Dennis Grab Brazil School of Medicine, MD program
The neurological complications of sleeping sickness in man caused by Trypanosoma brucei gambiense are attributed to the penetration of the central nervous system by trypanosomes. Yet, how these parasites cross the blood-brain barrier (BBB) remains an unresolved issue. Using our in vitro BBB model constructed of human brain microvascular endothelial cells (HBMEC), it has been found that T. b. gambiense crosses the human BBB by generating intracellular calcium ([Ca2+]i) activation signals in brain microvascular endothelial cells through the activity of parasite cysteine proteases. Since the interaction of African trypanosomes with BMECs induce [Ca2+]i responses that are compatible with kinin receptor engagement, the possibility that vasoactive kinin may enhance parasite transmigration will be explored in association with the Brazilian group. Our objective will be to determine the role of African trypanosome-associated proteases and kinin-receptors in human BMEC activation. The recognition of key components in the signaling pathways we define will lead to lead to identification of targets for novel adjunct drug therapies to prevent African trypanosomes from entering the CNS when parasites in HAT patients are limited to the blood, thereby increasing their chances for successful recovery. | 
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