U. ROCHESTER (US)— New research in the fight against cerebral malaria is focusing on platelets—known for their role in blood clotting—as playing an important role in stimulating the immune system and turning on molecules that increase inflammation.

Cerebral malaria predominantly ravages the brains of children younger than the age of 10 living in malaria-endemic areas, such as sub-Saharan Africa and is fatal.

The inflammation leads to the obstruction of blood vessels in the brain, causing brain damage similar to that seen with a stroke.

“Malaria is a complex disease and we need to look at it from every possible angle, focusing on both vaccine research and basic research,” says Craig Morrell, assistant professor at the University of Rochester Medical Center and lead author of a new study published online in the journal PLoS One.

“Our findings increase our knowledge of cerebral malaria and suggest that targeting platelets may prove to be a viable intervention strategy.”

Malaria is one of the world’s biggest killers, accounting for approximately 1 million deaths each year. New therapies to treat malaria are needed, as the parasite that causes malaria—Plasmodium falciparum— is becoming resistant to current treatments.

Morrell’s team is studying the development and progression of cerebral malaria, with the goal finding new ways to intervene and treat the disease.

Malaria occurs when Plasmodium falciparum infects red blood cells. Once infected, red blood cells activate platelets, which secrete a key protein—platelet factor 4 or PF4/CXCL4.

Morrell’s lab found that PF4 jumpstarts the activity of the immune system, whose job it is to protect against foreign intruders—in this case, the malaria parasite—by turning on pro-inflammatory cells, known as monocytes. Monocytes contribute to the inflammation in the blood vessels that leads to obstructions in the brain.

Morrell’s prior research demonstrated that mice without the PF4 protein are protected from cerebral malaria compared to mice with PF4 intact. When PF4 is removed monocytes are not activated, and mice experience less inflammation and consequently less cerebral malaria.

Morrell hopes that future experimental therapies targeting PF4 will prove to be practical treatment options for cerebral malaria.

Researchers also identified a key transcription factor—KLF4—that is important for the development and overall function of monocytes in cerebral malaria. Targeting KLF4 may also hold promise for treating other vascular inflammatory diseases, such as atherosclerosis.

“Dr. Morrell’s research is highly significant. He has discovered that platelets play a big role in malaria. His research may lead to novel treatments for malaria that target platelets instead of the parasite,” says Charles Lowenstein, chief of cardiology at the University of Rochester.

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