can be crossed when performing at least one of them:

  • the substance should not exceed 500 kDa by weight;
  • the substance must use natural mechanisms for the transition of the BBB;
  • the substance must be lipophilic, since affinity for fat-containing compounds allows transit through the basement membrane.

98% of the medicines do not fulfill any of these conditions. So, they cannot realize their pharmacological effect in the cerebrum.

Published at 10/14/2018

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