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Updated: Jun 21, 2026
Selection of Plasmodium falciparum Parasites for Cytoadhesion to Human Brain Endothelial Cells
Published on: January 3, 2012
Perillyl alcohol modulates activation, permeability and integrity of human brain endothelial cells induced by
Adriana A Marin1,2, Annette Juillard2, Alejandro M Katzin1
1Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Parasitologia, São Paulo, SP, Brasil.
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.
Insights
Perillyl alcohol (POH) effectively protects human brain endothelial cells from Plasmodium falciparum infection. It prevents increased permeability and maintains the integrity of the brain-blood barrier, crucial for cerebral malaria treatment.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Cerebral malaria (CM) is a severe brain vasculopathy caused by Plasmodium falciparum.
- Parasitized red blood cells (pRBCs) sequester in brain microvessels, leading to inflammation and blood-brain barrier (BBB) breakdown.
- Terpenes, like perillyl alcohol (POH), show promise in preventing CM-related pathologies in experimental models.
Purpose of the Study:
- To investigate the effects of perillyl alcohol (POH) on human brain endothelial cells (HBECs) co-cultured with pRBCs.
- To assess POH's impact on endothelial activation, integrity, and permeability.
Main Methods:
- Quantitative immunofluorescence evaluated tight junction proteins (TJPs) and adhesion molecules (ICAM-1, VCAM-1).
- Flow cytometry measured microvesicle (MV) release from HBECs.
- Trans-endothelial electrical resistance (TEER) assessed POH's ability to restore monolayer permeability.
Main Results:
- POH significantly inhibited pRBC-induced upregulation of ICAM-1 and VCAM-1.
- POH reduced MV release and improved TEER in HBEC monolayers.
- POH restored the distribution of key TJPs, including VE-cadherin, Occludin, and JAM-A.
Conclusions:
- POH is a potent monoterpene that effectively counteracts Plasmodium falciparum-induced changes in brain endothelial cells.
- POH prevents endothelial activation, increased permeability, and integrity alterations relevant to CM pathogenesis.
- POH demonstrates therapeutic potential for managing cerebral malaria by protecting the brain endothelium.
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