Poster abstracts

Poster number 70 submitted by Samuel Houle

Stress Exposure Following Traumatic Brain Injury Dampens Acute Inflammatory Gene Transcription

Sam Houle (Neuroscience Graduate Program), Shannon Dobres (Department of Neuroscience), Olga N. Kokiko-Cochran (Department of Neuroscience)

Abstract:
Following TBI, microglial-driven neuroinflammation is essential for appropriately responding to cellular damage and debris. This microglial activity can be exacerbated by exposure to stress and heightened, chronic, neuroinflammation can impair recovery. Environmental sleep fragmentation (SF) is known to exact a stress response and is highly reported in TBI survivors. Here, we hypothesize that SF stress will exaggerate the acute expression of genes responsible for regulating the inflammatory response to TBI and stress. Following lateral fluid percussion injury or sham surgeries mice were either exposed to four hours of SF daily (6am – 10am) to induce a stress response or were left undisturbed. 3 days post-injury (DPI), injured cortices were collected, and RNA was extracted for analysis via Nanostring nCounter glial profiling panels.
Contrary to what we hypothesized, acute post-TBI SF did not result in exacerbated neuroinflammatory gene expression in the injured cortex. In fact, post-TBI SF decreased many genes that are increased as part of the response to both SF and TBI. Therefore, these data suggest TBI and SF can synergize to impair the acute neuroinflammatory response to injury or stress. Genes with increased expression due to TBI that were suppressed by SF are involved in a variety of inflammatory mechanisms such as microglial chemotaxis and phagocytosis, interferon signaling, and the complement cascade. Pathway enrichment analysis reveals that several pathways are increased by TBI and suppressed by post-TBI SF. These pathways include Macrophage activation signaling, Neuroinflammation signaling, Interferon signaling, and the Complement cascade. Altogether, these data show that stress following TBI dampens the expression of genes and inhibits pathways that are typically activated as part of the TBI response. Future studies will be needed to determine the downstream effects of such inhibition, including whether stress impairs the ability of microglia to engage in debris clearance during the acute response to TBI.

Keywords: TBI, Stress, Neuroinflammation