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Study of the neurotoxicity of indoor airborne nanoparticles based on a 3D human blood-brain barrier chip
Highlights We replicated the 3D human blood-brain barrier (BBB) to simulates the physiological responses of the BBB to the exposure of indoor nanoscale particulate matter. The indoor airborne nanoscale matter affects the blood-brain barrier biofunction. The tissue-engineered 3D BBB model is able to provide human homology data.
Abstract Background There is growing public awareness regarding the health effects of indoor nanoscale particulate matter (INPM) since people spend the majority of their time indoors. INPM could have a direct entry route into the brain via the axons of the olfactory nerve and migrating across the blood-brain barrier (BBB). Using animals to explore this possibility is not a reliable method to fully demonstrate human physiological responses. We, therefore, set out to develop a human 3D functional blood-brain barrier model to examine the potential effects of INPM on the cerebral nervous system. Methods Human astrocytes were co-cultured and human umbilical vein endothelial cells in 3D within a microfluidic chip to simulate the micro-complex physiological structure of the human BBB. This 3D human organotypic model has then been made to investigate any INPM-induced BBB dysfunction linked to potential cellular responses. Results A 3D human functional blood-brain barrier was constructed in this study. We observed the translocation of INPM across the blood-brain barrier. The 3D human organotypic chip initially reflected damage to the nervous system with abnormal astrocyte proliferation and a decline in cell viability. We also looked at the behavior of oxidative stress-related biomarkers (ROS, GSH-Px, and MDA). INPM was implicated in aggravating inflammation via reactive oxygen species (ROS). The Keap1-Nrf2-ARE pathway is a key mechanism in cellular resistance to oxidative stress by mediating and activating a variety of antioxidant and detoxification enzymes. Following ROS accumulation, INPM induced abnormal expression of nuclear transcription factor Nrf2. This behavior disturbed the expression of, γ-glutamate synthase (γ-GCS) and heme oxygenase (HO-1), which further exacerbated the imbalance of the antioxidant system. Conclusions This functional 3D human organotypic chip effectively mimics the physiological response of the human BBB. The chip provides a micro-complex structure to simulate the internal environment of the human blood-brain barrier, and partially simulates the physiological responses of the BBB to INPM exposure. Based on this model, INPM was shown to affect the blood-brain barrier biofunction by disrupting the Keap1-Nrf2-ARE pathways.
Study of the neurotoxicity of indoor airborne nanoparticles based on a 3D human blood-brain barrier chip
Highlights We replicated the 3D human blood-brain barrier (BBB) to simulates the physiological responses of the BBB to the exposure of indoor nanoscale particulate matter. The indoor airborne nanoscale matter affects the blood-brain barrier biofunction. The tissue-engineered 3D BBB model is able to provide human homology data.
Abstract Background There is growing public awareness regarding the health effects of indoor nanoscale particulate matter (INPM) since people spend the majority of their time indoors. INPM could have a direct entry route into the brain via the axons of the olfactory nerve and migrating across the blood-brain barrier (BBB). Using animals to explore this possibility is not a reliable method to fully demonstrate human physiological responses. We, therefore, set out to develop a human 3D functional blood-brain barrier model to examine the potential effects of INPM on the cerebral nervous system. Methods Human astrocytes were co-cultured and human umbilical vein endothelial cells in 3D within a microfluidic chip to simulate the micro-complex physiological structure of the human BBB. This 3D human organotypic model has then been made to investigate any INPM-induced BBB dysfunction linked to potential cellular responses. Results A 3D human functional blood-brain barrier was constructed in this study. We observed the translocation of INPM across the blood-brain barrier. The 3D human organotypic chip initially reflected damage to the nervous system with abnormal astrocyte proliferation and a decline in cell viability. We also looked at the behavior of oxidative stress-related biomarkers (ROS, GSH-Px, and MDA). INPM was implicated in aggravating inflammation via reactive oxygen species (ROS). The Keap1-Nrf2-ARE pathway is a key mechanism in cellular resistance to oxidative stress by mediating and activating a variety of antioxidant and detoxification enzymes. Following ROS accumulation, INPM induced abnormal expression of nuclear transcription factor Nrf2. This behavior disturbed the expression of, γ-glutamate synthase (γ-GCS) and heme oxygenase (HO-1), which further exacerbated the imbalance of the antioxidant system. Conclusions This functional 3D human organotypic chip effectively mimics the physiological response of the human BBB. The chip provides a micro-complex structure to simulate the internal environment of the human blood-brain barrier, and partially simulates the physiological responses of the BBB to INPM exposure. Based on this model, INPM was shown to affect the blood-brain barrier biofunction by disrupting the Keap1-Nrf2-ARE pathways.
Study of the neurotoxicity of indoor airborne nanoparticles based on a 3D human blood-brain barrier chip
Li, Yan (author) / Liu, Yan (author) / Hu, Chuanlin (author) / Chang, Qing (author) / Deng, Qihong (author) / Yang, Xu (author) / Wu, Yang (author)
2020-02-18
Article (Journal)
Electronic Resource
English
INPM , indoor nanoscale particulate matter , PM , particulate matter , BBB , blood-brain barrier , CNS , central nervous system , HUVECs , human umbilical vein endothelial cells , ACs , astrocytes , GSH , glutathione , ARE , antioxidant response elements , Nrf2 , nuclear factor (erythroid-derived 2)-like 2 , SEM , scanning electron microscope , HO-1 , heme oxygenase 1 , γ-GCS , γ-glutamylcysteine synthetase , Indoor nanoscale particulate matter , 3D microfluidic chip , Oxidative stress , Nrf2/Keap1 signal pathway
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