AI Article Synopsis
- Cerebral malaria (CM), caused by Plasmodium falciparum, leads to severe complications due to the clumping of infected red blood cells in brain microvessels and triggers significant inflammation and disruptions in the brain-blood barrier.
- Previous research suggests that terpenes like perillyl alcohol (POH) can combat these issues by reducing inflammation and protecting the brain's microvascular structures in experimental models of CM.
- The study demonstrated that POH effectively inhibited harmful endothelial changes induced by parasitized red blood cells, restored tight junction protein distribution, and improved the permeability of human brain endothelial cell layers, indicating its potential as a therapeutic agent for cerebral malaria.
Article Abstract
Background: Cerebral malaria (CM) is a severe immunovasculopathy caused for Plasmodium falciparum infection, which is characterised by the sequestration of parasitised red blood cells (pRBCs) in brain microvessels. Previous studies have shown that some terpenes, such as perillyl alcohol (POH), exhibit a marked efficacy in preventing cerebrovascular inflammation, breakdown of the brain-blood barrier (BBB) and brain leucocyte accumulation in experimental CM models.
Objective: To analyse the effects of POH on the endothelium using human brain endothelial cell (HBEC) monolayers co-cultured with pRBCs.
Methodology: The loss of tight junction proteins (TJPs) and features of endothelial activation, such as ICAM-1 and VCAM-1 expression were evaluated by quantitative immunofluorescence. Microvesicle (MV) release by HBEC upon stimulation by P. falciparum was evaluated by flow cytometry. Finally, the capacity of POH to revert P. falciparum-induced HBEC monolayer permeability was examined by monitoring trans-endothelial electrical resistance (TEER).
Findings: POH significantly prevented pRBCs-induced endothelial adhesion molecule (ICAM-1, VCAM-1) upregulation and MV release by HBEC, improved their trans-endothelial resistance, and restored their distribution of TJPs such as VE-cadherin, Occludin, and JAM-A.
Conclusions: POH is a potent monoterpene that is efficient in preventing P. falciparum-pRBCs-induced changes in HBEC, namely their activation, increased permeability and alterations of integrity, all parameters of relevance to CM pathogenesis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10317308 | PMC |
| http://dx.doi.org/10.1590/0074-02760230033 | DOI Listing |
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