Abstract
The blood‐brain barrier (BBB) is a selectively permeable barrier made up of tight junctions formed by endothelial cells that separates the circulating blood from the brain extracellular fluid. The primary function of this barrier is to keep toxins, bacteria, viruses, and drugs from entering the brain. In the event of an ischemic stroke, the BBB becomes leaky due to the activation of hypoxia inducible factor 1‐alpha (HIF1‐a) and neurons become apoptotic. It is known that activation of the WNT pathway results in the production of B‐catenin, which has been shown to enhance HIF1‐a mediated transcription, which promotes the survival of cells and their adaptation to hypoxia. Currently, there are no drugs that have been formulated to restore the BBB function as well as neuron survival following ischemic stress. The purpose of our study was to determine the effect of small molecules on the BBB/WNT pathway during ischemia/re‐oxygenation. Brain microvascular endothelial cells (BMECs) derived from iPSCs and the immortalized human brain endothelial cell line, HCMEC/D3, were cultured and placed in ischemic stress for 6hrs, followed by a 24 hour period of re‐oxygenation. At the time of re‐oxygenation, cells were treated with small molecules CHIR99021, TWS (WNT activators), IWP‐4, IWR, and XAV (WNT inhibitors) in order to determine the effect of the WNT pathway on cell survival. Transendothelial Electrical Resistance (TEER) and permeability were performed to assess the effect that the WNT pathway has barrier integrity following re‐oxygenation. Further, MTT and ICC were performed to determine cell viability and tight junction expression, respectively. Preliminary results of this study have shown that inhibition of the WNT pathway during re‐oxygenation results in up‐regulation of tight junction proteins and an increase in cell viability as well as an increase in barrier function.Support or Funding InformationLaura W. Bush Institute for Women's HealthThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
