Evaluating the Efficacy of Young Blood Plasma Injections for the Treatment of Mild Repetitive Traumatic Brain Injuries in Mice

Rachel Barkey

Advisor: Jane M Flinn, PhD, Department of Psychology

Committee Members: Craig McDonald, Geraldine Grant

David J. King Hall, #2027
October 26, 2022, 11:00 AM to 01:00 PM

Abstract:

This study investigated the efficacy of young blood plasma injections for the immediate and delayed treatment of behavioral and neuropathological effects of repetitive mild traumatic brain injury (rmTBI) in mice. Beginning at 8 weeks of age, C57Bl/6J mice received either a total of 5 mTBIs or underwent a sham procedure at 48 hour intervals. One group of mice began treatment with young blood taken from 8-week-old mice 24 hours after the final injury; a second group began plasma treatment 30 days after the final injury. Mice received either 150µL of plasma or 150µL of saline via tail vein injections once every 48 hours for a total of 16 injections. Following the completion of the plasma treatment, mice underwent behavioral testing in Morris water maze (MWM), Open Field (OF), Elevated Zero Maze (EZM), nesting, burrowing, circadian activity (CA) and gait assessment. Brains were analyzed following behavioral testing using cresyl-violet/Luxol FastBlue (CV-LFB) staining, and western blot analysis. Results show that in immediately treated mice, rmTBI mice have a greater number of head dips in EZM, a longer latency to center in OF, greater expression of GFAP-α (p = .045), and higher levels of Il-1β expression. Plasma mice have a wider gait, spend a longer time in the target quadrant in MWM, an earlier time of onset in CA, reduced levels of Il-1β, GFAP-ΔEx7 and -Δ164 in plasma treated mice. In delayed treatment mice, rmTBI mice have a wider gait, show higher number of head dips and spend more time in the open arms in EZM, have a longer latency to center in OF, a longer latency to platform in MWM during the visual trail, as well as a slower velocity, and have greater daily activity in CA. Plasma treated mice have greater activity in CA. For both immediate and delayed treatment mice, rmTBI plasma treated mice have a greater cell density in the corpus callosum, infralimbic region of the prefrontal cortex (IL), parietal association cortex, and entorhinal cortex than rmTBI saline treated mice (p < .01). Overall, this study demonstrates that treatment with young blood plasma after rmTBI ameliorates neuronal loss and may rescue behavioral deficits related to neurodegeneration.