Poster abstracts
Poster number 67 submitted by Lynde Wangler
Amplified gliosis and interferon-associated inflammation in aged mice following diffuse traumatic brain injury
Lynde M. Wangler (Neuroscience Graduate Program), Chelsea E. Bray (College of Medicine, OSU), Jonathan M. Packer (Neuroscience Graduate Program), Zoe M. Tapp, Amara C. Davis (Neuroscience Graduate Program), Shane M. ONeil (Department of Neurosurgery, Duke University), Kara Baetz, Michelle Ouvina, Mollie Witzel (Institute for Behavioral Medicine)
Abstract:
Traumatic brain injury (TBI) is associated with an increased risk of cognitive, psychiatric, and neurodegenerative complications that may persist years after injury. Aged individuals are especially vulnerable to fall-related TBI and account for the majority of TBI-related hospitalizations and deaths. The neurobiological mechanisms of aging that support worse outcomes after TBI are undefined. Our main objective was to compare the neuroinflammatory response to diffuse TBI between adult and aged mice to elucidate mechanisms of aging that confer risk of worse outcomes. Here, adult (2 mo) and aged (16-18 mo) C57BL/6 mice were subjected to a mild diffuse brain injury, induced by midline fluid percussion, after which several biochemical and behavioral parameters were assessed 7 days post injury (dpi). Acute cognitive impairment was evident in both adult and aged TBI mice. There was enhanced reactive morphology of microglia and astrocytes in the cortex and hippocampus of aged mice compared to adults. Neuropathology mRNA analysis showed amplified cytokine/chemokine, complement, innate immune, and interferon-associated gene expression in the cortex of aged mice after TBI compared to adults. Ingenuity Pathway Analysis indicated mediators of interferon (IFN) signaling as robust upstream regulators of genes enhanced with age after TBI. Based on these results, we used DMXAA, a STING (stimulator of interferon genes) agonist, to determine if enhanced IFN signaling would worsen neuroinflammation after TBI in adult mice. Adult mice administered DMXAA after TBI had amplified expression of myriad genes that were amplified in Aged-TBI mice. Overall, IFN signaling induced by TBI is critical in the transition from acute to chronic neuroinflammation, and activation of this pathway is especially prominent in aged mice.
Keywords: Aging, Traumatic Brain Injury, Interferons