Student: Glenna Embrador
Project Mentors: Dr. Sarah Stabenfeldt – SBHSE
Dr. Rachael Sirianni – UTHealth
Dr. Christopher Plaisier – SBHSE
YouTube Link: View the video link below before joining the zoom meeting
Zoom Link: https://asu.zoom.us/j/91898043679
Zoom meeting time: 10am - noon
Abstract
Traumatic brain injury (TBI) is a leading cause of death in the United States, with an average of 1.7 million people sustaining a TBI annually. Following a TBI event, the body initiates a proinflammatory response which in excess, can lead to neurodegeneration or even the initiation of multiple cell death processes. Recent studies found histone deacetylases (HDAC) as a major player in regulating neuroinflammation, making its inhibition attractive for TBI treatments. Current HDAC inhibitors has shown efficacious treatment in cancer applications by modulating gene expressions of cancerous cells. However, there has been limited research in selecting the most effective and potent HDAC inhibitors as a TBI therapeutic. This project aims to test and research the efficacy of HDACi in reducing neuroinflammation following injury in vitro using human astrocyte cultures. Three second generation HDACi drugs: quisinostat, panobinostat, and givinostat underwent preliminary characterization in addition to robust literature research to evaluate its efficacy as a TBI therapeutic. The HDACi drugs were added to human astrocyte cultures following 48 hours of growth at 4 different concentrations: 10-3 μM, 10-2 μM, 10-1 μM, and 1 μM at the same time as the neuroinflammation stimulant, lipopolysaccharide (LPS, 100ng/mL). The supernatant and cell lysates were collected after 6 hours of incubation. Based off of literature research, it is expected that the cells treated with the drugs will inhibit HDAC protein activity which would in turn reduce inflammatory cytokine levels compared to a control with no drug intervention following neuroinflammation. We also expect to see a trend with the varying HDACi concentrations where the higher the concentration, the greater decrease in HDAC activity and therefore reduced neural damage. Future work includes performing Western blot and ELISA analysis to detect HDAC and cytokine activity respectively to quantitatively assess their performance. The results from this study will contribute towards the growing understanding of traumatic brain injury treatments.