Compounds that interact with Group II metabotropic glutamate receptors (mGluRs) have antipsychotic effects in animal models. These drugs have also shown efficacy in the treatment of schizophrenia in humans. The mechanism of action is believed to arise from a reduction of glutamatergic transmission in limbic and forebrain regions commonly associated with this disorder. Previous anatomical tracer and lesion studies have revealed that neurons of the paraventricular nucleus of the thalamus (PVT) are an important source of the glutamatergic drive to these specific regions. However, the function of Group II mGluRs in the PVT remains to be determined. Whole-cell recordings from PVT neurons reveal that activation of these receptors has two interesting effects; it reduces calcium entry through voltage-gated calcium channels and it causes neurons to hyperpolarize. These two effects may contribute to affect the excitability of PVT neurons, an action that may underlie the effectiveness of Group II mGluR-activating compounds.

Nucleus replacement has recently come into favor as a possible treatment for Degenerative Disc Disease. Replacing degenerative nucleus tissue with a synthetic material that mimics healthy nucleus tissue may restore normal function and biomechanics to the disc and delay or obviate the need for more invasive procedures such as total disc replacement and fusion. This thesis evaluated a novel protein polymer hydrogel composed of silk and elastin as a nucleus replacement material. There are three experimental components; one in vivo and two in vitro portions. In the first experimental portion, a large animal model was developed to evaluate the biocompatibility of the material as well as the effect on surrounding boney and soft tissues. Three discs were evaluated in each animal; sham, discectomy and discectomy treated with hydrogel. Discs were evaluated at 4, 26 and 52 weeks. The hydrogel group showed a quiet cellular response, as well as decreased boney remodeling and fewer degenerative changes when compared to the discectomy group. The second experimental portion evaluated the biomechanics of 9 cadaveric motion segments loaded in axial rotation, lateral bending, flexion/extension (FE) and compression. Specimens were tested sequentially in the intact state, following annulotomy, discectomy and after hydrogel treatment. Range of Motion (ROM) in FE was shown to increase from the intact state (8.50+/-1.44˚) to the discectomy state (9.86+/-1.77˚) and decrease following hydrogel treatment (8.66+/-0.76˚) to be similar to the intact ROM. The third experimental portion investigates the effect of three commonly applied testing conditions on the mechanical properties of spinal segments. 27 motion segments were tested at 18˚C wrapped with Phosphate Buffered Saline (PBS), at 37˚C in a PBS bath, and at 37˚C and 100% humidity. Specimens were tested hourly for 6 hours. The heated conditions were shown to have lower stiffness and increased range of motion when compared 18 ˚C tests. Repeated testing with time increased neutral zone and ROM for all modes of bending. As tests are repeated over time, tissue properties change and may mask the ability of a nucleus replacement to restore biomechanics.

Proefschrift Universiteit van Amsterdam. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Diss. (sammanfattning) Uppsala : Univ., 2001. / Härtill 3 uppsatser.

Thesis (Ph. D.)--West Virginia University, 2009. / Title from document title page. Document formatted into pages; contains x, 192 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.

The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on September 10, 2009). Thesis advisor: Dr. Satish S. Nair, Dr. Jeffery T. Potts. Includes "Presentations and Publications" by author. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1982. / Typescript. Vita. Includes bibliographical references (leaves 234-241).

Thesis (Ph.D.)--East Carolina University, 2009. / Presented to the faculty of the Department of Physiology. Advisor: Jian Ding. Title from PDF t.p. (viewed June 12, 2010). Includes bibliographical references.

Dissertation (Ph.D.)--University of Toledo, 2005. / Typescript. "A dissertation [submitted] as partial fulfillment of the requirements of the Doctor of Philosophy degree in Engineering." Bibliography: leaves 128-141.

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