Thesis (Ph. D.)--Michigan State University. Dept. of Neuroscience, 2008. / Title from PDF t.p. (viewed on July 23, 2009) Includes bibliographical references. Also issued in print.

Thesis (M.A.)--Kutztown University of Pennsylvania, 1996. / Source: Masters Abstracts International, Volume: 45-06, page: 3324. Typescript. Untitled abstract follows first title page. Includes bibliographical references (leaves 24-26).

Inaug.-Diss.--Königsberg. / Vita. Bibliography: p. 30.

No description available.

Sequestration of nerve growth factor (NGF) significantly attenuates skeletal pain in both animals and humans. However, relatively little is known about the specific cell types that express NGF or its cognate receptors tropomyosin receptor kinase A (TrkA) and p75 in the intact bone and articular cartilage. In the present study, antibodies raised against NGF, TrkA, and p75 (also known as CD271) were used to explore the expression of these antigens in the non-decalcified young mouse femur. In general, all three antigens displayed a remarkably restricted expression in bone and cartilage with less than 2% of all DAPI+ cells in the femur displaying expression of any one of the three antigens. Robust NGF immunoreactivity was found in mostly CD-31- blood vessel-associated cells, a small subset of CD-31+ endothelial cells, an unidentified group of cells located at the subchondral bone/articular cartilage interface, and a few isolated, single cells in the bone marrow. In contrast, p75 and TrkA were almost exclusively expressed by nerve fibers located nearby NGF+ blood vessels. The only non-neuronal expression of either p75 or TrkA in the femur was the expression of p75 by a subset of cells located in the deep and middle zone of the articular cartilage. Understanding the factors that tightly regulate the basal level of expression in normal bone and how the expression of NGF, TrkA, and p75 change in injury, disease, and aging may provide insights into novel therapies that can reduce skeletal pain and improve skeletal health.

Master of Science / Department of Kinesiology / Steven Copp / Hindlimb skeletal muscle stretch (i.e., selective activation of the muscle mechanoreflex) in decerebrate rats evokes reflex increases in blood pressure and sympathetic nerve activity. Bradykinin has been found to sensitize mechano-gated channels through a bradykinin B2 receptor-dependent mechanism. Moreover, bradykinin B2 receptor expression on sensory neurons is increased following chronic femoral artery ligation in the rat (a model of simulated peripheral artery disease). We tested the hypothesis that, in decerebrate, unanesthetized rats, the injection of bradykinin into the arterial supply of a hindlimb would acutely augment (i.e., sensitize) the increase in blood pressure and renal sympathetic nerve activity (RSNA) during hindlimb muscle stretch to a greater extent in rats with a ligated femoral artery than in rats with freely perfused femoral arteries. The pressor response during static hindlimb muscle stretch was compared before and after the hindlimb arterial injection of 0.5 µg of bradykinin. The injection of bradykinin itself increased blood pressure to a greater extent in “ligated” rats (n=10) than in “freely perfused” rats (n=10). The increase in blood pressure during hindlimb muscle stretch, however, was not different before compared to after bradykinin injection in either freely perfused (control: 14±2, post-bradykinin: 15±2 mmHg, p=0.62) or ligated (control: 15±3, post-bradykinin: 14±2 mmHg, p=0.80) rats. Likewise, the increase in RSNA during stretch was not different before compared to after bradykinin injection in either group of rats. We conclude that bradykinin did not acutely sensitize the pressor response during hindlimb skeletal muscle stretch in either freely perfused or ligated decerebrate rats.

Metabolic homeostasis is orchestrated by the hypothalamus through the neuroendocrine and the autonomic nervous systems. The hypothalamic nuclei respond to the peptide leptin secreted from adipose tissue to suppress feeding and increase energy expenditure by promoting fat metabolism via sympathetic activity. Another important, but perhaps less appreciated function of central leptin signaling is to elevate peripheral insulin sensitivity. Environmental and genetic risk factors that affect hypothalamic leptin signaling can lead to obesity and type 2 diabetes mellitus (T2DM). Here, we discovered that LIM domain only 4, LMO4, is a novel protein participating in central leptin signaling. In a process strikingly similar to T2DM in humans, CaMKIIα-Cre;LMO4flox/flox mice, which have LMO4 knocked out in the postnatal brain including the hypothalamus, develop visceral adiposity, reduced insulin sensitivity, obesity and diabetes when fed with regular chow. Central leptin signaling was significantly lost in key hypothalamic nuclei of mutant mice. Caloric restriction prevents obesity but not insulin resistance in these mice. Taken together, our results suggest that LMO4 function in the brain is required for central leptin signaling to control fat metabolism and peripheral insulin sensitivity.

Transformers are essential components facilitating transmission and distribution of electric power. Energisation of transformers, however, can cause core operating at deep saturation region and thereby induce transient inrush currents of high magnitude and with rich harmonics. This can lead to undesirable effects including potential damage to the transformer itself, relay mal-operation, harmonic resonant overvoltages, and reduced power quality in the system (mainly in the form of voltage dips). This thesis investigates voltage dips caused by energising generator step-up (GSU) transformers and two types of generation connection are studied: one is a combine cycle gas turbine (CCGT) plant connected to a 400 kV transmission grid and the other is a large offshore wind farm connected to a 132 kV distribution grid. To carry out the investigation, detailed network models were developed in alternative transients program/electromagnetic transients program (ATP/EMTP) and validated with the help of field measurements. For the connection of generation in the transmission grid, deterministic assessment was conducted to comparatively analyse voltage dips caused by energising large GSU transformers under different energisation conditions and different network conditions; special attention was paid to the energisation cases involving sympathetic inrush between transformers by addressing its prolonging effects on voltage dips, with sensitivity studies further carried out to identify the key influential parameters. In addition, stochastic assessment was conducted by applying Monte Carlo method, which helps identify the dip frequency pattern and the likelihood of reaching the dip magnitude resulted from the commonly agreed worst case energisation condition; their sensitivities to the variation of circuit breaker closing time span, transformer core residual flux, system condition and the number of transformers being energized together were also investigated. Furthermore, possible cost-effective operational approaches to mitigate the voltage dips were explored and compared. For the connection of large offshore wind farm, voltage dips caused by energising wind turbine transformers under different scenarios were assessed; in particular, sympathetic inrush between wind turbine transformers were studied, and the energisation sequence resulting in less sympathetic inrush was deterministically identified and stochastically validated. The simulation results of deterministic studies indicate that, when carrying out energisation of a large GSU transformer in the transmission grid under the commonly agreed worst case energisation condition, the dip magnitude can reach 9.6% and the duration 2.7 seconds; moreover, when coupled with sympathetic inrush, the duration can be prolonged by 136%, lasting for 6.4 seconds. The sensitivity studies show that transformer core saturation inductance is the key parameter determining dip magnitude and transformer copper losses is the key parameter determining dip duration. Stochastic assessment of voltage dips shows that, out of 1000 stochastic dip events, less than 0.5% of the dips can reach the worst case dip magnitude and about 80% are of magnitudes less than 0.6 pu of the worst case dip magnitude; the dip frequency pattern is found to be insensitive to the circuit breaker closing time variation but can be considerably influenced by the residual flux distribution. In terms of mitigation measures, it was proven that, by adjusting tap changer position, applying static var compensator and even opening coupler circuit breaker in the substation, the degree of voltage dip especially the dip duration can be significantly reduced. Contrasting to those observed in the transmission grid, voltage dips resulted from energising wind turbine transformers in large offshore wind farms are of less concern; dip magnitudes are no more than 1% in the case of energising a stand-alone wind turbine transformer. However, sympathetic inrush between wind turbine transformers within one feeder was found to be significant and the energisation sequence resulting in less sympathetic inrush is to separately energise the wind turbine transformer from the one closest to the offshore platform to the one farthest away from the platform.

To investigate the effects of chronic diabetes on baroreflex control of renal sympathetic nerve activity (RSNA), OVE26 diabetic (transgenic mouse line which develops hyperglycemia within the first 3 weeks after birth) and FVB control mice 5-6 months old were studied. Under anesthesia, RSNA in response to sodium nitroprusside (SNP)- and phenylephrine (PE)-induced mean arterial pressure changes (ΔMAP) were measured. Baroreflex-induced inhibition of RSNA during PE infusion was characterized using the sigmoid logistic function curve. Baroreflex-induced excitation of RSNA during SNP infusion was characterized by the RSNA vs. ΔMAP relationship. Mean arterial pressure (MAP) responses to the left aortic depressor nerve (ADN) stimulation were evaluated. Compared to FVB control, we found in OVE26 mice that (1) RSNA in response to MAP increase during PE infusion was dramatically reduced, as characterized by the maximal gain of the RSNA sigmoid logistic function curve (FVB: -20.0±5.1; OVE26: -7.6±0.8%/mm Hg, P<0.05); (2) RSNA in response to MAP decrease during SNP infusion was also attenuated (P<0.05); (3) MAP responses to ADN stimulation were reduced (P<0.05). We concluded that chronic diabetes impairs baroreflex control of RSNA in OVE26 diabetic mice. The use of the transgenic OVE26 diabetic mouse model may underlie a foundation for the further understanding of diabetes-induced autonomic neuropathy.

Experiments were performed to test the postulate that exercise training (ExT) improves the blunted renal excretory response to acute volume expansion (VE), in part, by normalizing the neural component of the volume reflex typically observed in chronic heart failure (HF). Diuretic and natriuretic responses to acute VE were examined in sedentary and ExT groups of rats with either HF or sham-operated controls. Experiments were performed in anesthetized (Inactin) rats 6 wk after coronary ligation surgery. Histological data indicated that there was a 34.9 ± 3.0% outer and 42.5 ± 3.2% inner infarct of the myocardium in the HF group. Sham rats had no observable damage to the myocardium. In sedentary rats with HF, VE produced a blunted diuresis (46% of sham) and natriuresis (35% of sham) compared with sham-operated control rats. However, acute VE-induced diuresis and natriuresis in ExT rats with HF were comparable to sham rats and significantly higher than sedentary HF rats. Renal denervation abolished the salutary effects of ExT on renal excretory response to acute VE in HF. Since glomerular filtration rates were not significantly different between the groups, renal hemodynamic changes may not account for the blunted renal responses in rats with HF. Additional experiments confirmed that renal sympathetic nerve activity responses to acute VE were blunted in sedentary HF rats; however, ExT normalized the renal sympathoinhibition in HF rats. These results confirm an impairment of neurally mediated excretory responses to acute VE in rats with HF. ExT restored the blunted excretory responses as well as the renal sympathoinhibitory response to acute VE in HF rats. Thus the beneficial effects of ExT on cardiovascular regulation in HF may be partly due to improvement of the neural component of volume reflex. Copyright © 2006 the American Physiological Society.