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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
61

KUS121, a VCP modulator, attenuates ischemic retinal cell death via suppressing endoplasmic reticulum stress / VCP modulatorであるKUS121は、小胞体ストレスを抑制することで虚血性網膜細胞死を抑制する

Hata, Masayuki 26 March 2018 (has links)
京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13161号 / 論医博第2148号 / 新制||医||1029(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 大森 孝一, 教授 松本 智裕, 教授 秋山 芳展 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM
62

The Safeguarding Microglia: Central Role for P2Y12 Receptors

Lin, Si-Si, Tang, Yong, Illes, Peter, Verkhratsky, Alexei 30 March 2023 (has links)
No description available.
63

Stroke Study: Novel Animal Models and Innovative Treatment Strategy

Yu, Xinge 04 August 2016 (has links)
No description available.
64

Riluzole–Triazole Hybrids as Novel Chemical Probes for Neuroprotection in Amyotrophic Lateral Sclerosis

Sweeney, J.B., Rattray, Marcus, Pugh, V., Powell, L.A. 30 May 2018 (has links)
Yes / Despite intense attention from biomedical and chemical researchers, there are few approved treatments for amyotrophic lateral sclerosis (ALS), with only riluzole (Rilutek) and edaravone (Radicava) currently available to patients. Moreover, the mechanistic basis of the activity of these drugs is currently not well-defined, limiting the ability to design new medicines for ALS. This Letter describes the synthesis of triazole-containing riluzole analogues, and their testing in a novel neuroprotective assay. Seven compounds were identified as having neuroprotective activity, with two compounds having similar activity to riluzole.
65

Neuroprotective effects of the active principles from selected Chinese medicinal herbs on b-amyloid-induced toxicity in PC12 cells.

January 2007 (has links)
Hoi, Chu Peng. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 81-103). / Abstracts in English and Chinese. / Acknowledgements --- p.II / Abstract --- p.III / Abstract (in Chinese) --- p.V / List of Abbreviations --- p.VI / List of Figures --- p.VIII / List of Tables --- p.X / Table of Contents --- p.XI / Chapter Chapter One --- General introduction --- p.1 / Chapter 1.1 --- Alzheimer's disease --- p.1 / Chapter 1.1.1 --- Epidemiology and risk factors --- p.2 / Chapter 1.1.2 --- Clinical manifestation and course --- p.4 / Chapter 1.1.3 --- Clinical diagnosis --- p.5 / Chapter 1.1.4 --- Neuropathology and pathogenesis of AD --- p.8 / Chapter 1.1.5 --- Drug therapy of AD --- p.11 / Chapter 1.1.5.1 --- Drugs for symptomatic treatment --- p.11 / Chapter 1.1.5.2 --- Drugs based on epidemiology --- p.12 / Chapter 1.1.5.3 --- Drugs with potential disease-modifying effects --- p.14 / Chapter 1.1.5.4 --- Herbal supplements --- p.15 / Chapter 1.2 --- Models for drug discovery in Alzheimer Disease --- p.15 / Chapter 1.2.1 --- In vivo (animal) models --- p.16 / Chapter 1.2.2 --- In vitro (cellular) models --- p.18 / Chapter 1.3 --- Chinese herbs for the treatment of AD --- p.20 / Chapter 1.3.1 --- Ginkgo biloba L --- p.21 / Chapter 1.3.2 --- Magnolia officinalis --- p.24 / Chapter 1.3.3 --- Acori graminei Rhizoma (AGR) --- p.26 / Chapter 1.3.4 --- Gastrodia elata (G. elata) --- p.27 / Chapter 1.3.5 --- Rhodiola rosea L.( R. rosea) --- p.29 / Chapter 1.3.6 --- Scutellariae baicalensis --- p.30 / Chapter 1.3.7 --- Curcuma longa L.(Zingiberaceae) --- p.31 / Chapter 1.4 --- Aims of the study --- p.33 / Chapter Chapter Two --- Materials and Methods --- p.34 / Chapter 2.1 --- Materials --- p.34 / Chapter 2.1.1 --- Chemicals and reagents --- p.34 / Chapter 2.1.2 --- Materials for cell culture --- p.35 / Chapter 2.1.3 --- Instruments --- p.35 / Chapter 2.2 --- Methods --- p.36 / Chapter 2.2.1 --- Cell culture --- p.36 / Chapter 2.2.2 --- MTT cell viability assay --- p.38 / Chapter 2.2.3 --- Characterization of the cytotoxicity of Aβ peptide in NGF-differentiated PC 12 cells --- p.38 / Chapter 2.2.4 --- Screening of the neuroprotective effect of major principles from selected herbs on PC 12 cells against Aβ-induced cytotoxicity --- p.39 / Chapter 2.2.5 --- Measurement of reactive oxygen species (ROS) --- p.40 / Chapter 2.2.6 --- Measurement of intracellular calcium levels --- p.41 / Chapter 2.2.7 --- Measurement of caspase-3 activity --- p.42 / Chapter 2.2.8 --- Propidium iodide (PI) staining to evaluate apoptosis and necrosis --- p.43 / Chapter 2.3 --- Statistics --- p.45 / Chapter Chapter Three --- Results --- p.46 / Chapter 3.1 --- NGF-differentiated PC 12 cells --- p.46 / Chapter 3.1.1 --- Determination of an appropriate cell density for the screening experiments --- p.46 / Chapter 3.1.2 --- Characterization of Aβ-induced cytotoxicity in NGF-differentiated PC 12 cells --- p.47 / Chapter 3.1.2.1 --- Cytotoxicity of Aβ-related fragments in NGF-differentiated PC 12 cells --- p.48 / Chapter 3.1.2.2 --- Dose-dependent cytotoxic effect of Aβ on PC 12 cells --- p.48 / Chapter 3.1.2.3 --- Time-dependent effect of Aβ-induced toxicity on PC12 cells --- p.50 / Chapter 3.1.3 --- Protective effect of selected active principles against Aβ1-4-induced toxicity in PC 12 cells --- p.51 / Chapter 3.2 --- Measurement of reactive oxygen species (ROS) --- p.54 / Chapter 3.2.1 --- Measurement of ROS induced by H202 --- p.54 / Chapter 3.2.2 --- Measurement of ROS induced by Aβ --- p.56 / Chapter 3.3 --- Measurement of Intracellular calcium levels --- p.57 / Chapter 3.4 --- Measurement of caspase-3 activity --- p.58 / Chapter 3.4.1 --- AMC reference standard curve --- p.59 / Chapter 3.4.2 --- Measurement of caspase-3 activity --- p.59 / Chapter 3.5 --- PI staining for evaluate apoptosis and necrosis --- p.60 / Chapter Chapter Four --- Discussion --- p.64 / Chapter 4.1 --- Aβ-induced cytotoxicity in NGF-differentiated PC 12 cells as an in vitro model of Alzheimer's disease --- p.64 / Chapter 4.1.1 --- Cell line selection --- p.65 / Chapter 4.1.2 --- Characterization of Aβ-induced cytotoxicity in NGF-differentiated PC 12 cells --- p.66 / Chapter 4.2 --- Screening of the neuroprotective effects of selected active principles against Aβ-induced cytotoxicity in NGF-differentiated PC 12 cells --- p.67 / Chapter 4.3 --- Neuroprotection via inhibition of the ROS generation --- p.71 / Chapter 4.4 --- Neuroprotection via suppression of calcium homeostasis --- p.73 / Chapter 4.5 --- Neuroprotective via inhibition of Aβ-induced apoptosis --- p.75 / Chapter 4.5.1 --- Inhibition of caspase-3 activation --- p.75 / Chapter 4.5.2 --- PI staining for evaluation of apoptosis and necrosis --- p.76 / Chapter Chapter Five --- Conclusion and future work --- p.79 / Chapter 5.1 --- Conclusion --- p.79 / Chapter 5.2 --- Future work --- p.80 / References --- p.81
66

Significance of a cognition-enhancing Chinese herb Fructus alpiniae oxyphyllae as a source for potential neuroprotective agents. / CUHK electronic theses & dissertations collection

January 2010 (has links)
Hong, Sijia. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 197-234). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.
67

Investigating beta-amyloid peptide neurotoxicity from neuronal apoptosis to endoplasmic reticulum collapse: translational research back to basic science research

Lai, Sau-wan., 賴秀芸. January 2009 (has links)
published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy
68

Etude méthodologique du couplage d’acides aminés trifluorométhylés et application à la synthèse d’analogues du GPE, un tripeptide à visée thérapeutique / Methodological study of trifluoromethylated amino acids coupling and application to the synthesis of GPE analogs, a therapeutic peptide candidate

Simon, Julien 28 November 2012 (has links)
Le tripeptide GPE possède une activité neuroprotectrice intéressante in-vitro et in-vivo pour différents types de dommage neuronaux. L'objectif de cette thèse est de mettre au point des méthodes de couplage peptidique pour les acides aminés trifluorométhylés et de réaliser des analogues trifluorométhylés du GPE.Au cours de cette thèse, la synthèse d'acides aminés trifluorométhylés cycliques énantiopurs (proline, pseudoproline) a été réalisée à l'échelle du gramme.Ensuite, une étude méthodologique de l'incorporation de ces acides aminés trifluorométhylés dans des peptides a été effectuée.Des expériences RMN ont été menées pour étudier la conformation cis/trans de la liaison amide de ces peptides trifluorométhylés.Enfin, des analogues du tripeptides GPE ont été synthétisé en remplaçant le motif proline par une proline ou pseudoproline trifluorométhylé. Des tests biologiques sont actuellement en cours pour évaluer leur activité sur divers troubles neuronaux. / GPE is a tripeptide with neuroprotecting activity both in-vitro and in-vivo for various neuronal dammage. The goal of this thesis was to work out peptide coupling methods for trifluoromethylated amino acids and the synthesis of trifluoromethylated analogs of GPE.During this thesis, the synthesis of enantiopure cyclic trifluoromethylated amino acids (proline and pseudoprolines) was performed successfully on grams scale.Then, methodological study of their incorporation in peptide was performed.NMR experiments were made to investigate the cis/trans conformation of the amide bound of trifluoromethylated peptide. At last, analogs of the tripeptide GPE were made with trifluoromethylated proline and pseudoprolines instead of the proline. Biological tests are currently under progress to evaluate their activity on various neuronal disorders.
69

Estudo do efeito neuroprotetor da estimulação magnética transcraniana e hipotermia em modelo de isquemia cerebral induzida / Study of the neuroprotective effect of the Transcranial Magnetic Stimulation and hypothermia in a animal model of induced cerebral ischemia

Macri, Fábio Teixeira 03 August 2011 (has links)
Introdução: Muitos estudos veem sendo realizados com a finalidade de identificar agentes que possam ter efeito benéfico no tratamento ou prevenção das lesões causadas nos neurônios devido à isquemia. A hipotermia já demonstrou resultados consistentes em estudos experimentais e a Estimulação Magnética Transcraniana (EMTr) já foi usada visando reduzir danos em neurônios hipocampais de animais submetidos a isquemia cerebral. Com a propriedade de aumentar ou diminuir a excitabilidade cortical a partir do estímulo magnético, estima-se que ocorra uma interferência na produção de alguns neurotransmissores e receptores de membrana, que promoveriam efeito protetor a estas células. Neste estudo avaliamos a capacidade da EMTr de proteger os neurônios de uma lesão por hipóxia, e sua possível interferência no efeito protetor da hipotermia, tentando identificar alguns mecanismos que possivelmente estariam envolvidos neste fenômeno. Métodos: Como modelo de isquemia, foram utilizados Gerbils previamente submetidos a uma avaliação de comportamento e memória por meio do teste de esquiva. O protocolo de EMTr foi a partir de sessões diárias com 25 séries de 5 segundo a 25Hz, com um intervalo de 45 segundos entre as séries, por sete dias consecutivos, com um total de 21 875 pulsos com uma intensidade de 100% do limiar motor, e sendo realizada a indução da isquemia logo após o término da última sessão, ou na isquemia após a EMTr, em sessões diárias com 25 séries de 5 segundos a 25Hz, com um intervalo de 45 segundos entre as séries, durante 3 dias consecutivos, começando imediatamente após a cirurgia. Foi mantida a temperatura de 36 °C durante o período de oclusão do vaso e os 30 minutos consecutivos, ou 31 a 32 °C quando em hipotermia. O preparo das lâminas teve cortes envolvendo a região do hipocampo, corados com hematoxilina e eosina, além de outros preparos, a marcação de TUNEL e Caspase, que visam evidenciar a ocorrência de apoptose. Resultados: Embora sem significância estatística, os animais que receberam EMTr aparentemente tiveram uma melhor performance no teste da esquiva, principalmente se aplicado após a indução da isquemia. A hipotermia demonstrou uma eficiência significativa, tanto na análise histológica quanto no teste da esquiva, associado ou não à EMTr, e nestes animais submetidos a isquemia durante a hipotermia, os que receberam EMTr tiveram área de sobrevida no hipocampo significativamente maior na análise histológica com hematoxilina e eosina. Nos animais submetidos à isquemia durante a temperatura normal, a EMTr não demonstrou aumentar a área de sobrevida das células do hipocampo. Conclusões: A EMTr (ativa ou placebo, prévia ou posterior à isquemia) pareceu ter um efeito positivo no teste de esquiva. O procedimento de estimulação pareceu bastante traumático e estressante para os animais, tendo ocorrido alguns óbitos durante a imobilização, provavelmente por asfixia. A EMTr apresentou efeito protetor significativo apenas nos animais submetidos a isquemia durante hipotermia / Introduction: Over the time many researches have been conducted with the aim of identifying agents that may have beneficial effects in the treatment or prevention of cerebral ischemia, hypothermia has shown consistent results in experimental trials and Repetitive Trans Cranial Magnetic Stimulation (rTMS) has been used in a study attempting to reduce damage in hippocampal neurons. With the property to increase or decrease cortical excitability from the repetitive magnetic stimulus, it is estimated that an interference occurs in the production of some neurotransmitters and receptors of neuronal membrane, which therefore protects these cells from hypoxia. In this study we evaluated the ability of rTMS to protect neurons from injury due to hypoxia, and its possible interference in the protective effect of hypothermia and we tried to identify some mechanisms that possibly are involved in this phenomenon. Methods: Ischemia model was performed using Gerbil that was subsequently submitted to an evaluation of behavior and memory through passive avoidance task. The rTMS protocol was daily sessions with 25 series of 5 seconds at 25Hz with an interval of 45 seconds between series, for 7 consecutive days, with a total of 21 875 pulses with an intensity of 100% of motor threshold, and being carried through the induction of ischemia soon after the end of the last session, or rTMS after ischemia, in daily sessions with 25 series of 5 seconds at 25Hz with an interval of 45 seconds between series, for 3 consecutive days, starting immediately after surgery. The temperature of 36 °C was maintained during the period of vessel occlusion and subsequent 30 minutes, or 31 °C to 32 °C when in hypothermia. The preparation of the slices had sections of the region involving the hippocampus, stained with hematoxylin and eosin in addition to other preparations, TUNEL and caspase, which aim to evidence the occurrence of apoptosis. Results: Although not statistically significant, animals that received rTMS, apparently had better performance in passive avoidance task especially when applied after ischemia. The hypothermia demonstrated a significant efficiency, both in the histological analysis and in the passive avoidance task, associated or not to applications of rTMS and, in these animals undergoing ischemia during hypothermia, the ones who received rTMS had survival area in hippocampus significantly higher in histological analysis with hematoxylin and eosin. In animals undergone to ischemia during normal temperature, the rTMS has not shown to increase the area of hippocampal cell survival. Conclusions: rTMS (placebo or active, after or before the ischemia) seems to have a positive effect on passive avoidance task. The stimulation procedure appeared to be very traumatic and stressful for the animal, in which a few deaths occurred during the procedure, probably from asphyxiation due to restraint. The rTMS had a significant protective effect only in animals undergoing ischemia during hypothermia, as demonstrated in the histological analysis with hematoxylin and eosin
70

Alga marinha vermelha Gracilaria cornea: novas perspectivas biotecnolÃgicas e implicaÃÃes neurofarmacolÃgicas / Red seaweed Gracilaria cornea: new biotechnological perspectives and neuropharmacological implications

Ricardo Basto Souza 05 March 2015 (has links)
CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior / The red seaweed Gracilaria cornea is presented as a natural source still little explored, with potential bioactive, such as sulfated polysaccharides. Its sulfated polysaccharide, agaran-type (AS-Gc), wherein its structure and has anti-inflammatory and anti-nociceptive activity reported in the literature. However, methodological evaluations in their extraction process as well as new potential biological activities are still little reported in the literature. Thus, this study aimed to analyze a new reagent for isolation of AS-Gc and then evaluate its effects and possible mechanisms of action on valuation models psychotropic activity and neuroprotective in vivo and in vitro. Initially, we evaluated the method for isolating sulfated polysaccharides from algae G. cornea using isoamyl alcohol (IAA), in relation to the classical method using 1-hexadecylpyridinium chloride (CPC), considering qualitative and quantitative parameters (percentage yield analysis, physical-chemical and structural characterization) and evaluation of anticoagulant activity in vitro. For analysis of psychotropic effects of AS-Gc, we evaluated the acute administration of three doses (0.3, 3 or 30 mg / kg) and two routes of administration (per os-p.o. or subcutaneous-s.c.) in mice. Then, animals were assessed in physiological and neurobehavioural tests indicative of action level on nervous system and locomotive disorders and behaviors associated with anxiety, depression and sedation. To investigate the potential neuroprotective, we carried out the Parkinson's disease model in rats induced by intrastriatal injection of the neurotoxin 6-hydroxydopamine (6-OHDA), followed by a single dose of ASGC (15, 30 or 60 μg) via intrastriatal. After 14 days, locomotives, neurobehavioral and physiological analyzes were performed. After euthanasia, brain areas (hippocampus, the prefrontal cortex and striatum) were dissected and used to neurochemical and transcriptional analyzes. Additionally, we evaluated the antioxidant potential of AS-Gc in in vivo and in vitro. The results suggest that the classical method using CCP has greater efficiency and quality to obtain a AS-Gc, in relation to the use of AIA. However, the alternative method, using AIA showed potential biotechnological applications to obtain other molecules of commercial and scientific interest. AS-Gc (30 mg / kg, p.o. and s.c.) presented a safety pharmacology and promoted increased exploratory activity in mice. AS-Gc (60 μg, intraestrital) promoted a neuroprotective activity in vivo and in vitro through mitochondrial protection, reduced glutathione induction, lipid peroxidation and nitrite levels reduction, and modulation of transcriptional pathways in the striatum of rats and returning locomotive and renal activities to normal conditions. Thus, this study show new perspectives for biotechnological obtaining chemically different molecules seaweed and suggests new neuropharmacological implications for the use of sulfated agaran from G. cornea. Furthermore, the AS-Gc present therapeutic potential against neurodegenerative disorders. / A alga marinha vermelha Gracilaria cornea apresenta-se como uma fonte natural ainda pouco explorada, com bioativos em potencial, como os polissacarÃdeos sulfatados. Seu polissacarÃdeo sulfatado, do tipo agarana (AS-Gc), possui sua estrutura caracterizada e atividade anti-inflamatÃria e anti-nociceptiva reportada na literatura. Entretanto, avaliaÃÃes metodolÃgicas no seu processo de extraÃÃo, bem como novas atividades biolÃgicas em potencial ainda sÃo pouco reportadas na literatura. Deste modo, o presente estudo objetivou analisar um novo reagente para o isolamento de AS-Gc e, posteriormente, avaliar seus efeitos e possÃveis mecanismos de aÃÃo em modelos de avaliaÃÃo de atividades psicotrÃpicas e neuroprotetoras in vivo e in vitro. Inicialmente, realizou-se uma avaliaÃÃo da metodologia de isolamento de polissacarÃdeos sulfatados isolados da alga G. cornea utilizando Ãlcool isoamÃlico (AIA), em relaÃÃo ao mÃtodo clÃssico utilizando cloreto de 1-hexadecilpiridinio (CCP), considerando parÃmetros qualitativos e quantitativos (anÃlises de percentual de rendimento, de caracterizaÃÃo fÃsico-quÃmica e estrutural) e de uma avaliaÃÃo de atividade anticoagulante in vitro. Para anÃlise de efeitos psicotrÃpicos de AS-Gc, avaliou-se a administraÃÃo aguda de trÃs doses (0,3; 3 ou 30 mg/Kg) e duas vias de administraÃÃo (oral-v.o. ou subcutÃnea-s.c.) em camundongos. Em seguida, os animais foram submetidos a avaliaÃÃo fisiolÃgica e a ensaios neurocomportamentais, indicativo de nÃvel de aÃÃo no sistema nervoso e relacionados a alteraÃÃes locomotoras e de comportamentos associados de ansiedade, depressÃo e sedaÃÃo. Para a investigaÃÃo do potencial neuroprotetor, realizou-se o modelo de induÃÃo de doenÃa de Parkinson em ratos com injeÃÃo intraestriatal da neurotoxina 6-hidroxidopamina (6-OHDA), seguido por Ãnica administraÃÃo de AS-Gc (15, 30 ou 60 Âg), via intraestriatal. ApÃs 14 dias, os animais foram submetidos a anÃlises locomotoras, neurocomportamentais e fisiolÃgicas. ApÃs eutanÃsia, Ãreas cerebrais (hipocampo, cÃrtex prÃ-frontal e corpos estriados) foram dissecadas e utilizadas para anÃlises neuroquÃmicas e transcricionais. Adicionalmente, avaliou-se o potencial antioxidante de AS-Gc em ensaios in vivo e in vitro. Os resultados sugerem que o mÃtodo clÃssico, utilizando CCP, apresenta maior eficiÃncia e qualidade para obtenÃÃo de AS-Gc, em relaÃÃo ao uso de AIA. Entretanto, o mÃtodo alternativo, utilizando AIA, demonstrou potenciais aplicaÃÃes biotecnolÃgicas para obtenÃÃo de outras molÃculas de interesse comercial e cientÃfico. AS-Gc (30 mg/kg, v.o. e s.c.) apresentou uma seguranÃa farmacolÃgica e promoveu o aumento da atividade exploratÃria em camundongos. AS-Gc (60 Âg, intraestrital) promoveu uma atividade neuroprotetora in vivo e in vitro, atravÃs de proteÃÃo mitocondrial, induÃÃo de glutationa reduzida, reduÃÃo dos nÃveis de peroxidaÃÃo lipÃdica e de nitrito, e modulaÃÃo de vias transcricionais em corpo estriado de ratos, retornando atividades locomotoras e renais a condiÃÃes normais. Desta forma, o presente estudo apresenta novas perspectivas biotecnolÃgicas para obtenÃÃo de molÃculas quimicamente diferentes de algas marinhas e sugere novas implicaÃÃes neurofarmacolÃgicas para o uso da agarana sulfatada de G. cornea. Adicionalmente, AS-Gc apresenta potencial terapÃutico contra desordens neurodegenerativas.

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