Paul Ehrlich can be considered the founder of immunology. He discovered much about the variety of different blood cells using staining techniques. In 1885 he observed that a dye injected into the bloodstream stained all body tissues with the notable exception of the central nervous system (CNS). This was later interpreted as an indication that there is a kind of partition, the blood-brain barrier (BBB), which prevents the dye from entering the brain. This was later confirmed by showing that a dye injected into the cerebrospinal fluid stains only the tissues of the CNS and nothing else.
The central nervous system consists of the brain, the spinal cord and certain particular nerves such as the optic nerve. All the other nerves in the body constitute the peripheral nervous system. What is this BBB which encloses the CNS? The walls of normal capillaries, the smallest blood vessels, consist of endothelial cells. These walls allow many kinds of chemical substances and cells to move rather freely between the bloodstream and the tissues. The smallest blood vessels adjacent to the CNS are different. There the endothelial cells are stuck together in a much stronger way through so-called tight junctions. The walls of these vessels let a much more restricted variety of cells and substances pass. This is the basis of the BBB but in fact it is a much more complicated structure. For instance, it is supported on the side facing the CNS by processes of astrocytes called ‘feet’. An idea of the complexity of the matter can be got from a review article of Hawkins and Davis (Pharmacol. Rev. 57, 173). The BBB acts to prevent pathogens such as bacteria entering the brain. It also keeps many elements of the immune system out. Breakdown of the normal function of the BBB seems to be a key element in multiple sclerosis. It results in immune cells getting access to the CNS and causing damage there. Some drugs use to treat MS have the property of sealing the BBB (see the previous post) Breakdown of the BBB has also been suggested to play a role, whether as cause or effect of the main events, in other illnesses such as Alzheimer’s disease and stroke. The BBB also has an important role to play in the treatment of diseases of the brain such as tumours. In some cases doctors would like to administer certain drugs to tissues within the brain and this is hindered by the BBB. Thus there is interest in finding controlled ways of increasing its permeability.
Hydrobates 
November 9, 2009 at 7:12 pm |
[…] where detailed information is given on certain aspects of the way that activated T cells cross the blood-brain barrier during the development of the disease EAE in rats. In fact the authors were able to film the […]
March 5, 2010 at 1:33 pm |
A recent paper of Hans Lassmann (Clinical and Experimental Neuroimmunology 1, 2-11) presents a novel scenario for the role of the BBB in MS. In many MS patients the disease starts in a relapsing-remitting phase and later goes over into a progressive phase. The suggestion of the paper is that this transition actually corresponds to definitive closing of the BBB. After that relapses, which correspond to opening of the BBB, no longer take place. After this it may happen that an inflammatory process of uncertain nature continues in the CNS and this is what constitutes progressive MS. The best therapies for MS seem to be rather ineffective against the progressive form. Some of these help by closing the BBB. In the scenario presented by Lassmann it is clear why they cannot help in the progressive form of the disease. Moreover even those which act by other mechanisms may be in trouble. For if the drug cannot cross the BBB it cannot reach the site of inflammation.