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April 21, 2017

Cause of Stroke Immunodeficiency Uncovered

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    New findings help explain why patients have a greater risk of catching life-threatening infections after stroke. [NIH]

    As if the devastating effects on the brain after having a stroke weren’t enough, new research from investigators at the Roslin Institute, located on the University of Edinburgh's Easter Bush Campus, points to immune cells being damaged as a result of the acute neurologic event. Findings from the new study—published recently in Nature Communications in an article entitled “Adrenergic-Mediated Loss of Splenic Marginal Zone B Cells Contributes to Infection Susceptibility after Stroke”—may be helpful in developing therapies that boost survival of the affected immune cells or compensate for their damage and could help improve the recovery of stroke patients

    "Our work shows that stroke has damaging effects on the normal ability of the immune system to protect us from infections such as pneumonia, which are particularly life-threatening in stroke patients,” explained senior study investigator Barry McColl, Ph.D., group leader at the Roslin Institute. “This could partly explain why people who have strokes are so prone to getting infections.”

    In the current study, the researchers found that patients had reduced levels of protective antibodies (immunoglobulin M, or IgM) in their blood after having a stroke, which might explain why they are more susceptible to infections. Moreover, tests with mice revealed those who experienced a stroke had fewer numbers of specialized immune cells called marginal zone (MZ) B cells, which produce antibodies.

    "We show that experimental stroke in mice induces a marked loss of MZ B cells, deficiencies in capturing blood-borne antigen and suppression of circulating IgM,” the authors wrote. “These deficits are accompanied by a spontaneous bacterial lung infection. IgM levels are similarly suppressed in stroke patients. β-adrenergic receptor antagonism after experimental stroke prevents loss of splenic MZ B cells, preserves IgM levels, and reduces bacterial burden.”

    Interestingly, the Roslin team noticed the loss of B cells was caused by a chemical called noradrenaline—which is produced by nerves activated during stroke—and that they could protect the mice from infections using a therapy to block the effects of noradrenaline. Noradrenaline is part of the body's fight or flight response. It helps to prepare the body for action and has a range of effects, such as raising heart rate, boosting blood supply, and triggering the release of energy from stores.

    While the investigators cautioned that blocking noradrenaline would probably be could potentially be too dangerous in stroke patients, the development of other therapies that block or bypass the damage to the immune system could offer new approaches to help cut the risk of infection after stroke.

    "We now plan to build on our findings by developing and testing new treatments that can block or bypass these immune deficits with B cells a particular target," Dr. McColl remarked.

    Around one-third of stroke patients are stricken by infections, which can lessen their chances of making a good recovery. The researchers are optimistic that these findings could also lead to new tests to identify which stroke patients have the highest chances of developing an infection so that they can be monitored more closely.

    "Infections are a major complication of stroke and lead to a worse outcome for patients,” concluded study co-author Craig Smith, M.D., a consultant with the research group at Salford Royal NHS Foundation Trust. “This is an important study that provides new insights about how stroke affects the immune system, which we hope will lead to new approaches to preventing infections after stroke."

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