Traumatic brain injury (TBI) today remains a major health and social problem for both developed and developing countries. It is the leading cause of death and disability under the age of 40, and despite the significance of this public health problem, no effective therapy exists. While a number of factors have been shown to be associated with the development of irreversible tissue injury after TBI, the formation of oedema and opening of the blood brain barrier (BBB) have been shown to be of major significance to outcome. Oedema formation in the brain, when left uncontrolled, results in increased intracranial pressure that may lead to a decrease in brain tissue perfusion, localised hypoxia and ischemia, and ultimately tissue herniation and death. The mechanisms associated with the development of oedema are largely unclear, and accordingly, current therapies are generally ineffective, often resulting in dehydration, hypotension and renal problems. This thesis describes the characterisation of neurogenic inflammation in the development of post-traumatic brain oedema and functional deficits, and particularly the role of substance P (SP) in mediating their development, using rodent models of both focal and diffuse TBI. Results from this thesis demonstrate that increased SP immunoreactivity, particularly at the level of the vasculature, is a ubiquitous feature of TBI implying a potential role in the breakdown of the blood brain barrier (BBB) following TBI. This was confirmed through the use of the NK[subscript 1] receptor antagonists, which attenuated BBB and oedema formation as well as deleterious morphological events such as dark cell change and axonal injury. The NK[subscript 1] receptor antagonists also resulted in an associated improvement in both motor and cognitive deficits, as assessed using a battery of functional outcome tests. Possible mechanisms of action of the NK[subscript 1] receptor antagonist included effects on the BBB, SP release, intracellular free magnesium concentration and aquaporin-4 channels. Neuroprotection could be facilitated with administration of a non-lipid permeable NK[subscript 1] receptor antagonist in the immediate postinjury period, or up to 12 h after TBI with a lipid permeable NK[subscript 1] receptor antagonist, suggesting that this class of drugs have a clinically viable therapeutic window. We conclude that SP has a significant role in the secondary injury process following TBI and may offer a novel target for the development of interventional pharmacological strategies. / Thesis (Ph.D.)--School of Medical Sciences, 2006.

Thesis (MA(Counselling Psychology)--University of Pretoria, 2006. / Includes bibliographical references (leaves 101-110).

Thesis (M. Med. Sc.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 83-93).

Thesis (M.A.)--Miami University, Dept. of Speech Pathology and Audiology, 2002. / Title from first page of PDF document. Document formatted into pages; contains ix, 86 p. Includes bibliographical references (p. 69-75).

Thesis (Ph. D.)--University of Oregon, 2003. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 124-128). Also available for download via the World Wide Web; free to University of Oregon users.

Thesis (Ph. D.)--University of Queensland, 2002. / Includes bibliographical references.

Thesis (M.S.)--Worcester Polytechnic Institute. / Keywords: Ependymin; anti-oxidative enzyme SOD. Includes bibliographical references (p. 65-69).

This thesis examines the various approaches which have been taken to investigate the concrete/abstract word distinction both in normal subjects and in patients who, as a result of brain damage, have an impairment of lexical semantic representations. The nature of the definition task as a tool for assessing the semantic representations of concrete and abstract terms was examined. It was found that definitions for abstract words differed from those of concrete words only in style, not in semantic content. The metalinguistic demands of the definition task therefore make it inappropriate for assessing the semantic representations of concrete and abstract terms in patients with any form of language impairment. The performance of four patients with semantic impairments was examined using a variety of tasks designed to assess concrete and abstract word comprehension. While some of the data can be accommodated within the framework of several theories, no single theory can adequately account for the patterns of performance in all four patients. An alternative model of semantic memory is therefore proposed in which concreteness and frequency interact at the semantic level. Jones' Ease of Predication Hypothesis, which states that the difference between concrete and abstract terms can be explained in terms of disproportionate numbers of underlying semantic features (or "predicates") was also investigated. It was found that the ease of predication variable does not accurately reflect either predicate or feature distributions, and is simply another index of concreteness. As such, the validity of this concept as the basis of theories of semantic representation should be questioned. Models based on the assumption of a "richer" semantic representation for concrete words (e.g.: Plaut & Shallice, 1993) are therefore undermined by these data. The possibility that concrete and abstract concepts can be accessed from their most salient predicates and/or features was examined in a series of semantic priming experiments. It was concluded that it is not possible to prime either concrete or abstract concepts from their constituent parts. Significant facilitation only occurred for items in which the prime and target were synonymous and therefore map onto concepts which share almost identical semantic representations. In summary, it is apparent that no current theory of semantic representation can adequately account for the range of findings with regard to the concrete/abstract word distinction. The most plausible account is some form of distributed connectionist model. However, such models are based on unsubstantiated assumptions about the nature of abstract word representations in the semantic network. Alternative proposals are therefore discussed.

Graduate

published_or_final_version / Paediatrics / Master / Master of Philosophy