Traumatic brain injury (TBI) is a prominent disease in developed countries, and age is an important factor in functional outcome. Although aged patients typically show diminished recovery compared to young patients, and have higher mortality and morbidity following TBI, the mechanism is not well understood. To date, there is no effective therapeutic for TBI. Previous studies indicate a secondary injury in TBI begins immediately after impact, and is likely the major contribution to delayed neuron dysfunction and loss. Studies also suggest mitochondrial dysfunction and increased free radical species (ROS) production following TBI may play a key role in the process. To evaluate oxidative damage following TBI, especially in aging, young (3 months), middle aged (12 months) and aged (22 months) Fisher-344 rats were subjected to a unilateral controlled cortical impact (CCI) injury, and tissue sparing, 4-hydroxynonenal (HNE) and acrolein levels, and antioxidant enzyme activities, and DNA oxidative damage were measured. In order to evaluate changes in mitochondria following TBI, mitochondrial protein levels were investigated using young adult animals. To evaluate a potential therapeutic for TBI, the effect of creatine on oxidative damage was evaluated. These studies show an age dependent increase of oxidative damage following TBI, demonstrated by increased levels of 4-HNE, acrolein and 8-hydroxyguanine. Middle aged and aged animals showed increased tissue loss compared to young animals 7 days post injury. Mitochondrial proteins involved in the respiratory chain, carrier proteins and channel proteins were significantly decreased 24 h post injury in ipsilateral cortex, but increased in both ipsilateral and contralateral hippocampus. To study potentially protective compounds in TBI, animals were fed with creatine two weeks before TBI and showed less oxidative damage and increased antioxidant capacity, which suggests creatine may be a potential drug for clinical treatment of TBI. The work described in this dissertation is the first to show increased oxidative damage and diminished antioxidant capacity in TBI in aging. The study of mitochondriafollowing TBI using quantitative proteomics is also the first time to show multiple mitochondrial proteins change following TBI. These data are also the first to show creatine can increase antioxidant defenses. These studies contribute to our understanding the mechanisms of secondary injury in TBI in aging.

Alzheimer Disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and dementia. Both energy metabolism and the function of creatine kinase are known to be affected in Alzheimer diseased brain. With synchrotron FTIR microscopy, extensive deposits of crystalline creatine (Cr) had been discovered in TgCRND8 mouse brain tissue by previous students in our lab. In this thesis, regions of hippocampus and caudate of 5 pairs of transgenic mice and their non-transgenic littermate controls were mapped using Raman and IR microspectroscopy to find clues to Cr origin in transgenic mouse brain. Raman spectra obtained at higher spatial resolution (1-2 µm) were used for better delineation of the Cr crystalline deposits and their environs. These results indicate that Cr crystals were formed after snap-freezing and desiccation of brain tissue. Therefore, it can be speculated that Cr might be exist in solution form in vivo.

Thesis (M.S.)--University of Hawaii at Manoa, 2005. / Includes bibliographical references (leaves 34-36). / viii, 36 leaves, bound col. ill. 29 cm

Thesis (M.S. Ed.)--Baylor University, 2008. / Includes bibliographical references (p. 73-77)

Thesis (M.S.)--University of North Carolina at Wilmington, 2006.

Made available in DSpace on 2014-06-11T19:31:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-12-21Bitstream added on 2014-06-13T18:41:47Z : No. of bitstreams: 1 pereira_dm_me_jabo.pdf: 580192 bytes, checksum: b2b81a55bd0260aba59a035c51c133ee (MD5) / Universidade Estadual Paulista (UNESP) / Pretendeu-se avaliar o efeito da creatina sobre as mensuraçóes ecocardiográficas do ventrículo esquerdo em eqüinos treinados em esteira rolante. Os 15 animais foram divididos em grupos após avaliação clínica para constatar higidez, sendo um grupo composto de sete animais suplementados com 75g de creatina adicionada na ração (Gtc) e um grupo, composto de oito animais que não receberam creatina (Gt). Os dados referentes às mensurações do ventrículo esquerdo, foram obtidos por meio de ecocardiografia em Modo M e registrados mensalmente durante cento e vinte dias (MO, M1, M2, M3, M4), em ambos os grupos. Os índices ventriculares e o débito cardíaco serviram para avaliar os efeitos do condicionamento físico associado ou não à suplementação com creatina sobre a musculatura cardíaca. Os resultados referentes a variação de espessura das paredes ventriculares e do diâmetro interno da câmara ventricular no grupo de animais treinados sem suplementação se assemelharam aos da literatura compilada. A metodologia aplicada e os resultados obtidos permitiram concluir que a utilização de 75g de creatina adicionadas a ração de eqüinos treinados em esteira rolante por um período de 120 dias, causa menor hipertrofia cardíaca do que aquela observada nos animais que não receberam suplementação. / The present study evaluated the effects of the exerci se and the association creatine - exercise in size and left ventricular index by echocardiography in fifteen adults equine each month during four months (MO, M1, M2, M3, M4). The fifteen animais were divided in two groups, trainned and supplemented group (Gtc), with seven horses, that received 75g of creatine added in fed and a trained group only (Gt) with eight animais. The ventricular index and cardiac output were usefull to evaluate the effects of physicaJ conditioning and the association of creatine suplementation and trainning on the heart musculature. The results at thickness of the ventricular walls and diameter of ventricular chamber at Gt were similar to the compiled literature The applied methodology and the results permit to conclude that creatine causes smaller heart hipertrophy than that observed in the animais that didn't received the suplementation.

O exercício de enduro é caracterizado por um esforço aeróbico prolongado, de intensidade variável em que o cavalo é submetido a um trabalho permanente o qual exige dos sistemas orgânicos a manutenção da homeostasia. A habilidade dos músculos em gerar energia rapidamente via produção de lactato, é essencial para o desempenho em exercícios de elevada intensidade. Entretanto, a produção de lactato pode também suprimir muitos dos processos vitais necessários pra sustentar a atividade muscular. A associação de lactato com a fadiga muscular tem levado à busca de suplementos alimentares que reduzem o acúmulo de lactato. N,N-Dimetilglicina (DMG), um intermediário do metabolismo da colina, é um suplemento atualmente comercializado, porém não há dados consistentes na literatura sobre sua eficácia para equinos atletas. Objetivando avaliar o efeito da DMG, utilizou-se 12 animais em treinamento para provas de enduro, dos quais seis receberam suplementação oral; utilizou-se delineamento inteiramente casualizado, com medidas repetidas no tempo. Foram coletadas amostras de sangue em sete tempos diferentes, a cada 15 dias; dessas amostras obteve-se valores das enzimas creatina quinase e aspartato aminotransferase e também valores de glicose e lactato, além de medições de freqüência cardíaca e respiratória. Após 30 dias da última amostragem, realizaram-se coletas de sangue em intervalos curtos de tempo, após exercício, a fim de se realizar uma curva de lactato, e também comparar dados analisados em laboratório com analisados via lactímetro. Dos dados analisados, houve interação entre tempo e aumento da enzima creatina quinase, o que pode ser justificado pelo aumento da demanda muscular durante exercício físico constante. A enzima aspartato aminotransferase diminuiu com o passar do tempo, em ambos os grupos, porém oscilou dentro da normalidade, o que pode caracterizar baixa permeabilidade da membrana celular, comum em animais condicionados. A alteração da glicose foi a mesma ao longo do tempo para ambos os grupos. As médias de lactato não diferiram no grupo suplementado, mas sua variação dentro do grupo não suplementado sugere que a suplementação com DMG pode influenciar na manutenção da integridade muscular. Em comparação entre as formas de dosagem do lactato plasmático, pode-se concluir que o lactímetro é uma ferramenta eficaz na obtenção de dados a campo, pois suas médias não diferiram das médias de lactato obtidas através de análise laboratorial. A suplementação oral com dimetilglicina não influenciou o desempenho atlético de cavalos em treinamento para enduro equestre. / The exercise endurance is characterized by a prolonged aerobic work, of varying intensity in which the horse is subjected to a permanent job which requires organ systems maintain homeostasis. The ability of muscles to generate energy quickly via production of lactate is essential for the performance of high intensity exercise. However, the production of lactate may also suppress many of the vital processes necessary to sustain muscle activity. The combination of lactate in muscle fatigue has led to the search for dietary supplements that reduce the accumulation of lactate. N, N-dimethylglycine (DMG), an intermediate in the metabolism of choline, is a supplement currently marketed, but there is no consistent data in the literature on its effectiveness for equine athletes. In order to evaluate the effect of DMG, we used 12 animals in training for endurance events, of which six received oral supplementation, we used a completely randomized design with repeated measures on time. Blood samples were collected in seven different times, every 15 days, these samples gave values of the enzymes creatine kinase and aspartate aminotransferase values as well as glucose and lactate, and easurements of heart rate and breathing. After 30 days the last sampling, there were blood samples at short intervals of time after exercise in order to perform a lactate curve, and also compare data analyzed in laboratory and analyzed via lactimeter. Of the data analyzed, there was interaction between time and increased the enzyme creatine kinase, which can be explained by increased demand constant muscle during exercise. The enzyme aspartate aminotransferase decreased over time in both groups, but varied within the normal range, which can characterize low permeability of the cell membrane, which is common in animals conditioned. The change in glucose was the same over time for both groups. The mean lactate did not differ in the supplemented group, but the variation in the unsupplemented group suggests that supplementation with DMG can influence the maintenance of muscle integrity. In comparison dosage forms of lactate, it can be concluded that the lactimeter is an effective tool for getting data into the field, because their means did not differ from average lactate obtained through laboratory analysis. Oral supplementation with dimethylglicine did not influence athletic performance of horses in training for endurance riding.

A realização de uma sessão com ações excêntricas provoca dano na estrutura muscular. Durante o processo de recuperação, essa estrutura sofre adaptações que a protegem da ocorrência de dano nas sessões subseqüentes. Essas adaptações são chamadas de Efeito da Carga Repetida (ECR). Esse efeito foi estudado com a realização de apenas duas sessões de exercícios. A velocidade da ação excêntrica também pode contribuir para a variabilidade do dano induzido. O objetivo desse estudo foi investigar através da análise dos indicadores indiretos, creatina quinase (CK), força, dor, circunferência e amplitude de movimento (ADM), o dano induzido por diferentes velocidades da ação excêntrica e o efeito da carga repetida com a realização das diferentes velocidades (60ºs-1 (Exc60) e 180ºs-1 (Exc180)); e verificar se o efeito da carga repetida seria maior com a realização de três sessões de exercícios. Os resultados dos indicadores analisados tiveram alterações semelhantes nos grupos Exc60 e Exc180, sugerindo que as diferentes velocidades parecem não interferir na magnitude do dano induzido. O ECR não foi diferente entre as velocidades, pois o comportamento das variáveis analisadas foi semelhante entre os dois grupos nas duas sessões iniciais. A realização da terceira sessão de exercícios excêntricos não promove o aumento do efeito protetor, visto que não houve diferenças significantes entre a segunda e a terceira sessão. Indicando que o ECR advém principalmente da realização da primeira sessão / Performing a bout of eccentric exercise causes muscle damage. During recovery, some adaptations occur that can protect muscle structure. These adaptations are known as Repeated Bout Effect. However, this phenomenon has been studied with two bouts. Velocity of eccentric action has been referred as one possible factor which can affect the extension of muscle damage. The aim of this study was to investigate muscle damage induced by different velocities, the repeated bout effect with different velocities and to verify if the repeated bout effect could be larger if three bouts of eccentric exercise were performed. Results of indirect markers of muscle damage (CK, DOR, upper-arm circumference, maximal isometric force) showed similar alterations in groups Exc60 and Exc180, suggesting that different velocities do not affect the extension of muscle damage. Repeated bout effect is not different between velocities, because changes in markers were comparable in both groups after the first two bouts. After performing a third bout of eccentric exercise, there was not any significant differences between second and third bouts. It indicates that the first bout is responsible for the adaptations of the repeated bout effect

Eight competitive cyclists performed two cycling trials, one following a high carbohydrate diet (H-CHO) and the other following a low carbohydrate diet (L-CHO). Trials consisted of repeated 60s maximal effort sprints to fatigue at a workload designed to elicit 125-135% VO_2peak at 90rpm. Three min of recovery separated sprints. Muscle biopsies taken at rest (biopsy 1), 85% max interval rpm (biopsy 2), and 70% max interval rpm (biopsy 3) revealed a main effect of diet on muscle glycogen levels: 609 ± 38 HCHO vs. 390 ± 42 mmol/kgdw L-CHO at biopsy 1, 383 ± 29 vs. 252 ± 28 mmol/kgdw at biopsy 2, and 346 ± 29 vs. 196 ± 18 mmol/kgdw at biopsy 3 (p<0.01). Similar decreases in muscle glycogen (45%), creatine phosphate (CP) (35%), and sarcoplasmic reticulum (SR) Ca²⁺-uptake (56%) were shown in both trials from biopsy 1 to 3. SR Ca²⁺-release decreased by 53% in H-CHO subjects and 36% in L-CHO subjects. Total exercise time tended to be longer in H-CHO than L-CHO subjects (57.5 ± 10 vs. 42.0 ± .89min) (p=0.09). H-CHO subjects exercised significantly longer than L-CHO subjects from biopsy 2 to 3 (33.6 ± 10 vs. 18 ± 3.6min) (p< 0.05). Results suggest that fatigue from 40- 60min of intermittent 60s high intensity cycling intervals is associated with reductions in muscle glycogen, CP, and SR function, and that the latter part of performance is impaired by low muscle glycogen. These data do not support a relationship between muscle glycogen status and SR function in intermittent high intensity exercise. / Master of Science

This study examined the effects of carbohydrate supplementation on resistance exercise performance, cortisol levels, and creatine kinase levels in trained males undergoing energy restriction. Sixteen experimental subjects were randomly assigned to a carbohydrate (C, n=8) or placebo group (P, n=8). The remaining six subjects served as controls (N). Performance tests were done before (Trials 1 and 2) and after (Trial 3) energy restriction. Experimental subjects consumed a low calorie formula diet for three days (18 kcal-1 kg-1 d-1). They had blood drawn before and after T2 and T3. For T3, they consumed either a carbohydrate (1g kg-1) or a placebo beverage 30 minutes before exercise. There was a significant increase in resting cortisol levels following energy restriction. CK levels were significantly elevated after exercise, suggestion muscle damage. Carbohydrate supplementation had no effect on blood glucose, cortisol, creatine kinase, or RPE. The number of repetitions performed during the final set of bench press showed significant interaction between groups and time. P and N increased the number of repetitions performed from T2 to T3 (15.0 + 1.4 to 17.3 + 0.8 for P, 15.0 + 2.7 to 16.7 + 2.3 for N). C decreased the number of repetitions performed 17.6 + 0.7 to 17.3 + 1.0). The number of repetitions performed during the final set of leg extensions showed no interaction between groups and time (p=0.801). This study did not support a benefit of consuming carbohydrate prior to resistance exercise for dieting athletes but illustrates that energy restriction increases a catabolic hormone. / Master of Science