Last Updated: 06/10/2025
Study of the disruption of vascular signaling pathways in cerebral malaria using 3D models of the blood-brain barrier
Objectives
This project aims to use both models (3D model of microvessels composed of primary brain endothelial cells and, a 3D model of the blood-brain barrier composed of endothelial cells, pericytes and astrocytes) to uncover the molecular mechanisms of cerebral malaria. The primary objective is to identify whether the sequestration of P. falciparum-infected erythrocytes in the cerebral microvascular system is the primary cause of the disease, or whether circulating toxins secreted by the parasite are the triggering stimulus. This project also aims to discover which endothelial and vascular signaling pathways are altered by the action of the parasite. In this context, will also explore both the short-term effects and the long-term damage caused by repeated exposure to the parasite.
Cerebral malaria is a fatal disease characterized by the sequestration of P. falciparum-infected red blood cells in the brain’s microvessels and by neurovascular disorders. The most likely cause of death in childhood cerebral malaria is cerebral edema caused by disruptions in the blood-brain barrier. However, the molecular mechanisms that cause severity in humans are poorly understood. This is because both in vitro and rodent models of cerebral malaria have limitations. Three-dimensional (3D) model bioengineering offers an unprecedented alternative for studying the molecular mechanisms of vascular diseases such as cerebral malaria. These living models are a simplified version of the human brain microvasculature and allow the controlled introduction of different parameters, both biochemical, biomechanical and cellular. The researcher’s group has developed a 3D model of microvessels composed of primary brain endothelial cells and, recently, a 3D model of the blood-brain barrier composed of endothelial cells, pericytes and astrocytes.
The overall results of this project will deepen our understanding of the molecular mechanisms of vascular dysfunction in cerebral malaria and reveal which cell signaling pathways can be pharmacologically interfered with to prevent mortality.
Jan 2022
$249,711
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