Blood-brain barrier

What is the blood-brain barrier?

The blood-brain barrier is a tightly packed layer of cells that line the blood vessels in the brain and spinal cord. This barrier prevents large molecules, immune cells, and disease-causing organisms such as bacteria and viruses from passing from the blood stream into the central nervous system (CNS).

The brain and spinal cord have very specific requirements to enable them to function efficiently. Brain and nerve cells in the CNS need to be able to get oxygen and glucose from the blood but not to become infected by disease or to be influenced by hormones produced elsewhere in the body. 

Throughout most of your body, the tiny blood vessels (capillaries) are lined by endothelial cells, but substances can seep in and out of them between the gaps in the cell layer. In the brain and spinal cord, the endothelial cells are tightly joined together, and substances can only cross the barrier through controlled transport channels or under special circumstances. The blood-brain barrier (BBB) is maintained by glial cells, including astrocytes.

Why does the blood-brain barrier matter in MS?

It is thought that there are a series of events that lead to multiple sclerosis. A breakdown in the blood-brain barrier (BBB) is thought to be an early stage in this process. If the BBB is damaged or weakened in some way, immune cells are able to cross. These cells then attack the myelin around your nerves, which leads to nerve damage and MS symptoms.

The BBB can be damaged or disrupted by many things including stress, inflammation, or chemical processes thought to be triggered by disease, drugs, air pollution or smoking. Possible links between gut health and the strength of the BBB have been explored through work on the microbiome.

Several of the disease modifying drugs currently available or in development act on the blood-brain barrier itself, or aim to stop immune cells from passing through the BBB. These include Tysabri (natalizumab), which binds to immune cells so they can't get through the barrier. Gilenya (fingolimod) targets receptors on the BBB to strengthen the barrier, and also traps immune cells in the lymph glands so they don't cross into the central nervous system. Siponimod, Ponesimod and Ozanimod target the same receptors as Gilenya (fingolimod).

Alvarez JI, et al.
Focal disturbances in the blood-brain barrier are associated with formation of neuroinflammatory lesions.
Neurobiology Of Disease 2015;74:14-24.
Summary (link is external)
Ortiz GG, et al.
Role of the blood-brain barrier in multiple sclerosis.
Archives Of Medical Research 2014;45(8):687-697.
Summary (link is external)
Larochelle C, et al.
How do immune cells overcome the blood-brain barrier in multiple sclerosis?
FEBS Letters 2011;585(23):3770-3780.
Summary (link is external)
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