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Updated: Jul 22, 2025
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Published on: April 6, 2022
μF-hBBB Chip Together with Tetrahedral DNA Frameworks for Visualization of LPS-Mediated Inflammation
Yi Xu1,2, Shuainan Li2, Chenguang Wang3
1National Key Laboratory of Materials for Integrated Circuits, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China.
Abstract:
The blood-brain barrier (BBB) is essential for maintaining central nervous system (CNS) stability, and neuroinflammation may cause the dysfunction of the BBB. MicroRNA-146a (miR-146a) is closely associated with neuroinflammation, which showed significant upregulation in response to lipopolysaccharide (LPS) induction. Elucidating the relationship between LPS-induced miR-146a expression and the BBB could decipher the mechanism of many neurological diseases. Here, we constructed an in vitro microfluidic human-BBB (μF-hBBB) chip consisting of human umbilical vein vascular endothelial cells (HUVECs) and human astrocyte (HAs) cells. A tetrahedral DNA framework (TDF-3MB) nanoprobe was used to label miR-146a in HUVECs on μF-hBBB chips before and after LPS induction, and the study revealed a significant increase in miR-146a expression after LPS induction. We believe that such a μF-hBBB chip is a promising in vitro platform for further use in understanding CNS diseases.
Insights
Neuroinflammation increases microRNA-146a (miR-146a) in the blood-brain barrier (BBB). This study used a microfluidic human-BBB chip to observe miR-146a changes, offering insights into neurological disease mechanisms.
Area of Science:
- Neuroscience
- Biotechnology
- Molecular Biology
Background:
- The blood-brain barrier (BBB) is crucial for central nervous system (CNS) stability.
- Neuroinflammation can disrupt BBB function, contributing to neurological disorders.
- MicroRNA-146a (miR-146a) is implicated in neuroinflammation, with elevated levels observed after lipopolysaccharide (LPS) exposure.
Purpose of the Study:
- To investigate the relationship between LPS-induced miR-146a expression and BBB integrity.
- To establish a novel in vitro microfluidic human-BBB (μF-hBBB) chip model for studying CNS diseases.
- To quantify changes in miR-146a levels within the BBB model.
Main Methods:
- Construction of a μF-hBBB chip using human umbilical vein vascular endothelial cells (HUVECs) and human astrocyte (HAs) cells.
- Utilized a tetrahedral DNA framework (TDF-3MB) nanoprobe for sensitive detection and quantification of miR-146a.
- Measured miR-146a expression in HUVECs on the μF-hBBB chip before and after LPS induction.
Main Results:
- Demonstrated a significant upregulation of miR-146a in HUVECs following LPS induction within the μF-hBBB chip.
- Successfully visualized and quantified miR-146a changes in a dynamic in vitro BBB model.
- The μF-hBBB chip effectively mimicked aspects of BBB response to inflammatory stimuli.
Conclusions:
- The study confirms that LPS induction leads to increased miR-146a expression in the BBB.
- The developed μF-hBBB chip serves as a valuable platform for investigating neuroinflammation and BBB dysfunction.
- This model holds promise for advancing the understanding of mechanisms underlying various CNS diseases.
