Effects of Toxoplasma gondii infection on the function and integrity of human cerebrovascular endothelial cells and the influence of Verapamil treatment in vitro

Harun, M.S.R.; Marsh, Victoria; Elsaied, Nashwa A.; Webb, Kevin F.; Elsheikha, Hany M.

Abstract

Toxoplasma gondii can cause parasitic encephalitis, a life-threatening infection that predominately occurs in immunocompromised individuals. T. gondii has the ability to invade the brain, but the mechanisms by which this parasite crosses the blood–brain-barrier (BBB) remain incompletely understood. The present study reports the changes associated with infection and replication of T. gondii within human brain microvascular endothelial cells (BMECs) in vitro. Our results indicated that exposure to T. gondii had an adverse impact on the function and integrity of the BMECs – through induction of cell cycle arrest, disruption of the BMEC barrier integrity, reduction of cellular viability and vitality, depolarization of the mitochondrial membrane potential, increase of the DNA fragmentation, and alteration of the expression of immune response and tight junction genes. The calcium channel/P-glycoprotein transporter inhibitor verapamil was effective in inhibiting T. gondii crossing the BMECs in a dose-dependent manner. The present study showed that T. gondii can compromise several functions of BMECs and demonstrated the ability of verapamil to inhibit T. gondii crossing of the BMECs in vitro.

Citation

Harun, M., Marsh, V., Elsaied, N. A., Webb, K. F., & Elsheikha, H. M. (2020). Effects of Toxoplasma gondii infection on the function and integrity of human cerebrovascular endothelial cells and the influence of Verapamil treatment in vitro. Brain Research, 1746, Article 147002. https://doi.org/10.1016/j.brainres.2020.147002

• Journal Article Type: Article
• Acceptance Date: Jun 20, 2020
• Online Publication Date: Jun 24, 2020
• Publication Date: Nov 1, 2020
• Deposit Date: Oct 21, 2021
• Journal: Brain Research
• Print ISSN: 0006-8993
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 1746
• Article Number: 147002
• DOI: https://doi.org/10.1016/j.brainres.2020.147002
• Keywords: Developmental Biology; General Neuroscience; Molecular Biology; Clinical Neurology
• Public URL: https://nottingham-repository.worktribe.com/output/4736764
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0006899320303589?via%3Dihub