Defense Date


Document Type


Degree Name

Master of Science


Anatomy & Neurobiology

First Advisor

Dong Sun


Traumatic brain injury (TBI) affects 3 out of every 1000 Americans each year, and is the leading cause of morbidity and mortality after trauma, accounting for as many as 56,000 deaths per year (Dutton and McCunn, 2003). The Centers for Disease and Control and Prevention found that TBI most commonly occurs in adolescents and young adults aged from 15 to 24 years and in the elderly (75 years and older). Following injury, the secondary injury begins almost immediately after the primary injury and is the result of a number of cascades where once activated, exacerbate the already altered homeostasis of the injured brain. Brain trauma leads to complex secondary injury responses that trigger many cellular and molecular pathways, especially inflammation. The cerebral inflammation that occurs after TBI has been described through the processes of glial activation followed by leukocyte recruitment, and upreglation and secretion of cytokines and chemokines. With aging there is a decrease in the production of anti-inflammatory cytokines along with increasing amounts of pro-inflammatory cytokines by peripheral blood monoculear cells, microglia, and astrocytes. Studies have shown that inflammation has a strong negative effect on neurogenesis in the adult brain due to the impact of the pro-inflammatory cytokines that are released following the acute injury or disease. In this study, we first examined the differences in glial cells responses in young adult brain and aged brain following a moderate lateral fluid percussion injury and the correlation of glial cell activation with hippocampal neurogenesis. We then examined the effect of anti-inflammation treatment on glial cell response in the young and aged brain. The levels of astrocytic and microglial responses in the DG of the hippocampus following injury at 3, 7 or 28 days post-injury were measured using densitometry image analysis on GFAP or Iba1 immunofluorescent labeled brain tissue sections. We found that injury increased both astrocyte and microglial activation and proliferation in both young and aged brain. The young injured animals exhibited greater levels of GFAP while the aged injured animals exhibited greater levels of Iba1 expression at all three time points. We also found that short time anti-inflammatory treatment with minocycline decreased levels of Iba1 expression while increased levels of GFAP expression in both young and aged brain following injury. Our data suggests that there are differences in glial response in the injured young and aged brain that may contribute to the differences in the regenerative and recovery potential in the two age groups following injury.


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Date of Submission

July 2011