Temporal Analysis Of Neurogenesis And Microglia Changes After Mild Traumatic Brain Injury In The Adult Male C57bl/6j Mouse

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Degree type
Doctor of Philosophy (PhD)
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Neuroscience
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Neuroscience and Neurobiology
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2022-09-09T20:21:00-07:00
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Clark, Lyles
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Abstract

Traumatic brain injury (TBI) affects millions of people every year. Injuries canhave a range of severities from mild to severe, but all injuries have the potential to result in lasting cognitive deficits. The underlying cause of these deficits is not known, but many of the symptoms people experience is in hippocampal-dependent behavior. One cellular candidate for mediating this hippocampal dysfunction is adult neurogenesis - a process known to be 1) affected by other types of injury, 2) involved in dentate gyrus-dependent cognitive function, and 3) modulated by microglia-mediated inflammation. In this thesis, I investigated how a mild TBI (mTBI) impacts adult neurogenesis and microglia populations in the dentate gyrus. Adult male mice were given lateral fluid percussion injury (LFPI) or Sham surgery and injected with BrdU 3 days post-injury (dpi). Mice were sacrificed 3, 7, or 31 dpi, and brain tissue was stained for Ki67, DCX, BrdU, and Iba1 to examine numbers of proliferating cells, immature neurons, surviving cells, and microglia, respectively. I found that after mild LFPI, there is an increase in Ki67+ cells 3 dpi; DCX+ cells 7 dpi; and BrdU+ cells 31 dpi. There was also an increase in Iba1+ cells 3 dpi. Together, these data suggest a transient increase in proliferation and neurogenesis, leading to increased survival of newborn neurons in injured mice, and this neurogenic increase is accompanied by microglial activation at the short-term time point. These results provide essential spatiotemporal detail to the literature on injury-induced neurogenesis and identify a therapeutically relevant window for immune modulation.

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Amelia J. Eisch
Date of degree
2021-01-01
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