While reading about multiple sclerosis, you may have come across the blood-brain barrier and wondered what it’s all about. Many people think of the blood brain barrier (BBB) as some sort of membrane or casing that surrounds the brain and keeps anything from moving in and out. In fact, the BBB is a feature of the walls making up the blood vessels that supply the central nervous system (CNS), including the brain. The BBB is selectively permeable; that is, it lets certain substances pass across it between the blood and the CNS (and vice versa) while blocking the movement of others. This way, the BBB wields precise control over anything that enters or leaves the brain, in turn helping the brain to maintain a constant environment.
In other parts of the body, the smallest blood vessels – called the capillaries – that course through our tissues are lined with specialized cells called endothelial cells; these cells are interspersed with gaps that allow molecules to move freely across the blood vessel wall. In the CNS, on the other hand, the endothelial cells in capillaries are so tightly packed that very few substances can diffuse across. Exceptions to this rule include water, gases like oxygen and carbon dioxide, and some small, fat-soluble molecules, while amino acids and glucose (the primary source of fuel for the brain) are carried across the blood vessel walls by specialized transport proteins. Critically, pathogens and cells of the immune system (as well as their antibodies) are normally prevented from crossing the healthy BBB; thus, the BBB is a critical line of defense that protects nerve cells from both foreign substances and potentially destructive immune cells.
A hallmark of MS is the abnormal entry and accumulation of leukocytes – also known as white blood cells – in the CNS, where they are crucial players in the disease mechanisms underlying brain inflammation and the breakdown of myelin around nerve cells that leads to the signs of symptoms of MS. Although the phenomenon by which the BBB breaks down in MS is not completely understood, pivotal work by MS Society-funded researcher Dr. Alexandre Prat and colleagues recently demonstrated that breakdown of the BBB is one of the earliest events in MS and occurs before the onset of inflammation, demyelination and disease symptoms in mice with an MS-like disease. Another team of MS Society-funded researchers led by Dr. Steve Lacroix showed that neutrophils – specific types of leukocytes that are normally the first-responders among inflammatory cells during inflammation – may play a central role in triggering damage to the BBB. A key finding in their study was that therapeutically eliminating neutrophils from mice with an MS-like disease maintained the integrity of the BBB and delayed the appearance of MS-like symptoms, positioning neutrophils as important targets for therapeutic strategies for people living with MS.
Therapies that target the BBB represent an up-and-coming tool in the arsenal in the fight against MS. Right now, Tysabri is the only approved MS drug that works by directly restricting the movement of leukocytes across the BBB into the CNS where they cause inflammation and damage to myelin. Other “gate-keeper” substances that work at the level of the BBB being actively studied, including the promising molecule Del-1 that prevents the infiltration of damaging inflammatory cytokines into the CNS in mice with an MS-like disease. Recently, the approved disease-modifying therapy Gilenya, which was originally thought to work exclusively by lowering the number of certain leukocytes circulating in the blood, has now been shown to repair some of the damage to the BBB in people with both relapsing-remitting and secondary progressive MS.
Do you have any questions about the blood-brain barrier and how it works? Leave your questions and comments below.