Sierra Musial
Research Mentor: Joseph Wider
Mentor Department: Emergency Medicine, Medicine
Author(s): Joseph Wider, Reagan Speas, Jubetzy Crespo, Sarita Raghunayakula, Sierra Musial
Session: Session 4 (1:00 PM – 1:50 PM)
Presentation Type: Poster 118
Abstract
Traumatic brain injury (TBI) is damage to the brain caused by an external force, such as a strong impact or hit to the head. TBI is a neurological condition and a leading cause of disability worldwide, associated with physical, cognitive, and emotional deficiencies. There are two phases of TBI: primary, immediate damage due to the impact or force exerted to the head, and secondary, further harm to brain tissue through a cascade including the buildup of reactive oxygen species (ROS), a severe state of energy dysregulation, and ultimately neuronal death. A driver of cell death within this cascade is excitotoxicity, the overactivation of neurons, which depletes the cell’s energy and increases ROS production. In response to excitotoxicity, the mitochondria within neurons attempt to compensate for the increased energetic demand by producing more ATP, but in doing so disrupt the mitochondrial membrane potential (MMP), leading to hyperpolarization and increasing ROS production. The role of mitochondrial membrane hyperpolarization remains unclear in the production of ROS and cell death during the excitotoxic cascade. To isolate the effect of MMP hyperpolarization, we used HT22s treated with oligomycin, an ATP synthase inhibitor, to hyperpolarize the mitochondrial membrane. Live cell imaging was used to track membrane polarization and ROS production with TMRE and MitoSOX dyes. We hypothesize mitochondrial membrane hyperpolarization to have a direct influence on ROS production, with more hyperpolarized membranes being associated with higher ROS production. We are currently evaluating the effects of MMP hyperpolarization on oxidative stress and replicating results.
