Endothelial disruption by challenged astrocytes
2017
University of Catania, Catania, Italy
The integrity of the blood-brain barrier is essential for normal brain homeostasis. However, it can be easily disrupted if any of its cellular components is altered. This is the case in several pathologies, like Alzheimer's disease. In this study, an in vitro blood-brain barrier human model is used to study the interaction between human endothelial cells and human astrocytes after exposure to amyloid-beta. In co-culture conditions, the exposure to amyloid-beta 1-42 induced the dysfunction of endothelial cells in a permeability assay, contrary to when endothelial cells are cultured alone. Furthermore, the disruption of endothelial cells could be reproduced with conditioned media of astrocytes exposed to amyloid-beta. The researchers found out that this was a consequence of the increased activity of matrix metalloprotease 9 mediated by astrocytic vascular endothelial growth factor. Overall, the results elucidate a key mechanism involved in endothelial malfunction driven by challenged astrocytes exposed to amyloid-beta in a human model. This knowledge could be a great advance to understand the degradation of the blood-brain barrier in Alzheimer's disease and to develop new therapeutical strategies to target this pathology.
Astrocytes contribute to Aβ-induced blood–brain barrier damage through activation of endothelial MMP9
Maria Angela Sortino
Added on: 08-17-2021
[1] https://onlinelibrary.wiley.com/doi/10.1111/jnc.14068[2] https://data.jrc.ec.europa.eu/dataset/a8fd26ef-b113-47ab-92ba-fd2be449c7eb
