Breaking Through the Brain's Defenses

BALTIMORE, MARYLAND--The night sweats and fatigue of malaria are bad enough, but when the parasite finds its way to brain, the disease can be especially dangerous. A new study presented here today at the Third International Malaria Research Conference shows how the malarial parasite weakens the blood-brain barrier, once thought impenetrable to foreign invaders.

Each year, 200,000 African children fall victim to cerebral malaria. Red blood cells infected with the malarial parasite accumulate in the brain, causing seizures, comas, and in up to 30% of cases, death. The condition has puzzled scientists because the malarial parasite shouldn't be able to cross the so-called blood-brain barrier--a layer of cells lining the brain's surface that guard against any harmful molecules the blood might be harboring.

To find out how the parasite storms the gates, cell biologist Monique Stins of the Johns Hopkins School of Medicine in Baltimore and colleagues shocked the barrier cells. They grew the brain cells on a dish of gold plated electrodes, exposed them to either malaria-infected red blood cells or uninfected red blood cells, and then zapped them. If the current could penetrate the normally well-insulated brain surface cells, it would mean they had a chink in their armor. Compared with brain cells exposed to uninfected red blood cells, brain cells in contact with infected red blood cells were 40% less able to block electrical impulses.

So what was causing the barrier breakdown? The researchers blew apart infected red blood cells. When they exposed brain surface cells to the internal debris, electrical resistance fell 20% compared to unexposed cells. Stins believes a protein inside the infected blood cells might help send a signal that breaks down brain cells, allowing parasite proteins to penetrate the brain. "If you can block this," says Stins, "maybe you can block the other neurological effects."

Other researchers presenting work on the blood-brain barrier have suggested alternative mechanisms for cerebral malaria's harmful effects. One idea proposes that small pouches of lipid might "bud" out from cellular membranes and trigger small brain hemorrhages. But pathologist Gareth Turner of Oxford University, U.K., says this is "really useful" work. "It's something we can look to point the way forward in identifying [cerebral malaria] therapies."

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