Swelling and bleeding within the brain is a fatal complication of cerebral malaria in humans, but the mechanism causing this disease is not completely understood. Using intravital microscopy, researchers at the National Institutes of Health (NIH) filmed what happens to the brains of mice with cerebral malaria and an antibody therapy that may treat it (see video below). The results are published in a recent article in PLOS Pathogens.1

In this animal model study, researchers found that the red blood cells containing the parasite stick to cerebral blood vessels. Despite the immune system’s attempts to fight the parasite, “endothelial cells making up the walls of cerebral blood vessels shed bits of the parasite, which CD8+ T cells recognize, causing those immune cells to attach to and attack the vessels.”2 This interaction led to vascular leakage and swelling in the brain, which was fatal. It was observed that the CD8+ T cells only interacted with blood vessels in the brain.

Testing a potential therapy, Dorian B. McGavern, PhD, of the viral immunology and intravital imaging section at the National institute of Neurological Disorders and Stroke at the NIH, and colleagues used an intravenous administration of antibodies that interfered with CD8+ T cells adhering to blood vessels. This approach displaced CD8+ T cells from the blood vessels and prevented fatal brain swelling.


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“These movies show us a terrible side effect sometimes associated with malaria—the parasite can fool the body’s immune system into attacking the blood vessels within its own brain,” said Dr McGavern in a news release.

Future studies will examine “how the interaction between CD8+T cells and cerebral vessels causes blood leakage and ways in which the brain recovers from cerebral malaria infection.”  Furthermore, intravital microscopy may be used to see how Zika and dengue affect the brain.

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References

  1. Swanson PA 2nd, Hart GT, Russo MV, et al. CD8+ T cells induce fatal brainstem pathology during cerebral malaria via luminal antigen-specific engagement of brain vasculature. PLoS Pathog. 2016;12:e1006022. doi: 10.1371/journal.ppat.1006022
  2. Raising the curtain on cerebral malaria’s deadly agents [news release]. Bethesda, MD: National Institutes of Health; Published December 6, 2016.