GDNF and cAMP significantly enhance in vitro blood-brain barrier integrity in a humanized tricellular transwell model
Issued Date
2024-10-30
Resource Type
eISSN
24058440
Scopus ID
2-s2.0-85206319781
Journal Title
Heliyon
Volume
10
Issue
20
Rights Holder(s)
SCOPUS
Bibliographic Citation
Heliyon Vol.10 No.20 (2024)
Suggested Citation
Kanjanasirirat P., Saengsawang W., Ketsawatsomkron P., Asavapanumas N., Borwornpinyo S., Soodvilai S., Hongeng S., Charoensutthivarakul S. GDNF and cAMP significantly enhance in vitro blood-brain barrier integrity in a humanized tricellular transwell model. Heliyon Vol.10 No.20 (2024). doi:10.1016/j.heliyon.2024.e39343 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/101719
Title
GDNF and cAMP significantly enhance in vitro blood-brain barrier integrity in a humanized tricellular transwell model
Corresponding Author(s)
Other Contributor(s)
Abstract
Blood-brain barrier (BBB) is a crucial membrane safeguarding neural tissue by controlling the molecular exchange between blood and the brain. However, assessing BBB permeability presents challenges for central nervous system (CNS) drug development. In vitro studies of BBB-permeable agents before animal testing are essential to mitigate failures. Improved in vitro models are needed to mimic physiologically relevant BBB integrity. Here, we established an in vitro human-derived triculture BBB model, coculturing hCMEC/D3 with primary astrocytes and pericytes in a transwell format. This study found that the triculture BBB model exhibited significantly higher paracellular tightness (TEER 147.6 ± 6.5 Ω × cm2) than its monoculture counterpart (106.3 ± 1.0 Ω × cm2). Additionally, BBB permeability in the triculture model was significantly lower. While GDNF and cAMP have been shown to promote BBB integrity in monoculture models, their effect in our model was previously unreported. Our study demonstrates that both GDNF and cAMP increased TEER values (around 200 Ω × cm2 for each; 237.6 ± 17.7 Ω × cm2 for co-treatment) compared to untreated control, and decreased BBB permeability, mediated by increased claudin-5 expression. In summary, this humanized triculture BBB model, enhanced by GDNF and cAMP, offers an alternative for exploring in vitro drug penetration into the human brain.