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Researchers have uncovered how the malaria parasite ‘Plasmodium falciparum’ damages the brain, a discovery that could guide the development of treatments to prevent or even repair the injury it causes.
Cerebral malaria is among the deadliest forms of the disease, claiming the lives of one in five children who contract it and leaving half of the survivors with long-term disabilities.
The illness is triggered when ‘Plasmodium falciparum’ multiplies inside red blood cells before breaking free to infect new ones.
When the parasite reaches the blood–brain barrier (BBB), a vital defence that shields the brain from harmful agents, it can weaken it, leading to severe complications.
To study this process, scientists at the European Molecular Biology Laboratory (EMBL) in Barcelona designed a lab-grown model of the BBB to observe how the parasite compromises its integrity.
“You have to imagine the BBB as a system of tightly sealed pipes that prevent leaks. The malaria parasite is capable of developing cracks in those pipes and creating a leak that starts dripping infected fluid into the brain, causing swelling and making the disease irreversible,” explained Livia Piatti, a postdoctoral researcher at EMBL.
The model BBB, also called a 3D-BBB, incorporated essential components such as endothelial cells lining the vessels, pericytes that provide support, and astrocytes, star-shaped brain cells, all arranged in a 3D structure with circulating fluid.
Researchers exposed this model to the parasite during its most aggressive stage, when it bursts out of red blood cells in a process known as egress.
Results published in ‘Nature Communications’ showed that the BBB became more permeable under attack.
Detailed genetic analysis revealed that the barrier’s cells produced fewer proteins to keep it sealed and more molecules that drive inflammation.
Encouragingly, the team tested an existing drug, Ruxolitinib, on the 3D-BBB and found signs that it may help in severe malaria.
By calming inflammation in brain blood vessels, the drug reduced the barrier’s leakiness, the researchers reported.
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