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By Alexandra Lowery, Neurobiology
Advisor: Jennifer McGuire
Presentation ID: AM_B45
Abstract: Traumatic brain injury (TBI) is a leading cause of disability in the United States, affecting an estimated 2.8 million people annually. While preventative measures can be taken, there is currently no effective treatment for TBI or the cognitive deficits that arise from it. Additionally, secondary injury cascades such as metabolic dysfunction occur throughout the months following injury and exacerbate these deficits. This is largely due to the fact that neurotransmission is heavily dependent upon the supply of energy from metabolic pathways. We hypothesized that by improving the efficiency of energy metabolism, we could rescue some of the cognitive deficits seen in the weeks after TBI. We dosed rats with pioglitazone, an FDA approved drug for diabetes, beginning 46 days after lateral fluid percussion injury. We found that chronic pioglitazone administration improves working memory performance in a radial arm maze (RAM) compared to untreated TBI. While pioglitazone increased the activity of the glycolytic enzyme hexokinase in the hippocampus, western blot analysis showed that this was not due to an upregulation of glucose transporter or hexokinase levels. The expression of GFAP and Iba-1, two glial markers indicative of neuroinflammation, were not influenced by pioglitazone treatment. This suggests that cognitive deficits in chronic TBI can be attenuated by targeting brain metabolism within the hippocampus in particular.