Date of Award
Master of Arts
Traumatic brain injury (TBI) is one of the leading causes of death and disability in children. The prefrontal cortex (PFC) is most susceptible to injury which leads to deficits in executive function, sociability, and cognitive flexibility. The oxytocin (OT) system plays a significant role in the modulation of species-typical social behaviors, such as social recognition and memory. Intranasal OT (IN-OT) has been shown to be neuroprotective against neuronal insults and social deficits through various mechanisms. Due to this and OT’s role in the modulation of social behaviors, it is possible that IN-OT could improve the social deficits caused by a PFC injury. The primary goal of this study was to determine the effects of a TBI on the development of the OT system. The secondary goal was to address the efficacy of IN-OT as a treatment for the social deficits observed following a TBI. For these studies, animals received a single cortical contusion injury bilaterally damaging the medial pre-frontal cortex. Immediately following injury (1-2 minutes), animals were given a single dose of IN-OT (20 μg, 1 μg/1 μl Ringer’s solution), placebo, or no treatment and sacrificed at days 1, 14, and 30 post-injury. Animals were assessed using behavioral and histological measures. It was predicted that animals that received IN-OT would demonstrate fewer social deficits on the behavioral measures and a smaller lesion size. Additionally, it was expected that a TBI would increase inflammation levels and decrease the levels of OT and OT receptors compared to sham animals. The results indicate that OT treatment did not significantly improve histopathological outcomes. However, the vehicle that was utilized impaired outcomes. Additionally, there was minimal changes to the OT system at the injury site, in the anterior olfactory nucleus, and in the caudate putamen due to injury. But vehicle treatment altered the expression levels of the OT peptide and receptors. Behaviorally, OT treatment improved performance in the Morris water maze in TBI animals compared to vehicle-treated and untreated TBI animals, but not other behaviors. However, vehicle-treated, and OT-treated animals were more likely to be aggressive than expected and untreated sham animals were less likely to be aggressive than expected. Taken together, it was observed that administration of a hypotonic saline solution following TBI significantly increases pathophysiology after TBI, and these effects translate into increased aggression levels. Although, learning and memory remained unaffected by the vehicle. Thus, further studies are needed to examine the effects of OT on TBI for behavioral and pathophysiological improvements.
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