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Payette, Daniel. "Neuronal dysfunction and degeneration in Alzheimer's disease and brain trauma." Oklahoma City : [s.n.], 2008.
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Sahar, Muhammad Sana Ullah. "Development of a nerve stretching device to facilitate peripheral nerve repair." Thesis, Griffith University, 2020. http://hdl.handle.net/10072/396190.
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Advancements in biomedical engineering have improved medical technology by redefining surgical standards and developing medical devices to carry out complex repairs at a tissue level; however, effective surgical management for segmental defects (nerve gaps) in peripheral nerves clinically, remains a challenging endeavour. Traditional nerve gap management surgical techniques cannot bridge longer defects effectively, while contemporary techniques using a variety of nerve conduits to facilitate nerve regeneration have consistently failed to reproduce reliable results. One of the root causes of these inconsistent results lies in the nerve’s inability to regrow expediently after injury and hence the ‘slow rate of nerve regeneration’ is one of the main factors in unsuccessful nerve gap management.
This situation demands a satisfactory approach to address the aforementioned problem. In the past, researchers have attempted to increase the growth rate of axons by stretching them mechanically outside the body and have proved that axons can respond to mechanical stimulus where their growth rate depends on the type and degree of mechanical strain. These promising findings, however, are difficult to translate to in-vivo applications, because stretching a nerve in-vivo is not analogous to pulling it ex-vivo, and need appropriate resources to provide such translation, which limits the effectiveness of this technique clinically.
This thesis aimed to address the slow rate of peripheral nerve regeneration post-trauma and presents a solution to expedite nerve growth rate. During this research work, a novel method of stretching a whole nerve in a conduit using a controlled negative pressure (vacuum) was developed. The rationale behind proposing negative pressure as a stretching agent was that, it would promote angiogenesis by drawing more blood, from the microvessels coursing in the epineurium, to nourish growing sprouts of axons.
Appropriate bioengineering tools were fabricated to carry out the in-vivo nerve stretch which included building a vacuum generating device (nerve stretcher) and fabricating a synthetic T-shaped conduit to hold and stretch the transected nerve stumps using the generated vacuum.
Firstly, safe limits of applying vacuum to nerve stumps were ascertained during a pilot study on cadaveric rats (Chapter 3), where, a surgical procedure was also developed to implant T-shaped conduits, and ability of the nerve stretcher in generating a stable vacuum was tested at various vacuum levels. Secondly, the developed technique for in-vivo nerve stretching was then preliminarily tested on live rats (Chapter 4) and based on the experimental observations, the strategy for implanting the nerve conduit for a longer post-surgical period was revised. Finally, the modified approach was tested on 30 rats to study the in-vivo mechanotransduction effect of the injured peripheral nerves in response to vacuum. These in-vivo experiments involved transecting sciatic nerves of rats, placing the respective nerve ends into T-shaped conduits and then applying vacuum. Nerve stumps were tractioned at various negative pressure levels for seven days. After seven days, nerves were excised, and each nerve stump was sectioned and stained using histological and immuno-histochemical staining methods, slides were analysed qualitatively and quantitatively to measure the extent of nerve growth in response to negative pressure.
The results of in-vivo nerve stretch-growth showed that the three treatment groups displayed better outcomes in terms of absolute growth of nerve stumps, higher rates of angiogenesis, and a greater quantity of nissl substance in cytoplasm over the control group. First, absolute growth of the nerve stumps in all three treatment groups provided direct quantitative evidence of enhanced growth in sciatic nerves in response to mechanical stress acting in the form of negative pressure. Second, a higher quantity of blood vessels in the treatment group confirmed the efficacy of negative pressure in promoting angiogenesis. Third, the presence of nissl substance in greater amounts in the treatment groups signalled that the effect of nerve injury has started to resolve (on injury to a nerve, neurons deploy macrophages to clear up the cell debris to make room for Schwann cells that perform myelination of axons). During result analysis, each treatment group was compared against each other and the control group, and it was found that a negative pressure of 20 mmHg displayed the most superior outcomes, favouring both nerve lengthening and angiogenesis. The results of this research work successfully justified the hypothesis of this thesis (Chapter 2), that an in-vivo application of negative pressure acting directly to transected rat sciatic nerves will enhance nerve regrowth by promoting angiogenesis and nerve lengthening.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Eng & Built Env
Science, Environment, Engineering and Technology
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Bruno, Martin. "Nerve Growth Factor, Aging and Alzheimer's disease." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=18741.
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Since the cholinergic hypothesis of geriatric memory dysfunction was proposed by Bartus and colleagues in 1982, studies conducted in animals and humans so far have failed to obtain evidence for the involvement of NGF in normal Aging and/or in the pathophysiology of Alzheimer's disease (AD). It has been hypothesized that age-related degeneration of basal forebrain cholinergic neurons (BFCN) may be caused by the altered endogenous NGF maturation either by reduced responsiveness to NGF, by reduced NGF transport or by the failure in coupling to second messengers. NGF administered in the CNS of AD patients led to undesirable side effects, most likely mediated by p75 neurotropin receptor (p75NTR) rather than through its specific TrkA receptor. Thus, we decided to treat behaviorally characterize age-impaired (AI) rats with small proteolytic- resistant peptide mimetic of the TrkA receptor, named D3. This selective partial agonist of the TrkA receptor reversed the atrophy of the BFCN, ameliorating the cognitive decline observed in AI rats. The realization that the precursor of NGF (proNGF) might play a biological role in the CNS, raised questions regarding the regulatory mechanisms leading to its release, as well as the control of the proNGF to NGF ratio and, ultimately, the degradation of the NGF molecule. To answer these questions, we performed in vitro and in vivo studies aimed at elucidating the preferential NGF form released from the cerebral cortex, and the biochemical pathway leading to NGF maturation and degradation. These studies have revealed that proNGF is the main releasable form of the neurotrophin and that the maturation and degradation of NGF largely occurs in the extracellular space with the involvement of a complex protease cascade. The newly described mechanism for NGF conversion and degradation was found compromised in Alzheimer's disease. In brief, we found a failure in the conversion of proNGF to NGF, which was exacerbated by an increased NGF degradDepuis que l'hypothèse cholinergique sur la dysfonction de la mémoire chez la personne âgée a été proposée par Bartus et collègues en 1982, toutes les études cherchant à mettre en évidence l'implication du NGF chez les sujets normaux âgés et ceux atteints de la Maladie D'Alzheimer (MDA) ont échoué à la fois chez l'homme et chez l'animal. L'hypothèse émise fût que la dégénérescence des Neurones Cholinergiques du Cerveau Antérieur Basal (NCCAB) liée à l'âge pourrait être due soit à une maturation altérée du NGF endogène soit à une réponse réduite au NGF, par un transport déficient, ou bien encore à un défaut de couplage aux seconds messagers. Le NGF administré dans le SNC de patients atteints de MDA conduit à des effets secondaires indésirables principalement causés par p75 ou le récepteur neurotropique (p75NTR) plutôt qu'à travers son récepteur spécifique, TrkA. Par conséquent, nous avons décidé de traiter des rats caractérisés comme âgé-déficients (AD) avec de petits peptides résistant à la protéolyse appelés D3 et mimant l'action du NGF sur les récepteurs TrkA. Cet agoniste partiel du récepteur TrkA remédie à l'atrophie des neurones cholinergiques du CAB, réduisant le déclin cognitif observé chez les rats AD. Le fait que le précurseur du NGF (proNGF) pourrait jouer un rôle biologique, soulève des questions quant aux mécanismes régulant sa libération, ainsi que ceux contrôlant le ratio proNGF/NGF et enfin ceux contrôlant la dégradation finale du NGF. Pour répondre à ces questions, nous avons réalisé des expériences in vitro et in vivo afin de savoir sous quelle forme préférentielle le NGF était libéré dans le cortex cérébral, et afin de connaitre les chemins biochimiques menant à la maturation et la dégradation du NGF. Ces études ont révélé que le proNGF représentait la forme principale de libération de cette neurotrophine et que la maturation et la dégradation du NGF$
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Sander, Anthony. "Penetrating Abdominal Trauma: Spectrum of disease in a Level 1 Trauma Centre." Master's thesis, Faculty of Health Sciences, 2019. http://hdl.handle.net/11427/31208.
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Background: Penetrating abdominal trauma (PAT) in South Africa represents a significant burden of disease. The current global trend has seen management shift towards selective conservatism. The purpose of this study is to describe the presentation, management and outcomes of PAT in a level I trauma unit, which routinely practices selective non-operative management (SNOM). Methods: This was a retrospective descriptive audit of prospectively collected data. The Setting was Groote Schuur Hospital Trauma Centre, Cape Town, South Africa over 24 months (1 May 2015 to 30 April 2017). All patients presenting to the centre with PAT during the study period were included. The data captured and analysed included: basic demographics; admission vital signs; blood investigations; number of traumatic insults; penetrating wound positions; radiological investigations and interventions; indication for laparotomy; operative or nonoperative management; laparotomy findings: negative, therapeutic or non-therapeutic; abdominal visceral injuries and associated injuries. The Revised Trauma Score (RTS); Injury Severity Score (ISS); Penetrating Abdominal Trauma Index (PATI); and Kampala Trauma Score (KTS) were then calculated. The descriptive end points included the following: Length of hospital stay (LOS); ICU admission time; relaparotomy; readmission; mortality; and in-hospital complications. Results: During the study period, 805 patients with penetrating abdominal trauma were managed. There were 502 (62.4%) and 303 (37.6%) patients with gunshot and stab wounds, respectively. The majority were young men (762 – 94.7%) with a mean age of 28.3 (95%CI: 27.7-28.9) years. The median trauma scores were as follows: RTS – 7.84 (IQR: 7.00-7.84); ISS: 13 (IQR: 9-22), PATI: 6 (IQR: 1-14); and KTS: 14 (IQR: 14-15). Abdominal penetration was thoracoabdominal in 332 (41.2%), abdominal in 694 (86.5%), and pelvic in 192 (23.9%) patients. Immediate laparotomy was performed in 446 (55.4%) patients for: haemodynamic instability – 42 (5.2%); peritonism – 296 (36.8%); evisceration - 27 (3.4%); unreliable clinical evaluation – 24 (3.0%); and positive radiological findings – 57 (7.1%). There were 406 (50.4%) therapeutic laparotomies; 18 (2.3%) negative laparotomies; and 22 (2.7%) nontherapeutic laparotomies in the immediately operated group. Initial SNOM was performed in 359 (44.5%) patients, of which 208 (68.7%) sustained stab wounds and 151 (30.1%) gunshot wounds. Thirty-five (4.3%) patients failed SNOM and underwent delayed laparotomy. Should a policy of mandatory laparotomy have been implemented in this series, 206 (68.0%) SW and 163 (32.5%) GSW patients would have underwent unnecessary exploration. Overall non-fatal complications were 179 (22.2%) which were then further classified according to the Clavien-Dindo grading system. The median hospital stay was 4.5 (IQR: 3-7) and 7 (IQR: 5-12) days for SW and GSW, respectively. Overall 114 (14.2%) patients required admission to critical care unit for a median stay of 3 (IQR: 2-5) days. Total mortality was 7.2% (n=58). Conclusion: Clinical evaluation (haemodynamic instability, peritonism and evisceration) was remarkably accurate in determining the need for early laparotomy. The unnecessary laparotomy rate of this group was 5.0% (negative: 2.3% and nontherapeutic: 2.7%) overall. Selective nonoperative management was performed in 44.5% of patients with a successful SNOM rate of 90.3%. The overall mortality was 7.2 %.
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Yang, In Hong. "The study of the neurophysiology of high strain rate nerve injury." Texas A&M University, 2003. http://hdl.handle.net/1969.1/416.
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The study of the mechanism of traumatic brain injury (TBI) processes at the cellular level is vital to obtain characterization of nerve cell damage after mechanical deformation. This understanding is needed to find feasible therapeutic targets for mechanically damaged neurons. To study the cellular level of TBI damage, development of a new in vitro cellular model of TBI might be done to simulate in vivo cellular TBI.
In this research, two studies were performed: (1) the design and construction of an in vitro cell stretching device to mechanically injure cells and (2) the characterization of the molecular and cellular level of the TBI mechanism. The cell stretching device design allows for the precise control of cell strain and duration of stretching cells such that TBI can be mimicked. Analysis of the cellular and molecular level mechanisms of TBI in the proposed in vitro model might help in the design of therapeutic strategies for the treatment of TBI. Our proposed mechanism of injury due to TBI is as follows: after the cell is stretched, a cellular signaling molecule is released to activate the cellular signaling pathway. The activated cell signal may activate kinases which phosphorylate proteins and initiate new protein synthesis. Newly phosphorylated and synthesized proteins may activate the apoptotic process.
Using a variety of pharmacological agents, one could block steps in the hypothesized mechanism and examine the effect of those agents on downstream cellular processes and cell apoptosis. For example, the inhibitions of calcium transport, protein synthesis, and caspases were performed to examine the initial activation of the signaling pathway and the role of both in the apoptosis process. Proteomics of TBI may help the understanding of the mechanism of TBI related protein expression. This work will contribute to the discovery of new therapeutic targets and better treatments for TBI.
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Ogilvie, Alan L. "Vagal function in oesophageal disease." Thesis, University of Cambridge, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262775.
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Fidler, Larry E. "Gas bubble trauma in fish." Thesis, University of British Columbia, 1988. http://hdl.handle.net/2429/28659.
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Fish exposed to gas supersaturated water often experience a form of stress known as Gas Bubble Trauma (GBT). GBT is an acute condition involving various forms of bubble growth both internal and external to the animal. Theoretical models are developed which establish thresholds for bubble growth. These models apply to:
1. ) Bubble growth in the vascular systems of fish.
2. ) Bubble growth in the environmental water that can occur in the buccal cavity and between gill lamella.
4.) Overinflation of the swimbladder.
3. ) Sub-dermal bubbles that occur on external skin surfaces such as the opercular flaps, between fin rays and in the lining of the mouth.
In order to develop the models for general use, it was necessary to establish the effective size of nucleation sites and other physiological parameters contained in the bubble growth threshold equations. This was accomplished through a review of data from the scientific literature and a two phase experimental program.
The literature review resulted in the compilation of a database containing over 1000 records of supersaturation data on salmonids. Various filters based on length, species, total gas pressure (TGP), partial pressure of oxygen (PO₂) and other criteria were applied to the database. The filtering operations established the existence of GBT mortality thresholds and identified relationships between other experimental parameters. The results of this analysis suggest that a lower threshold occurs at a water TGP of 1.10 Atms. and a higher threshold occurs at 1.15 to 1.18 Atms. However, it was not established that the apparent mortality thresholds correspond to thresholds for bubble growth predicted by the theoretical models.
To make this correlation, a preliminary experimental study examined the physiological response of fish exposed to supersaturated water. It was found that arterial PO₂, hematocrit and blood pressure yield unique responses to bubble growth over specific ranges of water TGP. The results of these experiments also indicate that the lower mortality threshold of the database analyses is associated with a combination of sub-dermal bubble growth in the mouth and extracorporeal bubbles growing between gill lamella.
The second phase of experimental study included surveys of blood PO₂, hematocrit and pH along with microscopic studies of intravascular and extracorporeal bubble growth in gills. The results of these experiments confirm the source of mortality for the lower threshold at a water TGP of 1.1 Atms. In addition, the data demonstrate that the upper TGP threshold of 1.15 to 1.18 Atms. of the database analysis corresponds to the threshold for intravascular bubble growth. The results further confirm that, as predicted by the theoretical model, intravascular bubble growth thresholds are dependent on water PO₂ .
Combining the results of the database analysis and the experimental studies permitted the effective size of nucleation sites responsible for bubble growth to be back calculated from the theoretical equations. This completed the development of the bubble growth threshold equations. The equations can now be used to predict thresholds for the various forms of bubble growth and mortality that occur in fish exposed to supersaturated water. The experimental results also provide valuable information regarding the physiological response of fish to gas supersaturated water.Science, Faculty of
Zoology, Department of
Graduate
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De’Ath, Henry D. I. "Trauma associated cardiac injury & dysfunction." Thesis, Queen Mary, University of London, 2013. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8466.
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The existence of a trauma induced secondary cardiac injury (TISCI) remains in doubt. The risk factors and pathological processes that lead to its development are not known, whilst the effects of TISCI on injured patient outcome are uncertain. Concurrently, the incidence of coronary heart disease (CHD) in a trauma population and its influence on mortality are inconclusive. The aim of this research project was to address these specific areas of uncertainty. Critically injured patients (n=135) were retrospectively investigated for the incidence and nature of adverse cardiac events (ACEs), and levels of the cardiac specific biomarkers Troponin I, B-type Natriuretic Peptide and Heart-type Fatty Acid Binding Protein were measured. Biomarkers and cardiac events were evaluated against outcome. Thereafter, the relationship of pro-inflammatory cytokines with TISCI was explored. A prospective cohort study of 199 trauma patients followed, to confirm the existence of TISCI and describe its clinical features, risk factors and outcomes. Finally, coronary artery calcium, as a marker of CHD, was evaluated on 432 CT scans of the chest of trauma patients aged 45 years or over, and its association with survival after injury was established. ACEs and early biomarker rises occurred in trauma patients and both were unrelated to the severity of chest injury. Each was associated with higher mortality, and confirmed the existence of TISCI. Risk factors for the development of the condition included increasing age, worsening tissue injury and shock. A relationship with cytokines was demonstrated, and implicated acute inflammation in the pathogenesis of TISCI. Calcification on CT scans revealed the incidence of CHD in an injured cohort approached 70%, although its presence did not impact survival. There exists a trauma induced secondary cardiac injury which was related to poorer outcome. The condition was associated with inflammation. CHD was widespread in older trauma patients but was not associated with increased in-hospital mortality.
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Friberg, Danielle. "Nerve lesions in pharynx - an aetiology of obstructive sleep apnoea /." Stockholm, 1997. http://diss.kib.ki.se/1997/91-628-2721-9.
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Eckert, Bodil. "Hypoglycaemia studies on central and peripheral nerve function /." Lund : Dept. of Internal Medicine, University of Lund, 1998. http://catalog.hathitrust.org/api/volumes/oclc/57426099.html.
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Williamson, Ritchie. "Mechanisms of nerve cell death in Down's syndrome and Alzheimer's disease." Thesis, King's College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271632.
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Kiernan, Matthew C. Clinical School Prince of Wales Hospital Faculty of Medicine UNSW. "Central and peripheral nerve excitability: developing an understanding of the pathophysiology of neurological disease." Awarded by:University of New South Wales. Clinical School - Prince of Wales Hospital, 2008. http://handle.unsw.edu.au/1959.4/42951.
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Hazlewood, Ralph Jeremiah II. "Molecular genetics of optic nerve disease using patients with cavitary optic disc anomaly." Diss., University of Iowa, 2015. https://ir.uiowa.edu/etd/1622.
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Glaucoma is the second leading cause of irreversible blindness in the United States and is the leading cause of blindness in African Americans. Cupping or excavation of the optic nerve, which sends the visual signal from the photoreceptors in the eye to the brain, is a chief feature of glaucoma. A similar excavated appearance of the optic nerve is also the primary clinical sign of other congenital malformations of the eye including optic nerve head coloboma, optic pit, and morning glory disc anomaly collectively termed cavitary optic disc anomaly (CODA). Clinical similarities between CODA and glaucoma have suggested that these conditions may have overlapping pathophysiology. Although risk factors are known, such as the elevated intraocular pressure (IOP) observed in some glaucoma subjects, the biological pathways and molecular events that lead to excavation of the optic disc in glaucoma and in CODA are incompletely understood, which has hindered efforts to improve diagnosis and treatment of these diseases. Consequently, there is a critical need to clarify the biological mechanisms that lead to excavation of the optic nerve, which will lead to improvements in our understanding of these important disease processes. Because of their similar clinical phenotypes and the limited therapy geared at lowering IOP in glaucoma patients, our central hypothesis is that genes involved in Mendelian forms of CODA would also be involved in a subset of glaucoma cases and may provide insight into glaucomatous optic neuropathy.
The purpose of my research project has been to identify and functionally characterize the gene that causes congenital autosomal dominant CODA in a multiplex family with 17 affected members. The gene that causes CODA was previously mapped to chromosome 12q14 and following screening of candidate genes within the region that did not yield any plausible coding sequence mutations, a triplication of a 6KB segment of DNA upstream of the matrix metalloproteinase 19 (MMP19) gene was subsequently identified using comparative genomic hybridization arrays and qPCR. This copy number variation (CNV) was present in all affected family members but absent in unaffected family members, a panel of 78 normal control subjects, and the Database of Genomic Variants. In a case-control study of singleton CODA subjects, CNVs were also detected; we detected the same 6KB triplication in 1 of 24 subjects screened. This subject was part of another 3-generation autosomal dominant CODA pedigree where affected members each have the same CNV identified in the larger CODA pedigree. A separate case-control study with 172 glaucoma cases (primary open angle glaucoma = 84, normal tension glaucoma = 88) was evaluated for MMP19 CNVs, however none were detected. Although our cohort of CODA patients is small limiting our ability to accurately determine the proportion of CODA caused by MMP19 mutations, our data indicates that the MMP19 CNV is not an isolated case and additional CODA subjects may have MMP19 defects. Because of the location of the CNV, we evaluated its effect on downstream gene expression with luciferase reporter gene assays. These assays revealed that the 6KB sequence spanned by the CNV in CODA subjects functioned as a transcriptional enhancer; in particular, a 773bp segment had a strong positive influence (8-fold higher) on downstream gene expression. MMP19, a largely understudied gene, was further characterized by expression studies in the optic nerve and retina. Using frozen sections from normal donor eyes, we demonstrated that MMP19 is predominantly localized to the optic nerve head in the lamina cribrosa region with moderate labeling in the postlaminar region, and weak labeling in the prelaminar region and retina. We also evaluated MMP19 expression in relation to the cell types that populate the optic nerve such as astrocytes and retinal ganglion cells. The pattern of expression is consistent with MMP19 being a secreted protein accumulating in the extracellular spaces and basement membranes of the optic nerve. Our studies have identified the first gene associated with CODA and future research is focused on recapitulating CODA phenotypes in animal models and assessing the mechanism of MMP19 involvement during development.
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Welleford, Andrew. "Autologous Peripheral Nerve Grafts to the Brain for the Treatment of Parkinson's Disease." UKnowledge, 2019. https://uknowledge.uky.edu/neurobio_etds/23.
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Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that aim to develop a disease-modifying therapy that slows the progression of PD. These clinical trials are evaluating the safety and feasibility of an autologous peripheral nerve graft to the substantia nigra in combination with Deep Brain Stimulation (DBS) for the treatment of PD. By grafting peripheral nerve tissue to the Substantia Nigra, the researchers aim to introduce peripheral nerve tissue, which is capable of functional regeneration after injury, to the degenerating Substantia Nigra of patients with PD. The central hypothesis of these clinical trials is that the grafted tissue will slow degeneration of the target brain region through neural repair actions of Schwann cells as well as other pro-regenerative features of the peripheral nerve tissue.
This dissertation details analysis of the peripheral nerve tissue used in the above clinical trials with respect to tissue composition and gene expression, both of injury-naive human peripheral nerve as well as the post-conditioning injury nerve tissue used in the grafting procedure. RNA-seq analysis of sural nerve tissue pre and post-conditioning show significant changes in gene expression corresponding with transdifferentiation of Schwann cells from a myelinating to a repair phenotype, release of growth factors, activation of macrophages and other immune cells, and an increase in anti-apoptotic and neuroprotective gene transcripts. These results reveal in vivo gene expression changes involved in the human peripheral nerve injury repair process, which has relevance beyond this clinical trial to the fields of Schwann cell biology and peripheral nerve repair. To assess the neurobiology of the graft post-implantation we developed an animal model of the grafting procedure, termed Neuro-Avatars, which feature human graft tissue implanted into athymic nude rats. Survival and infiltration of human graft cells into the host brain were shown using immunohistochemistry of Human Nuclear Antigen. Surgical methods and outcomes from the ongoing development of this animal model are reported. To connect the results of these laboratory studies to the clinical trial we compared the severity of motor symptoms before surgery to one year post-surgery in patients who received the analyzed graft tissue. Motor symptom severity was assessed using the Unified Parkinson’s Disease Rating Scale Part III. Finally, the implications and future directions of this research is discussed. In summary, this dissertation advances the translational science cycle by using clinical trial findings and samples to answer basic science questions that will in turn guide future clinical trial design.
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Christopher, Mark Allen. "Computational methods to model disease and genetic effects on optic nerve head structure." Diss., University of Iowa, 2015. https://ir.uiowa.edu/etd/1959.
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Glaucoma is a leading cause of blindness throughout the world and is estimated to affect 80 million by 2020. This disease causes progressive loss of vision and, left untreated, can lead to complete blindness. With treatment, however, disease progression can be slowed dramatically. This makes early detection and intervention crucial in preserving the vision of affected individuals.
Onset and progression of glaucoma are associated with structural changes to an anatomical feature known as the optic nerve head (ONH). The ONH is the site of attachment between the retina and the optic nerve that carries all visual information to the brain. As glaucoma progresses, characteristic changes related to cell death and loss of vision can be observed in the three-dimensional structure of the ONH. A common modality used to observe these changes is stereo fundus imaging. This modality captures three-dimensional information via stereo imaging and is commonly used in clinical settings to diagnose and monitor glaucoma. A limitation of using stereo fundus images is the need for review by glaucoma specialists to identify disease related features of ONH structure. Further, even when expert evaluation is possible, the subjective nature of the process can lead due large discrepancies in the evaluations and resultant clinical decisions. The work presented here seeks address these concerns by providing automated, computational tools that can be used to characterize ONH structure.
Specifically, this thesis outlines the development of computational methods for inferring three-dimensional information from stereo fundus images and identifying objective, quantitative measurements of ONH structure. The resulting computational tools were applied to image and clinical data collected from a large cohort of individuals to identify hidden relationships between ONH structure, clinical measurements, and glaucoma. These tools were then applied to develop methods for estimating the impact of individual genetic factors on the ONH. Finally, using a longitudinal dataset collected over more than a decade, computational analysis was used to investigate how ONH structure changes over time in response to aging, other disease-related factors, and glaucoma progression.
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Weise, David, Melanie Adamidis, Fabio Pizzolato, Jost-Julian Rumpf, Christopher Fricke, and Joseph Classen. "Assessment of brainstem function with auricular branch of vagus nerve stimulation in Parkinson’s disease." Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-169463.
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Background: The efferent dorsal motor nucleus of the vagal nuclei complex may degenerate early in the course of Parkinson’s disease (PD), while efferent nucleus ambiguous, the principal source
of parasympathetic vagal neurons innervating the heart, and afferent somatosensory nuclei remain intact.
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Biro, Andrew J. "Specific aspects of neurodegenerative disease." Thesis, University of British Columbia, 1989. http://hdl.handle.net/2429/28919.
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This thesis is broken into four chapters. The first two chapters summarize two separate lines of investigation into the role of a putative neurotoxin in the pathogenesis of Huntington's Disease (HD). The third chapter outlines an investigation of the putative role of beta-N-methylamino-L-alanine (BMAA) in the pathogenesis of amyotrophic lateral sclerosis (ALS), while the final chapter details a post-mortem investigation of the contents of biogenic amines and amino acids in the brain of a man who died of a familial form of parkinsonism.
Chapter I is a description of a chromatographic technique developed to isolate quinolinic acid (QA), an endogenous compound implicated in the pathogenesis of HD, from deproteinized human sera. A cation exchange column was used to selectively isolate QA, which was eluted with 10 mM HCl. The eluted fractions were analyzed by UV spectrometry to isolate and quantify QA. Once the fractions corresponding the elution of authentic QA were isolated, concentrated and the excess HCl removed, the fractions were added to growing fetal rat striatal explant cultures as an assay of neurotoxicity. Since HD involves the selective degeneration of GABAergic neurons in the striatum, the activity of glutamic acid decarboxylase, the final enzyme in the synthesis of GABA, was used to determine the viability of the cultures. Unfortunately, the method was confounded by the contamination of all effluents by compounds originating from the cation exchange
resin, which were discovered to be neurotoxic to the striatal cultures, and as a result the investigation had to be abandoned.
Chapter II describes an investigation designed to further characterize the nature of neurotoxicity observed in the sera obtained from patients with HD (Perry et al. 1987). Compounds with the capacity to selectively stimulate neurons at the N-methyl-D-aspartate (NMDA) receptor have been implicated in a variety of neurodegenerative disorders, including HD. Selective antagonists at the NMDA receptor have been shown to protect neurons from the degenerative effects of such "excitotoxins". The investigation described used MK-801, a potent noncompetitive
NMDA antagonist, in an attempt to protect fetal rat striatal cultures from the neurodegenerative effects of the sera obtained from HD patients. The results obtained were equivocal. No evidence was obtained to support a role of the NMDA receptor in the mediation of the neurotoxicity, and in addition the neurodegenerative effects of HD sera were not reproduced in the present investigation. A variety of possible explanations for the apparent discrepancy are suggested.
Chapter III describes an experiment intended to produce an animal model of ALS based on the observations by Spencer et al. 1987 that chronic oral administration of BMAA in monkeys produced the histological and behavioural characteristics of this disease. In the present investigation synthetic D,L-BMAA was given by gavage to mice over an eleven week period. Since BMAA is known to act at the NMDA receptor, a subset of the mice were also given MK-801 in an effort to protect them
from any deleterious effects based on the action of BMAA at this receptor. The animals were sacrificed at the end of the experiment, and biochemical analyses were performed on the striata and cortices of the animals. In addition, neuropathological studies were performed on the spinal cords, basal ganglia and related structures. The results indicated no biochemical or neuropathological abnormality as a result of BMAA administration.
Chapter IV describes a post-mortem investigation of a man who was a member of a well described pedigree which carries an autosomal dominant form of parkinsonism. The object of the investigation was to determine post-mortem levels of dopamine, noradrenaline, serotonin and their metabolites, in addition to amino acids in various regions of brain. Although conflicting evidence was obtained during life, neuropathological findings and the present neurochemical analyses confirm the degeneration of the nigrostriatal dopaminergic tract, characteristic of parkinsonism, in this man.Medicine, Faculty of
Anesthesiology, Pharmacology and Therapeutics, Department of
Graduate
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Törnqvist, Nina. "On transplantation of fetal ventral mesencephalon with focus on dopaminergic nerve fiber formation /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-177-2/.
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Fidler, Larry E. "A study of biophysical phenomena associated with gas bubble trauma in fish." Thesis, University of British Columbia, 1985. http://hdl.handle.net/2429/24660.
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The condition of Gas Bubble Trauma in fish was examined in terms of specific symptoms involving bubble development in the circulatory system and buccal cavities of fish. Based on a comparison between the conditions for bubble growth in fish exposed to supersaturated water and mammals exposed to hyperbaric and hypobaric decompression a mathematical model was developed describing environmental water threshold needed to initiate bubble growth in fish. The equation development yielded expressions which related the thresholds in total dissolved gas pressure required to initiate bubble growth in the circulatory system to the partial pressure ratio of dissolved oxygen in the environmental water, oxygen uptake ratio across the gill, the size of nucleation sites in the circulatory system, the surface tension of fish blood and environmental parameters such as water temperature, depth and barometric pressure. In the case of bubble growth in the buccal cavity, environmental water thresholds were related to total gas pressure, nuclei radius, water surface tension, water temperature, depth and barometric pressure. Bubble growth thresholds were examined for a range of the above dependent parameters.Science, Faculty of
Zoology, Department of
Graduate
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Uhrig, Brent A. "Tissue regeneration in composite injury models of limb trauma." Diss., Georgia Institute of Technology, 2013. http://hdl.handle.net/1853/49080.
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Severe extremity trauma often involves significant damage to multiple tissue types, including bones, skeletal muscles, peripheral nerves, and blood vessels. Such injuries present unique challenges for reconstruction, and improving structural and functional outcomes of intervention remains a pressing, unmet clinical need. While tissue engineering/regenerative medicine (TE/RM) therapeutics offer promising potential to overcome the status quo limitations of surgical reconstruction, very few products have transitioned to clinical practice. Improving treatment options will likely require advancing our understanding of the biological interactions occurring in the repair of damaged tissues.
Bone tissue is known to be innervated and highly vascularized, and both tissue types are involved in normal bone physiology. However, the degree to which these tissue relationships influence the repair of large, multi-tissue defects remains unknown. Accordingly, the goal of this thesis was to investigate tissue regeneration in two novel composite injury models. First, we characterized interactions in a composite bone and nerve injury model where a segmental bone defect was combined with a peripheral nerve gap. Our results indicated that although tissue regeneration was not impaired, the composite injury group experienced a marked functional deficit in the operated limb compared to single-tissue injury. Second, we developed a model of composite bone and vascular extremity trauma by combining a critically-sized segmental bone defect with surgically-induced hind limb ischemia to evaluate the effects on BMP-2-mediated bone repair. Interestingly, our results demonstrated a stimulatory effect of the recovery response to ischemia on bone regeneration. Finally, we investigated early vascular growth and gene expression as potential mechanisms coupling the response to ischemia with bone defect repair. Although the response to ischemia promoted robust vascular growth in the thigh, it did not directly augment vascularization at the site of bone regeneration. In addition, the stimulatory effects of ischemia on bone regeneration could not be explained by gene expression alone based on the genes and time points investigated.
Taken together, this thesis presents pioneering work on a new thrust of TE/RM research – tissue regeneration in models of composite injury. This work has provided new insights on the complexity of composite tissue repair, specifically in regard to the relationship between vascular tissue growth and bone healing. Going forward, successful leverage of models of composite tissue injuries will provide valuable test beds for screening new technologies, advance the understanding of tissue repair biology, and ultimately, may produce new therapeutic interventions for limb salvage and reconstruction that improve outcomes for extremity trauma patients.
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Illanes, O. G. "Morphological and morphometric of peripheral nerves in adult Beagle dogs and nerves of rabbits experimentally infected with alpha-Herpesvirus saimiri (H. tamarinus)." Thesis, University of Liverpool, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.382080.
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Owen, Deborah Louise. "The neurotrophic actions of human melanotropin potentiating factor (hMPF)." Thesis, University of Liverpool, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.385290.
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Коленко, Фаіна Григорівна, Фаина Григорьевна Коленко, and Faina Hryhorivna Kolenko. "Досвід і перспективи викладання курсу нервових хвороб на медичному факультеті." Thesis, Видавництво СумДУ, 2002. http://essuir.sumdu.edu.ua/handle/123456789/23952.
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Beach, Sarah C. "Impact of Age on Submucosal Nerve Measurements in Rectal Biopsies from Patients with Hirschsprung Disease." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1586548909282138.
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Beck, Melanie Lea Simmer Bray Kimberly Krust. "Comparison of muscle activity associated with varying structural differences in dental hygiene mirrors." Diss., UMK access, 2004.
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Thesis (M.S.)--School of Dentistry. University of Missouri--Kansas City, 2004."A thesis in dental hygiene education." Typescript. Advisor: Kimberly Krust Bray. Vita. Title from "catalog record" of the print edition Description based on contents viewed Feb. 22, 2006. Includes bibliographical references (leaves 68-70). Online version of the print edition.
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Berling, Holm Katarina. "The Chorda Tympani Nerve : Role in Taste Impairment in Middle Ear Disease and after Ear Surgery." Doctoral thesis, Uppsala universitet, Centrum för klinisk forskning, Västerås, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-316591.
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The chorda tympani nerve, also known as the taste nerve, runs uncovered through the middle ear cavity, a localization that exposes the nerve to pathological processes and surgical trauma in the middle ear. People operated on for otosclerosis tend to complain more about postoperative taste disturbances than those operated on for chronic otitis media. It has been suggested that this difference may be explained by gradual deterioration of chorda tympani nerve function caused by chronic otitis media infection and that further impairment caused by surgery is less noticeable in these patients. This thesis aimed to evaluate the function of the chorda tympani nerve, the effects of middle ear disease on taste and complications resulting from ear surgery for chronic otitis media or otosclerosis. This information will help to improve the ear surgeon’s ability to predict the prognosis of iatrogenic taste disturbances in patients with middle ear disease and after ear surgery. Taste was assessed using electrogustometry and the filter paper disc method before and after surgery for chronic otitis media or otosclerosis. Patients also completed questionnaires about symptoms and quality of life. The status of the chorda tympani nerve upon surgical opening of the ear and grading of the trauma to the nerve during the surgery were recorded. The ultrastructure of the chorda tympani nerve from healthy ears and from ears with chronic otitis media was examined. Electrogustometry and the filter paper disc method were evaluated. The results of electrogustometry and the filter paper disc method were highly reproducible, although their correlation was moderate. Patients with chronic otitis media, patients with a more traumatized nerve, female patients and younger patients were more likely to report postoperative taste disturbances. Most of the patients recovered their taste after 1 year. The quality of life study showed only minor changes after surgery. Electron microscopic observations of nerves from ears with chronic otitis media showed signs of structural degeneration, although signs of regeneration, such as sprouting were also observed. This results may explain the recovery of taste postoperatively and indicate that the nerve should be carefully handled during surgery.
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Nishio, Takahiro. "Hepatic vagus nerve regulates Kupffer cell activation via α7 nicotinic acetylcholine receptor in nonalcoholic steatohepatitis." Kyoto University, 2017. http://hdl.handle.net/2433/225984.
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Terzi, Menderes Yusuf [Verfasser]. "The role and influence of pigment epithelium-derived factor (PEDF) on peripheral nerve tumor, brain trauma and stroke / Menderes Yusuf Terzi." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2015. http://d-nb.info/1071088068/34.
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Rogers, Edmond A. "Simultaneous Electrophysiological and Morphological Assessment of Impact Damage to Nerve Cell Networks." Thesis, University of North Texas, 2018. https://digital.library.unt.edu/ark:/67531/metadc1157638/.
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A ballistic pendulum impulse generator was used to impact networks in primary culture growing on microelectrode arrays. This approach has the advantage of imparting pure tangential acceleration insults (50 to 300 g) with simultaneous morphological and electrophysiological multichannel monitoring for days before and after the impact. Action potential (AP) production, network activity patterns, and cell electrode coupling of individual units using AP waveshape templates were quantified. Network adhesion was maintained after tangential impacts up to 300g with minimal loss of pre-selected active units. Time lapse phase contrast microscopy revealed stable nuclei pre-impact, but post impact nuclear rotation in 95% of observations (n= 30). All recording experiments (n=31) showed a repeatable two-phase spike production response profile: recovery to near reference in 1-2 hrs, followed by a slow activity decay to a stable, level plateau approximately 30-40% below reference. Phase 1 consisted of a complex two-step recovery: rapid activity increase to an average 23.6% (range: 11-34%) below reference, forming a level plateau lasting from 5 to 20 min, followed by a climb to within 20% of reference where a second plateau was established for 1 to 2 hrs. Cross correlation profiles showed changes in firing hierarchy after impact, and in spontaneous network oscillatory activity. Native oscillations were found in the Delta band (2 to 3 Hz), and decreased by approximately 20% after impact. Under network disinhibition with bicuculline, oscillations were slower (0.8-1Hz) and decreased 40% after impact. These data link network performance deficits with microscopically observable subcellular changes.
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Spies, Georgina. "Neurocognitive outcomes in HIV and childhood trauma." Thesis, Stellenbosch : Stellenbosch University, 2011. http://hdl.handle.net/10019.1/18097.
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Thesis (PhD)--Stellenbosch Univesity, 2011.ENGLISH ABSTRACT: It is well established that South African women are disproportionately affected by HIV/AIDS and gender based violence. Research to date has provided evidence for neurocognitive decline in individuals infected with HIV/AIDS and in individuals who have experienced early life trauma. However, many gaps remain in our knowledge about the neurocognitive profile of HIV and childhood trauma in South African women. The present study focused on the neurocognitive effects of HIV infection and childhood trauma, both separately and in combination in South African women. The primary aim of the study was to assess neurocognitive functioning in HIV-positive and matched HIVnegative controls, with and without a history of childhood trauma. Moreover, the study sought to assess the synergistic relationship between HIV and childhood trauma in influencing neurocognitive outcomes, a relationship which has not yet been investigated. A neuropsychological battery sensitive to HIV-related impairments was administered to 83 HIV-positive and 47 matched HIV-negative women with histories of childhood trauma. A history of childhood trauma was assessed using the Childhood Trauma Questionnaire short form (CTQ-SF). Forty eight of the 83 HIV-positive women were exposed to childhood trauma. Among the control subjects, a total of twenty women were exposed to childhood trauma. Findings of the present study revealed neurocognitive deficits in memory and executive functions. Results demonstrated significant HIV effects in memory (HVLT-R learning and delay trials), and executive functions (Halstead Category test). Similarly, a trauma effect was evident in delayed recall (HVLT-R delay). Moreover, results revealed a significant interaction effect between HIV status and trauma status on the WAIS-III Symbol Search Task, a task of psychomotor speed. However, HIV-negative controls with a history of childhood trauma scored the highest on this task. Although this finding was unexpected, it may suggest that psychomotor speed may not be a sensitive or discriminating test of childhood trauma in healthy adults. The present study demonstrated evidence for HIV and trauma effects in the ability domains of learning and delayed recall and executive functions. Although the present study did not find evidence for a synergistic relationship between HIV and trauma, it did provide evidence for both HIV and trauma effects on neurocognition, a finding in keeping with previous studies. Future research should be prospective in nature and should better delineate the nature, severity, and temporal relationship of childhood trauma to neurocognitive outcomes, as well as the mediators and moderators of these outcomes.
AFRIKAANSE OPSOMMING: Dit is alombekend dat Suid-Afrikaanse vroue buite verhouding swaar deur MIV/vigs en geslagsgebaseerde geweld getref word. Navorsing tot dusver lewer bewyse van neurokognitiewe verswakking by individue met MIV/vigs sowel as individue wat vroeg in hulle lewe reeds trauma ervaar het. Tog is daar steeds vele gapings in ons kennis oor die neurokognitiewe profiel met betrekking tot MIV en kindertrauma onder Suid- Afrikaanse vroue. Hierdie studie konsentreer op die neurokognitiewe uitwerking van MIV-infeksie en kindertrauma, afsonderlik sowel as gesamentlik, op Suid-Afrikaanse vroue. Die hoofdoel van die studie was om neurokognitiewe funksionering by MIV-positiewe vroue te bepaal en dit met gepaste MIV-negatiewe kontrolepersone te vergelyk, met én sonder 'n geskiedenis van kindertrauma. Daarbenewens wou die studie die sinergistiese verwantskap tussen MIV en kindertrauma in hul impak op neurokognitiewe uitkomste bepaal – 'n verwantskap wat tot dusver nog nie ondersoek is nie. 'n Neurosielkundige toetsbattery wat gevoelig is vir MIV-verwante swakhede is onder 83 MIV-positiewe vroue en 47 gepaste MIV-negatiewe kontrolepersone met 'n geskiedenis van kindertrauma afgeneem. 'n Geskiedenis van kindertrauma is met behulp van die kort weergawe van die kindertraumavraelys (CTQ-SF) vasgestel. Agt-en-veertig van die 83 MIV-positiewe vroue is as kinders aan trauma blootgestel. Van die kontrolegroep het 20 vroue in hul kindertyd trauma beleef. Die studie het neurokognitiewe tekorte in korttermyngeheue én uitvoerende funksies aan die lig gebring. Die resultate het 'n beduidende MIV-verwante uitwerking op korttermyngeheue (hersiene Hopkins- verbale leer-en-vertragingstoets, oftewel HVLT-R) sowel as uitvoerende funksies (Halstead-kategorietoets) getoon. Eweneens het die studie op 'n duidelike traumaverwante uitwerking op herinneringsvermoë (HVLT-R-vertraging) gedui. Daarbenewens het die WAIS-II- (Wechsler-volwassene-intelligensieskaal) simboolsoekopdrag – 'n psigomotoriese spoedtoets – 'n beduidende wisselwerkingseffek tussen MIV-status en traumastatus getoon. Tog het MIV-negatiewe kontrolepersone met 'n geskiedenis van kindertrauma die beste in hierdie opdrag gevaar. Hoewel hierdie bevinding verrassend was, kan dit daarop dui dat psigomotoriese spoed dalk nie 'n gevoelige of diskriminerende toets van kindertrauma by gesonde volwassenes is nie. Die studie het bewys gelewer van MIV- en traumaverwante uitwerkings op korttermyngeheue en uitvoerende funksies. Hoewel die ondersoek nie bewyse van 'n sinergistiese verwantskap tussen MIV en trauma kon vind nie, het dit wél bevestig dat MIV en trauma neurokognitiewe werking beïnvloed – 'n bevinding wat in pas is met vorige studies. Toekomstige navorsing behoort ondersoekend te wees en die aard, felheid en tydgebondenheid van die verwantskap tussen kindertrauma en neurokognitiewe uitkomste, sowel as die mediator- en moderatorveranderlikes van hierdie uitkomste, beter te omskryf.
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Randolph, Joann K. "A COMPARISON OF FLEXION AND EXTENSION EXERCISES IN WORKERS AT RISK FOR DEVELOPING CUMULATIVE TRAUMA DISORDER." University of Cincinnati / OhioLINK, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=ucin992446724.
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McCorquodale, Donald S. III. "Identification of Novel Phospholipid Related Functions of Mitofusin 2 in Cell Models of Charcot-Marie-Tooth Disease 2A." Scholarly Repository, 2011. http://scholarlyrepository.miami.edu/oa_dissertations/580.
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The mitofusin 1 and 2 (MFN and MFN2) proteins reside in the outer mitochondrial membrane and have been shown to regulate mitochondrial network architecture by mediating tethering and fusion of mitochondria. Mitochondria normally form a tubular and branched reticular network dynamically regulated by a balance of fusion and fission events. Absence of either Mfn1 or Mfn2 results in a fragmented mitochondrial network. Züchner et al. previously described mutations in the gene mitofusin 2 (MFN2) as the cause of the major autosomal-dominant, axonal form of Charcot-Marie-Tooth neuropathy (CMT2A). CMT type 2 (CMT2) is characterized by chronic axonal degeneration of peripheral nerves leading to the loss of functional nerve fibers. Mutations in MFN2 are the most common cause of CMT2, and in Chapter 2 we report the results from a genetic screen of MFN2 in a CMT2 patient cohort. The original finding that mutations in MFN2 cause CMT2A led to investigations focused on deficiencies of mitochondrial fusion and transport, specifically in the context of long axonal processes affected in CMT. While some experimental work supports disrupted mitochondrial transport in the etiology of CMT2A, other studies on CMT2A patient fibroblasts and cell models suggest abnormal mitochondrial fusion and dynamics do not underlie the etiology of this. In the first half of Chapter 3, we present some of our initial investigations prior to de Brito and Scorrano’s report published in 2008 regarding a novel role for Mfn2 in tethering the endoplasmic reticulum (ER) to mitochondria. In Mfn2 null mouse embryonic fibroblasts (MEFs) regions of contact between mitochondria and the endoplasmic reticulum (ER) are significantly reduced. These regions of contact are thought to form specialized subdomains of the ER, called mitochondrial associated membranes (MAM). Besides observing a fragmented ER network in Mfn2 knockout (KO) mouse embryonic (MEF) cells, de Brito and Scorrano presented several lines of evidence which suggest that the underlying pathogenic mechanism in CMT2A stems from disrupted ER-mitochondria. As this observation had not been replicated in the literature, we describe our attempts to replicate these finding in the last half of Chapter 3. The MAM represents a sub-domain of the ER in close association with the mitochondrial outer membrane. The movement of phosphatidylserine (PS) from the MAM domains of the ER to mitochondria and its subsequent decarboxylation to phosphatidylethanolamine (PE) by the enzyme PS decarboxylase (Pisd) has been well characterized and is known to depend on the existence of an outer mitochondrial membrane protein. As PE has curvature inducing and fusogenic biophysical characteristics, a deficiency in PE would be an attractive mechanism contributing to the morphological and fusion defects observed in Mfn2 null cell models. We hypothesized that loss of Mfn2 would lead to specific decreases in mitochondrial and cellular levels of PE. Chapter 4 describes experiments designed to test this hypothesis. We observed significantly lower levels of PE in Mfn2 null cells, yet observe similar changes in Mfn1 null cells. Likewise, other lipid species such as ether linked PE (ePE) are decreased. To investigate how CMT2A mutations in MFN2 influence cellular phospholipid profiles, we then profiled cellular phospholipids of CMT2A patients and control lymphoblasts. We hypothesized that mutations in MFN2 would result in decreased levels of PE. In Chapter 5, we report the results of a phospholipid screen which reveal changes in ePE in CMT2A patient lymphoblasts, without the drastic decreases in PE previously observed in Mfn2 null lines. In conclusion, our data indicates an important role for both mitofusins in the mitochondrial synthesis of PE. In the context of CMT2A mutations, ePE levels are specifically reduced. Future studies may reveal how deficiencies in ePE might have important functional consequences in the pathogenesis of CMT2A.
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Davis, W. Sumner. "Association Between Psychological Trauma From Assault in Childhood and Metabolic Syndrome." ScholarWorks, 2015. https://scholarworks.waldenu.edu/dissertations/1256.
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Metabolic syndrome and its component conditions of hypertension, obesity, and insulin resistance are on the increase in United States. Metabolic syndrome substantially increases the risk of cardiovascular disease and type 2 diabetes (T2D). To date, no published study has examined the relationship between psychological traumas from physical and/or sexual assault in childhood and metabolic syndrome or its components. This study, using the psychoneuroimmunology (PNI) model, investigated associations between psychological trauma (physical/sexual abuse) in childhood and metabolic syndrome in adulthood using data from the Midlife in the United States II (MIDUS-II) study. This research was undertaken to investigate whether a history of psychological trauma was associated with an elevated risk for metabolic syndrome. Chi-square test and logistic regression were used to investigate the respective associations. Metabolic syndrome was the dependent variable, assault in childhood was the independent variable, and the relevant covariates included in the logistic regression model were age, gender, cigarette and alcohol consumption, and ethnicity. While there was no significant association between assault in childhood and metabolic syndrome (p = 0.146), there were significant associations between metabolic syndrome and age group (p =< 0.026). In the adjusted logistic regression model, the only covariate that showed significant association with metabolic syndrome was Age Group 2 (41-55; p = 0.016). Also significant was the association between sexual assault in childhood and high blood pressure (p = 0.041). The results of this study suggest that clinicians may wish to watch for evidence of abuse, given the potential for future health impacts.
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Mkhathini, Maxwell Menzi. "Personal traumatic experience of HIV/AIDS challenges pastoral care." Pretoria : [s.n.], 2006. http://upetd.up.ac.za/thesis/available/etd-10302007-150028/.
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Palejwala, Sheri K., Jesse Skoch, and G. Michael Lemole. "Removal of symptomatic craniofacial titanium hardware following craniotomy: Case series and review." Elsevier, 2015. http://hdl.handle.net/10150/621246.
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UA Open Access Publishing FundTitanium craniofacial hardware has become commonplace for reconstruction and bone flap fixation following craniotomy. Complications of titanium hardware include palpability, visibility, infection, exposure, pain, and hardware malfunction, which can necessitate hardware removal. We describe three patients who underwent craniofacial reconstruction following craniotomies for trauma with post-operative courses complicated by medically intractable facial pain. All three patients subsequently underwent removal of the symptomatic craniofacial titanium hardware and experienced rapid resolution of their painful parasthesias. Symptomatic plates were found in the region of the frontozygomatic suture or MacCarty keyhole, or in close proximity with the supraorbital nerve. Titanium plates, though relatively safe and low profile, can cause local nerve irritation or neuropathy. Surgeons should be cognizant of the potential complications of titanium craniofacial hardware and locations that are at higher risk for becoming symptomatic necessitating a second surgery for removal.
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Chroni, Elisabeth. "F chronodispersion and F tacheodispersion : a study of conduction properties of motor nerve fibres in normal and pathological conditions." Thesis, King's College London (University of London), 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.320463.
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Liu, Xiaoying. "Pattern of synapse loss in neurodegenerative disorders a comparison between frontal lobe degeneration of non-Alzheimer type and Alzheimer's disease /." Lund : Dept. of Neuropathology, Institute of Pathology, Lund University, 1995. http://catalog.hathitrust.org/api/volumes/oclc/39783697.html.
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Miller, Rebecca Louise. "The mechanism for paraquat toxicity involves oxidative stress and inflammation a model for Parkinson's disease /." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/4764.
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Thesis (Ph. D.)--University of Missouri-Columbia, 2007.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "May 2007" Includes bibliographical references.
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Scherer, aus Pullach Patricia. "Diagnose HIV+ trauma oder chance? : das human immunodeficiency virus uns das acquired immune deficiency syndrome als "voodoo-formeln" der moderne /." München : Ludwig-Maximilians-Universität, 1996. http://catalog.hathitrust.org/api/volumes/oclc/38175768.html.
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Gryth, Dan. "Hemodynamic, respiratory and neurophysiological reactions after high-velocity behind armor blunt trauma /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-355-9/.
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Wang, Baiping. "The functions of FE65 proteins and their roles in dementias of the Alzheimer type /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/6331.
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Kempf, Evan Alexander. "Chronic femoral artery ligation exaggerates the pressor and sympathetic nerve responses during dynamic skeletal muscle stretch in decerebrate rats." Thesis, Kansas State University, 2017. http://hdl.handle.net/2097/38193.
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Master of ScienceDepartment of Kinesiology
Steven Copp
Mechanical and metabolic signals arising during skeletal muscle contraction reflexly increase sympathetic nerve activity and blood pressure (i.e., the exercise pressor reflex). In a rat model of simulated peripheral artery disease (PAD) in which a femoral artery is chronically (~72 hours) ligated, the mechanically-sensitive component of the exercise pressor reflex during 1 Hz dynamic contraction is exaggerated compared to that found in normal rats. Whether this is due to an enhanced acute sensitization of mechanoreceptors by metabolites produced during contraction or involves a chronic sensitization of mechanoreceptors is unknown. To investigate this issue, in decerebrate, unanesthetized rats we tested the hypothesis that the increases in mean arterial blood pressure (MAP) and renal sympathetic nerve activity (RSNA) during 1 Hz dynamic stretch are larger when evoked from a previously “ligated” hindlimb compared to those evoked from the contralateral “freely perfused” hindlimb. Dynamic stretch provided a mechanical stimulus in the absence of contraction-induced metabolite production that replicated closely the pattern of the mechanical stimulus present during dynamic contraction. We found that the increases in MAP (freely perfused: 14±1, ligated: 23±3 mmHg, p=0.02) and RSNA were significantly greater during dynamic stretch of the ligated hindlimb compared to the increases during dynamic stretch of the freely perfused hindlimb. These findings suggest that the exaggerated mechanically-sensitive component of the exercise pressor reflex found during dynamic muscle contraction in this rat model of simulated PAD involves a chronic sensitizing effect of ligation on muscle mechanoreceptors and cannot be attributed solely to acute contraction-induced metabolite sensitization.
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Kostyszyn, Beata. "Studies of presenilin function in neurodegeneration and in human embryonic CNS during development /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-961-7/.
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Wirdefeldt, Karin. "Studies of genetic and environmental influences on Parkinson's disease /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-771-1/.
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Craig, Lorraine Clare. "The experience of trauma and health anxiety in complex Chronic Obstructive Pulmonary Disease (COPD) : a cross sectional study." Thesis, University of Leicester, 2016. http://hdl.handle.net/2381/38221.
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Chronic Obstructive Pulmonary Disease (COPD) is a degenerative respiratory condition in which lung functioning is significantly impaired. COPD is one of the leading causes of morbidity and mortality worldwide and is associated with significant societal and personal costs. This thesis sought to better understand the psychological impact of COPD on individuals with the disease and those who provide familial/informal care to individuals with COPD. Literature Review: COPD confers significant burden to individuals undertaking informal care, yet no previous reviews had focused exclusively or systematically on the psychological impact of caregiving in COPD. The current review examined quantitative studies assessing the prevalence and predictors of psychological distress in COPD carers. Twelve studies were elicited, revealing caring for individuals with COPD was associated with increased psychological distress, notably high prevalence of self-reported anxiety and depression. Findings related to the predictors of psychological morbidity in COPD carers were equivocal, not allowing for firm conclusions to be drawn; further research regarding predictors of psychological morbidity amongst COPD caregivers is warranted. Empirical Study: The current study examined the prevalence of posttraumatic stress disorder (PTSD) and health anxiety in individuals with complex COPD, and whether these variables predicted the variance in psychological morbidity and health related quality of life. A total of sixty COPD patients were recruited from an outpatient clinic. Results indicated clinically significant PTSD in 13% of the sample, and 48% of the sample had clinically significant health anxiety. Health anxiety accounted for a small but significant amount of variance in anxiety, depression and health related quality of life. PTSD symptom severity showed no relationship with the same variables, which was surprising. Possible explanations were explored. Further research examining these relationships is recommended, to support the development of targeted interventions for those with COPD.
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Machhada, A. "Control of the heart by neurones of the dorsal motor nucleus of the vagus nerve (DVMN) in health and disease." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1473291/.
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The strength, functional significance and origins of parasympathetic (vagal) control of left ventricular function remain controversial. Experimental studies conducted on rats and mice using methods of genetic neuronal targeting, functional neuroanatomical mapping, and pharmaco- and optogenetics were employed to test the hypothesis that parasympathetic control of the left ventricle is provided by vagal preganglionic neurones of the dorsal motor nucleus (DVMN). The results of the experiments described in this thesis suggest that (i) activity of the DVMN vagal preganglionic neurones are responsible for tonic parasympathetic control of ventricular excitability, likely to be mediated by nitric oxide; (ii) synuclein deficiency (a model relevant to Parkinson's disease) results in a reduction in the activity of the DVMN neurones affecting the electrophysiological properties of the ventricle; (iii) tonic muscarinic influence on left ventricular contractility is provided by a subpopulation of vagal preganglionic neurones located in the caudal region of the left DVMN; (iv) reduced activity of the DVMN neurones is associated with a severely compromised aerobic exercise capacity; (v) increased activity of the DVMN neurones improves left ventricular performance and exercise capacity; and (vi) recruitment of the DVMN activity is sufficient to preserve exercise capacity and left ventricular function in heart failure developing after a myocardial infarction. These findings provide the first insight into the central nervous substrate that underlies functional parasympathetic innervation of the ventricles and highlight its importance in controlling cardiac function. The data obtained suggest that the DVMN neuronal projections provide tonic restraining influence on the ventricular arrhythmic potential and contractility, and have a trophic effect maintaining the ability of the heart to mount an appropriate inotropic response during exercise. As such, DVMN activity has a significant beneficial effect on the healthy left ventricle as well as ventricular myocardium compromised by occlusion of a major coronary artery.
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Singer, Cherie A. "Neurotrophic and neuroprotective effects of estrogen /." Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/6301.
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Feltrin, Fabrício Stewan. "Estudo prospectivo dos achados de ressonância magnética de pacientes com lesão axonial difusa traumática." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5151/tde-11092017-091106/.
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Introdução: Pacientes que sobrevivem ao traumatismo crânio-encefálico (TCE) apresentam declínio cognitivo e sinais indiretos de atrofia cerebral maiores que o esperado para a população normal. Dentro do universo das lesões englobadas sob o termo TCE há diferentes tipos de lesões, que podem ser divididas entre focais e difusas. A lesão axonial difusa (LAD), está presente em quase todos os pacientes com TCE moderado e grave. Não há estudos que descrevam longitudinalmente o que ocorre nos exames de imagem após o TCE em um grupo com diagnóstico clínico e radiológico de LAD sem lesões focais significativas. Este estudo tem como objetivo avaliar a carga de lesões da LAD através de uma contagem sistematizada, avaliar a taxa de atrofia de diferentes compartimentos do encéfalo de forma longitudinal, e verificar se o número de lesões mostra correlação com tais taxas de atrofia e ou com testes neuropsicológicos que avaliam desempenho executivo e de memória. Método: Foram selecionados 24 pacientes com diagnóstico clínico-radiológico de LAD e realizados exames de RM nos meses 2 (fase 1), 6 (fase 2) e 12 (fase 3) após o TCE. Nas fases 2 e 3 foi realizada avaliação neuropsicológica. Foi realizada contagem de lesões segundo a Microbleed Anatomical and Rating Scale (MARS). Nos definidos momentos foi realizada avaliação do volume do encéfalo através do software FreeSurfer. Foram avaliados a capacidade executiva através dos testes Trail Making Test (TMT) A e B, e a capacidade de recordação através do teste Hopkins Verbal Learning Test (HLVT) em seus componente de recordação imediata (HVLT-RI), tardia (RVLT-RT) e reconhecimento (HVLT-R). Foi testada correlação da carga lesional com a redução de volume dos compartimentos substância branca (VSB), substância cinzenta cortical (VCC), substância cinzenta subcortical (VCS) volume cerebral total (VCT). Foram ainda realizados testes de correlação da carga lesional total e por sítio anatômico com os testes TMT e HVLT e de correlação do grau de atrofia do VSB, VCC, VCS e VCT com os testes HVLT e TMT. Foram considerados positivos os resultados com p<0,05. Resultados: O VSB foi significativamente diferente entre as fases 2 e 3 e entre as fases 1 e 3, com redução de volume de 4,0% no intervalo total do estudo. O VCT foi significativamente diferente entre as fases 2 e 3 meses e entre as fases 1 e 3, com redução de volume de 1,9% no intervalo total do estudo. O VCC não foi significativamente diferente nas 3 fases. O VCS foi significativamente diferente entre as fases 1 e 2; fases 2 e 3 e entre as fases 1 e 3, com redução de volume de 3,7%. O número médio de lesões pela tabela MARS foi de 128 (DP 95), e mostrou correlação positiva e significativa com a redução do VSB, e não demonstrou correlação com a redução de volume dos demais compartimentos. Houve diferença significativa nos resultados dos testes TMT-A e TMT-B entre as fases 2 e 3, com maior rapidez na execução do teste na fase 3. Houve diferença significativa entre os resultados do teste HVLT-RI as fases 2 e 3, com maior número de palavras recordada na fase 3. Não houve diferença significativa nos resultados dos testes HVLT-RT e HVLT-R nas 2 fases. Houve correlação entre o resultado dos testes TMT-B nas fases 2 e 3 com a redução do VCT e entre os resultados do teste TMT-A na fase 3 com a redução do VSB. Não foi encontrada qualquer correlação entre o número de lesões segundo o sítio anatômico da tabela MARS com o desempenho nos testes TMT-A ou TMT-B. Não foi encontrada correlação entre os testes HVLT-RI, HVLT-RT ou HVLT-R com a redução dos volumes de VCT, VSB ou VCC. Discussão e Conclusões: Houve redução significativa do VCT, VSB e VCC ao longo do intervalo entre as fases 1 e 3 do estudo, e simultaneamente houve melhora no desempenho dos testes executivos TMT-A e TMT-B. Tais achados podem ser interpretados como uma resultante daquilo que modelos animais têm demonstrado na evolução do TCE: existe um processo contínuo no tecido cerebral após o TCE, que inclui o clareamento dos debris celulares irremediavelmente lesados e reparação de parte do tecido neural que sofreu lesões reversíveis no momento do trauma, tudo isso contribuindo para uma melhora no desempenho cognitivo, ao mesmo tempo em que ocorre redução do volume dos compartimentos encefálicos. A avaliação da carga lesional mostrou-se de valor prognóstico, pois manteve correlação com o grau de atrofia do VSB no intervalo do estudoIntroduction: Patients who survive traumatic brain injury (TBI) present cognitive decline and indirect signs of brain atrophy greater than expected for the normal population. Within the universe of injuries encompassed under the term TBI there are different types of injuries, which can be divided between focal and diffuse. Diffuse axonal injury (DAI) is present in almost all patients with moderate and severe TBI. There are no longitudinal studies describing imaging findings after TBI in a group with clinical and radiological diagnosis of DAI without significant focal lesions. This study aims to evaluate the DAI lesion load through a systematic counting approach, to evaluate longitudinally the atrophy rate of various brain compartments and to verify correlations between the lesion load and atrophy rates and their correlation with neuropsychological tests evaluating executive and memory performances. Method: 24 patients with clinical and radiological diagnosis of DAI were selected and they were submitted to MRI scans in 2, 6 and 12 months after TBI, as defined as the phase 1, phase 2, and phase 3 of the study. In phases 2 and 3 neuropsychological assessment was performed. Lesion load was quantified according to Microbleed Anatomical and Rating Scale (MARS). In all the 3 phases brain volume assessment was performed by FreeSurfer software. The executive capacity was evaluated by the Trail Making Test (TMT) A and B, and the memory capacity by the Hopkins Verbal Learning Test (HLVT) in its immediate recall component (HVLT-IR), late recall (RVLT-LR) and recognition (HVLT-R). The lesional load was correlated to the reduction in white matter volume (WMV), cortical gray matter volume (CGV), and subcortical gray matter (SGV) and total brain volume (TBV). Correlation of the total lesion load and anatomical site were correlated to TMT and HVLT tests. It was also performed correlation between degree of atrophy of the WMV, CGV, SGV and TGV with HVLT and TMT tests. Positive results were considered with p < 0.05. Results: The WMV was significantly different between phases 2 and 3 and between phases 1 and 3, with volume reduction of 4.0% in the total study interval. TBV was significantly different between the phases 2 and 3 and between phases 1 and 3, with volume reduction of 1.9% in the total study interval. The CGV was not significantly different in any of the 3 phases. The SGV was significantly different between phases 1 and 2, phases 2 and 3 and between phases 1 and 3, with 3.7% volume reduction in the total study interval. The mean lesion load assessment by MARS was 128 (SD 95) and showed a positive and significant correlation with the reduction in the WMV, and no correlation with the volume reduction of the other evaluated compartments. There were significant differences in the results of the TMT-A and TMT-B tests between phases 2 and 3, with faster execution of the test in phase 3. There were significant differences between the HVLT-IR results phases 2 and 3, with the largest number of words recalled in phase 3. There were no significant differences in the results of HVLT-LR tests and HVLT-R in 2 phases. There were correlations between the result of TMT-B test at phases 2 and 3 to the reduction of the TBV and the results of the TMT at phase 3 to the WMV reduction. There were no correlations between the anatomical site lesion load with the performance in the TMT-A and TMT-B. No correlations were found between HVLT-IR, HVLT-LR or HVLT-R with volume reduction of TBV, WMV or CGM. Discussion and Conclusions: There was a significant volume reduction in TBV, WMV and SGV during the study interval, while there was an improvement the executive tests TMT-A and TMT-B performance. These findings can be interpreted as a result of what animal models have shown the evolution of the ECT: there is a continuous process in the brain tissue after TBI, including clearing irreparably damaged cell debris and repair of the neural tissue components that suffered reversible injuries at the moment of trauma. Those processes contribute to an improvement in cognitive performance, while reduction of the volume of the encephalic compartments occurs at the same time. The lesion evaluation has proven its prognostic value as it showed correlation with the degree of WMV reduction
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Tzekova, Nevena [Verfasser], Patrick [Akademischer Betreuer] Küry, and Thomas [Akademischer Betreuer] Klein. "Immunoglobulin dependent modulation of Schwann cell differentiation: Implications for peripheral nerve damage and disease. / Nevena Tzekova. Gutachter: Patrick Küry ; Thomas Klein." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2016. http://d-nb.info/1084873141/34.
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Johnson, Luke A. "Locus Coeruleus and Hippocampal Tyrosine Hydroxylase Levels in a Pressure-Overload Model of Heart Disease." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/honors/288.
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Studies have indicated that approximately 30% of people with heart disease experience major depressive disorder (MDD). Despite strong clinical evidence of a link between the two diseases, the neurobiological processes involved in the relationship are poorly understood. A growing number of studies are revealing similar neuroanatomical and neurochemical abnormalities resulting from both depression and heart disease. The locus coeruleus (LC) is a group of neurons in the pons that synthesize and release norepinephrine, and that is known to play a significant role in depression pathobiology. For example, there is evidence that tyrosine hydroxylase (TH) is elevated in the LC in depression. In addition, there is evidence that the LC plays a role in cardiovascular autonomic regulation. The hippocampus is another region that exhibits abnormalities in both depression and heart disease. In this study, the levels of TH in the hippocampus and LC were examined in the guinea pig pressure-overload model of heart disease. TH levels were also measured in the pressure-overload model treated with vagal nerve stimulation, a new investigational therapeutic intervention in heart disease. This study found that there were no changes in TH levels in the LC or the hippocampus of the pressure-overload model or in the pressure-overload model treated with vagal nerve stimulation.