Traumatic Brain Injury & Acidosis
Traumatic Brain Injury (TBI) is a significant cause of death in the United States, and is the leading cause of disability in children and young adults. Acidosis is one of the most frequent secondary brain injuries and is associated with longer Intensive Care and hospital length of stay. This thesis investigated the interaction between a primary mechanical injury and a secondary acidosis injury using an innovative experimental TBI model consisting of organotypic cultured rat hippocampus. Propidium Iodide imaging was used to assess percent cell death, with results tentatively suggesting an additive rather than a sensitizing interaction between TBI and acidosis. However, analysis of the dentate gyrus indicated that there may be both regional specificity of vulnerability and regional interaction between TBI and acidosis. Amiloride and psalmotoxin were investigated as possible neuroprotective agents, with psalmotoxin but not amiloride producing promising results for reducing cell death by acidosis. Immunocytochemistry and Western blot techniques were utilized to confirm presence of ASIC channels in the organotypic rat hippocampus cultures, with results demonstrating presence of ASIC1a and ASIC2a in control cultures, and a decrease in ASIC1a concentration following TBI. Dendritic spine imaging was used to explore synaptic structural changes resulting from TBI and acidosis. The data obtained from these imaging studies suggests that following an injury dendritic spine density decreases while varicosity density increases, implying that the mechanisms of cell death for TBI and acidosis are likely not spine mediated. Taken together, these results further our understanding of the interactions between TBI and acidosis and are important for considering the clinical treatment of TBI. Future research should investigate further the regional specificity of injury, psalmotoxin as a possible neuroprotective agent, and the role of dendritic spine remodeling following TBI and/or acidosis.