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Updated: Aug 11, 2026
3-D Imaging and Analysis of Neurons Infected In Vivo with Toxoplasma gondii
Published on: December 9, 2014
Structural, Functional, and Metabolic Alterations in Human Cerebrovascular Endothelial Cells during Toxoplasma gondii
Alaa T Al-Sandaqchi1,2, Victoria Marsh1, Huw E L Williams3
1Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire LE12 5RD, UK.
Insights
Toxoplasma gondii infection disrupts the blood-brain barrier by damaging brain endothelial cells. Verapamil treatment effectively protected these cells and inhibited parasite growth.
Area of Science:
- Neuroscience
- Infectious Diseases
- Cell Biology
Background:
- Toxoplasma gondii (T. gondii) causes toxoplasmosis, a common brain infection.
- Understanding T. gondii's interaction with the blood-brain barrier (BBB) is crucial for treating brain infections.
- Mechanisms of T. gondii crossing the BBB require further investigation.
Purpose of the Study:
- To investigate the effects of T. gondii infection on human brain microvascular endothelial cells (BMECs) in vitro.
- To identify metabolic changes in infected BMECs using metabolomics.
- To evaluate the therapeutic potential of verapamil against T. gondii-induced BBB damage.
Main Methods:
- In vitro infection of human BMECs with T. gondii.
- Assessment of cellular viability, barrier integrity, and permeability.
- Proton nuclear magnetic resonance (1H NMR)-based metabolomics and multivariate data analysis.
- Treatment of infected BMECs with the calcium channel blocker verapamil.
Main Results:
- T. gondii proliferated within BMECs, reducing cellular viability and disrupting intercellular junctions.
- Infection increased BMEC monolayer permeability and altered lipid homeostasis.
- Metabolomics revealed infection-specific metabolic profiles, including changes in amino acids and fatty acids.
- Verapamil treatment restored BMEC barrier integrity and inhibited T. gondii replication.
Conclusions:
- T. gondii infection causes significant structural and functional damage to the cerebrovascular barrier.
- Metabolomic analysis provides insights into the host-parasite interactions within BMECs.
- Verapamil demonstrates potential as a therapeutic agent to counteract T. gondii-induced BBB dysfunction and infection.
Abstract:
Toxoplasma gondii (T. gondii), the causative agent of toxoplasmosis, is a frequent cause of brain infection. Despite its known ability to invade the brain, there is still a dire need to better understand the mechanisms by which this parasite interacts with and crosses the blood-brain barrier (BBB). The present study revealed structural and functional changes associated with infection and replication of T. gondii within human brain microvascular endothelial cells (BMECs) in vitro. T. gondii proliferated within the BMECs and disrupted the integrity of the cerebrovascular barrier through diminishing the cellular viability, disruption of the intercellular junctions and increasing permeability of the BMEC monolayer, as well as altering lipid homeostasis. Proton nuclear magnetic resonance (1H NMR)-based metabolomics combined with multivariate data analysis revealed profiles that can be attributed to infection and variations in the amounts of certain metabolites (e.g., amino acids, fatty acids) in the extracts of infected compared to control cells. Notably, treatment with the Ca2+ channel blocker verapamil rescued BMEC barrier integrity and restricted intracellular replication of the tachyzoites regardless of the time of treatment application (i.e., prior to infection, early- and late-infection). This study provides new insights into the structural and functional changes that accompany T. gondii infection of the BMECs, and sheds light upon the ability of verapamil to inhibit the parasite proliferation and to ameliorate the adverse effects caused by T. gondii infection.
