Poster abstracts
Poster number 101 submitted by Samuel Houle
Sleep Fragmentation Following Traumatic Brain Injury Exacerbates Sub-Acute Behavioral Deficits and Transcriptional Changes at Chronic Time Points
Sam Houle (Department of Neuroscience, Institute for Behavioral Medicine Research), Zoe Tapp, Christopher Cotter, (Department of Neuroscience, Institute for Behavioral Medicine Research), Zach Zimomra (Institute for Behavioral Medicine Research), Siena Robertson, Yvanna Reyes, Sakeef Ahsan, Shannon Dobres, Jessica Mitsch (Department of Neuroscience, Institute for Behavioral Medicine Research), John Sheridan, Jonathan Godbout (Department of Neuroscience, Institute for Behavioral Medicine Research), Olga N. Kokiko-Cochran (Department of Neuroscience, Institute for Behavioral Medicine Research)
Abstract:
Stressful experiences elicit an immune response that is initially adaptive. However, persistent stress shifts the immune response to be detrimental. Stress-immune interactions may worsen long-term outcome in traumatic brain injury (TBI) survivors, who commonly have impaired stress response. Here, we leverage sleep fragmentation (SF) as a common physiological consequence of stress to study post-TBI neuroinflammation. We hypothesize that post-injury SF exacerbates TBI-induced sleep-wake disturbances, neuroinflammation, and cognitive impairments. Adult male and female mice received either a moderate lateral fluid percussion TBI or a sham injury. Mice were exposed to SF 5am-10am beginning one hour prior to light cycle or remained in control housing for 14 days post-injury (DPI). At 14 DPI mice were allowed to recover until 30 DPI. Sleep-wake activity was acquired for all mice using custom piezo-electric sensors for 30 DPI.
TBI increased sleep for 4 hours following injury. Unexpectedly, all mice exposed to SF slept more than control mice through 7 DPI. Post-TBI SF exacerbated spatial learning and memory deficits in the Morris water maze 14 DPI. By the last week of recovery SF mice slept comparably to control animals. However, transcriptional changes were present 30 DPI. Post-TBI SF increased transcription of cortical inflammation (Spi1, Abca1, Itga7), neurodegeneration (Abca1, Atg2b), and immunometabolic (Abca1, Lpl, Mef2a, Prkab2) genes. Additionally, transcripts of the gene Romo1 were increased by TBI SF indicating possible increased presence of reactive oxygen species 30 DPI. Canonical pathway analysis revealed that post-TBI SF upregulated the complement cascade, and nitric oxide and reactive oxygen species production in macrophages. Together, these results indicate that post-injury stress impairs the ability of the brain to adequately respond to and recover from injury.
Keywords: TBI, Neuroinflammation, Sleep