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brain endothelium

Dimethyl fumarate reduces TNF and Plasmodium falciparum induced brain endothelium activation in vitro

October 22, 2020 - 15:42 -- Open Access
Author(s): 
Neida K. Mita-Mendoza, Ariel Magallon-Tejada, Priyanka Parmar, Raquel Furtado, Margaret Aldrich, Alex Saidi, Terrie Taylor, Joe Smith, Karl Seydel and Johanna P. Daily
Reference: 
Malaria Journal 2020 19:376, 21 October 2020

Cerebral malaria (CM) is associated with morbidity and mortality despite the use of potent anti-malarial agents. Brain endothelial cell activation and dysfunction from oxidative and inflammatory host responses and products released by Plasmodium falciparum-infected erythrocytes (IE), are likely the major contributors to the encephalopathy, seizures, and brain swelling that are associated with CM. The development of adjunctive therapy to reduce the pathological consequences of host response pathways could improve outcomes. A potentially protective role of the nuclear factor E2-related factor 2 (NRF2) pathway, which serves as a therapeutic target in brain microvascular diseases and central nervous system (CNS) inflammatory diseases such as multiple sclerosis was tested to protect endothelial cells in an in vitro culture system subjected to tumour necrosis factor (TNF) or infected red blood cell exposure. NRF2 is a transcription factor that mediates anti-oxidant and anti-inflammatory responses.

Parasite histones are toxic to brain endothelium and link blood barrier breakdown and thrombosis in cerebral malaria

July 15, 2020 - 14:22 -- Open Access
Author(s): 
Moxon CA, Alhamdi Y, Storm J, Toh CH, et al.
Reference: 
Blood Adv. 2020 Jul 14; 4(13):2851-2864

Microvascular thrombosis and blood-brain barrier (BBB) breakdown are key components of cerebral malaria (CM) pathogenesis in African children and are implicated in fatal brain swelling. How Plasmodium falciparum infection causes this endothelial disruption and why this occurs, particularly in the brain, is not fully understood. In this study, we have demonstrated that circulating extracellular histones, equally of host and parasite origin, are significantly elevated in CM patients. Higher histone levels are associated with brain swelling on magnetic resonance imaging.

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