Traumatic brain injury is a leading cause of death and disability in the United States. The injury is often composed of two processes: the primary injury, which can involve irreversible loss of tissue, and the secondary injury, which involves a cascade of reactive processes such as excitotoxicity that occur in the hours and days after the initial insult. Excitotoxic stimulation of neuronal circuits can lead to cellular dysfunction and modulation of neuronal sensitivity. One mechanism of dysfunction involves the calcium-regulated phosphatase, calcineurin. Calcineurin has been shown to be involved in the modulation of the neuronal post-synaptic structures known as dendritic spines. One means by which CaN regulates spine structure is through the dephosphorylation of the down-stream effector proteins such as, cofilin. This study tracks the changes in CaN activity levels as well as the phosphorylation state of cofilin in the cortex and hippocampus in each hemisphere of the laterally injured brain. We report that the lateral brain injury causes an increase in CaN activity in the hippocampus with a corresponding dephosphorylation of cofilin. Trauma-induced changes in CaN follow a slightly different time course in cortical tissue, as there is a biphasic modulation of cofilin that begins with an increased phosphorylation which is followed by an extended dephosphorylation. This dephosphorylation is partially prevented by a single post-injury injection of FK506, a calcineurin inhibitor. Since dephosphorylation of cofilin is a rate-limiting step in dendritic spine collapse, the results of this study demonstrate a potential cellular mechanism through which traumatic brain injury results in altered neuronal function.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-2891 |
| Date | 29 July 2009 |
| Creators | Low, Brian |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © The Author |
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