Cerebral malaria – modelling interactions at the blood–brain barrier in vitro

Abstract

The blood–brain barrier (BBB) is a continuous endothelial barrier that is supported by pericytes and astrocytes and regulates the passage of solutes between the bloodstream and the brain. This structure is called the neurovascular unit and serves to protect the brain from blood-borne disease-causing agents and other risk factors. In the past decade, great strides have been made to investigate the neurovascular unit for delivery of chemotherapeutics and for understanding how pathogens can circumvent the barrier, leading to severe and, at times, fatal complications. One such complication is cerebral malaria, in which Plasmodium falciparum-infected red blood cells disrupt the barrier function of the BBB, causing severe brain swelling. Multiple in vitro models of the BBB are available to investigate the mechanisms underlying the pathogenesis of cerebral malaria and other diseases. These range from single-cell monolayer cultures to multicellular BBB organoids and highly complex cerebral organoids. Here, we review the technologies available in malaria research to investigate the interaction between P. falciparum-infected red blood cells and the BBB, and discuss the advantages and disadvantages of each model.

Identifying effective diagnostic biomarkers for childhood cerebral malaria in Africa integrating coexpression analysis with machine learning algorithm

“…It's reported that excess expressions of immune-related pathways were associated with disease development or poor prognosis in CM [ 34 ]. Huppert, Jula et al disclosed that IL-17 is involved in the disruption of the BBB [ 35 ], which is frequently fatal and related to long-term neurological sequelae [ 36 ]. Therefore, the downregulation of LEF1 may suggest the disruption of the BBB and the poor prognosis of CM.…”

Editorial: Models to study malaria parasite-host interactions and pathogenesis

“…However, even within cytoadherence research, the complexity of the model can step up significantly, such as the use of non-human primates (NHP) in revealing the role of SICA in Plasmodium knowlesi in mediating binding ( Peterson et al ). Recent advances in tissue engineering are increasing the complexity of in vitro models, including the development of 3D-microfluidic devices ( Bernabeu et al., 2021 ) and organoids ( Adams and Jensen, 2022 ), or stem cell approaches. For example, the extensive work done in developing cellular and in vivo models of erythropoiesis that have been adapted for malaria research on the effect of infection on anaemia and the behaviour of gametocytes in the bone marrow ( Feldman and Egan ).…”