scholarly journals Development of Real-Time Transendothelial Electrical Resistance Monitoring for an In Vitro Blood-Brain Barrier System

Micromachines ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 37
Author(s):  
Kai-Hong Tu ◽  
Ling-Shan Yu ◽  
Zong-Han Sie ◽  
Han-Yi Hsu ◽  
Khuloud T. Al-Jamal ◽  
...  

Three-dimensional (3D) cell cultures and organs-on-a-chip have been developed to construct microenvironments that resemble the environment within the human body and to provide a platform that enables clear observation and accurate assessments of cell behavior. However, direct observation of transendothelial electrical resistance (TEER) has been challenging. To improve the efficiency in monitoring the cell development in organs-on-a-chip, in this study, we designed and integrated commercially available TEER measurement electrodes into an in vitro blood-brain barrier (BBB)-on-chip system to quantify TEER variation. Moreover, a flowing culture medium was added to the monolayered cells to simulate the promotion of continuous shear stress on cerebrovascular cells. Compared with static 3D cell culture, the proposed BBB-on-chip integrated with electrodes could measure TEER in a real-time manner over a long period. It also allowed cell growth angle measurement, providing instant reports of cell growth information online. Overall, the results demonstrated that the developed system can aid in the quantification of the continuous cell-pattern variations for future studies in drug testing.

2020 ◽  
Author(s):  
Shuaishuai Gong ◽  
Jieman Wang ◽  
Zhuo Chen ◽  
Xuewei Pan ◽  
Yunhao Wu ◽  
...  

Abstract Background : Cerebral ischemia-reperfusion (I/R) injury as a serious threat to human health is characterized by cerebral endothelial leakage, as a result of the damage of blood-brain barrier (BBB). It is thus quite attractive to realize real-time monitoring of BBB damage for therapeutic surveillance.Methods : In this study, a radioactive probe is constructed by conjugating ruscogenin (Rus), a neuroprotectants, to technetium-99m (Tc 99m ) to assess the damage of cerebral endothelial in BBB.Results : In vitro study proves that the probe can penetrate more efficiently in damaged BBB. Then, longitudinal nuclear imaging distinguishes mice with BBB leakage from normal ones, which is validated by evans blue staining of brain tissue. Higher nuclear signal also correlates with poorer blood circulation in brain. Further, by visualizing brain signal during drug treatment, the probe finds that the most obvious protective efficacy of Rus occurs at 12 h post administration, which is superior than edaravone (Edara).Conclusion : Altogether, the probe is promising to monitor I/R injury real-time by radioactive-imaging of BBB integrity. Importantly, Rus as a neuroprotectants may serve as a potential theranostic agent for I/R treatment.


1996 ◽  
Vol 24 (3) ◽  
pp. 349-357
Author(s):  
Bellina Veronesi ◽  
Kent Carlsón ◽  
Marion Ehrich

The development of a cell culture model which simulates the properties of the blood–brain barrier (BBB) is necessary for the detection of neurotoxic chemicals that can disrupt the barrier, and to provide a more “risk relevant” in vitro screening battery. The present study evaluates the Madin-Darby canine kidney (MDCK) epithelial cell line for this purpose. Changes in electrical resistance and enzyme activities were correlated in confluent MDCK cells exposed to the neurotoxic metal, triethyl tin (TET). Concentrations of TET (0.001–10μM) were established that produced depression in electrical resistance of the MDCK cells after exposure for 8 hours or caused fluorescein leakage after exposure for 72 hours. Confluent cultures of MDCK cells were then exposed to these concentrations of TET and assayed after exposure for 24 hours and 72 hours for changes in those enzymes common to both epithelial and cerebral endothelial cells. The results indicated that increased alkaline phosphatase (APP), γ-glutamyl transpeptidase (GGTP) and superoxide dismutase (SOD) characterised the loss of electrical resistance and permeability disruption in TET-exposed MDCK confluent cultures. Relative increases in APP and decreases in GGTP activities preceded cytotoxicity, which was associated with a high SOD activity. Such enzyme changes may be predictive endpoints of barrier cell disruption by neurotoxic metals in this cell line and support the additional evaluation of the MDCK cell line as an in vitro “screen” for chemicals that disrupt the BBB.


2021 ◽  
Author(s):  
Huaiying Zhang ◽  
Winant L. van Os ◽  
Xiaobo Tian ◽  
Guangyue Zu ◽  
Laís Ribovski ◽  
...  

Zein-polydopamine nanoparticles functionalized with G23 peptide cross an in vitro blood–brain barrier and penetrate tumor spheroids. When loaded with curcumin they effectively reduce proliferation, migration, and viability of C6 glioma cells.


Lab on a Chip ◽  
2021 ◽  
Author(s):  
Elsbeth G. B. M. Bossink ◽  
Mariia Zakharova ◽  
Douwe S. de Bruijn ◽  
Mathieu Odijk ◽  
Loes I. Segerink

A cleanroom-free method to integrate electrodes for transepithelial/transendothelial electrical resistance (TEER) measurements in Organ-on-Chips (OoCs) is presented and validated for a gut and a blood-brain barrier model.


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