Poster abstracts
Poster number 82 submitted by Lynde Wangler
Amplified gliosis and interferon-associated inflammation in the aging brain 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 chronic psychiatric complications and increased risk for development of neurodegenerative pathology. Aged individuals account for most TBI-related hospitalizations and deaths. Nonetheless, neurobiological mechanisms that underlie worsened functional outcomes after TBI in the elderly remain unclear. Therefore, this study aimed to identify pathways that govern differential responses to TBI with age. Here, adult (2 mo) and aged (16-18 mo) male C57BL/6 mice were subjected to diffuse brain injury (midline fluid percussion), and cognition, gliosis, and neuroinflammation were determined 7 or 30 days post injury (dpi). Cognitive impairment was evident 7 dpi, independent of age. There was enhanced morphological restructuring of microglia (IBA1) and astrocytes (GFAP) 7 dpi in the cortex and hippocampus of aged mice compared to adults. Transcriptional analysis revealed robust age-dependent amplification of cytokine/chemokine (Ccl5, Ccl2, Il1, Il6), complement (C1qa/b/c), innate immune (Tlr2/4), and interferonassociated (Irf3/7, Ifna/b, STING) inflammatory gene expression in the cortex 7 dpi. Ingenuity Pathway Analysis of the transcriptional data showed that type I interferon (IFN) signaling was significantly enhanced in the aged brain after TBI compared to adults. Age prolonged inflammatory signaling and microgliosis 30 dpi with increased presence of rod microglia. Based on these results, a STING (stimulator of interferon genes) agonist DMXAA was used to determine if augmenting IFN signaling worsened cortical inflammation and gliosis after TBI. DMXAA-treated Adult-TBI mice showed comparable expression of myriad genes that were overexpressed in the cortex of Aged-TBI mice, including Irf7, Clec7a, Cxcl10, and Ccl5. Overall, diffuse TBI promoted amplified IFN signaling in aged mice, resulting in extended inflammation and gliosis.
Keywords: Aging, Traumatic Brain Injury, Inflammation