Biochemical Sequelae of Repetitive Mild Traumatic Brain Injury in a Murine Model Treated with Young Blood Plasma

Erin Nichole Doherty

Advisor: Jane M Flinn, PhD, Department of Psychology

Committee Members: Geraldine Grant, Craig McDonald

David J. King Hall, #2027
November 20, 2023, 01:00 PM to 03:00 PM


This study assessed for biochemical changes in the blood plasma and brain tissue of mice that were subjected to repetitive mild traumatic brain injury (rmTBI) and treated with immediate or delayed injections of healthy young blood plasma. Samples were preserved from a 2022 doctoral dissertation by Rachel Barkey for George Mason University, using a controlled cortical impact model of rmTBI (5 mild TBI or sham procedure) in C57Bl/6J mice starting at 8 weeks of age. After the final TBI, rmTBI and sham mice received 16 total tail-vein injections of 150 μL healthy young blood plasma (donated from 8–10-week-old non-injury mice) or 150 μL saline every 48 hours. Plasma and saline injections were delivered in the form of either immediate treatment (24 hours after TBI) or delayed treatment (1 month after TBI). To investigate the neurochemical effects of rmTBI and young blood plasma treatment, this study conducted ELISA and western blot assays on key proteins involved in inflammation, synaptic plasticity, and circulatory processes. ELISA analyses probed for growth differentiation factor 11 (GDF11), chemokine CCL11, and interleukin-6 (IL-6) in the mouse blood plasma. Primary western blot targets in the affected brain tissue include the cAMP-response element binding (CREB) protein, phosphorylated CREB, synaptophysin, and ubiquitin C- terminal hydrolase-L1 (UCH-L1). When compared to sham mice, it is hypothesized that rmTBI will increase inflammatory biomarkers and pathogenetic proteins (CCL11, IL-6, UCH-L1) while decreasing proteins associated with normal synaptic function and cognition (GDF11, CREB, phosphorylated CREB, synaptophysin). Mice treated with young blood plasma (as compared to saline treatment) are expected to show reversals in these TBI-induced imbalances, as healthy young plasma is hypothesized to improve the inflammation and protein abnormalities associated with injury.