Browsing by Author "Davis, Brittany C."

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    Propranolol treatment during repetitive mild traumatic brain injuries induces transcriptomic changes in the bone marrow of mice
    (Frontiers Media, 2023-09-12) Smith, Jared A.; Nguyen, Tyler; Davis, Brittany C.; Lahiri, Debomoy K.; Hato, Takashi; Obukhov, Alexander G.; White, Fletcher A.; Anesthesia, School of Medicine
    Introduction: There are 1.5 million new mild traumatic brain injuries (mTBI) annually in the US, with many of the injured experiencing long-term consequences lasting months after the injury. Although the post injury mechanisms are not well understood, current knowledge indicates peripheral immune system activation as a causal link between mTBI and long-term side effects. Through a variety of mechanisms, peripheral innate immune cells are recruited to the CNS after TBI to repair and heal the injured tissue; however, the recruitment and activation of these cells leads to further inflammation. Emerging evidence suggests sympathetic nervous system (SNS) activity plays a substantial role in the recruitment of immune cells post injury. Methods: We sought to identify the peripheral innate immune response after repeated TBIs in addition to repurposing the nonselective beta blocker propranolol as a novel mTBI therapy to limit SNS activity and mTBI pathophysiology in the mouse. Mice underwent repetitive mTBI or sham injury followed by i.p. saline or propranolol. Isolated mRNA derived from femur bone marrow of mice was assayed for changes in gene expression at one day, one week, and four weeks using Nanostring nCounter® stem cell characterization panel. Results: Differential gene expression analysis for bone marrow uncovered significant changes in many genes following drug alone, mTBI alone and drug combined with mTBI. Discussion: Our data displays changes in mRNA at various timepoints, most pronounced in the mTBI propranolol group, suggesting a single dose propranolol injection as a viable future mTBI therapy in the acute setting.
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    Repeated Mild Traumatic Brain Injury in Mice Elicits Long Term Innate Immune Cell Alterations in Blood, Spleen, and Brain
    (Elsevier, 2023) Smith, Jared A.; Nguyen, Tyler; Karnik, Sonali; Davis, Brittany C.; Al-Juboori, Mohammed H.; Kacena, Melissa A.; Obukhov, Alexander G.; White, Fletcher A.; Anesthesia, School of Medicine
    Mild traumatic brain injury is an insidious event whereby the initial injury leads to ongoing secondary neuro- and systemic inflammation through various cellular pathways lasting days to months after injury. Here, we investigated the impact of repeated mild traumatic brain injury (rmTBI) and the resultant systemic immune response in male C57B6 mice using flow cytometric methodology on white blood cells (WBCs) derived from the blood and spleen. Isolated mRNA derived from spleens and brains of rmTBI mice was assayed for changes in gene expression at one day, one week, and one month following the injury paradigm. We observed increases in Ly6C+, Ly6C-, and total monocyte percentages in both blood and spleen at one month after rmTBI. Differential gene expression analysis for the brain and spleen tissues uncovered significant changes in many genes, including csf1r, itgam, cd99, jak1,cd3ε, tnfaip6, and nfil3. Additional analysis revealed alterations in several immune signaling pathways over the course of one month in the brain and spleen of rmTBI mice. Together, these results indicate that rmTBI produces pronounced gene expression changes in the brain and spleen. Furthermore, our data suggest that monocyte populations may reprogram towards the proinflammatory phenotype over extended periods of time after rmTBI.