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Updated: Jul 4, 2026

A Human Blood-Brain Interface Model to Study Barrier Crossings by Pathogens or Medicines and Their Interactions with the Brain
Published on: April 9, 2019
Beyond Viral Control: Tenofovir's Hidden Impact on Blood-Brain Barrier Endothelial Cells
Saarah Behardien1, Khayelihle Brian Makhathini1, Chontrelle Willemse1
1Neurobiology Research Group, Department of Medical Biosciences, Faculty of Natural Sciences, University of the Western Cape, Cape Town, South Africa.
Abstract:
The blood-brain barrier (BBB) is a dynamic endothelial interface that protects the brain from harmful agents while regulating molecular exchange. Human immunodeficiency virus (HIV) compromises BBB integrity, promoting neurological damage. Antiretroviral (ARV) therapies suppress HIV replication, preventing immune system deterioration and progression to AIDS. Although Tenofovir-based ARV regimens are vital for HIV treatment and prevention, their impact on cerebrovascular function remains unclear.
Aim:
This study examined Tenofovir's effects on murine brain endothelial cells using an in vitro BBB model.
Methods:
Brain endothelial cells (bEnd.5) were treated with Tenofovir Disoproxil Fumarate (TDF; 9.8-98 ng/mL) or Tenofovir Alafenamide (TAF; 1-10 ng/mL) for 24-96 h. Cell proliferation, cell cycle progression (via flow cytometry) and monolayer permeability (via Transendothelial Electrical Resistance) were evaluated.
Results:
Both TDF and TAF treatments suppressed cell division by S-phase disruption of the cell cycle and increased monolayer permeability.
Conclusion:
These findings suggest that prolonged TDF or TAF exposure compromises BBB integrity by inhibiting endothelial cell division and altering barrier function, which could have implications for HIV-ARV-induced neurodegeneration in individuals receiving long-term Tenofovir-based therapy.
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