Defense Date

2010

Document Type

Thesis

Degree Name

Master of Science

Department

Anatomy & Neurobiology

First Advisor

Dong Sun

Abstract

The mature mammalian brain continually generates new neurons in the subventricular zone and hippocampus throughout life. Adult neurogenesis in the hippocampus is associated with hippocampal-dependent learning and memory function. During aging, this endogenous neurogenic potential is reduced which is accompanied by decreased cognitive function seen in the aging population. We have previously found that the injured adult brain shows heightened levels of endogenous neurogenesis and this response is associated with innate cognitive recovery. We have also found that basic fibroblast growth factor (bFGF), a potent neurotrophic polypeptide, can enhance injury-induced hippocampal neurogenesis and improve cognitive recovery following TBI. In this study, we administered bFGF into the lateral ventricle of aged rats following TBI and assessed the effect of bFGF treatment on hippocampal neurogenesis and cognitive recovery in aged animals. Specifically, male Fisher-344 rats at the age of 20 months received intraventricular infusion of bFGF for 7 days through osmotic mini-pump immediately following a moderate lateral fluid percussion injury. To label cell proliferation, animals received daily single i.p. BrdU injections for 6 days beginning 48 hr after injury. One group of animals was perfused at 1 wk after injury to assess cell proliferation. Another group of animals was first assessed for cognitive performance using the Morris water maze (MWM) at 21-25 days post-injury, then sacrificed at 4 weeks after injury to examine differentiation of newly generated cells. Brain sections were sliced and immunostained for BrdU, early neuronal marker doublecortin (DCX) and other cell type specific markers. Results showed that at 1 week post-injury, injured-aged animals infused with either vehicle or bFGF had a significantly higher number of cell proliferation in the dentate gyrus compared to sham animals. However, cell proliferation in the bFGF-infused animals was not significantly higher than vehicle-treated animals. Nevertheless, the number of DCX-labeled early stage neurons was significantly higher in the injured bFGF-treated animals than in vehicle-treated sham and injured animals. In MWM tests, unlike what we have observed in bFGF-treated younger animals, injured aged rats treated with bFGF did not show improved cognitive function. Furthermore, at 4 weeks post-injury, higher numbers of BrdU-labeled proliferative cells persisted in both injured groups, many of these cells labeled with glial and inflammatory cell markers. Collectively, the current data suggests that bFGF can enhance neurogenesis in the injured-aged hippocampus; however, this effect is not sufficient to improve functional recovery of aged rats following TBI due to the profound injury-induced inflammatory response.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

August 2010

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