Malaria is one of the most prevalent diseases in the tropical and sub tropical world. It is caused by infection with parasites of the genus Plasmodium. In addition to the common symptoms there is also the possibility of developing Cerebral Malaria. This is a rare occurrence but accounts for over two million deaths a year in children under 5 years of age. Examination of the brain tissue of diseased individuals shows blockage of brain microvessicles. These blockages are composed primarily of host platelets and Plasmodium infected red blood cells, sometimes with the presence of leukocytes. The damage to the brain can only be studied in deceased human patients. However, the use of a Murine (mouse) model illustrates the course the disease is likely to take in humans.

The breakdown of the blood brain barrier is key to the pathogenesis of the disease. The mouse model implicates the host platelets as having a key role in this. There are three possible ways that platelets can alter the blood-brain barrier (endothelial cells). They can secrete inflammatory mediators like IL-1, affect leukocytes directly, and congregate with infected red blood cells forming clumps. To study this interaction more thoroughly the authors developed an in vitro model of a cerebral malaria endothelial lesion. The findings corresponded with what was known about the pathogenesis in humans. Platelets were found in higher levels in the brain microvessicles of those that died of cerebral malaria. Platelets express large amounts of CD36 on their surface. This protein is known to assist in the binding of the platelet-infected RBC aggregate to endothelial cells. These observations indicate a definite role for platelets in the pathogenesis of cerebral malaria. The accumulation of these cells in brain micovessicles may contribute directly to the microvascular damage.

Microparticles have also been implicated in the disease process. Microparticles are phospholipid micro vesicles containing cell surface proteins from their parent cell. These are released during membrane rearrangement and vesiculation in eukaryotic cells. Plasma samples from individuals with acute cerebral malaria indicated far higher levels of endothelial microparticles than are present in a standard malaria infection. These levels also correlated to increased levels of TNF, which is known to increase the release of endothelial microparticles.

In a mouse model using knockout mice deficient in ABCA1 (a protein relating to erythrocyte vesiculation) the disease process was tracked. The mice lacking ABCA1 had no legions and did not contract cerebral malaria. Levels of TNF and microparticles were also much lower in the experimental mice as compared to the control group. This seems to indicate that microparticles are involved as with decreased vesiculation comes less microparticle production. While it can not yet be proposed that microparticles have a definite role it seems possible as we know they can act as effector molecules. Additional tests show that microparticles from the control animals caused more clotting than the microparticles from the knockout mice.

These discoveries could result in new therapies for cerebral malaria. If the cell to cell interactions of platelets and infected red blood cells could be lessened it would likely result in resistance to the breakdown of the blood-brain barrier. In addition microparticles may also be targeted. The decrease in microparticles in knockout animals seemed to protect them from the neurological symptoms.