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MURANO, CARMEN. « Channelopathies and epileptic syndromes : characterization of novel variants associated with progressive epileptic encephalopathy and in vitro validation of therapeutic approaches ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2022. http://hdl.handle.net/10281/365090.
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L’epilessia è un disturbo neurologico caratterizzato da episodi ricorrenti di disfunzioni elettriche cerebrali chiamate crisi epilettiche. Il coinvolgimento dei canali ionici HCN (Hyperpolarization-activated Cyclic Nucleotide-gated) nel processo di epilettogenesi è stato recentemente messo in evidenza. Questo studio presenta il caso di un paziente affetto da encefalopatia epilettica progressiva farmaco-resistente. La malattia è caratterizzata da un grave ritardo nello sviluppo, atassia, distonia, deficit visivo cerebrale. L’analisi genetica ha riscontrato nel paziente una mutazione missenso a carico del gene HCN2 cha causa una sostituzione amminoacidica a livello del residuo Glicina in posizione 460 del segmento transmembrana S6 (p.Gly460Asp). Esperimenti condotti con la tecnica del patch-clamp in modalità whole-cell su cellule HEK293 e su colture primarie di neuroni corticali di ratti neonatali hanno evidenziato una significativa riduzione della corrente ionica in presenza della mutazione. Inoltre, risulta alterata anche l’eccitabilità della membrana neuronale. Gli esperimenti di immunofluorescenza suggeriscono una compromissione della traslocazione della proteina HCN2 mutata in membrana, la quale sembra accumularsi in posizione peri-nucleare. Inoltre, la proteina mutata p.Gly460Asp ha effetti negativi anche sulla funzionalità del canale HCN1, con il quale HCN2 forma eteromeri funzionali. Si tratta quindi di una mutazione che provoca una loss-of-function della proteina coinvolta e che, potenzialmente, ha effetto anche sul controllo generale dell’eccitabilità neuronale. I dati ottenuti sono parte di un manoscritto che verrà a breve sottomesso.
Dal punto di vista farmacologico, il paziente mostra un’eccellente risposta clinica alla dieta chetogenica, un regime alimentare ad alto contenuto di grassi e bassa quantità di carboidrati che, attraverso la β-ossidazione degli acidi grassi, porta alla produzione epatica di corpi chetonici, usati in molti tessuti extra-epatici come fonte di energia e come agenti pleiotropici ad azione anti-infiammatoria. Pertanto, si ritiene che il regime chetogenico possa migliorare le condizioni cliniche dei pazienti influenzando l’organismo nel suo insieme. Per queste ragioni, una linea della ricerca condotta si è concentrata sugli effetti di ambiente chetogenico su una coltura neuronale. L’interesse riguardo gli effetti positivi della dieta chetogenica su pazienti epilettici, ha portato alla pubblicazione di una review (Murano C, et al. Effect of the ketogenic diet in excitable tissues. Am J Physiol Cell Physiol. 2021;320(4):C547-C553. doi: 10.1152/ajpcell.00458.2020. PMID: 33502948), mentre per quanto riguarda la sezione sperimentale, i dati sono parte di un manoscritto attualmente in preparazione.
L’encefalopatia epilettica dello sviluppo è associata anche a varianti in canali di potassio voltaggio dipendenti della sottofamiglia Q membro 2 (KCNQ2). Grazie ad una collaborazione in essere con l’Università Federico II di Napoli, la variante p.G310S nel gene KCNQ2, responsabile del disturbo, è stata caratterizzata in un modello di cellule CHO (Chinese Hamster Ovary) e in un modello di neuroni corticali derivanti da ratti neonatali risultando in una loss-of-function. Il paziente portatore della mutazione mostrava una completa disorganizzazione dell’attività di fondo nelle registrazioni elettroencefalografiche (EEG), migliorate dopo trattamento con Gabapentin, un attivatore del canale. Sono stati indagati gli effetti di Gabapentin su questa specifica mutazione p.G310S fornendo prove dell’effetto positivo nel trattamento dell’encefalopatia epilettica dello sviluppo causata da mutazioni loss-of-function a carico di KCNQ2. I risultati ottenuti sono stati recentemente pubblicati (Soldovieri MV, et al. Gabapentin treatment in a patient with KCNQ2 developmental epileptic encephalopathy. Pharmacol Res. 2020;160:105200. doi: 10.1016/j.phrs.2020.105200. PMID: 32942014).Epilepsy is a chronic neurological disorder supported by recurrent episodes of brain electrical dysfunctions called epileptic seizures. The involvement of HCN (Hyperpolarization-activated Cyclic Nucleotide-gated) ion channels in the epileptogenesis process has recently been highlighted. This study presents the case of a patient with drug-resistant progressive epileptic encephalopathy. Clinically, the disease is characterized by severe developmental delay, ataxia, dystonia, cerebral visual impairment. Genetic analysis revealed the presence in the DNA of the patient a missense mutation in the HCN2 gene which causes an amino acid substitution at the level of the Glycine residue in position 460 of the transmembrane segment S6 (p.Gly460Asp). Experiments conducted with the whole-cell patch-clamp technique on HEK293 cells and primary cultures of cortical neurons from neonatal rats showed a significant reduction in the ion current density when the mutation was present. Furthermore, the excitability of the neuronal membrane was also altered. Immunofluorescence experiments suggest an impairment of the translocation of the membrane-mutated HCN2 protein, which appears to accumulate in a peri-nuclear position. Furthermore, the mutated protein p.Gly460Asp also had negative effects on the functionality of the HCN1 channel, with which HCN2 forms functional heteromers. Therefore, this mutation causes a loss-of-function of the protein involved and, potentially, it also has an effect on the general control of neuronal excitability. The data obtained are part of a manuscript that will be submitted shortly. The patient showed an excellent clinical response to the ketogenic diet, a high fat and low carbohydrates diet which, through the β-oxidation of fatty acids, leads to the hepatic production of ketone bodies, used in many extra-hepatic tissues as a source of energy and as pleiotropic and anti-inflammatory agents. Ketogenic regimen can improve the clinical condition of patients affect the organism as a whole. For these reasons, a line of research conducted has focused on the effects of the ketogenic environment on a neuronal culture and in particular on the characterization of the p.Gly460Asp mutation. The interest in the positive effects of the ketogenic diet on epileptic patients led to the publication of a review (Murano C, et al. Effect of the ketogenic diet in excitable tissues. Am J Physiol Cell Physiol. 2021; 320 (4): C547-C553. Doi: 10.1152 / ajpcell.00458.2020. PMID: 33502948), while for the experimental section, the data are part of a manuscript currently in preparation. Developmental epileptic encephalopathy is also associated with variants in voltage-dependent potassium channels of the subfamily Q member 2 (KCNQ2). Thanks to an existing collaboration with Prof. Taglialatela at the Federico II University of Naples, the p.G310S variant in the KCNQ2 gene, responsible for early onset epileptic encephalopathy, has been functionally characterized in a CHO (Chinese Hamster Ovary) cell model and in a model of cortical neurons derived from neonatal rats resulting in a loss-of-function. The patient carrying the mutation showed a complete disorganization of the background activity in the electroencephalographic (EEG) recordings. The "burst-suppression pattern" shown in the EEG improved after treatment with Gabapentin, a channel activator. Based on this clinical improvement, the effects of Gabapentin on p.G310S mutation were investigated providing evidence of the positive effect of this specific drug in the treatment of developmental epileptic encephalopathy caused by loss-of-function mutations by KCNQ2. Again, the results obtained have been recently published (Soldovieri MV, et al. Gabapentin treatment in a patient with KCNQ2 developmental epileptic encephalopathy. Pharmacol Res. 2020; 160: 105200. Doi: 10.1016 / j.phrs.2020.105200. PMID : 32942014).
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Wadzinski, Jim, Ronald Franks, David S. Roane et Max Bayard. « Valproate Associated Hyperammonemic Encephalopathy ». Digital Commons @ East Tennessee State University, 2007. https://dc.etsu.edu/etsu-works/7167.
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The use of valproic acid (VPA) (also known as Depakote, Depakene, and others) frequently results in elevated plasma ammonia. In some people, hyperammonemia may be clinically significant, resulting in hyperammonemic encephalopathy, which may be severe. Valproic acid-induced hyperammonemic encephalopathy may occur in people with normal liver function, despite normal doses and serum levels of VPA. We describe 2 cases of valproic acid-induced hyperammonemic encephalopathy in patients with supratherapeutic VPA levels, although the condition has been described in people with normal VPA levels. With the increasing indications and off-label uses of VPA, family physicians should be aware of this potential complication of VPA and check ammonia levels in patients taking VPA who present with alterations in mental status. Treatment with L-carnitine may be beneficial in reducing ammonia levels.
Valproic acid (VPA) is effective in the treatment of seizure disorders, bipolar disorder, migraine headache prophylaxis, neuropathic pain, restless legs syndrome, dementia-related agitation, and social anxiety disorder, among other conditions. VPA has numerous drug interactions and toxicities; severe toxicities include hepatic damage, pancreatitis, teratogenicity, thrombocytopenia, and hyperammonemia. Here we depict 2 case reports of VPA-induced hyperammonemic encephalopathy (VHE), both occurring in patietns with no history of underlying liver disease. In one instance, the patient was able to function, but with significant cognitive limitations. In the second case, the patient was comatose. Both of the patients we describe also had supratherapeutic VPA levels, but VHE is a well-documented potential complication of the use of VPA in the medical literature, and it may occur in people with normal VPA levels.1 Because of the wide spectrum of symptoms associated with VHE, physicians should consider hyperammonemia in the differential diagnosis of any patient taking VPA who shows changes in behavior, cognition, or orientation
3
Hadjihambi, Anna. « Neurochemistry of the hepatic encephalopathy ». Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/10038691/.
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The pathogenesis of hepatic encephalopathy (HE) in cirrhosis is multifactorial and the role of ammonia remains controversial. Experimental studies conducted in animal (rat) models of HE, in combination with pharmacological approaches, were used to test the hypothesis that during HE, chronic exposure to elevated ammonia concentrations alters cerebral oxygenation, compromises lactate transport between astrocytes and neurons, and impairs uptake of neurotransmitters. It was also hypothesised that HE impairs glymphatic clearance mechanisms, either as a cause or a consequence of the disease, which exacerbates the detrimental central nervous effects of the accumulated toxins. The results of the experiments described in this thesis suggest that in HE: a) ammonia compromises cerebral oxygenation, but does not affect cerebrovascular reactivity, b) ammonia mediates cortical hemichannel dysfunction and impairs channel-mediated lactate release, potentially interfering with the astrocyte-neuron lactate shuttle, c) hyperammonemia results in a significant increase in cortical extracellular glutamate concentration, which is exacerbated under hypoxic conditions, and d) efficacy of glymphatic clearance is affected in discrete regions of the brain, which aligns with specific cognitive/behavioral impairments. These findings provide the first evidence of a critical pathophysiological role of ammonia in inducing neuronal energy deficit in HE due to impaired cerebral oxygenation, compromised hemichannel-mediated lactate transport between astrocytes and neurons and affected glymphatic clearance.
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Tvayedg, Naceem Saad Munan. « Attention function in children undergoing encephalopathy ». Thesis, Sumy State University, 2015. http://essuir.sumdu.edu.ua/handle/123456789/41252.
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Gorden, Zachary Newton. « Chronic traumatic encephalopathy : a literary review ». Thesis, Boston University, 2012. https://hdl.handle.net/2144/12398.
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Thesis (M.A.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.As early as the 1920's it has been established that repetitive brain trauma, through activities such as boxing, can lead to progressive neurological degeneration. This was termed Dementia Pugilistica until the more recent and greater encompassing term Chronic Traumatic Encephalopathy came into use. Chronic Traumatic Encephalopathy is a progressive neurodegenerative disease that is believed to be caused, or at least associated with, repetitive brain trauma on the concussive and sub concussive level. Clinically, Chronic Traumatic Encephalopathy is associated with a bevy of abnormal symptoms; ranging from personality changes, behavioral abnormalities, memory and mood disturbances as well as certain Parkinsonian symptoms like speech and gait abnormalities. Pathologically, Chronic Traumatic Encephalopathy is distinguished by a certain gross scale criteria, including but not limited too: wide spread atrophy of the brain tissue (most notably the cerebral hemispheres) and dilation of the ventricles and fenestration of the cavum septum pellucidum. The microscopic pathology of Chronic Traumatic Encephalopathy is also well established; it consists of extensive tau-immunoreactive neurofibrillary tangles and neuropil neurites concentrated in the depths of the sulci and perivascularly. In roughly half the cases of Chronic Traumatic Encephalopathy there is deposition of beta-amyloid plaques along with the tau-immunoreactive neurofibrillary tangles. Chronic Traumatic Encephalopathy can only be diagnosed post-mortem, leading to a vast array of issues in the detection and treatment of the disease. Much research has gone into potential diagnostic techniques that could greatly alter the lives of the athletes, military and civilians who are su±Iering from the symptoms of this disease. There is strong belief that early detection methods will be found, and these ideas center around in vivo imaging techniques, such as; Functional Magnetic Resonance Imaging and Single Photon Emission Computed Tomography, that would allow for physicians to pathologies before their overwhelming detriment. There is also study into proposed biomarkers, such as apolipoprotein-E, that could give indication of a higher susceptibility to degenerative neurologic disease such as Chronic Traumatic Encephalopathy.
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DI, MEO IVANO. « Altered Sulfide Metabolism in Ethylmalonic Encephalopathy ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2012. http://hdl.handle.net/10281/29887.
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Ethylmalonic Encephalopathy, EE, is an autosomal recessive, invariably fatal disorder characterized by early-onset brain failure, microangiopathy, chronic diarrhoea, defective cytochrome c oxidase (COX) in muscle and brain, and high excretion of ethylmalonic acid (EMA) in urine. ETHE1, a gene encoding a mitochondrial beta-lactamase-like, iron-coordinating metalloprotein, is mutated in EE. We generated an Ethe1-null mouse that manifested the EE cardinal features. We found that thiosulfate was excreted in massive amount in urines of both Ethe1-/- mice and EE patients. High thiosulfate (H2SSO3) and sulfide (H2S) levels were present in Ethe1-/- mouse tissues. Sulfide is a powerful inhibitor of COX and terminal beta-oxidation, with vasoactive and vasotoxic effects that could explain the microangiopathy in EE patients. Sulfide is detoxified by a mitochondrial pathway that includes a sulfur dioxygenase (SDO). SDO activity was absent in Ethe1-/- mice, whereas ETHE1 overexpression in HeLa cells and E. coli markedly increased it. Therefore, ETHE1 is a mitochondrial SDO involved in catabolism of sulfide, which accumulates to toxic levels in EE.
An important question that warranted the PhD experimental work concerns the source of H2S in ETHE1 mutant patients, and how accumulated sulfide can act on the cytochrome c oxidase complex at molecular level. The presence of elevated levels of thiosulfate in several tissues of the Ethe1-/- mouse suggests endogenous production of H2S from catabolism of cysteine and other sulfur-containing organic compounds. H2S is also a major product of the intestinal bacterial flora, especially anaerobic species residing in the colon. The presence of a gradient of COX deficiency in luminal vs. cryptal colonocytes in Ethe1-/- colon mucosa suggests that a defect of ETHE1-SDO activity results in faulty detoxification of exogenously produced H2S. In order to achieve effective reduction of H2S production, it is crucial to clarify which are the sources of this compound in the body that can then constitute specific targets for therapy. Another important issue is to understand the organ-specific mechanisms, which lead to failure of some organs, such as the brain and the skeletal muscle, but not of others, such as the liver. These aims can be implemented through the creation and characterization of conditional tissue-specific KO animals.
A further research line concerns the improvement of biochemical and molecular approaches for the diagnosis of EE.
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Vessal, Mani. « A spongiform encephalopathy outbreak, anthropophagy or not ? » Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ48417.pdf.
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Shawcross, Deborah Lindsay. « Ammonia, infection and inflammation in hepatic encephalopathy ». Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1445060/.
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For over a century, we have known that ammonia is important in the pathogenesis of hepatic encephalopathy. Studies in patients with acute liver failure have shown rapid progression to severe encephalopathy in those patients with evidence of a systemic inflammatory response, suggesting a possible link between inflammation and encephalopathy. In view of the growing evidence to support the role of inflammation in increasing the susceptibility of the brain to the effects of hyperammonemia in liver disease, 3 hypotheses were explored: 1: Inflammation and infection are important in hepatic encephalopathy. 2: Inflammation and infection act synergistically with ammonia. 3: Ammonia makes the immune system more susceptible to infection. In the first of 2 clinical studies, inflammation was shown to be an important determinant of the presence and severity of minimal hepatic encephalopathy. In a second study, significant deterioration of neuropsychological test scores in patients with cirrhosis following induced hyperammonemia during the inflammatory state, but not after its resolution, suggested that inflammation may be important in modulating the cerebral effect of ammonia in liver disease, supporting the first hypothesis. Ammonia and inflammation were shown to be synergistic in the bile duct ligated rat which showed increased brain water and astrocyte swelling exacerbated by endotoxin and accompanied by a rise in nitric oxide and brain nitrotyrosine, but not in plasma ammonia, suggesting nitric oxide may play an important synergistic role in the pathogenesis of hepatic encephalopathy. Ammonia was shown to impair neutrophil function by reducing phagocytosis, inducing spontaneous respiratory burst and cell swelling. The p38"MAPK pathway was shown to be important and a p38"MAPK agonist prevented neutrophils from swelling in the presence of ammonia and improved phagocytosis. While cultures of muscle cells were a potentially interesting direction to take to investigate the effect of inflammation on the muscle uptake of ammonia, unfortunately the resulting data demonstrated a low glutamine synthetase activity. In conclusion, these studies illustrate the important factors that modulate the manifestation of symptoms of hepatic encephalopathy in cirrhosis, the most important of which is the synergistic role of inflammation and ammonia. Furthermore, the ammonia-induced impairment of neutrophil function may, in part, account for the increased susceptibility to infection found in patients with cirrhosis.
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Vessal, Mani Carleton University Dissertation Sociology and Anthropology. « A Spongiform encephalopathy outbreak : anthropophagy or not ? » Ottawa, 1999.
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Bergqvist, Peter B. F. « Tryptophan-related neurotransmission in the brain disturbances associated with experimental hepatic encephalopathy / ». Lund : Dept. of Clinical Pharmacology, Institute of Labortaory Medicine, Lund University Hospital, 1997. http://catalog.hathitrust.org/api/volumes/oclc/39761954.html.
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Hazell, Alan Stewart. « The pathophysiology of pyrithiamine-induced thiamine deficiency encephalopathy ». Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=28776.
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Pyrithiamine-induced thiamine deficiency (PTD) in the rat results in a metabolic disorder associated with selective cerebral vulnerability. The basis of the histological lesions that develop in areas that include the thalamus, medial geniculate, and inferior colliculus is undetermined but an underlying glutamate-mediated form of excitotoxicity may be responsible. This work examines the possibility that PTD leads to changes in extracellular glutamate concentration, membrane polarization status, and gene expression consistent with a decreased ability to maintain homeostatic integrity.At the acute symptomatic stage, extracellular glutamate by concentration as determined microdialysis was found to be elevated in the thalamus but within normal limits in the non-vulnerable parietal cortex. This result suggests an involvement of glutamate in the pathogenesis of thiamine deficiency lesions. An in vivo examination of L-type voltage-sensitive calcium channel activity using quantitative autoradiography and ($ sp3$H) -nimodipine at the same stage of PTD revealed that increased activity was present in and localized to the thalamus, but was absent in areas resistant to histological damage. The finding indicates a likelihood of regional depolarization. Finally, induction of the proto-oncogene c-fos was detected in the thalamus and inferior colliculus with quantitative in situ hybridization analysis at the acute symptomatic stage, thereby confirming the association of PTD with depolarization-related events occurring in advance of the appearance of frank infarction.
Together, these results suggest that vulnerability in the thalamus may be determined by an inability to maintain spatial buffering of extracellular glutamate under energy-compromised conditions. Such an environment may be sufficient to set into motion event cascades in these cells that lead to the demise of the structure as a whole.
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Harijan, Pooja Devi. « Defining features and aetiology of hypoxic-ischaemic encephalopathy ». Thesis, University of Leicester, 2018. http://hdl.handle.net/2381/42929.
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This thesis seeks to set out the background, methods, results and discussion and conclusion of an observational study of the defining features and aetiology of moderate-severe hypoxic-ischaemic encephalopathy (HIE). Firstly, the epidemiology, pathophysiology and treatment of HIE are outlined. A number of existing epidemiological definitions are described, compared and contrasted. The difficulties of defining HIE clearly and consistently for epidemiological purposes are discussed. The role of intrapartum hypoxia and other aetiological factors in HIE is introduced. The challenges of exploring the aetiology of HIE are discussed. The consideration of potential methodologies to study this topic is described. The aims and objectives of the study are presented. The design of the study and study components are each then described in turn. These include the pilot study, retrospective cohort study, development of a reference standard by expert consensus, observational study of possible aetiological factors, and measurement of validity of epidemiological definitions are each described in turn. The results of the study are described in turn. 168 infants with symptoms of neonatal encephalopathy were identified and notes were obtained for 153 of these infants. The observed maternal, neonatal and paediatric features of these infants and the development of a reference standard by expert consensus are described. The application of the reference standard to the study population leading to the identification of 54 infants with neonatal encephalopathy (NE) of whom 29 (53.7%) infants had moderate-severe HIE, is described. The prevalence of possible aetiological factors in infants with NE and the HIE and non-HIE subgroups are described. Finally, the study findings, strengths and limitations are discussed. The defining features of HIE and the prevalence of risk factors in this population compared to similar studies where available, are presented. The implications of these findings for future clinical practice and research are discussed.
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Lerch, Stefanie. « Studies into the mechanism of ifosfamide-induced encephalopathy / ». Basel : [s.n.], 2004. http://edoc.unibas.ch/diss/DissB_6833.
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Dennis, Claude Vincent. « The Role Of Cell Proliferation In Hepatic Encephalopathy ». Thesis, The University of Sydney, 2017. http://hdl.handle.net/2123/17568.
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Chronic alcohol misuse or alcohol use disorder is a common problem worldwide. Excessive alcohol consumption can affect almost every organ in the body but neurological complications can occur due to acute intoxicating effects as well as longer term damage known as alcohol-related brain damage. The cognitive impairments associated with chronic alcohol misuse can be compounded by associated liver damage leading to an increase in circulating neurotoxic substances such as ammonia giving rise to a condition known as hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is currently unknown however animal models of alcohol misuse suggest that aberrant cell proliferation attributed to neurogenesis may play a role. Neurogenesis occurs in the adult mammalian brain in two neurogenic niches the subventricular zone lining the lateral ventricles and the subgranular zone of the hippocampus and involves the proliferation of a neural stem cell and eventual integration of an immature neuron into the existing circuitry. Although this process has been widely proven in animals its existence in humans remains controversial. So, prior to addressing a role for neurogenesis in disease its existence needs to be proven in normal individuals. Here, cell proliferation and neurogenesis were simultaneously examined in the subventricular zone and subgranular zone of 23 individuals aged 0.2-59 years, using immunohistochemistry and immunofluorescence in combination with unbiased stereology. This demonstrated a marked decline in proliferating cells in both the subventricular zone and subgranular zone in early infancy such that the levels of proliferation were similar to the adjacent parenchyma by four and one years, respectively. Furthermore, the phenotype of proliferating cells changed with age such that in the adult subventricular zone and subgranular zone, and adjacent parenchyma, all proliferating cells co-localised with the microglial marker, Iba1. Taken together this suggests that adult neurogenesis is a residual process and that any potential disease-related alterations in proliferation in the adult brain are likely associated with microglia. Indeed, widespread proliferating cells that co-localised with the microglial marker Iba1 were found in a subset of chronic alcoholics with a pathological diagnosis of HE. In contrast cases without microglial proliferation displayed microglial dystrophy and associated neuronal loss in the prefrontal cortex. There were no obvious differences between these subsets from the clinical and pathological data available. To determine the cause and pathogenic significance of this microglial proliferation, a pilot study was conducted to develop an animal model of chronic hepatic encephalopathy using the hepatotoxin, thioacetamide and combinations of known risk factors for hepatic encephalopathy; chronic alcohol use and a high-fat diet. Animals receiving thioacetamide had macroscopic evidence of liver injury, elevations of transaminases and associated anxiety-like behaviour measured in an open-field test. There were however no associated microglial or astrocytic changes in these animals and combinations of alcohol and high-fat diet had no additional effects. In conclusion, this work has shown that the majority of the rare proliferative events in the adult human brain are microglia. Chronic alcoholism with a pathological diagnosis of hepatic encephalopathy results in shifts in microglial phenotype with one subset of patients demonstrating proliferation and another dystrophy. Future work is required to develop an animal model of chronic hepatic encephalopathy, where the role of microglial dysfunction in hepatic encephalopathy pathogenesis can be further elucidated.
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Malaguarnera, Michele. « Role of Acetyl-L-Carnitine in Hepatic Encephalopathy ». Doctoral thesis, Università di Catania, 2014. http://hdl.handle.net/10761/1518.
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Hepatic encephalopathy is a common complication of hepatic cirrhosis. The clinical diagnosis is based on two concurrent types of symptoms: impaired mental status and impaired neuromotor function. Impaired mental status is characterized by deterioration in mental status with psychomotor dysfunction, impaired memory, and increased reaction time, sensory abnormalities, poor concentration, disorientation and coma. Impaired neuromotor function include hyperreflexia, rigidity, myoclonus and asterixis. The pathogenesis of hepatic encephalopathy has not been clearly defined. The general consensus is that elevated levels of ammonia and an inflammatory response work in synergy to cause astrocyte to swell and fluid to accumulate in the brain which is thought to explain the symptoms of hepatic encephalopathy. Acetyl-L-carnitine, the short-chain ester of carnitine is endogenously produced within mitochondria and peroxisomes and is involved in the transport of acetyl-moieties across the membranes of these organelles. Acetyl-L-carnitine administration has shown the recovery of neuropsychological activities related to attention/concentration, visual scanning and tracking, psychomotor speed and mental flexibility, language short-term memory, attention, and computing ability. In fact, Acetyl-L-carnitine induces ureagenesis leading to decreased blood and brain ammonia levels. Acetyl-L-carnitine treatment decreases the severity of mental and physical fatigue, depression cognitive impairment and improves health-related quality of life. The aim of this review was to provide an explanation on the possible toxic effects of ammonia in HE and evaluate the potential clinical benefits of ALC.
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García, Martínez Rita. « Cognotive function and liver transplantation : implications of hepatic encephalopathy ». Doctoral thesis, Universitat Autònoma de Barcelona, 2011. http://hdl.handle.net/10803/48640.
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La encefalopatía hepática ha sido históricamente considerada como un síndrome neuropsiquiátrico reversible y el astrocito la célula diana afectada. El trasplante hepático ha demostrado su capacidad de mejorar las alteraciones cognitivas y neurorradiológicas asociadas con el fallo hepático y por otra parte, ha evidenciado la persistencia de déficits neuropsicológicos en algunos casos. Además, estudios de neuroimagen llevados a cabo en las últimas décadas han revelado la existencia de atrofia cerebral en pacientes con encefalopatía hepática crónica. Así pues, en los últimos años se ha sugerido que la encefalopatía hepática puede causar daño cerebral estructural y secuelas.
Esta tesis investiga la evolución de la función neuropsicológica y de la estructura cerebral después del trasplante hepático. Específicamente analiza el efecto de la encefalopatía hepática en la evolución neurológica postrasplante. Otras variables con posible influencia en la función cognitiva fueron también evaluadas.
Los objetivos de esta investigación se llevaron a cabo utilizando tests neuropsicológicos y resonancia magnética cerebral en estudios clínicos longitudinales.
Se documentó una evolución cognitiva heterogénea un año después del trasplante hepático. Varias condiciones clínicas pre-trasplante pueden afectar la función neurológica pos-trasplante. La encefalopatía hepática previa al trasplante se asoció a una alteración neurológica persistente (predominantemente en la función psicomotora) junto con el abuso de alcohol y la diabetes mellitus. Además, la encefalopatía hepática se asoció a un menor volumen cerebral, lo que sugiere una destrucción de tejido cerebral. El análisis de espectroscopia sugiere pérdida neuronal en relación a un menor volumen cerebral.
A largo plazo, la función cognitiva permanece estable a menos que se desarrollen enfermedades neurológicas de novo que causen deterioro cognitivo. De hecho, la enfermedad cerebrovascular de pequeño vaso se asoció con pérdida de memoria en aquellos pacientes que presentaban un mayor riesgo cardiovascular como la asociación de diabetes, hipertensión arterial e insuficiencia renal.
Algunos factores posiblemente implicados en el daño neurológico pos-trasplante podrían no haber sido adecuadamente investigados, debido principalmente a cuestiones metodológicas tales como el efecto de los fármacos inmunosupresores o la isquemia perioperatoria. Además, el hecho de que varios factores (alcohol, diabetes) afecten la función cognitiva hace difícil delimitar el daño causado estrictamente por la encefalopatía hepática. A pesar de estas limitaciones, esta investigación fuertemente sugiere que la encefalopatía hepática está asociada con daño cerebral estructural permanente y pérdida neuronal. Este concepto está refrendado por otras evidencias como la activación de mecanismos de muerte celular (estrés oxidativo, fracaso energético, inflamación) en la encefalopatía hepática. Además, la pérdida neuronal ha sido previamente demostrada en otras complicaciones neurológicas asociadas a la insuficiencia hepática como la degeneración cerebelosa y la degeneración hepatocerebral adquirida (no Wilsoniana).
Es importante destacar que el daño persistente es leve y que la función cognitiva después del trasplante hepático está globalmente, dentro de los límites de la normalidad.
Establecer una relación de causalidad entre encefalopatía hepática y pérdida de neuronas requiere mayor investigación. Sin embargo, los resultados de estos estudios pueden tener importantes implicaciones.
Desde un punto de vista patogénico, el concepto clásico de la encefalopatía hepática como una enfermedad exclusivamente astrocitaria debe ser reconsiderada.
Desde un punto de vista pronóstico, deben tenerse en cuenta algunas consideraciones. Así, estrategias dirigidas a evitar o minimizar la ocurrencia de la encefalopatía hepática pueden prevenir el deterioro cognitivo. Esto puede ser especialmente importante en aquellos pacientes con otras comorbilidades neurológicas o en riesgo de desarrollar deterioro cognitivo como los pacientes candidatos a trasplante hepático.Summary Historically, hepatic encephalopathy has been considered a reversible neuropsychiatric syndrome with the astrocyte as the pathological target. Implementation of liver transplantation showed the ability to improve cognitive and neuroradiological abnormalities related to liver failure and on the other hand revealed persistence of neuropsychological deficits in some cases. In addition, neuroimaging studies performed in recent decades unfolded brain atrophy in patients with chronic hepatic encephalopathy. Thus, last years pointed that hepatic encephalopathy may cause structural brain injure and sequels. This research investigates the outcome of neuropsychological function and brain structure following successful liver transplant. Specifically, the effect of hepatic encephalopathy and its outcome have been analyzed. Other variables with suspected influence in the cognitive function were also evaluated. These objectives were assessed by a dual approach of neuropsychological tests and magnetic resonance in longitudinal studies. A heterogeneous cognitive outcome was found after one year of successful liver transplantation. Several pre-transplant conditions can impair the pos-transplant neurological function. Hepatic encephalopathy has been linked to a persistent damage (predominantly in psychomotor function) in addition to alcohol abuse and diabetes mellitus. Besides, hepatic encephalopathy was associated to a decreased brain volume evoking loss of brain tissue. Spectroscopic analyses suggested neuronal loss with the smaller brain volume. At long-term, cognitive function remained stable unless de novo neurological diseases cause cognitive decline. In fact, small vessel cerebrovascular disease was associated with loss of memory in those patients with accumulation of cardiovascular risk factors such as diabetes mellitus and arterial hypertension. Some factors implicated in neurological injury may not be appropriately investigated due to methodological issues as immunosuppressive drug effects or perioperative ischemia. Additionally, the fact that other factors (e.g. alcohol, diabetes) affect cognitive function make difficult to define the damage due to hepatic encephalopathy. Despite these limitations, the present research strongly suggests that hepatic encephalopathy is associated with permanent structural injury and loss of neurons. This concept is supported by other lines of evidence such as activation of mechanism of cell death (oxidative/nitrosative stress, energy impairment and inflammation) in hepatic encephalopathy. Besides, neuronal loss has been previously demonstrated in other neurological diseases associated with liver failure as cerebellar degeneration and acquired hepatocerebral degeneration (non-Wilsonian). It is important to note that persistent damage is mild and on average, cognitive function after liver transplant remains within normal range. In order to establish a causal relationship further investigation is required. However, the results of this research can have important implications. From a pathogenic perspective, the classical consideration of hepatic encephalopathy as exclusively an astrocytic disease needs re-evaluation. From a clinical and prognostic point of view some considerations must be taken into consideration. Strategies focussed on avoiding or minimizing the occurrence of hepatic encephalopathy may prevent cognitive decline, especially in those patients with other neurological comorbidities and in those at risk of cognitive damage as liver transplant candidates.
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Brown, Katherine Frances Doel. « Reproductive performance of cattle affected with bovine spongiform encephalopathy ». Thesis, University of London, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269471.
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Smart, Kevin Arthur. « The mechanism by which hyperammonaemia may cause hepatic encephalopathy ». Thesis, King's College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267312.
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Khalid, Tanzeela Yasmin. « Breath analysis for the early recognition of hepatic encephalopathy ». Thesis, University of the West of England, Bristol, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.573489.
Texte intégralRésumé :
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome which develops commonly in liver cirrhosis following the build up of toxic substances in the blood that cross the blood-brain barrier and affect normal brain function. The diagnosis of HE is difficult due to only subtle impairments of cognitive function at early stages of the disease and the lack of a gold standard test that specifically and reliably detects the condition. HE is associated with a poor prognosis and effective treatment largely depends on early diagnosis. Thus the aim of this work was to investigate the use of breath analysis as a non-invasive and simpler means of diagnosing HE in cirrhotic patients. This was based on the hypothesis that toxins accumulating in the blood may, if sufficiently volatile, undergo alveolar gas exchange in the lungs to be excreted in the breath. Bespoke breath testing devices were utilised for the collection of breath onto Solid-Phase Micro-Extraction (SPME) fibres and adsorbent packed Automated Thermal Desorption (A TD) tubes from cirrhotic patients with and without HE, patients with early alcohol-related health problems, patients with respiratory disease, and healthy controls. Analysis of the breath samples collected was undertaken using Gas Chromatography Mass Spectrometry. In total, 237 different compounds were identified from all samples collected using the SPME breath analyser system and 385 using the ATD breath sampling device. Multivariate discriminant analysis was used to identify Volatile Organic Compounds (VOCs) that will discriminate patients according to disease status. More compounds were associated with the presence of HE compared to the absence of HE in alcoholic cirrhotic patients. Classification rules based on the presence or absence of volatiles correctly classified the presence of HE in 86% of patients tested with the SPME technique and 88% of patients tested with the A TD technique. Breath tests based on the presence or absence of discriminatory volatiles, correctly predicted the presence of cirrhosis in 93% and 96% of alcoholic patients tested using the SPME and ATD techniques, respectively. The presence or absence of four key volatiles on the breath also helped discriminate patients with early alcohol related health problems (ARHP) from healthy cases, correctly predicting the presence of ARHP in 78% and 91 % of alcoholic patients tested using the SPME and ATD systems, respectively. The use of a targeted sensor-array device found that, on average, HE patients exhaled higher concentrations of hydrogen, alcohol, and total VOCs compared to alcoholic cirrhotic patients without clinical signs of HE, especially in the non- smoking cohort of subjects studied. This finding shows that the use of gas sensor technologies in clinical practice can provide useful diagnostic information for clinical conditions at the bedside of patients in real-time. Not all breath volatiles come from the alveolar-blood interface; many can also be produced in the oral cavity by the action of bacterial or salivary enzymes on a range of substrates. Thus gases were sampled from tongue biofilm models in vitro and this identified 32 compounds commonly detected on breath. This highlights the need for further research to determine the major source of breath volatiles in order that suitable markers of systemic disease or metabolic disorders can be identified. Overall, the results reported in this thesis suggest that breath analysis is a useful tool for the non-invasive diagnosis of a range of conditions associated with the liver such as HE, cirrhosis, and, most importantly the presence of early alcohol related health problems before any significant damage to the liver has occurred.
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Davies, Mark James. « The cytopathology of familial encephalopathy with neuroserpin inclusion bodies (FENIB) ». Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598334.
Texte intégralRésumé :
Neuroserpin is a 55 kDa glycoprotein that is secreted from axons of the central and peripheral nervous system. Point mutations within the neuroserpin gene underlie the novel inclusion body dementia Familial Encephalopathy with the Neuroserpin Inclusion Bodies (FENIB). These point mutations destabilise the molecule resulting in the formation of intracellular polymers by sequential insertion of the reactive centre loop of one molecule into β-sheet A of another. Here I postulate that endoplasmic reticulum (ER) inclusions of mutant serpins contribute to the molecular pathogenesis by directing a novel ER stress response. To assess this hypothesis I generated conditional PC-12 Tet-on cell lines expressing wild type neuroserpin, the Ser52Arg and Gly392Glu mutants that underlie FENIB and a novel-misfolding mutant (DeltaNS) predicted to stimulate the unfolded protein response (UPR). The mutants that cause FENIB accumulate within the ER as polymers that I can demonstrate by Western blot analysis and fluorescence confocal microscopy with novel monoclonal antibodies that detect the polymeric conformer of neuroserpin. Despite accumulating, the mutant neuroserpin does not elicit a UPR. However I demonstrate that the ER accumulation of mutant neuroserpin elicits an ER stress response resulting in activation of NF-κB, and this activation is calcium dependent. Taken together, I have used the disease-related neuroserpin inclusions to define and characterise a novel ER derived signalling cascade involved in sensing protein accumulation within the ER.
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Tsutsui, Toshiyuki. « Modelling bovine spongiform encephalopathy using a herd based stochastic approach ». Thesis, University of Reading, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326957.
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MacLeod, Ian. « A Drosophila model of familial encephalopathy with neuroserpin inclusion bodies ». Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611439.
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Cook, Carolyn M. « Impact of Chronic Traumatic Encephalopathy Information on Perceptions of Illness ». Ohio University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1562589809804291.
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Коленко, Оксана Іванівна, Оксана Ивановна Коленко, Oksana Ivanivna Kolenko, Фаіна Григорівна Коленко, Фаина Григорьевна Коленко et Faina Hryhorivna Kolenko. « Когнітивні порушення у хворих на гіпертонічну енцефалопатію ». Thesis, Видавництво СумДУ, 2008. http://essuir.sumdu.edu.ua/handle/123456789/5198.
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Попов, Сергій Віталійович, Сергей Витальевич Попов et Serhii Vitaliiovych Popov. « Вопросы диагностики гипоксически-ишемической энцефалопатии в работе врача семейной практики ». Thesis, Изд-во СумГУ, 2006. http://essuir.sumdu.edu.ua/handle/123456789/7713.
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Шальмина, М. А., et С. Н. Поливода. « Роль уровня эндотелина-1 в патогенезе развития хронической дисциркуляторной гипертензивной энцефалопатии у больных гипертонической болезнью ». Thesis, Видавництво СумДУ, 2005. http://essuir.sumdu.edu.ua/handle/123456789/12561.
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Попов, Сергій Віталійович, Сергей Витальевич Попов, Serhii Vitaliiovych Popov et С. М. Касян. « Особливості ураження органів і систем у разі гіпоксично-ішемічної енцефалопатії у дітей ». Thesis, Видавництво СумДУ, 2011. http://essuir.sumdu.edu.ua/handle/123456789/15091.
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Costa, Riu Carme. « Study of extracellular matrix and water channels in bovine spongiform encephalopathy ». Doctoral thesis, Universitat Autònoma de Barcelona, 2007. http://hdl.handle.net/10803/5742.
Texte intégralRésumé :
La matriu extracel·lular (MEC) del sistema nerviós central (SNC) es troba dispersa al neuròpil o formant agregats al voltant de les neurones, anomenats xarxes perineuronals (PNN). La MEC conté proteoglicans de tipus condroitin sulfat (CSPG), àcid hialurònic (AH) i tenascina-R. També es poden trobar proteoglicans de tipus heparan sulfat (HSPG) secretats a la MEC o formant part de la membrana cel·lular. Les aquaporines (AQP) són una família de proteïnes transmembrana que actuen com a canals d'aigua. L'AQP1 i l'AQP4 s'expressen àmpliament al SNC on tenen diverses funcions. Malgrat la importància de totes aquestes molècules, la seva distribució al SNC del ratolí només s'ha descrit parcialment. La distribució histoquímica de les PNNs, l'agrecà, l'AH, els HSPG i l'AQP4 es van valorar semiquantitativament al SNC del ratolí. Els resultats van demostrar que l'agrecà, l'AH i els HSPG tenen una distribució perineuronal, mentre que l'AQP4 té una distribució heterogènia al neuròpil del SNC. Es va observar una correlació inversa entre l'AQP4 i els components de la MEC, suggerint que poden tenir un paper complementari en el manteniment de la homeòstasi de l'aigua. L'AQP4 i els HSPG van presentar una localització comú al neuròpil del SNC.
La MEC i les AQPs es van estudiar a la encefalopatia espongiforme bovina (EEB) i a la tremolor ovina. Ambdues malalties pertanyen al grup de les encefalopaties espongiformes transmissibles (EET) o malalties priòniques, les quals es caracteritzen per l'acumulació de proteïna prió resistent (PrPres) al SNC, pèrdua neuronal, degeneració espongiforme i proliferació de cèl·lules glials.
L'estudi de la MEC es va desenvolupar en la línia de ratolí transgènic boTg110 infectat intracranialment amb EEB; i en el ratolins C57Bl6 infectats amb RML (una soca de tremolor ovina). En tots dos casos es va observar una alteració molt marcada de la MEC a l'estadi final de les dues malalties.
L'AQP1 i l'AQP4 es van estudiar al ratolí boTg110 per immunohistoquímica, i casos naturals d'EEB per immunohistoquímica i western blot. Les dues AQPs estaven sobreexpressades a la membrana dels astròcits a l'estadi terminal de la malaltia en el cas dels ratolins, i en vaques pre-clíniques.
Els canvis de la MEC i la sobreexpressió de les AQPs es va correlacionar amb l'acumulació de PrPres, i l'activació de les cèl·lules glials. Per això es va concloure que les alteracions a la MEC, l'AQP1 i l'AQP4 eren conseqüència de l'activació de les cèl·lules glials induïda per la PrPres, i tots aquests canvis podrien produir desequilibris en els iòns i l'aigua al SNC i contribuir a l'aparició de les lesions típiques de les EETs.
The extracellular matrix (ECM) of the central nervous system (CNS) is found dispersed in the neuropil or forming aggregates around the neurons called perineuronal nets (PNNs). The ECM mainly contains chondroitin sulphate proteoglycans (CSPG), hyaluronic acid (HA) and tenascin-R. Heparan sulphate proteoglycans (HSPG) can also be secreted in the ECM or be part of the cell membrane. Aquaporins (AQP) are a family of transmembrane proteins that act as water selective channels. AQP1 and AQP4 are widely expressed in the CNS where they play several roles. Nevertheless the importance of these elements, their distribution in the CNS of mice is only partially known.
The histochemical distribution of PNNs, aggrecan, HA, HSPGs and AQP4 were semiquantitatively evaluated in the whole CNS of mice. The results showed that aggrecan, HA and HSPGs have a perineuronal distribution, and AQP4 has an heterogeneous distribution throughout the neuropil of the CNS. An inverse correlation between AQP4 and ECM components was observed, suggesting a complementary role in the maintenance of water homeostasis. A common location for AQP4 and HSPGs was also observed in CNS neuropil.
ECM and AQPs were studied in bovine spongiform encephalopathy (BSE) and Scrapie. Both diseases belong to the group of animal transmissible spongiform encephalopathies (TSE) or prion diseases. They are characterized by the accumulation of resistant prion protein (PrPres) in the CNS, neuronal loss, spongiform degeneration and glial cell proliferation.
The ECM was studied by immunohistochemistry in the transgenic mice boTg110, overexpresing bovine PrPc, intracranially infected with cattle BSE; and in C57BL/6 mice intraperitoneally infected with RML scrapie strain. Both of them showed dramatical ECM disturbances at latest stage of both diseases.
AQP1 and AQP4 were studied in boTg110 mice by immunohistochemistry, and in BSE field cases by immunohistochemistry and western blot. Both AQPs were overexpressed in the membrane of astrocytes at terminal stage of the disease in mice with evident clinical signs, and in pre-clinical cattle.
The ECM changes and AQPs overexpression were correlated with PrPres accumulation, and activated glial cells. Therefore we conclude that alterations in the ECM, AQP1 and AQP4 are a consequence of glial cell activation induced by PrPres, and both changes could lead to ion and water imbalance in the CNS which could contribute to trigger the typical histopathological features of TSEs.
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Cheung, Hiu-wing, et 張曉穎. « Role of p75 neurotrophin receptor in neonatal mouse hypoxic ischemic encephalopathy ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31227247.
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Wong, Chee Piau. « Acute non traumatic encephalopathy in children : a prospective population based study ». Thesis, University of Newcastle Upon Tyne, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.310130.
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Naseem, Saad Munsan. « State some cognitive functionsin school age adolescents children undergoing neonatal encephalopathy ». Thesis, Sumy State University, 2014. http://essuir.sumdu.edu.ua/handle/123456789/36260.
Texte intégralRésumé :
At present, the frequency of hypoxic-ischemic encephalopathy is 5–6 per 1,000 live births. Besides this disease is one of the most common and is diagnosed in 25–30 % of the children in the neonatal period. Full recovery from hypoxic - ischemic encephalopathy observed only in 15–20 % of cases.
When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/36260
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Sprissler, Ryan S., Jacy L. Wagnon, Rosie K. Bunton-Stasyshyn, Miriam H. Meisler et Michael F. Hammer. « Altered gene expression profile in a mouse model of SCN8A encephalopathy ». ACADEMIC PRESS INC ELSEVIER SCIENCE, 2017. http://hdl.handle.net/10150/622816.
Texte intégralRésumé :
12 month embargo; Available online 9 November 2016SCN8A encephalopathy is a severe, early-onset epilepsy disorder resulting from de novo gain-of-function mutations in the voltage-gated sodium channel Na(v)1.6. To identify the effects of this disorder on mRNA expression, RNA-seq was performed on brain tissue from a knock-in mouse expressing the patient mutation p.Asn1768Asp (N1768D). RNA was isolated from forebrain, cerebellum, and brainstem both before and after seizure onset, and from age-matched wildtype littermates. Altered transcript profiles were observed only in forebrain and only after seizures. The abundance of 50 transcripts increased more than 3-fold and 15 transcripts decreased more than 3 fold after seizures. The elevated transcripts included two anti-convulsant neuropeptides and more than a dozen genes involved in reactive astrocytosis and response to neuronal damage. There was no change in the level of transcripts encoding other voltage-gated sodium, potassium or calcium channels. Reactive astrocytosis was observed in the hippocampus of mutant mice after seizures. There is considerable overlap between the genes affected in this genetic model of epilepsy and those altered by chemically induced seizures, traumatic brain injury, ischemia, and inflammation. The data support the view that gain-of-function mutations of SCN8A lead to pathogenic alterations in brain function contributing to encephalopathy.
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Doherr, Marcus Georg Eduard. « Surveillance systems for bovine spongiform encephalopathy (BSE) and scrapie in Europe / ». Bern : [s.n.], 2002. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Zeidler, Martin. « A new variant of Creutzfeldt-Jakob disease in the United Kingdom ». Thesis, University of Southampton, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274425.
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Ellis, Matthew Edward. « The public health importance of birth asphyxia in Kathmandu, Nepal ». Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341882.
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Vasylieva, Natalia Volodymyrivna. « The issue of neuroprotection in treatment of encephalopathies caused by endocrine disorders ». Thesis, ВДНЗ України "Буковинський державний медичний уніврситет", 2017. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/14084.
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Campbell, Susan L. « Transmissible spongiform encephalopathy : the relationship between PrPsc and infectivity in murine models ». Thesis, University of Edinburgh, 2004. http://hdl.handle.net/1842/24087.
Texte intégralRésumé :
A murine model of TSE had been produced in which the brains of infected animals, at disease end-point, exhibit very low levels of PrPSc, and in which infectivity can be further transmitted in short incubation times. This is contradictory to the prion hypothesis. Using bioassay, the titre of infectivity in brain from 3 animals of this model was measured. Other murine TSE models exhibiting high and intermediate levels of PrPSc in brain at disease end-point were compared with the low PrPSc model. The low PrPSc model displayed infectivity titres of a similar value to the high and intermediate PrPSc models. Furthermore, disease was transmitted from the low PrPSc model with shorter incubation times than from models with high and intermediate PrPSc levels. PrPSc levels in protease-treated brain homogenate were semi-quantatively measured using immunoblots. PrPSc levels in the low model were 8 to 32 times lower than found in the high PrPSc model, however surprisingly levels of total PrP (PrPC and PrPSc) were the same in all models. Therefore low PrPSc levels in the low model were not due to a reduced amount of PrP produced during disease in these animals. This suggested that infectivity in brain tissue of the low PrPSc model could possibly be associated with another form of PrP, not PrPSc, therefore investigation of alternative forms of PrP that might be responsible for infectivity in the low PrPSc model was undertaken. No evidence of increased amounts of transmembrane PrP was found in infected animals from the low PrPSc model. Further biochemical examination of the protease resistance and detergent solubility of PrP in infected animals, using proteinase-K (PK) treatment and solubilisation with sarkosyl, revealed the presence of protease-resistant, detergent insoluble PrPSc from the high and intermediate PrPSc models. In the low PrPSc model where infectivity was transmitted, one animal possessed protease-resistant, detergent insoluble PrPSc and two revealed only the protease-sensitive, detergent-soluble PrPC normally found in infected animals. In conclusion, contrary to the prion hypothesis, murine TSE models can transmit infectivity from brain tissue in which PrPSc levels are extremely low or non-detectable. Furthermore, this tissue can contain a high titre of infectivity. Alternative forms of PrP have been implicated in TSE disease, however no evidence of alternative PrP was found in the models investigated. Given that some infectious brain tissue only contained PrP with PrPC-like characteristics, PrPSc may not be the infectious agent of TSE. It may be possible that a form of PrP similar to PrPC is infectious, but it is also conceivable that a molecule other than PrP, not studied herein, is the infectious agent.
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Chen, Xuhua. « A missense mutation in Atf2 in standard poodles with fatal neonatal encephalopathy ». Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/6042.
Texte intégralRésumé :
Thesis (M.S.)--University of Missouri-Columbia, 2007."May 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. Includes bibliographical references.
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Sturm-Beiss, R. « An overview of the statistical analyses of the bovine spongiform encephalopathy epidemic / ». Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=30847.
Texte intégralRésumé :
In this thesis the statistical analyses that were used to study the by now well known bovine spongiform encephalopathy (BSE) epidemic are reviewed. Central to the analysis is a backcalculation survival model whose development is discussed in detail. Various techniques applied to examining the likelihood of a maternal infection route (in addition to the main feed infection route) are discussed. It is found that maternal transmission is likely to occur at low rates. Measures taken to eliminate meat and bone meal feed supplements, the main infection source, have essentially eliminated BSE. However, the magnitude of the latent effect of tainted meat on humans in the form of the linked new variant Creutzfeldt-Jacob disease is yet to be assessed.
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Palm, Justin E. « Comparing cerebellar pathology of chronic traumatic encephalopathy in football players vs. boxers ». Thesis, Boston University, 2013. https://hdl.handle.net/2144/12178.
Texte intégralRésumé :
Thesis (M.A.)--Boston UniversityChronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy and TDP-43 proteinopathy that has been documented in individuals with a history of repetitive mild brain trauma, such as boxers and football players. In addition to widespread deposits of hyperphosphorylated tau protein throughout the brain, there are also deposits of tau within the cerebellum of these individuals. Clinically CTE is associated with word finding difficulties, aggressive tendencies, short-term memory loss, executive dysfunction, attention and concentration loss, explosivity, paranoia, depression, impulsivity, visuo-spatial abnormalities and dementia. Interestingly, the symptoms found in boxers with advanced CTE are different from those reported in football players. Boxers with advanced CTE tend to have prominent gait and movement difficulties while these symptoms are rarely described in football players with CTE. This study set out to compare the pathology found in two different regions of the cerebellum (cerebellar tonsil and the superior cerebellum) in boxers with advanced CTE, to the cerebellar pathology found in football players with advanced CTE. These boxers and football players with CTE were compared against age and gender matched individuals with no evidence of neurodegenerative disease. The clinical symptoms and microscopic pathology were compared between groups using conventional staining and immunostaining techniques (p62, GFAP, AT8). We further support our findings by citing studies that report cognitive and emotional functioning of the cerebellum, cerebellar deficits following mild traumatic brain injury, and differing traumatic affects on the brain following either translational or rotational forces. This study confirmed that boxers and football players with stage four CTE manifest clinical symptoms and cerebellar pathology indicative of CTE. The dentate nucleus of the cerebellum often demonstrates significant tau pathology. Additionally, we assert the possibility that the superior cerebellum shows more widespread pathology in football players with CTE, and that the cerebellar tonsil of boxers with CTE is often more heavily affected than in football players with CTE. While these studies are intriguing, further studies should be conducted to precisely define these changes by sampling additional areas of the cerebellum, and including a larger number of brains.
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Slyvka, Nataliia Oleksyivna, O. V. Besedynska, V. O. Samsonyuk et Igor Antonovych Plesh. « WERNICKE’S ENCEPHALOPATHY AS A CAUSE OF DEATH IN ALCOHOL ADDICTS : AUTOPSY STUDY ». Thesis, Материалы научной конференции студентов-медиков с международным участием. - Актуальные проблемы современной медицинской науки. - Самарканд, 27 мая 2016 г, 2016. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/11619.
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Slyvka, N. O., O. V. Besedynska, V. O. Samsonyuk et Igor Antonovych Plesh. « WERNICKE’S ENCEPHALOPATHY AS A CAUSE OF DEATH IN ALCOHOL ADDICTS : AUTOPSY STUDY ». Thesis, Материалы научной конференции студентов-медиков с международным участием. - Актуальные проблемы современной медицинской науки. - Самарканд, 27 мая 2016 г, 2016. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/11717.
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Єжова, Ольга Олександрівна, Ольга Александровна Ежова, Olha Oleksandrivna Yezhova, K. Radych et T. Loboda. « The physiotherapeutic means in a complex rehabilitation of people with posthypoxic encephalopathy ». Thesis, Sumy State University, 2017. http://essuir.sumdu.edu.ua/handle/123456789/63612.
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Samson, Sirma. « Outcomes of brain damage in term neonates with severe hypoxic ischemic encephalopathy ». Thesis, Sumy State University, 2016. http://essuir.sumdu.edu.ua/handle/123456789/48200.
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Study is to describe clinical and neuroimaging data of term newborns admitted to neonatal
NICU, who presented clinical-neurological alterations and encephalomalacic lesions whose
presence was documented by ultrasonography or pathologic-anatomical conclusions. Stationary cards 18 full-term infants who were treat in NICU studied. In all infants a selective neuronal necrosis and diffuse necrosis of neurons, Subcortical Leukomalacia were diagnoses.
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Sisson, Rebecca. « Assessing and Addressing Family Members' Attitudes and Perceptions of Acute Necrotizing Encephalopathy ». University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337887857.
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Holdorf, Meghan Marie. « Characterization of Arabidopsis ETHE1, a Gene Associated With Ethylmalonic Encephalopathy ». Oxford, Ohio : Miami University, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=miami1200333267.
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Weissenfels, Robert. « CCL11 as a Biomarker for the In Vivo Diagnosis of Chronic Traumatic Encephalopathy ». Scholarship @ Claremont, 2018. http://scholarship.claremont.edu/cmc_theses/1823.
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Chronic traumatic encephalopathy is the neurodegenerative disease that is ascribed to the long term development of cognitive, behavioral, emotional, and motor deficits as a result of the exposure to high amounts of sub concussive traumatic brain injuries. The disease has gained recent popularity in the media for its prevalence in American football as a response to recent research that has suggested the prominence of the disease in nearly every NFL player that is examined post mortem. This has produced a growing concern for the consequences of head impact and participation in contact sports. Despite media attention, little is currently known about the specific causes of the disease and an in life diagnosis is still nonexistent. The present study proposes that the chemokine, CCL11, could prove to be a viable biomarker for recognizing the onset and progression of chronic traumatic encephalopathy. The results of our study suggest that football players who are clinically suspicious of CTE show significantly higher levels of CCL11 in their cerebrospinal fluid than do sedentary controls and noncontact athletes. Our results demonstrate that this increase in CCL11 is correlated with the number of years that a football player had participated in. We also suggest that this increase in CCL11 is associated with a unique immune response through results showing that the CCL11 expression increase is correlated with an increase in the expression of the cytokine IL-4 and substantial decrease in IFN-gamma. The analysis of CCL11 expression levels in the cerebrospinal fluid may prove to be a viable method of diagnosing and providing treatment for patients who may be at risk of chronic traumatic encephalopathy.
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Lu, Kaihui [Verfasser]. « Involvement of Autophagy and Mitophagy in the Pathogenesis of Hepatic Encephalopathy / Kaihui Lu ». Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2019. http://d-nb.info/1192974379/34.
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Shiveral, D. M. « A study of recombinant combinatorial antibodies as immunodetection reagents for Transmissable Spongiform Encephalopathy ». Thesis, Queen's University Belfast, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.419430.
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Alexander, Barry. « Mechanisms of portal-systemic encephalopathy : a study using isolated liver and brain perfusion ». Thesis, Imperial College London, 1990. http://hdl.handle.net/10044/1/47743.
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