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In Vitro Assays to Assess Blood-brain Barrier Mesh-like Vessel Formation and Disruption
Published on: June 20, 2017
Nanoparticles as an efficient strategy to eliminate senescent brain endothelial cells
Inês Tomé1, Susana Rosa2, David Sanfeliu-Redondo3
1Center for Neurosciences and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
Summary
Polymeric nanoparticles loaded with senolytics selectively eliminate senescent brain endothelial cells (BECs), restoring blood-brain barrier (BBB) integrity and improving cognitive function in aged rats.
Area of Science:
- Neuroscience
- Biotechnology
- Gerontology
Background:
- Physiological aging impairs the blood-brain barrier (BBB), contributing to cognitive decline and neurodegenerative diseases.
- Brain endothelial cell (BEC) senescence is a critical factor in BBB dysfunction during aging.
Purpose of the Study:
- To develop and evaluate polymeric nanoparticles (NPs) loaded with the senolytic agent Navitoclax for selective elimination of senescent BECs.
- To assess the efficacy of these NPs in restoring BBB integrity and improving cognitive function in aged rats.
Main Methods:
- Polymeric NPs loaded with Navitoclax were designed for targeted delivery to senescent BECs.
- NP degradation and drug release were triggered by senescence-associated beta-galactosidase (SA-β-gal).
- In vitro studies assessed NP selectivity for senescent vs. proliferative BECs.
- In vivo studies used chronologically aged rats to evaluate NP effects on BBB permeability, BEC senescence markers, and exploratory behavior.
Main Results:
- NPs selectively eliminated senescent BECs at lower doses than soluble Navitoclax, without affecting proliferative cells.
- In aged rats, NPs restored BBB integrity, reduced BBB permeability, and decreased the burden of senescent BECs.
- NPs, but not soluble senolytics, reduced p21+ and p16+ BECs and partially improved exploratory behavior.
Conclusions:
- Navitoclax-loaded NPs are a promising strategy for targeting BEC senescence and mitigating age-related BBB dysfunction.
- This NP-based senolytic approach offers a potential therapeutic intervention for age-related cognitive decline and neurodegeneration.
