An epidemiological shift towards the elderly population has occurred in traumatic brain injury (TBI). Age is believed to be one of the strongest prognostic indicators following TBI. Diffuse axonal injury (DAI), a prevalent feature of TBI, is believed to be the primary cause for much of the morbidity and mortality associated with TBI. The pathobiology associated with DAI is believed to occur in response to the primary injury in a progressive, secondary fashion. Though the injury mechanisms behind DAI have been shown to occur at numerous sites along the axon, recent work suggests that the axon initial segment (AIS) may show specific vulnerability to DAI and be the primary site of axonal pathobiogenesis. Despite its established predilection for injury, the mechanisms responsible for the pathobiology remain largely unclear – particularly with regard to the age. The current study aims to shed light on the mechanisms responsible for injury by investigating structural alterations to the AIS following DAI in young and old mice. To address this question we have used a central fluid percussion injury (cFPI) model to induce mild DAI on 22-month old aged mice and 3-month old young mice at 3-hours and 24-hours survival time. Double-labeling fluorescent immunohistochemistry was used to demonstrate colocalization of ankG, an AIS domain marker, and APP, a marker used to establish traumatic axonal injury (TAI). Qualitative-quantitative observations based on confocal microscopy demonstrated an increase in APP accumulation associated with AIS over time, post-injury. Initial segments displaying APP association consistently showed a significant overall shortening in young and aged groups at both survival times. No significant difference in AIS length was detected between AIS populations of young and aged mice. Qualitative findings, however, suggest that AIS degradation could be more profound with age, which could have implications on neuronal outcome.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-4420 |
| Date | 01 May 2014 |
| Creators | Behl, William |
| 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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