INTRODUÇÃO: A isquemia cerebral é uma doença de alta prevalência, com desfecho clínico imprevisível, e com profilaxia e tratamento ainda limitados. Na atividade neurocirúrgica, as duas situações em que a isquemia cerebral ocorre com maior freqüência são o vasoespasmo arterial, que ocorre após hemorragia subaracnóidea, e nas microneurocirurgias vasculares, especialmente naquelas em que são realizadas clipagens vasculares temporárias. Dentre todas as formas de neuroproteção a hipotermia tem se mostrado a mais promissora em estudos experimentais. Pode ser aplicada em diferentes momentos do processo isquêmico (pré, intra ou pós-isquemia), sendo a modalidade pré-isquêmica pouco explorada na literatura. O objetivo deste estudo foi avaliar comparativamente o efeito da hipotermia pré, intra e pós-isquêmica na isquemia focal temporária por oclusão da artéria cerebral média em ratos, através de análise morfométrica computacional. MATERIAL E MÉTODOS: Foram utilizados 74 ratos machos adultos da linhagem Wistar, divididos em 6 grupos, com 10 animais cada: Controle (C), Sham (S), Controle-Isquêmico (CI), Hipotermia Pré-Isquêmica (IH1), Hipotermia Intra-Isquêmica (IH2), Hipotermia Pós-Isquêmica (IH3). Todos os animais dos grupos isquêmicos foram submetidos à isquemia de 60 minutos, com um período reperfusional de 24 horas. A hipotermia utilizada foi do tipo leve (32 - 34 ºC). No grupo IH1 a hipotermia foi iniciada 30 min antes da oclusão arterial e mantida durante toda a isquemia; no grupo IH2 a hipotermia foi mantida somente durante a isquemia; no grupo IH3 a hipotermia foi mantida por 6 horas, sendo iniciada no exato momento da reperfusão. Após a eutanásia os cérebros foram perfundidos e fixados, sendo realizadas secções coronais de 10 micrômetros, em toda a extensão da área isquêmica, as quais foram coradas pela técnica Luxol Fast Blue. A morfometria foi realizada pelo programa KS400, Carl Zeiss, obtendo-se medidas diretas separadas de cada hemisfério, das áreas em azul (fibras mielinizadas) e em vermelho (corpos neuronais), bem como a área total de cada secção. Medidas derivadas (área isquêmica média, e volumes isquêmicos parcial e aproximado) de cada animal, foram obtidas nos grupos submetidos à isquemia. RESULTADOS: Os parâmetros da homeostase dos animais permaneceram dentro dos limites aceitáveis para este tipo de experimento. Em relação às áreas de fibras mielinizadas (azul) não houve diferença significativa entre os grupos C vs. S (p=0,39, Mann-Whitney-Wilcoxon), CI vs. IH3 (p=0,85, Mann-Whitney-Wilcoxon), e IH1 vs. IH2 (p=0,63, Mann-Whitney-Wilcoxon); ocorreu diferença estatística entre os grupos C vs. CI (p=0,0001, Mann-Whitney-Wilcoxon), CI vs. IH1 (p=0,01, Mann-Whitney-Wilcoxon), e CI vs. IH2 (p=0,03, Mann-Whitney-Wilcoxon). Em relação às áreas de corpos neuronais (vermelho), não houve diferença significativa entre os grupos C vs. S (p=0,48, Mann-Whitney-Wilcoxon), CI vs. IH3 (p=0,27, Mann-Whitney-Wilcoxon), e IH1 vs. IH2 (p=0,68, Mann-Whitney-Wilcoxon); ocorreu diferença estatística entre os grupos C vs. CI (p=0,0001, Mann-Whitney-Wilcoxon), CI vs. IH1 (p=0,009, Mann-Whitney-Wilcoxon), e CI vs. IH2 (p=0,03, Mann-Whitney-Wilcoxon). A análise estatística das áreas isquêmicas médias, e dos volumes isquêmicos parciais e aproximados não mostrou diferença significante na comparação entre os grupos CI vs. IH3 (p=0,57, Mann-Whitney-Wilcoxon), e IH1 vs. IH2 (p=0,79, Mann-Whitney-Wilcoxon); mostrou diferença significante entre os grupos CI vs. IH1 (p=0,0001, Mann-Whitney-Wilcoxon), e CI vs. IH2 (p=0,0011, Mann-Whitney-Wilcoxon). CONCLUSÕES: As hipotermias pré-isquêmica e intra-isquêmica mostraram-se neuroprotetoras de forma semelhante, o que não ocorreu com a hipotermia pós-isquêmica. / INTRODUCTION: Cerebral ischemia is a high prevalent disease, with unpredictable clinical outcome, and prophylaxis and treatment remains limited. In the neurosurgical practice cerebral ischemia occurs most frequently due arterial vasospasm after subarachnoid hemorrhage, and in vascular microneurosurgery, mainly when temporary vascular clipping is performed. Among all forms of experimental neuroprotection, hypothermia has been the most promising. It can be applied at different moments of ischemia (pre, intra or post-ischemia), and the pre-ischemic modality is little explored in literature. This study aimed to evaluate comparatively the effect of pre, intra and post-ischemic hypothermia in temporary focal ischemia obtained by middle cerebral artery occlusion in rats, by computational morphometric analysis. MATERIAL AND METHODS: We used 74 Wistar adult male rats divided into six groups of 10 animals each: Control (C), Sham (S), Ischemic-Control (IC), Pre-Ischemic Hypothermia (IH1), Intra-Ischemic Hypothermia (IH2), Post-Ischemic Hypothermia (IH3). All animals in the ischemic groups were subjected to ischemia for 60 minutes with a reperfusion period of 24 hours. It was used mild hypothermia (32 - 34 ºC). In IH1 group hypothermia was initiated 30 minutes before arterial occlusion and maintained throughout the ischemia, in IH2 group hypothermia was maintained only during ischemia, IH3 group hypothermia was maintained for 6 hours, starting at the beginning of the reperfusion. After euthanasia, the brains were perfused and fixed, and coronal sections of 10 microns were performed to the fullest extent of ischemic area, and these sections were stained by Luxol Fast Blue. The morphometry was performed by the KS400 software, Carl Zeiss, obtaining direct separated measurements in each hemisphere, of blue areas (myelinated fibers) and red areas (neuronal bodies) as well as the total area of each section. Derived measures (average ischemic area, and partial and approximated ischemic volumes) were also obtained from the ischemic groups. RESULTS: The animal homeostasis parameters remained within acceptable limits for this type of experiment. Regarding the myelinated areas (blue) there was no significant difference between groups C vs. S (p=0,39, Mann-Whitney-Wilcoxon), IC vs. IH3 (p=0,85, Mann-Whitney-Wilcoxon), and IH1 vs. IH2 (p=0,63, Mann-Whitney-Wilcoxon), and there was statistical difference between groups C vs. IC (p=0,0001, Mann-Whitney-Wilcoxon), IC vs. IH1 (p=0,01, Mann-Whitney-Wilcoxon), and IC vs. IH2 (p=0,03, Mann-Whitney-Wilcoxon). Regarding the neuronal bodies areas (red) there was no significant difference between groups C vs. S (p=0,48, Mann-Whitney-Wilcoxon), IC vs. IH3 (p=0,27, Mann-Whitney-Wilcoxon), and IH1 vs. IH2 (p=0,68, Mann-Whitney-Wilcoxon), and there was significant difference between C vs. IC groups (p=0,0001, Mann-Whitney-Wilcoxon), IC vs. IH1 (p=0,009, Mann-Whitney-Wilcoxon), and IC vs. IH2 (p=0,03, Mann-Whitney-Wilcoxon). Statistical analysis of average ischemic areas, and partial and approximated volumes of ischemic regions showed no significant difference between groups IC vs. IH3 (p=0,57, Mann-Whitney-Wilcoxon), and IH1 vs. IH2 (p=0,79, Mann-Whitney-Wilcoxon), and showed statistical difference between groups IC vs. iH1 (p = 0,0001, Mann-Whitney-Wilcoxon), and IC vs. IH2 (p = 0,0011, Mann-Whitney-Wilcoxon). CONCLUSIONS: Pre-ischemic and intra-ischemic hypothermia were shown to be similarly neuroprotective, but this was not true for post-ischemic hypothermia.

Introdução: o aumento da população idosa traz uma demanda significativa sobre as ciências da saúde para lidar com os problemas característicos do envelhecimento. Neste contexto, as demências são as desordens neuropsiquiátricas de maior impacto atualmente. Poucas pesquisas acerca do CCL foram dedicadas a analisar a função neuropsicológica da tomada de decisão. Esta é definida como o processo de escolher uma ação específica, dentro de um rol de alternativas possíveis, que produza o resultado mais vantajoso para o sujeito. Logo, ela possui papel clínico fundamental, pois subsidia importante espectro da funcionalidade. Objetivo: avaliar se idosos com CCL amnéstico de múltiplos domínios ou de único domínio apresentam prejuízos na tomada de decisão sob risco, quando comparados a idosos saudáveis. Métodos: foram analisados os desempenhos de 20 sujeitos (9 CCL e 11 controles) no teste de tomada de decisão Cambridge Gambling Task (CGT). Utilizou-se modelo linear geral acompanhado de análise de covariância para idade, anos de escolaridade e escore do Mini Exame do Estado Mental. Resultados: Foi verificado efeito de grupo e da idade sobre a aversão ao atraso, proporção global de aposta e assunção de risco. Conclusão: pacientes com CCL demonstraram maior impulsividade nas escolhas das apostas, além de terem apostado menos ao longo de todo o CGT. O déficit no controle da impulsividade pode ser um indicador de maior risco para conversão para demência, hipótese esta que necessita ser mais investigada. Apostas menores podem constituir estratégia compensatória em reação à impulsividade ou, ainda, ser resultado da menor confiança do paciente com CCL em suas capacidades para lidar com o teste / Introduction: The increase in elderly population brings a significant demand upon the health sciences to deal with aging-specific issues. In this context, dementia is currently the group of neuropsychiatric disorders with the greatest impact. Research on cerebral reserve shows the importance of early treatment in these syndromes, highlighting the need for comprehension about Mild Cognitive Impairment (MCI), classically defined by literature as a prodromic stage for dementia. Few existing studies on MCI aimed at investigating the neuropsychological function of decision-making, which is defined as the process of choosing a specific action among several options in order to achieve the most advantageous outcome. Therefore, this function has a fundamental clinical role, since it grants the basis for the individual functionality. Objective: investigate possible deficits in the decision-making of a sample of elderly patients diagnosed with amnestic MCI of multiple or single domain by comparing their performance with that of healthy ones. Methods: the performances of a sample 20 subjects (9 MCI and 11 controls) in the Cambridge Gambling Task (CGT) were analysed. General linear model with covariance analysis for age, years of schooling and the Mini Mental State Examination scores was used for the statistical analyses. Results: it was found that group and age effect on delay aversion, overall proportion bet, and risk taking. Conclusion: MCI patients showed higher impulsivity on bet choices and made smaller bets throughout the CGT run. The impulsivity control deficit can be an indicator of the conversion risk from MCI to dementia, hypothesis that needs further investigation. Smaller bets may be a compensatory strategy for the increased impulsivity or the result of MCI patients less confidence in their own cognitive ability to deal with the test

Obstructive sleep apnea (OSA) is a common breathing and sleeping disorder, characterized by repeated episodes of airway obstruction during sleep resulting in intermittent hypoxia (IH). From clinical reports, patients with OSA are associated with behavioral and neuropsychological deficits, including impaired spatial learning memory and cognitive deficiencies. Previous studies proposed that reactive oxygen species (ROS) and apoptosis caused by intermittent hypoxia (IH) contributed to this cognitive deficits. However, the exact mechanism is still poorly understood and not settled. / The endoplasmic reticulum (ER) is a cellular organelle in which all secretory and integral membrane proteins are folded and is also the site where proteins are post-translationally modified in ATP-dependent chaperone-mediated processes. In this study, we hypothesized that ER stress in the hippocampus is initiated in the OSA via elevated levels of ROS. Four groups of adult male mice were used, with two of them exposed to normoxia as control, and the other two exposed to IH treatment, each receiving either vehicle or tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor. Eight-armed radial maze was used to investigate the performance of reference memory during the whole IH/normoxia treatment. After behavior test, long-term potentiation (LTP) was measured to investigate synaptic plasticity in hippocampus. Furthermore, ER stress-associated pro-apoptotic effectors were detected by Western blotting, and ultra-structure of rough ER and the morphology of hippocampal dendritic spines and synapses in the hippocampal CA1 area were observed. / LTP was impaired in the hippocampus after IH treatment, which was rescued by TUDCA. Furthermore, ER stress-associated pro-apoptotic effectors, CHOP and caspase-12, were up-regulated after chronic IH treatment and was abolished by co-infusion of TUDCA. Meanwhile, increased cleaved-caspase-3 after chronic IH treatment was reduced by TUDCA via increased expression of Bcl-2. On the other hand, ultrastructural analysis of rough ER in the hippocampal CA1 revealed IH-induced ER luminal swelling, and was attenuated by TUDCA. In addition, the length of synaptic active zone was significantly reduced after chronic IH treatment and was partially rescued by the application of TUDCA. Golgi staining also showed a decrease in mature dendritic spines in IH group, and reversed by TUDCA. In behavioral analysis, the number of reference memory errors significantly increased after IH treatment and rescued by TUDCA injection. Overall, the data suggest a critical role of ER stress underlying the impairment of long-term synaptic plasticity and neurocognitive deficits in chronic IH. Targeting ER stress could be a potential therapeutic strategy for neural dysfunction in OSA. / On the other hand, neuronal firing, especially robust persistent activity of neuron in hippocampus, is critical role in memory formation. Increased ROS induced by IH has been implicated in long-term potentiation of neural activity. IH could be involved in a variety of K⁺ channels which eventually leads to excitotoxicity by increased Ca2⁺-dependent glutamate release. Although the results were just shown in acute IH treatment, the chronic effect of IH on the firing frequency of hippocampus is still unknown. / Therefore, to investigate the effect of chronic IH treatment on firing activities and local field potentials of hippocampal neurons, implantation of multi-channel micro-wires electrode array into hippocampus of OSA model rat was performed to monitor spontaneous discharge. The results were shown the firing frequency of pyramidal neurons (PNs) was significantly elevated after 8 hours IH in second and third days, on the other hand, interneurons (INs) seem to be more sensitive to intermittent hypoxia since the higher firing frequency was sustained from third day to seventh day after 8 hours IH, however, at the end of 14 days IH treatment, the firing frequencies of PNs and INs are all both dramatically reduced. Meanwhile, the results in this part will enable us to understand the exact change of firing pattern and local field potential during intermittent hypoxia. The percentage of complex burst spikes was decreased after 14 days IH in PNs and the power of theta rhythms was also impaired. It suggests that the disorder of neuronal pattern and the change of local field potential are associated with cognitive impairment in OSA model. After 1 week recovery, the firing frequency of PNs was rescued again, but not for that of INs. We also found that the power of theta rhythms which had an important role in memory formation was weaker after 2 weeks IH treatment, however, the precise mechanism was still unknown. From the effect of intermittent hypoxia on spontaneous discharges and LFP of hippocampal neurons in free moving rat, it may reveal some roles of IH in cognitive impairment via disorder neuronal function in CA1 region. / 阻塞性睡眠呼吸暫停(OSA) 是一種常見的睡眠障礙疾病，這種疾病的主要特徵是在睡眠過程中反復發作的氣道阻塞，從而導致间歇性缺氧(IH)。從臨床報導中發現，OSA患者表現出行為和神經心理缺陷，包括空間學習記憶的受損和認知缺陷。通過之前的研究表明，活性氧(ROS)的增多和細胞凋亡是間歇性缺氧所引起認知功能障礙的主要機制之一，然而，其具體的機制仍不清楚。 / 作為細胞重要的細胞器，內質網是分泌蛋白和膜蛋白折疊組裝的主要場所，同時，由ATP依賴的分子伴侶所介導的蛋白質翻譯後修飾這一過程也主要在內置網中完成。在本課題中，我們假設在OSA模型的海馬組織中，內質網應激的啟動是由於缺氧引起的與活性氧(ROS)的升高。在本課題中，我們使用了四組成年雄性小鼠，其中兩組作為正常對照組，分別接受生理鹽水和牛磺去氧膽酸（一種常用的內質網抑制劑）的腹腔注射，另外兩組接受缺氧處理，同時也分別接受照生理鹽水和牛磺去氧膽酸注射。八臂放射迷宮被用來研究參考記憶的表現。行為學結束之後，長時程增強(LTP)用來測定海馬的突觸可塑性。用免疫印跡的方法檢測內質網應激的相關凋亡蛋白的表達情況，並且觀察海馬CA1區域中，內質網超微結構和海馬樹突棘數目及突觸形態的變化。 / 從實驗結果中，LTP在缺氧後減弱，而TUDCA能夠部分恢復由於缺氧所導致的LTP的降低。除此之外，內質網應激相關的促凋亡蛋白(CHOP和caspase-12)在缺氧組中表達升高，但是在TUDCA組中有所減低，同時，我們還發現，TUDCA也能夠減低缺氧組中cleaved-caspase-3的表達，而這一作用，可能與提高Bcl-2蛋白的表達（一個可標記的抗凋亡蛋白）有關。在間歇性缺氧組的海馬CA1區域中，粗面內質網出現管腔的腫脹，這一超微結構的變化表明在內質網出現官腔中有的許多未折疊蛋白聚集，並通過TUDCA的注射能夠降解未折疊蛋白來緩解這一現象的發生。同時，在IH處理後，突觸超微結構也發生了形態上的變化。突觸活性區的長度在IH處理組中顯著減少，但是在TUDCA組中有一定程度的恢復。高爾基染色顯示，成熟樹突棘（海馬突觸可塑性的結構基礎）的數目在間歇性缺氧組中有所下降，而在TUDCA治療後，成熟樹突棘的數目有所上升。我們發現參考記憶錯誤次數在缺氧後都有明顯的升高，而在注射TUDCA後，參考記憶錯誤次數都有所降低。總之，這些結果證明，內質網應激在間歇性缺氧的所引起的長時程突觸可塑性減弱和神經認知功能的損傷起到關鍵的作用，而抑制內質網應激對OSA中的出現神經功能紊亂起到一定的預防和治療效果。 / 而另一方面，神經元的放電，特別是海馬中神經元穩定持久的放電形式，對記憶的形成起到關鍵的作用。間歇性缺氧所引起的ROS的升高對於長時程增強的神經活動存在一定的關係，因為，通過以往的研究發現，間歇性缺氧可以通過多種鉀離子通道的啟動，最終由於鈣離子依賴的谷氨酸釋放的增多从而導致興奮性毒性的神經遞質的釋放。而這些結果只在急性缺氧模型中發現，慢性的間歇性缺氧對海馬的放電頻率的影響仍是未知之數。 / 因此，為了探討長時程的間歇性缺氧對海馬神經元的放電頻率和局部場電位的影響，多管道微絲電極陣列植入OSA大鼠的海馬中來監控自發放電的影響。結果表明，錐體細胞的放電頻率在第二天和第三天的8小時的間歇性低氧後明顯的升高了。另一方面，我們觀察到中間神經元似乎對間歇性缺氧更敏感，因為，從第三天到第七天缺氧8小時後，神經元的放電頻率都明顯的增高。但是在間歇性缺氧14天后，錐體細胞和中間神經元的放電頻率都所有顯著性的減少。同時，這一部分結果準確表明了海馬神經元的放電模式和局部場電位在間歇性缺氧的模型的是如何變化的。我們發現錐體細胞所具有的複合簇狀放電的比例減少，同時，theta波(與記憶的形成有關)的能量也有所減低。而這種神經元活動和局部的場電位的異常變化可能與OSA模型中出現的總認知功能障礙有關。在恢復一周後，錐體細胞的放電頻率有所增加，基本上可以恢復到缺氧前的狀態，但是中間神經元的頻率卻沒有多大的改變, 但是，其具體機制仍不清楚。從間歇性缺氧對大鼠海馬神經元自發放電和場電位影響的結果，它揭示了間歇性缺氧通過擾亂海馬CA1區域神經元的功能從而導致認知功能損傷。 / Xu, Linhao. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 167-199). / Abstracts also in Chinese. / Title from PDF title page (viewed on 03, October, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

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Made available in DSpace on 2016-04-29T13:17:49Z (GMT). No. of bitstreams: 1 Laura Muniz Rocha.pdf: 1241168 bytes, checksum: eaaf1dca965f9aa61ee39990e47879dd (MD5) Previous issue date: 2013-06-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Chronic Mild Stress (CMS) is an experimental animal model of induced anhedonia by exposing rats to a protocol of mild stressors for a long period of time. This model is an attempt to reproduce in controlled environment conditions analogous to the real environment, seen as important to produce behavioral changes. To identify other effects of exposure to CMS, this study aimed to verify whether the exposure to chronic mild stress produces changes in the establishment of a simple discrimination after the expouse to the protocol. Therefore, the subjects of this study had their weight and food and water intake measured daily, tests of consumption and preference of liquid were realized weekly; subjects were exposed to the protocol stressors over six weeks and, after this period was initiated the discriminative training. The experiment consisted of four experimental conditions: (1) one subject was exposed, like all other subjects, to tests of consumption and preference of liquids, (2) four subjects were exposed to the protocol, (3) four subjects were exposed to the protocol and to a discrimination procedure(4) four subjects were exposed only to the discrimination procedure and they weren t exposoused to the chronic mild stress. The results obtained in this study indicate that: (a) subjects exposed to the protocol showed a greater loss and variation of the body weight; (b) during the protocol the average of water consumption increased and average food consumption decreased for subjects exposed to the protocol. (c) tests of consumption and preference of liquids did not show a reduction in preference for the sucrose subtance but an increase in the total fluid intake for subjects exposed to stress. And, finally, (d) observed that exposure protocol stressors interfere with the acquisition of a simple discrimination. For subjects exposed to the protocol were required, on average, twice as many sessions to reach the criterion of two consecutive sessions with discriminative indices above 80%. and (e) that the subjects exposed to the protocol showed differences in tests of generalization when compared with subjects exposed only to discrimination. And, lastly (d) observed that exposure to the protocol interfered the acquisition of a simple discrimination. The subjects exposed to the protocol required, on average, twice as many sessions to reach the criterion of two consecutive sessions with discriminative indices above 80% and (e) the subjects exposed to the protocol showed differences in the generalization tests when compared with subjects exposed only to discrimination.Thereby, the exposure to a condition of chronic mild stress and affects the acquisition of a simple discrimination established after the protocol. This result may indicate that exposure to stress condition altered the reinforcing value of the stimulus for the subjects who were exposed to it, this change may have been responsible for the differences obtained in the discrimination of subjects exposed to this condition and subjects who were not exposed to the protocol / O Chronic Mils Stress (CMS) é um modelo animal experimental de anedonia induzida através da exposição de ratos a um protocolo de estressores crônicos e moderados por um longo período de tempo. Este modelo é uma tentativa de reproduzir, em ambiente controlado, condições análogas às do ambiente real, vistas como importantes para a produção de alterações comportamentais. Visando identificar outros efeitos da exposição ao CMS, o presente estudo teve como objetivo verificar se a exposição a eventos aversivos crônicos e moderados produz alterações no estabelecimento de uma discriminação simples posterior ao protocolo de estressores. Para tanto, os sujeitos do presente estudo tiveram o peso e o consumo de ração aferidos diariamente; foram expostos a testes semanais de consumo e preferência de líquidos; foram expostos ao protocolo de estressores ao longo de seis semanas e, após o encerramento deste, foi iniciado o treino discriminativo. O delineamento foi composto por quatro condições experimentais: (1) um sujeito foi exposto, como todos os outros sujeitos, aos testes de consumo e preferência de líquidos, (2) quatro sujeitos foram expostos ao protocolo de estressores, (3) quatro sujeitos foram expostos ao protocolo de estressores e a discriminação simples e (4) quatro sujeitos foram expostos a uma discriminação simples sem exposição aos estímulos crônicos e moderados. Os resultados obtidos no presente estudo indicam que: (a)os sujeitos expostos ao protocolo de estressores apresentaram uma maior perda e variação no peso corporal; (b) durante o protocolo o consumo médio de água aumentou e o consumo médio de ração diminuiu para os sujeitos expostos ao protocolo. (c) nos testes de consumo e preferência de líquidos não foi observado uma redução na preferência por sacarose e sim um aumento no consumo total de líquidos para os sujeitos expostos a condição de estresse. E, por fim, (d) observou-se que a exposição ao protocolo de estressores interferiu na aquisição de uma discriminação simples. Para os sujeitos expostos ao protocolo foram necessárias, em média, o dobro de sessões para atingir o critério de duas sessões consecutivas com índices discriminativos superiores a 80% e (e) que os sujeitos expostos ao protocolo apresentaram diferenças nos testes de generalização se comparados com os sujeitos expostos somente à discriminação. Assim, é possível concluir que a exposição a uma condição de estresse crônica e moderada afeta a aquisição de uma discriminação simples posteriormente estabelecida. Esse resultado pode indicar que a exposição à condição de estresse alterou o valor reforçador do estímulo para os sujeitos que foram expostos a ele, essa alteração pode ter sido responsável pelas diferenças obtidas na discriminação dos sujeitos expostos a essa condição e dos sujeitos que não foram expostos aos estressores

Made available in DSpace on 2016-04-29T13:17:55Z (GMT). No. of bitstreams: 1 Paulo Eduardo da Silva.pdf: 1304608 bytes, checksum: 120f5cf5c36c91fabfb9829aab88df3f (MD5) Previous issue date: 2015-07-08 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The Chronic Mild Stress (CMS) has been described in the literature as an experimental model of anhedonia, central symptom of depression in humans. The anhedonia has been studied in this model looking for a decrease of water with sucrose consumption in rats. This result is usually observed after the animal had been subjected to a set of stressful stimuli in a moderated and chronical way, for six weeks in average. The present study aimed to investigate the effects of the Stressors Protocol in rats subjected to a continuous water deprivation regimen. Eleven male rats of Wistar lineage were studie,. All the rats were subjected to a water deprivation schedule until reaching 85% of their ad lib weights, and they were maintained at these weights for the whole study. Thirteen water and water with sucrose consumption tests were used for all the subjects, while S7 was exposed only to the liquids consumption tests. S3 subject was submitted only to the Stressors Protocol. S5 was exposed to the same conditions of S3, except that the Stressors Protocol involved only the grouping stressor. For the other eight subjects, first they had the bar press response to the two bars modeled, using water as reinforcement. Then these eight animals were subjected to a Conc VI 5 sec VI 5 sec reinforcement, each bar being associated to water or water with sucrose reinforcements (one for each bar). After four weeks in this reinforcement schedule these animals were subjected to the Stressors Protocol for six consecutive and uninterrupted weeks in their living cages. During the protocol, four subjects (S2, S6, S8 and S10) also had their bar press responses reinforced in a Conc VI 5 sec VI 5 sec schedule (group before, during and after). The other four rats (S1, S4, S9 and S11- group before and after) were not submitted to operant sessions as long as the Stressors Protocol was available. At the end of the phase when the Stressors Protocol was available, these eight subjects were again subjected to the base line condition. The main results were: (a) a weight stability for the animals subjected to the protocol, (b) a high alternation of water and water with sucrose consumption in the tests for the only subject submitted to the tests and to the protocol, not demonstrating anhedonia, (c) a reduction in the animal s food consumption and an increase of water consumption in the living cage during the protocol for seven subjects, (d) the stressors protocol was not followed by a modification of the distribution of water and water with sucrose reinforced responses by Conc VI 5sVI5s, neither during the protocol, nor after its cessation, and (e) it seems that the reinforcement value of the liquids alternated for some subjects over major of the sessions. The role of continuous water deprivation and the measures used as anhedonia indicators are discussed / O Chronic Mild Stress (CMS) tem sido descrito na literatura como um modelo experimental de anedonia, sintoma central na depressão em humanos. A anedonia tem sido estudada dentro desse modelo a partir do decréscimo no consumo de água com sacarose em ratos. Este resultado é geralmente observado após o animal ser submetido a um conjunto de estímulos estressores de forma moderada e crônica, durante seis semanas em média, O presente estudo teve como objetivo investigar os efeitos do Protocolo de Estressores em ratos submetidos a um regime contínuo de privação de água. Foram empregados 11 ratos machos, da linhagem Wistar. Todos os sujeitos foram submetidos a um esquema de privação de água até atingir 85% dos seus pesos ad lib. e foram mantidos nesses pesos durante todo o estudo. Foram empregados 13 testes de consumo de água e de água com sacarose, sendo que o Sujeito S7 só passou pelos testes de consumo dos líquidos. O Sujeito S3 foi submetido ao Protocolo de Estressores. O sujeito S5 passou pelas mesmas condições que o S3, exceto que o Protocolo de Estressores envolveu apenas o estressor agrupamento. Para os outros 8 sujeitos, primeiramente foram modeladas as respostas de pressão às duas barras, usando água como reforçador. Depois, esses 8 animais foram submetidos a um esquema Conc VI 5 seg VI 5 seg associado aos reforços água e água com sacarose (um para cada barra). Após quatro semanas nesse esquema de reforçamento esses animais foram submetidos ao Protocolo de Estressores por seis semanas consecutivas e ininterruptas nas suas gaiolas-viveiro. Durante o Protocolo, 4 sujeitos (S2, S6, S8, S10) também tiveram suas respostas de pressão à barra reforçadas num esquema Conc VI 5 seg VI 5 seg (grupo antes, durante e depois) e os outros 4 (S1, S4, S9, S11) não (grupo antes e depois). Ao término do Protocolo de estressores, esses 8 sujeitos foram submetidos novamente à condição de linha de base. Os principais resultados encontrados foram: (a) estabilidade nos pesos dos animais submetidos ao protocolo, (b) maior oscilação em relação ao consumo de água e de água com sacarose para o sujeito submetido apenas aos testes e ao protocolo, não demonstrando anedonia, (c) redução no consumo de ração e aumento no consumo de água na gaiola-viveiro durante o protocolo (d) o protocolo de estressores não foi acompanhada por uma alteração na distribuição de respostas reforçadas com água e água com sacarose, nem durante e nem após a suspensão do mesmo, e (e) o valor reforçador dos líquidos parece ter se alternado para alguns sujeitos ao longo da maioria das sessões. Discute-se o papel da privação contínua de água e as medidas utilizadas como indicativas a de anedonia

<div>Ketogenic diets (KDs) are high-fat low-carbohydrate diets that can exert positive effects on physical and neurological health. The more established therapeutic effects of KD are for treating epilepsy and diabetes. However, KD protective effects may apply to other inflammation related disorders associated with Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation, such as mood disorders. Chronic stress has been shown to elevate cytokine levels, disrupt neuroendocrine homeostasis, and cause anxiety and depressive-like behavior in animal models. In vitro experiments have shown that ketone bodies, a metabolite produced while on KD, can prevent the production of cytokines elevated in response to chronic stress and other pre-clinical experiments have suggested that ketone bodies can prevent anxiety-like behavior. Although this suggests that KDs have anti-inflammatory and mood stabilizing potential, these effects have yet to be explored. In this experiment, we assessed the behavioral and neuroendocrine effects of KD using male and female Long-Evans rats. Animals underwent three weeks of Chronic Mild Stress (CMS) while on KD or control Chow (CH). Body weight and food intake data were recorded daily, and depressive-like behaviors were assayed after the three weeks. Plasma Beta-Hydroxybutyrate (HB), Corticosterone (CORT) and Interleukin-1 beta (IL-1) were measured after behavior testing, along with hypothalamic Corticotropin-Releasing Hormone (CRH) and Neuropeptide Y (NPY) mRNA expression. CMS induced weight loss and reduced food intake in the control-diet groups, however the KD-fed male and female rats were resistant to CMS-induced weight loss and reduced food take. Female rats fed KD were protected from CMS-induced reductions in plasma CORT and hypothalamic NPY expression. Collectively, these data suggest anti-depressant potential of KDs against chronic stress, particularly in females. </div>

Objective: Following a sport related concussion (SRC) visible symptoms generally dissipate in 7-10 days post-injury. However, little is known about the cumulative effects of SRCs both in terms of structural damage to the white matter of the brain and neurocognitive performance. To address this issue, the relationship between the number of SRCs (frequency), axonal white matter (WM) damage and neurocognitive performance was examined. There were three predictions. First, increases in SRC frequency will be associated with decreases in performance on neurocognitive tests. Second, the frequency of SRC will be associated with axonal injury measured three WM tracts: the corpus callosum, the fronto-occipital fasciculus and the inferior longitudinal fasciculus. Third, less accurate and slower performance on a response inhibition task (STOP-IT) will be associated with greater axonal injury. Methods: A cross-sectional correlational design was utilised. Participants were rugby players with a history of SRC, rugby players with no history of SRC and control athletes (N=40) who completed a neurocognitive test battery and had a DTI brain scan. The neurocognitive battery consisted of the following standardised tests: Speed and Capacity of Language Processing Test, CogState Electronic Battery, Stroop Colour and Word Test, Controlled Oral Word Association Test, the Trail Making Test and the experimental test STOP-IT Electronic Test. White matter axonal injury was measured by DTI using fractional anisotropy (FA) and mean diffusivity (MD) metrics. The DTI data was processed using FSL to extract FA and MD DTI metrics in three a-priori regions of interest. Results: Spearman’s correlation analyses did not find significant associations between SRC frequency and neurocognitive performance on the FAS (rs=0.053, 95% CI [-0.27, 0.36]), TMT-A (rs=0.058, 95% CI [-0.26, 0.37]), TMT-B (rs= -0.046, 95% CI [-0.27, 0.36]) and the Stroop Interference (rs= -0.25, 95% CI [-0.07, 0.52]). Similarly, no significant Spearman’s correlations were found between SRC frequency and the computerised neurocognitive tests STOP-IT-SSRT (rs= -0.04, 95% CI [-0.28, 0.35])), STOP-IT–Accuracy (rs= -0.05, 95% CI [-0.27, 0.36]), CogState Detection subtest (rs= -0.15, 95% CI [-0.17, 0.44]), CogState Identification subtest (rs= -0.065, 95% CI [-0.26, 0.37]), CogState One card learning subtest (rs= 0.24, 95% CI [-0.08, 0.52]) or the CogState One back task subtest (rs= 0.06, 95% CI [-0.26, 0.37]). In terms of the DTI data there were no significant associations between SRC frequency and axonal injury measured by FA values in the CC (rs= 0.005, 95% CI [-0.31, 0.32]), ILF (rs= 0.028, 95% CI [-0.29, 0.34]) or FOF (rs= -0.022, 95% CI [-0.30, 0.33]). The same was pattern was found for MD values in the CC (rs= 0.081, 95% CI [-0.24, 0.39]), ILF (rs= -0.16, 95% CI [-0.16, 0.45]) or FOF (rs= -0.15, 95% CI [-0.17, 0.44]) Finally, there were no significant Spearman’s correlations between axonal injury FA values and the STOP-IT SSRT in any of the ROIs: CC (rs= 0.005, 95% CI [-0.31, 0.32]), ILF (rs= 0.028, 95% CI [-0.29, 0.34]) or FOF (rs= -0.022, 95% CI [-0.30, 0.33]). Equally, there were no significant correlations between MD values STOP-IT SSRT in the CC (rs= -0.028, 95% CI [-0.29, 0.34]), ILF (rs= -0.16, 95% CI [-0.16, 0.45]) or FOF (rs= -0.15, 95% CI [-0.17, 0.44]). Likewise, there were no significant Spearman’s correlations between accuracy on the STOP-IT and FA values and in any of the ROIs: CC (rs= 0.19, 95% CI [-0.13, 0.48]), ILF (rs= -0.045, 95% CI [-0.27, 0.35]) and FOF (rs= -0.032, 95% CI [-0.29, 0.34]), or MD values in the CC (rs= -0.11, 95% CI [-0.21, 0.41]), ILF (rs= 0.017, 95% CI [-0.30, 0.33]) or FOF (rs= 0.082, 95% CI [-0.24, 0.39]). This study did not find support for the hypothesis that cumulative SRCs are associated with poorer performance on neurocognitive tests or with axonal injury as measured by FA and MD DTI metrics. Conclusion: The null findings suggest that there are no cumulative effects of SRCs. The current findings are inconsistent with previous cross-sectional research that indicates that there are long-term changes to diffusivity measures present after single SRCs as well as cumulative effects in contact sport athletes. Likewise they are at odds with evidence suggesting that after three SRCs neurocognitive performance can be affected. The study needs to be extended to include a larger sample to ensure the results are not due to low statistical power.

The aim of the research in this thesis was to study how environmentally friendly corrosion inhibitors for cooling water systems might be developed and used. Firstly, reduced toxicity inorganic corrosion inhibitors (i.e. nitrite/molybdate) were considered. Secondly, non-toxic inhibitors based on mono and di-basic salts of carboxylic acids were studied systematically as a function of carbon chain length. For nitrite inhibitor alone, a concentration of 7 mM NaNO2 was effective to inhibit carbon steel in chloride media of 10 mM NaCl, while 10 mM nitrite was needed in sulphate media of 3.66 mM Na2SO4. However, it was found possible to significantly reduce the concentration of nitrite by adding molybdate in synergy. This was attributed to the nitrite passivation combined with ferrous molybdate salt film pore plugging thus promoting a continuous and protective film on the material within these media. Thus, in pH 6-10 an inhibition efficiency of 97% was recorded with a mixture of 3 mM nitrite/2 mM molybdate in both chloride and sulphate media and at 25°C and 60°C. However as the solution pH decreased below pH 4 the inhibition efficiency decreased to about 47%.In the second part of the study, the use of sodium salts of carboxylic acids with different chain lengths has been investigated. In this part a summary of the performances and limitations of both mono- and di-sodium carboxylate inhibitors are presented. For mono-carboxylates, the inhibition efficiency reached a maximum value of 95% in stagnant aerated solutions at a chain length of C=4 with a critical inhibition concentration of 6 mM in 10 mM NaCl solution. However the inhibition efficiency gradually decreased as the number of carbon atoms in the chain length increased to more than 8, or less than 4, and this was in agreement with surface hydrophobicity and contact angle results. For lower chain lengths, the carboxylate anion becomes more acidic and complexing of the metal ion while for longer chain lengths, the carboxylate anion becomes less soluble and tends to micellise wherby the active groups are no longer available for surface adsorption. For di-carboxylates the inhibition efficiency improved in 10 mM NaCl at a given chain length compared with mono-carboxylates, and continued to increase to C=8 (sebacate), which achieved excellent inhibition efficiency. However, sebacate is costly so a blend with ethyl hexanoate was found to be economically favoured.

Objetivo: Avaliar a atrofia do corpo caloso (CC) em pacientes com doença de Alzheimer (DA) e comprometimento cognitivo leve (CCL) e quantificar quais regiões dessa estrutura são mais acometidas nessa doença como uso de técnicas quantitativas de ressonância magnética. Metodologia: O estudo contou com a participação de 75 indivíduos sendo 22 controles normais (CN), 30 com CCL e 23 com DA. O volume total do corpo caloso e suas 3 diferentes sub regiões foram delimitadas em cortes sagitais de imagem de ressonância magnética. Os volumes obtidos foram corrigidos para a variação de volume intracraniano. As mascaras foram co-registradas a mapas de relaxometria e transferência de magnetização para analise quantitativa. Resultados: Encontramos atrofia e redução dos valores de relaxometria e transferência de magnetização nos pacientes do grupo DA. As tres sub regiões do corpo caloso apresentaram redução de volume na doença sendo que a atrofia foi maior nas regiões anteriores. Não encontramos diferença significativa nos parâmetros estudados entre CCL e CN. Conclusões: Embora o corpo caloso esteja envolvido no processo de desconexão cortical presente na doença de Alzheimer seu envolvimento não é precoce. / Objective: To evaluate the atrophy of the corpus callosum (CC) in patients with Alzheimer disease (AD) and mild cognitive impairment (CCL) and quantify which regions of this structure are most affected in this disease as using quantitative MRI techniques. Methodology: The study counted on the participation of 75 individuals being 22 normal controls (CN), 30 with CCL and 23 with AI). The total volume of the corpus callosum and its v 3 different sub regions were delimited in sagittal sections of magnetic resonance imaging. The volumes obtained were corrected for intracranial volume variation. The masks were recorded with maps of relaxometry and transfer of magnetization for quantitative analysis. Results: We found atrophy and reduced values of relaxometry and magnetization transfer in patients in the AD group. The three sub regions of the corpus callosum showed volume reduction in the disease, with atrophy being greater in the anterior region. We found no significant difference in the parameters studied between CCL and CN fit .Conclusions: Although the corpus callosum is involved in the process of cortical detachment present in Alzheimer\'s disease, its involvement is late.