IBSc-BME PhD Preliminary Exam Announcement for Rachel Stingel (R. Shi, advisor) Everyone is invited to attend the public presentation beginning at 9:00 AM EDT. Title: Acrolein-mediated excitotoxicity following spinal cord injury Date / Time: April 24, 2024 at 9AM EDT Location: MJIS 2001; Zoom link for those who cannot attend: meeting ID: 495 923 5472, https://purdue-edu.zoom.us/j/4959235472<https://nam04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fpurdue-edu.zoom.us%2Fj%2F4959235472&data=05%7C02%7Cbmegradstudents-list%40ecn.purdue.edu%7C067a4f5816674ce8599008dc59811038%7C4130bd397c53419cb1e58758d6d63f21%7C0%7C0%7C638483658055221903%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=yM5IGFHcZRNA84N2HFPIQqegg7hRWUBRp3BeX8DZTAk%3D&reserved=0> Committee: Riyi Shi (Chair, advisor), Hyowon (Hugh) Lee, Maria Dadarlat, George M. Smith Abstract: Traumatic spinal cord injury (SCI) causes significant sensory, motor, and autonomic dysfunction for which no established treatment option is available. As such, mechanistic investigation is needed to identify effective therapeutic targets to improve the management of SCI. SCI arises from an initial mechanical impact to the spinal cord (primary injury) and is followed by a series of biochemical cascades (secondary injury) that perpetuate the extent of damage. Oxidative stress and glutamate excitotoxicity are two particularly destructive events that manifest within the first two weeks of SCI. Oxidative stress induces lipid peroxidation (LPO), which results in the production of reactive aldehydes (RA) such as acrolein. Acrolein, a strong electrophile that perpetuates oxidative stress, can bind to and cause irreversible structural changes in target proteins. Glutamate transporter-1 (GLT-1), the chief regulator of extracellular glutamate levels, contains a number of nucleophilic amino acid residues that are likely targets of acrolein. Due to its high reactivity and peak levels coinciding with the progression of excitotoxicity, we hypothesize that acrolein binds to and disrupts the function of GLT-1, which underlies excitotoxicity in the secondary injury. Additionally, we have recently found evidence that acrolein damages aldehyde dehydrogenase 2 (ALDH2), an oxidoreductase that metabolizes RAs, making it largely ineffective in neurotraumatic states. We hypothesize that restoring ALDH2 function will reduce acrolein levels and rescue GLT-1, thereby mitigating excitotoxic damage. Completion of these studies will not only better our overall understanding of the mechanisms underlying secondary SCI, but could also be applied to other neurotraumatic injuries or degenerative diseases with similar underlying pathologies.