EphA2 contributes to disruption of the blood-brain barrier in cerebral malaria.
Thayer K DarlingPatrice N MimcheChristian BrayBanlanjo Abdulaziz UmaruLauren M BradyColleen StoneCarole Else Eboumbou MoukokoThomas E LaneLawrence S AyongTracey J LambPublished in: PLoS pathogens (2020)
Disruption of blood-brain barrier (BBB) function is a key feature of cerebral malaria. Increased barrier permeability occurs due to disassembly of tight and adherens junctions between endothelial cells, yet the mechanisms governing junction disassembly and vascular permeability during cerebral malaria remain poorly characterized. We found that EphA2 is a principal receptor tyrosine kinase mediating BBB breakdown during Plasmodium infection. Upregulated on brain microvascular endothelial cells in response to inflammatory cytokines, EphA2 is required for the loss of junction proteins on mouse and human brain microvascular endothelial cells. Furthermore, EphA2 is necessary for CD8+ T cell brain infiltration and subsequent BBB breakdown in a mouse model of cerebral malaria. Blocking EphA2 protects against BBB breakdown highlighting EphA2 as a potential therapeutic target for cerebral malaria.
Keyphrases
- blood brain barrier
- cerebral ischemia
- endothelial cells
- plasmodium falciparum
- subarachnoid hemorrhage
- tyrosine kinase
- mouse model
- high glucose
- epidermal growth factor receptor
- brain injury
- machine learning
- white matter
- vascular endothelial growth factor
- cerebral blood flow
- deep learning
- single molecule
- functional connectivity
- binding protein