IBSC-BME Preliminary Exam Announcement for Shatha J. Mufti (R. Shi, advisor) Everyone is invited to attend the public presentation beginning at 9:30 a.m. Research Title: Investigating Alterations in Neuronal Network Dynamics, Astrocyte Reactivity, and Oxidative Stress Post-Traumatic Brain Injury Utilizing in vitro TBI-On-A-Chip Model Exam day: Thursday, 6/6/2024 Exam time: 9:30 a.m. Exam location: MJIS 2001 and Zoom Zoom link: https://purdue-edu.zoom.us/j/99714871016?pwd=UmJNSWh0OFRONnFUa3liT0lEd2pVQT09<https://nam04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fpurdue-edu.zoom.us%2Fj%2F99714871016%3Fpwd%3DUmJNSWh0OFRONnFUa3liT0lEd2pVQT09&data=05%7C02%7Cbmegradstudents-list%40ecn.purdue.edu%7C3c2919e20e32475c6c1a08dc7b5eb4cb%7C4130bd397c53419cb1e58758d6d63f21%7C0%7C0%7C638520893889052397%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=cn2ZvQsShzw4bfdEQ6Hc3NIf%2BcN2jzPMhZcaNGcu0Wg%3D&reserved=0> Committee members: Riyi Shi (Chair, BME), Matthew Ward (BME), Yunjie Tong (BME), and GuangJun Zhang (CPB) Abstract: Traumatic brain injury (TBI) can induce critical changes in neuronal network dynamics and alter the structural and functional connectivity of affected brain regions, potentially leading to serious sequalae, such as seizures. Epileptogenesis results from a shift in network dynamics towards a hyperexcitable and highly synchronized state, which occurs after brain injury via unclear mechanisms. While in vivo TBI models offer crucial insight into pathophysiological changes occurring in the brain post-injury, it is often difficult to precisely control the injury extent (e.g., degree of tissue deformation) in animals, even with strict control of injury administration (e.g., rate of rapid acceleration injury or weight-drop). Unfortunately, this methodological-induced variation confounds experimental outcomes, further obfuscating our understanding of the mechanisms that underly injury pathologies such as seizure. To overcome these limitations by minimizing systemic confounding variables, we utilized our unique in vitro TBI-on-a-chip model to investigate changes in network dynamics and seizure-like activity (SLA) post-TBI, with relative ease of measuring functional and structural changes following injury. TBI-on-a-chip simulates concussion by applying clinically relevant, rapid acceleration injuries to murine cortical networks cultured on microelectrode arrays (MEAs), and allows real-time, cell-scale monitoring of electrophysiological and morphological changes that arise from the impact injury. Extracellular recordings of spike activity revealed that networks exposed to 10 rapidly (4-6 sec) administered 30 g impacts displayed heightened network synchronization, a hallmark of SLA. Furthermore, cross-correlation analysis revealed changes in network dynamics and neuronal firing hierarchy post-impact. Additionally, immunocytochemical studies on networks exposed to single 30, 100, and 200 g impacts showed progressive increases in the astrocyte reactivity marker, GFAP, and the lipid peroxidation product and oxidative stress marker, acrolein. Since astrocytes regulate ion and neurotransmitter concentrations in the extracellular space of synapses, and astrocyte dysfunction via increased reactivity can lead to neuronal hyperexcitability and increased susceptibility for seizures, these results suggest a potential mechanism underlying TBI-induced epilepsy. Moreover, we show that acrolein, even in the absence of injury, is capable of inducing increases in GFAP, suggesting that oxidative stress could increase astrocyte reactivity, and thereby contribute to post-TBI epilepsy. In summary, this work using the TBI-on-a-chip model could provide vital insights into functional and morphological changes in neurons and astrocytes following TBI, and enable investigation of the mechanisms underlying SLA, which could lead to the identification of potential therapeutic targets.