The circulatory system, of which blood is the central component, is the body's main transport system. Its role is to carry materials to and from all cells that make up the body. In most organs, the passage of materials from the blood to the cells is rather permissive. When it comes to the brain and the rest of the central nervous system (CNS), however, this is not the case. The blood-brain barrier (BBB) is a system which limits and regulates the passage of materials from the blood to the cells of the CNS. The BBB combines several molecular and cellular mechanisms with the unique structure of blood capillaries in the CNS to prevent the free passage of most materials from the vasculature (blood vessels) to the extracellular spaces.

The significance of the BBB is manifested through the following examples:

  • The brain is protected from materials with undesirable activity and is provided with a chemically-stable environment.

  • The brain is not accessible to many components of the body's immune system, and therefore a unique immune system functions in the brain.

  • Since brain cells (neurons) require many of the components transported in the blood, several molecular mechanisms have evolved to allow the selective passage of these materials.

  • One of the main challenges in the field of psychiatric and neurological medicine is that unlike most drugs, which enjoy a rather free access to their target cells when dissolved in the blood, it is much more difficult to design drugs that pass the BBB and reach their target cells in the CNS.

As mentioned, one of the main features of the BBB is the unique blood vessel wall structure: endothelial cells, which constitute the building blocks of this wall, are attached to each other by means of tight junctions. These special formations significantly hinder the passage of materials through the spaces between these cells. Despite endothelial cells being a dominant component in the BBB, several studies have identified cells outside the blood vessels (i.e. cells within the CNS) as playing key roles as well, including filtration of incoming materials and modulation of blood vessel endothelial cells. In addition to the cellular level, there are also several molecular mechanisms that enhance the selectivity in permitting materials from the blood into the CNS.

Hence, describing the BBB as a fortified, impenetrable wall would be rather inaccurate. Instead, a system of coordinated and integrated barriers would make a more appropriate definition. The development of the BBB can be likened to a maturation process. Does it exist in infants? The answer is yes. Is the development ("maturation") of the BBB completed prior to birth or does it continue postnatally? This question is still the subject of research, which I will try to describe briefly.

A. Isolated astrocyte as imaged in confocal microscope; B. Brain tissue – astrocytes are labeled red/orange and neurons are green; C. Model depicting a CNS blood capillary whose exterior wall is ensheathed by astrocytic extensions (purple). This phenomenon was at the center of the hypothesis that attributed a key role for astrocytes in BBB formation; D. Electron microscopic image of a tiny CNS blood vessel surrounded by a pericyte. The dark X-shaped structure (labeled "E") is a red blood cell inside the capillary. All images adopted from Wikipedia.

 

Aside from neurons, which are the functional cells of the central nervous system, the CNS is home to many types of supportive cells. One example is astrocytes, which come in close contact with the exterior walls of blood vessels (see images B and C) and were thus believed to play a major role in formation of the BBB. The fact that astrocytes develop in the brain only one week after birth (as observed in mice and believed to be similar in humans) gave rise to the notion that the BBB matures only a short period after birth. Recently, several published studies have recognized other cells, called pericytes, as critical to BBB maturation. Importantly, pericytes appear already during embryonic development. Pericytes, which come in contact with blood vessels in many parts of the body, are especially abundant in the brain. These studies have shown that failure in pericyte development prevents normal maturation of the BBB, to a higher degree than a similar failure in astrocyte development. In addition, mice studies have shown that the effectiveness of the BBB (with respect to its permeability to certain materials) during embryonic development increases in a process that parallels pericyte development.

In summary, babies do have a blood-brain barrier, but it is possible that some of its components continue to mature after birth.

Daniel Ben Halevy
Department of Biological Chemistry
Weizmann Institute of Science

 

A note to the reader

If you find these explanations insufficiently clear or if you have further questions on this topic, please write about this in our forum, and we will relate to your comments. Your suggestions and constructive criticism are always welcome.

0 comments