Investigators will study animals infected with malaria to try to learn how this infectious disease sometimes produces damage,called "cerebral malaria," to the brain The investigators hypothesize that in some people malaria infection causes their blood vessels to constrict, resulting in a reduced blood flow to the brain, which then damages brain cells.
People with cerebral malaria develop seizures, unsteadiness, and confusion; occasionally they slip into a coma. The investigators’ prior studies of cerebral malaria in a mouse model that they developed showed increased production of a protein called “endothelin” by cells that line blood vessels in the brain, and also by certain immune cells that participate in the immune inflammatory response. Increased endothelin is known to cause blood vessels to constrict, which reduces blood flow to brain and damages brain cells.
Now the investigators will inhibit endothelin production in the cerebral malaria mouse model, and use MRI and MRS to image the animals’ brains. This will enable the investigators to see whether the decreased endothelin levels correlate with functional and metabolic improvements in the animals’ brains.
Significance: The research could lead to human studies designed to identify malaria-infected people who are at risk of developing brain damage. The findings also may lead to development of preventative treatments to inhibit endothelin production to prevent cerebral malaria from occurring.