BME PhD Preliminary Exam Announcement for Nikita Krishnan (R. Shi, advisor) Everyone is invited to attend the public presentation beginning at 1:00pm. Research Title: An in vitro Model of the Blood-Brain Barrier after Blast Traumatic Brain Injury Date, Time, Place: November 25th at 1pm, DLR 221 Zoom: https://purdue-edu.zoom.us/j/95217017704?pwd=LJ2rCXliBraUSzaZcKRxyuxDIb4Zco.1<https://nam04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fpurdue-edu.zoom.us%2Fj%2F95217017704%3Fpwd%3DLJ2rCXliBraUSzaZcKRxyuxDIb4Zco.1&data=05%7C02%7Cbmeroundtable-list%40ecn.purdue.edu%7C9c0182a078404927b39b08dd08e15a3c%7C4130bd397c53419cb1e58758d6d63f21%7C0%7C0%7C638676486148182534%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=UBf%2FsE50%2BgKirHrPdMxUpcAXNHLFNixSI6mWc5Hx77k%3D&reserved=0> Thesis Committee Members: Dr. Riyi Shi (major professor), Dr. Daniel Suter, Dr. Estelle (Sunghee) Park, Dr. Taimoor Qazi Abstract: Blast traumatic brain injury (bTBI) is a highly-prevalent condition caused by shock waves from explosions. Even mild bTBI can increase the risk of developing neurodegenerative diseases like Alzheimer's Disease (AD), making the high prevalence of bTBI and repetitive bTBI amongst military personnel an urgent concern. A key pathological feature seen after bTBI is disruption of the blood-brain barrier (BBB), which normally functions to restrict the passage of biomolecules between the brain tissue and the systemic vasculature. After bTBI, the permeability of the BBB is temporarily increased, and the tight junction proteins (TJPs) normally present between the endothelial cells (ECs) that make up the BBB are temporarily expressed at lower levels. The disruption of the BBB and subsequent recovery of permeability and TJP expression are mediated by secondary injury mechanisms, or biochemical cascades that initiate immediately after primary mechanical exposure. Specifically, the activation of innate immune cells in the brain called microglia, which can be pro- or anti-inflammatory, and the generation of toxic lipid peroxidation product acrolein may play a critical role in mediating BBB dysfunction and recovery after bTBI. However, the exact roles of activated microglia and acrolein in post-injury BBB dysfunction have not been identified. The purpose of this thesis is to identify the effects of microglial activation state and acrolein levels on temporal BBB dynamics after mild bTBI by leveraging an in vitro model system of the cells of the BBB (ECs, astrocytes, and pericytes) and microglia. Microglial activation and acrolein levels will then be therapeutically targeted by biochemically promoting the anti-inflammatory activated microglial phenotype and reducing acrolein levels. This therapeutic approach will be investigated immediately after a single mild bTBI, after a single mild bTBI followed by a subsequent bTBI, and after multiple consecutive bTBIs. Treatment is expected to promote a quicker recovery of BBB permeability, TJP expression, and vascular stability marker expression both after a single injury and after repetitive injury. Understanding and promoting BBB recovery mechanisms after bTBI has the potential to mitigate pathology initiated or exacerbated by BBB permeability, and this could be critical to preventing severe consequences of single and repetitive mild bTBI. -- Bmeroundtable-list mailing list Bmeroundtable-list@ecn.purdue.edu https://engineering.purdue.edu/ECN/mailman/listinfo/bmeroundtable-list