Motivation behind the research
Stroke is a leading cause of death and disability worldwide and is most commonly caused by a blockage in an artery carrying blood to the brain. Currently, the only effective treatment is pharmaceutical or mechanical unblocking of the artery, and this is only available to a limited number of patients depending on the type of stroke and how quickly they are admitted to hospital. There are additional complicating factors of stroke that can worsen the damage in the brain and further impair the recovery of patients. Infection is the most common complication and can affect up to one-third of patients. Bacterial lung infections are the most common types of infections and are associated with increased death and reduced functional recovery of survivors. If we can understand why stroke patients are especially susceptible to these infections, we can identify new therapeutic targets to reduce the risk of infection and improve survival and recovery of patients after stroke.
Using an experimental model of stroke the in mice, research found that stroke results in the loss of a special population of antibody-producing immune cells in the spleen called “marginal zone B cells”. The antibodies produced by these cells are crucial for anti-bacterial defence. The numbers of marginal zone B cells and levels of their protective antibodies were greatly reduced after experimental stroke, and the animals developed bacterial lung infections. Signals from the brain to nerves in the spleen after stroke resulted in increased levels of the chemical noradrenaline, which was responsible for the loss of the marginal zone B cells.
Researchers blocked noradrenaline using a drug called propranolol. As a result, they successfully protected the cells after stroke, restored the antibody levels and reduced infection in the animals. Analysis of blood samples from stroke patients showed a similar reduction in protective antibodies which suggests the same loss of cells is also occurring in humans. Supporting this, patients who developed infections after stroke were those with the lowest levels of antibodies in their blood.
Identifying this previously unknown defect in our immune defences after stroke will give scientists and doctors a new target to try to restore the body’s own anti-bacterial defences and reduce infection levels in stroke patients. Targeting marginal zone B cells, or their functions, may provide a new approach to prevent infection in stroke patients. By preventing or minimising the impact of infection after stroke, researchers hope to improve survival of patients and reduce disability.
Research Article: Adrenergic-mediated loss of splenic marginal zone B cells contributes to infection susceptibility after stroke. Nature Communications 8, 5051 (2017). doi:10.1038/ncomms15051