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The development, maintenance, and survival of neurons depend on the function of neurotrophins such as nerve growth factor (NGF). One population of neurons that rely heavily on NGF for axonal growth and survival is the postganglionic sympathetic neurons. Trauma or disease resulting in injury to the peripheral nervous system causes an increase in the levels of this neurotrophin. This augmentation promotes the collateral sprouting of postganglionic sympathetic axons into those tissues having elevated levels of NGF. Often, NGF-induced sympathetic sprouting occurs in tissues that are normally innervated by these fibers however, high levels of NGF can also promote sprouting of axons into tissues that are normally devoid of sympathetic fibers, such as the sensory ganglia. When postganglionic sympathetic axons grow into the environment of sensory ganglia, they can converge and wrap around a subset of somata (i.e., cell bodies) belonging to primary sensory neurons. This phenomenon, referred to as sympathosensory plexuses is observed in adult mice and rats following peripheral nerve injury, and is also seen in adult transgenic mice that ectopically over express NGF. The overall aim for this project is to examine the morphological and neurochemical features, as well as the overall consequence of sympathosensory plexuses in nerve-injured adult mice and in adult transgenic mice that over express NGF. We hope that this novel information will add to our understanding of the underlying mechanisms associated with the formation of sympathosensory plexuses that occur following injury. / Thesis (Ph.D, Neuroscience Studies) -- Queen's University, 2013-07-23 18:51:47.902

The development, maintenance, and survival of neurons depend on the function of neurotrophins such as nerve growth factor (NGF). One population of neurons that rely heavily on NGF for axonal growth and survival is the postganglionic sympathetic neurons. Trauma or disease resulting in injury to the peripheral nervous system causes an increase in the levels of this neurotrophin. This augmentation promotes the collateral sprouting of postganglionic sympathetic axons into those tissues having elevated levels of NGF. Often, NGF-induced sympathetic sprouting occurs in tissues that are normally innervated by these fibers however, high levels of NGF can also promote sprouting of axons into tissues that are normally devoid of sympathetic fibers, such as the sensory ganglia. When postganglionic sympathetic axons grow into the environment of sensory ganglia, they can converge and wrap around a subset of somata (i.e., cell bodies) belonging to primary sensory neurons. This phenomenon, referred to as sympathosensory plexuses is observed in adult mice and rats following peripheral nerve injury, and is also seen in adult transgenic mice that ectopically over express NGF. The overall aim for this project is to examine the morphological and neurochemical features, as well as the overall consequence of sympathosensory plexuses in nerve-injured adult mice and in adult transgenic mice that over express NGF. We hope that this novel information will add to our understanding of the underlying mechanisms associated with the formation of sympathosensory plexuses that occur following injury. / Thesis (Ph.D, Neuroscience Studies) -- Queen's University, 2013-07-23 18:51:47.902

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Many promising Phase II trials have been carried out in head injury however to date there has been no successful translation of the positive results from these explanatory trials into improved patient outcomes in Phase III trials. Many reasons have been hypothesised for this failure. Outcomes in head injury trials are usually measured using the five point Glasgow Outcome Scale. Traditionally the ordinality of this scale is disregarded and it is dichotomised into two groups, favourable and unfavourable outcome. This thesis explores whether suboptimal statistical analysis techniques, including the dichotomisation of outcomes could have contributed to the reasons why Phase III trials have been unsuccessful. Based on eleven completed head injury studies, simulation modelling is used to compare outcome as assessed by the conventional dichotomy with both modelling that takes into account the ordered nature of the outcome (proportional odds modelling) and modelling which individualises a patient’s risk of a good or poor outcome ( the ‘sliding dichotomy’). The results of this modelling show that both analyses which use the full outcome scale and those which individualise risk show great efficiency gains (as measured by reduction in required sample sizes) over the conventional analysis of the binary outcome. These results are consistent both when the simulated treatment effects followed a proportional odds model and when they did not. Consistent results were also observed when targeting or restricting improvement to groups of subjects based on clinical characteristics or prognosis. Although proportional odds modelling shows consistently greater sample size reductions the choice of whether to use proportional odds modelling or the sliding dichotomy depends on the question of interest.

The mild head inured population accounts for 80 per cent of all head injuries and whilst research has identified no neurological abnormalities, this population still report to experience functional impairment. The current study set out to explore the biopsychosocial factors that could exacerbate the symptoms of mild head injury. In this respect, the study looks at the relationship between post concussion symptoms, social ability, psychological morbidity and coping style using the Rivermead Post-concussion symptoms Questionnaire, the Multidimensional Scale of Perceived Social Support, the Hospital Anxiety and Depression Scale and the COPE questionnaire. Questionnaires were sent out to 138 individuals at 6 months post injury to identify relationships between coping style, post concussion symptoms, social support and psychological morbidity. 32 respondents completed and returned the questionnaires. Post concussion symptoms were positively related to social support, depression and anxiety. Active coping was found to be negatively related to post concussion symptoms whereas emotion focused and avoidant coping were positively associated with post concussion symptoms. The results of the study suggest that in order to improve symptoms of mild head injury practitioners must address symptoms of depression and anxiety, in addition to promoting a more productive coping style.

Background: Increasing evidence indicates that oxidative injury exists in schizophrenia. Although it may not be the main cause, oxidative damage has been suggested to contribute to the pathophysiology and may account for deteriorating course and poor outcome in schizophrenia. There is increasing interest in the neuroprotective efficacy of antioxidants in modulating such processes with at least one polyphenolic being tested as a prophylactic in Alzheimer's disease. Beneficial effects of adjunctive ω-3 (n-3 series) polyunsaturated fatty acids with combined intakes of vitamin C and E on both the positive and negative symptoms of schizophrenia have been reported. Robust in vitro systems are desirable, enabling a mechanistic investigation of the molecular mechanisms underpinning such effects and identification of further potentially efficacious nutraceuticals. Materials and Method: Comparative studies employing a lymphoblastoid cell line of schizophrenic origin, a neuroblastoma IMR-32 cell line and the lymphoma U937 cell line was undertaken. The cytoprotective effects of phenolic antioxidants and essential fatty acids in affording protection to cellular DNA, protein and lipids from an oxidative challenge were assessed in the three cell lines. In addition, two human studies were undertaken. The first study utilised the non-invasive technique of breath hydrocarbon analysis and the lipid peroxidation products in a population of schizophrenic patients were compared to a population of apparently healthy aged-matched control subjects, while the second study investigated possible differences in biomarkers of DNA, lipid and protein oxidation in schizophrenic and control subjects. Plasma vitamin C levels were also compared in both groups. Results and Conclusion: Cell Culture Studies: Pre-treatment of peripheral and neuronal cells with antioxidant or ω-3 fatty acids followed by an oxidative challenge significantly reduced the levels of DNA damage. Treatment with H₂O₂ alone and following pre-treatment with EPA or DHA had no effect on the levels of protein carbonyls in U937 cells, however, DHA supplementation did appear to reduce endogenous and H2O2-induced protein carbonylation. Marked differences in the uptake of fatty acids by the cell types were found and the IMR-32 cell line was most susceptible to the oxidant challenge. Hydroxytyrosol gave significant cytoprotection in all three cell lines and this possible neuroprotective efficacy warrants further investigation, both in vitro and in vivo. Treatment of the three cell lines with a high concentration of H2O2 for 30min or 4 hours did not induce a significant increase in MDA. U937 cells were supplemented for 24 hours with fatty acids followed by a 4 hour oxidative stress. Both EPA and DHA treatment appeared to reduce LOOH levels in the U937 cells but not significantly. Cytoplasmic PLA2 activity in the three human cell lines was examined and the basal level of cPLA2 activity was found to be comparable in the lymphoblastoid and IMR-32 cells but significantly lower than that measured in the U937 cells. Supplementation of the U937 cell line with EPA caused a significant decrease (p<0.05) in cPLA2 activity relative to the vehicle treated control but neither EPA nor DHA supplementation appeared to have any significant effect on either total PLA2 or cPLA2 activity in IMR-32 or lymphoblastoid cell lines. Abstract v Human Studies: No significant difference was found between the levels of ethane and pentane in the breath from the schizophrenic patients and control samples. In addition, no significant difference in the levels of plasma MDA between the two groups was detected. Ethane levels and MDA levels were higher in the male schizophrenic samples than in the female schizophrenic samples but the results were not statistically significant. The pentane levels were higher in the female schizophrenic samples when compared to the male schizophrenia samples but again, these were not significantly greater. Finally, results of study 2 revealed that cellular DNA damage and plasma protein carbonyl levels were increased in the schizophrenic group compared to control subjects but not significantly. However, DNA damage in lymphocytes from the male schizophrenic group was significantly higher than the female group. Biomarkers of lipid peroxidation and plasma vitamin C levels also revealed no significant difference between the two groups under investigation, although a significant elevation in plasma vitamin C was observed in the female control group when compared to the male groups. Treatment of cells with EPA, DHA and hydroxytyrosol to reduce levels of oxidative damage warrants further investigation. Ultimately, it is important to investigate a range of biomarkers to determine whether the measurement of oxidative damage to lipids, proteins and DNA has clinical significance. This will enable better understanding of the disease of interest and allow these biomarkers to become potentially useful clinical tools.

Burn injury is considered a distressing and traumatic injury often leading to psychological disturbances such as depression, anxiety, posttraumatic stress disorder, and body image dissatisfaction. At the same time, the literature also suggests that people demonstrate surprising resiliency when dealing with their burn injury. How women who have experienced burns understand their injury and what it means to them to be a resilient, is largely ignored in the burn literature. This study addressed these shortcomings by exploring narratives from thirteen women, recruited from a regional burn center, who experienced a burn injury of up to 30% of their total body surface area (TBSA). Two interviews were conducted with each participant. The first interview employed a photo elicitation technique whereby photographs taken by the participant of her life with a burn injury were used to elicit stories in the context of the interview. The second interview was conducted using a semi-structured interview schedule developed to investigate experiences and understandings of distress and resiliency. The interview transcripts were analyzed using narrative analysis in order to explore how women constructed stories about distress and resiliency following burn injury. The findings show three main struggles the women faced in negotiating resiliency which all pertained to relational tension, that is, relationships with others. The three struggles of resiliency identified in the study are 1) feeling as though the body was public, 2) deciding how to share their burn experience with others, and 3) accepting support from others while maintaining independence. The findings of this study are discussed in the context of a relational theory named self-silencing which delineates how women behave socially to maintain relationships by inhibiting self-expression. Findings are also discussed relative to current research in the areas of burn injury and resiliency. / February 2017