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Updated: May 4, 2026
Analyzing the Permeability of the Blood-Brain Barrier by Microbial Traversal through Microvascular Endothelial Cells
Published on: February 14, 2020
[Construction and mechanisms of D-galactose-induced blood-brain barrier organoid aging model]
Jing Luan1, Qin Zhuo1, Jingbo Wang1
1NHC Key Laboratory of Public Nutrition and Health, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
Objective:
To establish a D-galactose-induced aging model of the blood-brain barrier(BBB) with organoid technology and explore the pathophysiological mechanisms of BBB aging.
Methods:
A BBB model was constructed on an organ-on-a-chip using human cerebral microvascular endothelial cells(hCMEC/D3), followed by D-galactose exposure to induce aging. The model was evaluated by measuring transendothelial electrical resistance(TEER), apparent permeability coefficient(Papp) of fluorescein, β-galactosidase staining, live/dead cell staining, lactate dehydrogenase(LDH) activity, and reactive oxygen species(ROS) levels. The expression of tight junction proteins(ZO-1, Occludin), senescence-associated gene(p53), and anti-inflammatory genes(HO-1, Nrf2) was assessed using RT-qPCR to characterize aging features.
Results:
The optimal concentration for inducing BBB organoid aging was 50 mg/mL D-galactose. The model group significantly reduced TEER((19.46±0.98)Ω·cm~2 vs. (22.07±0.21)Ω·cm~2, P<0.05), increased Papp of fluorescein((1.08±0.02)×10~(-4 )cm/s vs. (4.39±0.01)×10~(-5 )cm/s, P<0.05), elevated β-galactosidase-positive cells, decreased live cells, increased dead cells, and increased LDH release and ROS levels. RT-qPCR analysis showed downregulation of ZO-1 and Occludin, along with upregulation of p53, HO-1, and Nrf2.
Conclusion:
D-galactose induced aging-associated damage in the BBB organoid model, providing a reliable in vitro biomimetic platform for studying BBB aging mechanisms and potential therapeutic interventions for neurodegenerative diseases. This model contributes to the understanding of the pathophysiological processes underlying neurological disorders.
