Thesis (Ph.D.)--University of Florida, 2004. / Typescript. Title from title page of source document. Document formatted into pages; contains 127 pages. Includes Vita. Includes bibliographical references.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-10-20T11:46:36Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação de Mestrado Shirley Maria de Sousa.pdf: 975529 bytes, checksum: 53b510b6157f925fdbbc50de3bf646b3 (MD5) / Made available in DSpace on 2016-10-20T11:46:36Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação de Mestrado Shirley Maria de Sousa.pdf: 975529 bytes, checksum: 53b510b6157f925fdbbc50de3bf646b3 (MD5) Previous issue date: 2016-02-25 / CNPq / Durante o período reprodutivo,fêmeasproduzemelevados níveis deestrogênios.Os três principais sãoestrona (E1), 17-β-estradiol (E2) e o estriol (E3).O 17-β-estradiol é o estrogênio predominante durante os anos reprodutivos tanto em termos de níveis séricos absolutos como em termos de atividade estrogênica. Inúmeros relatos na literatura postulam que os estrogênios apresentam um importante papel cardioprotetor, e que essa ação protetora pode ocorrer tanto por expressão de genes como também pela ativação de proteínas de cascata de sinalização que culmina no efeito protetor dos estrogênios. Entretanto, o papel dos estrogênios no tecido cerebralcombatendo o estresse oxidativo ainda não é totalmente compreendido. No tronco encefálico, neurônio localizado especificamente na região do bulbo tem um importante papel no controle neuronal do sistema cardiovascular, pois atuam tanto no controle da atividade simpática como também na recepção dos sinais químicos e mecânicos provenientes de barorreceptores e quimiorreceptores. Em adição a essa rede neuronal do controle simpático e da decodificação de sinais aferentes, o tronco encefálico esta sob a influência das ações das espécies reativas de oxigênio-EROS, moléculas essas que tem alta capacidade de induzir a oxidação de lipídios de membrana, proteínas ou mesmo ao DNA, podendo levar a um quadro definido por estresse oxidativo. Hoje em dia, o estresse oxidativo é considerado um dos principais causadores de doenças neurológicas, tais como Parkinson, Alzheimer, Esclerose lateral amiotrófica entre outras. Dessa forma, o objetivo dessarevisãofoiinvestigar os efeitos neuromodulador dosestrogênios na prole fêmeas de mães que foram submetidas adesnutrição proteica no período perinatal (gestação e lactação). / During the reproductive age females significantly produce estrogens.The three major naturally estrogens in women are estrona (E1), 17-β-estradiol (E2) e o estriol (E3). Estradiol is the predominant estrogen during reproductive years both in terms of absolute serum levels as well as in terms of estrogenic activity. Numerous reports in the literature postulates that estrogens play an important cardioprotective role, and that this protective action may occur either by expression of genes but also by activating signaling cascade of proteins that culminates in cardiovascular protection. However, in the brainstem the role of estrogen is still not fully understood. In the brainstem, specifically neuron located in the bulb region, plays an important role in the neuronal control of the cardiovascular system because they act both on the control of sympathetic activity as well as the reception of chemical and mechanical signals. In addition to this neuronal network of sympathetic control and decoding of afferent signals, the brain stem is under the influence of the actions of reactive oxygen species-EROS, these molecules having high ability to induce the oxidation of membrane lipids, proteins or even leading to nuclear DNA to a frame defined by oxidative stress which appears as a major cause of neurological diseases such as Parkinson's, Alzheimer, Amyotrophic lateral sclerosis among others. Thus the aim of the present reviewwasinvestigated the neuromodulator effects of the estrogens on female offsprings from dams that received low protein diet during.

Objetivo: Avaliar e comparar os achados dos Potenciais Evocados Auditivos de Tronco Encefálico em indivíduos com holoprosencefalia (HPE) e holoprosencefalia-like (HPE-like). Modelo: Análise prospectiva comparando os achados dos PEATE entre três grupos: indivíduos com HPE clássica (GH), indivíduos com HPE-like (GHL) e grupo controle (GC), a um nível de significância de 5%. Local de Execução: Setor de Genética, HRAC-USP. Participantes: 57 pacientes, com idades entre 1 ano e 6 meses e 22 anos, sendo 13 com HPE clássica, 22 com HPE-like, e um grupo controle de 22 indivíduos normais. Variáveis: Latências absolutas das ondas I, III e V; latências interpicos I-V, III-V e I-III e diferença interaural da onda V do PEATE, em milissegundos, para cada orelha. Resultados: Os valores médios em milissegundos das latências absolutas e interpicos nas orelhas direita e esquerda respectivamente foram os seguintes. ara a onda I: 2,21 e 2,19 (GH); 1,99 e 2,01 (GHL); 1,92 e 1,91 (GC). Para a onda III: 4,35 e 4,52 (GH); 4,04 e 4,04 (GHL); 3,97 e 3,94 (GC). Para a onda V: 6,47 e 6,51 (GH); 5,95 e 5,94 (GHL); 5,90 e 5,90 (GC). Para o interpicos I-V: 4,20 e 4,24 (GH); 3,94 e 3,92 (GHL); 3,97 e 3,97 (GC). Para o interpicos III-V: 2,27 e 2,07 (GH); 1,91 e 1,90 (GHL); 1,92 e 1,95 (GC). Para o interpicos I-III: 2,14 e 2,33 (GH); 1,03 e 2,01 (GHL); 2,04 e 2,01 (GC). Os valores de diferença interaural da onda V foram: 0,13 (GH); 0,06 (GHL) e 0,03 (GC). Conclusões: Os dados sugerem que grande parte dos indivíduos com HPE clássica apresentam alterações de PEATE compatíveis com o grau de comprometimento neurológico, enquanto aqueles com HPE-like apresentam poucas alterações, sendo estas justificadas pelas patologias de orelha média decorrentes da fissura de palato. / Objective: To evaluate and compare Auditory Brainstem Response (ABR) findings in patients with holoprosencephaly (HPE) and the “HPE-like” phenotype. Model: A prospective analysis comparing ABR results among three different groups: patients with classic HPE (GH), patients with HPE-like (GHL) and control group (GC), at a 5% significance level. Setting: Genetics Department, HRAC-USP. Participants: 57 patients, aged from 18 months to 22 years. Thirteen of them had classic HPE, 22 had HPE-like, and 22 were audiologically normal individuals, who joined the GC. Variables: Waves I, III and V absolute latencies; interpeak intervals I-V, III-V and I-III and wave V interear difference of ABR, in milisseconds, considering both right and left ears. Results: Mean values, in milisseconds, of absolute latencies and interpeaks recorded from right and left ears, respectivelly, were: Wave I: 2,21 and 2,19 (GH); 1,99 and 2,01 (GHL); 1,92 and 1,91 (GC). Wave III: 4,35 and 4,52 (GH); 4,04 and 4,04 (GHL); 3,97 and 3,94 (GC). Wave V: 6,47 and 6,51 (GH); 5,95 and 5,94 (GHL); 5,90 and 5,90 (GC). Interpeak I-V: 4,20 and 4,24 (GH); 3,94 and 3,92 (GHL); 3,97 and 3,97 (GC). Interpeak III-V: 2,27 and 2,07 (GH); 1,91 and 1,90 (GHL); 1,92 and 1,95 (GC). Interpeak I-III: 2,14 and 2,33 (GH); 1,03 and 2,01 (GHL); 2,04 and 2,01 (GC). Wave V interear difference were: 0,13 (GH); 0,06 (GHL) and 0,03 (GC). Conclusions: Results suggest that most patients with classic HPE have abnormalities detected by ABR testing, which are related to the severity of neurologic impairment. Otherwise, those with the HPE-like phenotype have few alterations, most likely resulting from middle ear pathologies that occur in presence of cleft palate.

Projections from medial agranular cortex to brain stem in rat were determined by use of the anterograde tracers Phaseolus vulgaris leucoagglutinin, or wheat germ agglutinin conjugated horseradish peroxidase. Axonal trajectories were also followed by means of the Wiitanen modification of the Fink-Heimer degeneration technique. AGm was identified on the basis of its cytoarchitectonics. AGm projected to the anterior pretectal nucleus, the rostral interstitial nucleus of the medial longitudinal fasciculus, the medial accessory oculomotor nucleus of Bechterew, the interstitial nucleus of Cajal, the nucleus of Darkschewitsch, the nucleus cuneiformis and subcuneiformis, intermediate and deep superior collicular layers, the paramedian pontine reticular formation (reticularis pontis oralis and caudalis, and reticularis gigantocellularis), and raphe centralis superior. Differences in connections between rostral and caudal injections were observed: pontine and medullary projections were lighter from the rostral portion of AGm than from the more caudal portions of AGm. The heaviest projections to the anterior pretectal nucleus were from the caudal portion of AGm. The subcortical projections were very similar to those described for the frontal eye field in monkeys, and the majority of them targeted areas thought to be involved in coordination of gaze with head and neck movements. Thus AGm in rats may contain the homologue of the primate frontal eye fields.

No description available.

INTRODUÇÃO: O tronco encefálico é uma pequena estrutura com elevada concentração de núcleos e tratos. Historicamente, houve grande debate sobre indicações cirúrgicas às lesões no tronco encefálico. A despeito do desenvolvimento da microcirurgia, cirurgia da base do crânio e da neuronavegação, poucos grupos têm experiência no manejo daquelas lesões. Quando lesões no tronco encefálico não afloram à superfície pial, torna-se crucial o conhecimento de áreas de segurança de acesso ao tronco, as quais representam estreitos corredores em que há paucidade de estruturas eloquentes e ausência de vasos perfurantes. OBJETIVO: Quantificar a área de trabalho gerada pelos acessos cirúrgicos mais comumente utilizados ao tronco encefálico, além de definir as exposições angulares geradas pelos mesmos acessos às áreas de segurança por meio de dissecções cadavéricas. Adicionalmente, detalhamos a anatomia cirúrgica de treze acessos ao tronco encefálico, com fotografias passo a passo e descrições detalhadas para auxiliar na melhor difusão destas técnicas. MÉTODOS: Foi realizada dissecção anatômica de 10 cadáveres humanos para demonstração de 13 acessos cirúrgicos ao tronco encefálico e da anatomia das seguintes zonas de segurança: mesencefálica anterior, sulco mesencefálico lateral, intercolicular, peritrigeminal, supra-trigeminal, pontina lateral, supra-colicular, infra-colicular, sulco mediano do quarto ventrículo, sulco posteromediano e olivar. Os acessos estudados foram: orbitozigomático, subtemporal, subtemporal transtentorial, subtemporal transtentorial com petrosectomia anterior, suboccipital telovelar, supracerebelar infratentorial mediano, paramediano e lateral, retrossigmoideo, extremo lateral, petrosectomia anterior, retrolabiríntico, e combinado. A dissecção foi realizada entre Janeiro a Julho de 2010, no Laboratório de Base de Crânio do Barrow Neurological Institute, localizado em Phoenix, Arizona, EUA. Os espécimes fixados em formalina e com artérias e veias perfundidas com silicone colorido foram dissecados em suporte de Mayfield em mesa cirúrgica, com todo instrumental cirúrgico simulando um ambiente operatório. Após cada acesso, neuronavegador era utilizado para coletar coordenadas tridimensionais de pontos pré-definidos nas craniotomias e no campo operatório, os quais após análise em software específico, se traduziam em valores das seguintes variáveis: área de exposição, exposição angular e extensão de exposição. Os resultados obtidos foram comparados quando havia interseção de área ou zona de segurança. RESULTADOS: A área de exposição média do orbitozigomático no tronco foi de 164,7 ± 43,6 mm2. A exposição angular horizontal à zona mesencefálica anterior foi 37,9 ± 7,3o. A área média produzida pelo retrossigmoide foi 538,6 ± 161,0 mm2. As exposições angulares horizontal e vertical médias geradas por esse corredor para a zona pontina lateral foram 31,1 ± 6,7o e 49,3 ± 9,4o, respectivamente. A área média produzida pelo far-lateral foi 856,8 ± 139,7 mm2. As exposições angulares horizontal e vertical médias deste acesso para a zona olivar foram 40,8 ± 10,2o e 54,8 ± 6,8o. CONCLUSÃO: O acesso orbitozigomático oferece mínima área de exposição do tronco, mas melhor trajetória em relação à zona mesencefálica anterior que o subtemporal. O supracerebelar infratentorial extremo lateral oferece melhor trajetória e ângulos ao sulco mesencefálico lateral que o subtemporal. Não há diferença significativa entre as áreas de exposição e exposições angulares ao tronco entre o retrossigmoide e retrolabiríntico, mas este último oferece trajetória mais direta / INTRODUCTION: The brainstem is a small structure disposing of high concentration of nuclei and tract. Historically, there was enormous discussion on surgical indications to brainstem lesions. In spite of the evolution of microsurgery, skull base surgery, and neuronavigation, few groups bear experience managing this pathology. Whenever lesions do not surface on pia or ependyma, it is key using the safe entry zones, managing the brainstem, which represent tiny corridors where eloquent structures and perforators are sparse. OBJECTIVE: To quantify the working area provided by the main surgical approaches to brainstem, as well as angles of attack provided by the same approaches to the safe zones through cadaveric dissections. It was possible at the same time to detail the microanatomy of thirteen approaches, with stepwise images and descriptions, in order to aid spreading this knowledge in Portuguese. METHODS: Ten human cadavers were dissected in order to visually demonstrate 13 surgical approaches to brainstem and these safe zones: anterior mesencephalic, lateral mesencephalic sulcus, intercolicular, peritrigeminal, supratrigeminal, lateral pontine, supracollicular, infracollicular, median sulcus of the fourth ventricle, posteromedian sulcus and olivary. The following approaches were analyzed: orbitozigomatic, subtemporal, subtemporal transtentorial, subtemporal transtentorial with anterior petrosectomy, median suboccipital telovelar, median, paramedian and lateral supracerebellar infratentorial, retrossigmoid, far-lateral, anterior petrosectomy, retrolabyrinthine, and combined. Dissections were carried out from January to July 2010, at the Skull Base Laboratory in the Barrow Neurological Institute, Phoenix, Arizona, USA. The specimens were lightly fixed in formalin while arteries and veins were perfused with color silicone. They were dissected on a Mayfield head-holder, using a complete set of surgical instruments simulating an operative environment. Neuronavigation was utilized after every approach to collect tridimensional coordinates of predefined points on the craniotomy edges and within the surgical field. Using a specific software, these coordinates translate themselves into the following variables: areas of exposure, angles of attack and lengths of exposure. The variables were compared among them when 2 or more approaches addressed overlapped areas. RESULTS: The mean area of exposure provided by the orbitozygomatic on the brainstem was 164,7 ± 43,6 mm2. The horizontal angle of attack to the anterior mesencephalic zone was 37,9 ± 7,3o. Mean area delivered by the retrosigmoid was 538,6 ± 161,0 mm2. Mean horizontal and vertical angles of attack produced by this corridor aiming the lateral pontine zone were 31,1 ± 6,7o e 49,3 ± 9,4o, respectively. The farlateral approach produced a mean area of exposure of 856,8 ± 139,7 mm2. Mean horizontal and vertical angles of attack offered by this avenue aiming the olivary zone were 40,8 ± 10,2o e 54,8 ± 6,8o. CONCLUSION: The orbitozygomatic approach provides a minimum area of exposure, but a better trajectory concerning the anterior mesencephalic zone comparing to the subtemporal. The extreme lateral supracerebellar infratentorial yields better trajectory and wider angles to the lateral mesencephalic sulcus than the subtemporal. There is no significant difference regarding areas of exposure and angles of attack to the brainstem between the retrosigmoid and retrolabyrithine, but the latter produces a more direct trajectory

Objetivo: Realizar uma investigação do sistema auditivo em indivíduos com displasia frontonasal quanto à acuidade e quanto à condução do estímulo sonoro até o nível do tronco encefálico, correlacionando com as características clínicas. Modelo: Análise prospectiva descrevendo os achados da avaliação audiológica em indivíduos com sinais clínicos de displasia frontonasal. Local de Execução: Setor de Genética, HRAC-USP. Participantes: 21 pacientes, na faixa etária de 7 a 42 anos, sendo 14 do sexo feminino e 7 do sexo masculino. Variáveis: Limiares audiométricos em decibels nas frequências de 0,25 a 8 kHz nas duas orelhas, tipo de curva timpanométrica nas duas orelhas, latências absolutas das ondas I, III e V; latências interpicos I-V, III-V e I-III e diferença interaural da onda V do PEATE, em milissegundos, para cada orelha. Resultados: Limiares audiométricos normais em 15 (70%) indivíduos e alterados em 5 (25%), a maior parte dos casos compatíveis com perda auditiva condutiva. Na timpanometria, 30 orelhas (72%) apresentaram curva tipo A, 5 (12%) tipo C, 4 (9%) tipo Ar e 3 (7%) tipo B. Os valores médios em milissegundos das latências absolutas e interpicos nas orelhas direita e esquerda respectivamente foram os seguintes. Onda I: 1,92 e 1,91; onda III: 3,97 e 3,97; onda V: 5,88 e 5,88; interpicos I-V: 3,96 e 3,97; interpicos III-V: 1,91 e 1,92; interpicos I-III: 2,05 e 2,03 e diferença interaural da onda V: 0,04. Conclusões: Os indivíduos com DFN estudados não apresentaram alterações na via auditiva desde sua porção periférica até o tronco encefálico. As alterações condutivas encontradas são provavelmente relacionadas às patologias de orelha média decorrentes da fissura de palato, presente nesses casos. Sugerimos a avaliação de níveis mais altos dentro do sistema auditivo. / Objective: To evaluate the auditory system in patients with frontonasal dysplasia (FND) considering hearing sensitivity and sound stimulus conduction from cochlea to brainstem. Model: A prospective analysis describing audiological evaluation results in patients with clinical signs of FND. Setting: Genetics Department, HRAC-USP. Participants: 21 patients, aged from 7 to 42 years, 14 females and 7 males. Variables: Audiometric thresholds, in decibels, obtained by testing frequencies from 0,25 to 8 kHz, both ears; type of tympanometric curve in both ears; waves I, III and V absolute latencies; interpeak intervals I-V, III-V and I-III and wave V interear difference of ABR, in milisseconds, considering both right and left ears. Results: Hearing thresholds were normal in 15 (70%) patients and abnormal in 5 (25%), most with conductive hearing loss. Tympanometric curve was type A in 30 (72%) ears, type C in 5 (12%), type Ar in 4 (9%) and type B in 3 (7%). Mean values, in milisseconds, of absolute latencies and interpeaks recorded from right and left ears, respectivelly, were: wave I= 1,92 and 1,91; wave III= 3,97 and 3,97; wave V= 5,88 and 5,88; interpeak I-V= 3,96 and 3,97; interpeak III-V= 1,91 and 1,92; interpeak I-III= 2,05 and 2,03 and wave V interear difference= 0,04. Conclusions: Patients with FND showed no abnormalities in the auditory system from cochlea to brainstem in our study. Mild conductive hearing loss found in some of them is probably related to cleft palate, occurring in these cases. We suggest further evaluation of hearing pathways in higher levels.

Background and Purpose: Primary nocturnal enuresis (PNE) is a heterogeneous disorder with various underlying pathophysiological mechanisms. Results of our recent studies focused on the relationship of bladder function, sleep and brain function demonstrated a simultaneous occurrence of bladder and brain dysfunction in children with severe refractory PNE. We therefore proposed to use an animal model with altered bladder function to evaluate if abnormalities in bladder function induce functional derangement in brainstem micturition centers and/or sleep-arousal centers. / Materials and methods: In general, the study was divided in to 6 parts. Male Wistar rats (~ 1.5 months) were used for the study. / Study I: Establishment of animal model —— Male Wistar rats (200-220 g) underwent either Sham surgery or surgical reduction of bladder volume (RBV). Animals were used for further Cystometry, EEG, MRS and Cognitive function studies 4-5 weeks postoperatively. / Study II: Conventional Fill Cystometry (CFC) to evaluate bladder functional changes in response to surgical bladder volume reduction —— Twenty-four rats (RBV=12, SHAM 12) were used for the study. CFC was performed under conscious condition for evaluating the functional changes in response to surgical bladder capacity reduction. / Study III: Radiotelemetered EEG study to assess the impact of bladder dysfunction on sleep architecture and cortical arousals in rats —— Twenty-four rats (RBV=12, SHAM 12) were used for the study. Radiotelemeters were implanted in both groups 4 weeks post-operatively. The EEG biopotential and bladder pressure were monitored for 48 hours. Sleep architecture and cortical arousals were then evaluated manually. / Study IV: Evaluation of cognitive function following surgical bladder volume reduction —— Ninety eight rats (RBV=50, SHAM =48) were used for the study. / Morris Water Maze task: A circular plastic translucent pool half-filled with 26 ± 2ºC water, was used in the Morris Animals were given 9 consecutive training (2/day) sessions of Morris Water Maze (MWM) at 4 weeks postoperatively. / 8-arm Radial Maze: Food pellets were randomly placed inside each arm of the maze and the rats were allowed to explore the maze freely for 5 minutes. The rat was allowed to explore the maze for 5 minutes. Total time spent in each arm, total distance traveled in the maze was recorded. / Study V: Magnetic Resonance Spectroscopy to detect functional changes in brain in response to bladder dysfunction elicited by surgical bladder volume reduction —— Proton magnetic resonance spectroscopy was employed to examine brain metabolic changes in 24 rats (RBV=12, SHAM=12). Single voxel 1 H MRS experiments were performed using a 7 T MRI scanner. MR spectra were then processed using the jMRUI software. / Phase VI: Enzyme -linked immunosorbent assay for the assessment of associated changes in neurotransmitters —— Animals were euthanized after MRS study and brain samples were collected. Serotonin and dopamine levels were assessed in 10 mg of tissue extracts from brainstem and cortex, with ELISA kits. / Results: Study I: Bladder reduction surgery did not affect the increase in body weight post -operatively. Average body weight of the RBV and the sham groups were 340.2 ± 47.2 g and 340.5 ± 67.9 g respectively at 4 weeks post operatively. / Study II: Compared to sham group, the maximum cystometric capacity in animals with RBV was remarkably reduced at week 4 (0.78 ± 0.12 ml vs. 1.46 ± 0.22 ml, RBV vs. Sham respectively; p<0.005). Moreover, maximum detrusor pressure during voiding was significantly increased in RBV group at week 4 post operatively (32.4± 2.14 vs.23.27±1.2 5 cm H2O, RBV vs. Sham respectively). / Study III: Light non-repaid eye movement sleep occurred significantly more in RBV rats compared to sham group (61.8% vs 35%). Deep sleep and rapid eye movement sleep occurred significantly less in RBV group compared to that of sham group (30.7% vs 53.4%). / Study IV: Results showed that the RBV group used a significantly longer latency to locate the platform compared to Sham group (24.4s vs 17.19s, RBV vs. Sham respectively, p<0.001).. Moreover, significantly more animals from the RBV group could not complete the visit of the 8 arms of radial maze than that of the sham group. / Study V: Seven metabolites were detected and quantified. The results demonstrated significant changes in the lactate (Lac) metabolism in some specific regions of rat brain. At 4 weeks post - operatively, level of lactate significantly decreased in the hippocampus (43%, P<0.001) cingulate and retrosplenial cortex (29%, p<0.05) of RBV rats compared to that of sham rats. / Study VI: Results demonstrated a significant increase in Serotonin level in the brainstem of RBV rats compared to that of SHAM rats (23.726 + 0.88 ng/ml vs. 1.88 + 0.302 ng/ml). Dopamine levels decreased significantly in brainstem samples of RBV group compared to sham group (2.85 + 0.10 ng/ml vs. 6.85 + 0.84 ng/ml). / Conclusion: Surgical bladder volume reduction of bladder capacity can induce functional changes in the central nervous system. An alteration of the sleep architecture occurred in response to surgical reduction of bladder volume in rats, suggesting that there exists a potential for central consequences of bladder dysfunction. Bladder disorder chronically altered brain energy metabolism. Furthermore, bladder disorder altered the central neurotransmission in the brainstem and cortex. The finding of bladder dysfunction induced significant impairments in cognitive function in RBV rats, suggesting that the alteration in brain energy metabolism may contribute to the behavioral and attention problems, impaired learning and cognitive performance. / 研究背景： 原發性夜間遺尿症（PNE）是一種異質性疾病，涉及多種潛在的病理生理機制。我們最近的研究主要集中在膀胱功能，睡眠和腦功能的關係，結果顯示膀胱和腦功能障礙同時出現在患有嚴重難治性的PNE的兒童。因此，我們建議採用一種已改變膀胱功能的動物模型來評估膀胱功能異常會否引起腦幹排尿中心和/或睡眠 - 覺醒中心的功能紊亂 / 研究工具和方法： 研究被分成6個部分。雄性Wistar大鼠（約1.5個月）被用於研究。 / 研究I： 動物模型的建立 —— 雄性Wistar大鼠（200-220克），會先接受假手術或手術降低膀胱容量（RBV）。手術後4至5週，動物會進行進一步的膀胱測壓，腦電圖，MRS和認知功能研究。 / 研究II： 以常規填充膀胱測壓（CFC）評估減少膀胱容量手術對膀胱功能的變化 —— 二十四隻大鼠（RBV=12，對照=12）被用於研究。 CFC是用以評估在有意識的條件下，膀胱因膀胱容量減少的手術而引起的功能變化。 / 研究III： Radiotelemetered腦電圖研究，以評估在大鼠膀胱功能失調對睡眠結構和皮質覺醒的影響 —— 二十四隻大鼠（RBV=12，對照=12）被用於研究。膀胱容量減少的手術4週後，Radiotelemeters被植入在兩個組別的大鼠，並監測其腦電生物電勢和膀胱內壓48小時，然後手動評估睡眠結構和皮層覺醒。。 / 研究IV： 評估在膀胱容量減少的手術後對認知功能的影響 —— 103個大鼠（RBV=56，對照= =47）被用於研究。 / Morris水迷宮任務： 一個圓形的塑料半透明池盛載半滿的水，溫度介乎26 - ±2℃，手術4週後，該池被用在莫里斯動物進行連續9次Morris水迷宮（MWM）培訓（每天2次）。 / 八臂迷宮： 食物顆粒被隨機放置在迷宮的每個臂內，大鼠可以自由地探索迷宮5分鐘。大鼠被允許探索迷宮5分鐘。在每個手臂所用的總時間，以及在迷宮行走的總距離都會被記錄。 / 研究V： 以磁共振波譜檢測膀胱容量減少的手術所引起的膀胱功能障礙對腦功能的改變 —— 以質子磁共振波譜研究24隻大鼠腦內的代謝變化(RBV=12，對照==12）。以7 T MRI掃描儀進行磁共振波譜實驗，然後使用jMRUI軟件處理MR譜。 / 第六期： 以酶聯免疫吸附測定法評估神經遞質的相關變化 —— 動物在進行MRS研究後實施安樂死，並收集其腦樣品。從腦幹和皮層提取10毫克組織提取物，使用ELISA試劑盒，以評估羥色胺和多巴胺水平。 / 結果： 研究I： 膀胱容量減少手術並沒有影響體重增加。手術4週後，利巴韋林和對照實驗組的平均體重分別為340.2±47.2克和340.5±67.9克。 / 研究II： 相比起對照實驗組的動物，RBV組的最大膀胱容量顯著降低（0. 0.78 ± 0.12毫升對1.46±0.22毫升），排尿頻率顯著增加（2.53±0.30 對.0.53±0.05/hr）。此外，排尿時最大逼尿肌壓力亦顯著升高（32.0.8±2.19 比.20.37±1.2 5厘米水分子） / 研究III： 相比起對照實驗組的動物，光非快速動眼期睡眠顯著地較多發生於RBV大鼠身上（61.8％對35.6％），深層睡眠和快速動眼期睡眠顯著地較少發生在RBV組（32.3％對52.8％） / 研究IV： 結果表明，RBV組使用了顯著較長的時間來定位平台（24.4s vs. vs.17.19s）。而且，在RBV組，顯著地較多動物無法完成行走8臂的放射狀迷宮。 / 研究V： 進行檢測和定量七種代謝物。結果顯示乳酸（LAC）代謝在大鼠大腦的某些特定區域出現顯著變化。在手術4週後，相比起對照實驗組的動物，RBV組大鼠在海馬體（43％，P <0.001），扣帶和夾肌皮質（29％，P <0.05）的乳酸水平均顯著減少。 / 研究VI： 結果顯示RBV大鼠腦幹的血清素水平較對照實驗組的顯著增加（23.726+0.88納克/毫升與1.88±0.302ng/ml）。RBV大鼠腦幹的多巴胺水平則較對照實驗組的顯著下降（2.850.10納克/毫升與6.85+0.84毫微克/毫升）。 / 結論： 外科膀胱容量減少可誘導中樞神經系統的功能變化。以外科手術減少膀胱容量的大鼠亦引起睡眠結構改變，這顯示膀胱功能障礙對中樞有潛在影響。膀胱疾病長期改變大腦的能量代謝。此外，膀胱疾病亦改變了在腦幹和大腦皮層的中樞神經遞質傳遞。研究發現膀胱功能障礙顯著地損害RBV大鼠的認知功能，顯示改變大腦的能量代謝亦可導致行為和專注力的問題，從而損害學習和認知能力。 / Yeung, Chung Kwong. / Thesis Ph.D. Chinese University of Hong Kong 2014. / Includes bibliographical references (leaves 199-230). / Abstracts also in Chinese. / Title from PDF title page (viewed on 14, September, 2016). / Yeung, Chung Kwong. / 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. / 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. / 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. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

The neural and sensory mechanisms underlying appropriate muscle recruitment in response to balance challenges remains elusive. We asked whether the decerebrate cat preparation might be employed for further investigation of postural mechanisms. First, we evaluated the muscular activation patterns and three-dimensional whole limb forces generated by a modified premammillary decerebrated cat. We hypothesized that directionally appropriate muscle activation does not require the cerebral cortices. Furthermore, we hypothesized that the muscle responses would generate functionally appropriate and constrained force responses similar to those reported in the intact animal. Data confirmed both of our hypotheses and suggested important roles for the brainstem and spinal cord in mediating directionally appropriate muscular activation. Second, we investigated how individual muscle activation is translated to functional ground reaction forces. We hypothesized that muscles are selectively activated based upon their potential counteractive endpoint force. Data demonstrated that the endpoint force generated by each muscle through stimulation was directed oppositely to the principal direction of each muscle's EMG tuning curve. Further, muscles that have variable tuning curves were found to have variable endpoint forces in the XY plane. We further hypothesized that the biomechanical constraints of individual muscle actions generate the constrained ground reaction forces created in response to support surface perturbations. We found that there was a lack of muscles with strong medial-lateral actions in the XY plane. This was further exaggerated at long stance conditions, which corresponds to the increased force constraint present in the intact animal under the same conditions. Third, we investigated how loss of cutaneous feedback from the footpads affects the muscle recruitment in response to support surface perturbations. We utilized our decerebrate cat model as it allows 1) isolation of the proprioceptive system (cutaneous and muscle receptor) and 2) observation of the cutaneous loss before significant compensation by the animal. We hypothesized that muscle spindles drive directionally sensitive muscle activation during postural disturbances. Therefore, we expected that loss of cutaneous feedback from the foot soles would not alter the directional properties of muscle activation. While background activity was significantly diminished, the directionally sensitive muscular activation remained intact. Due to fixation of the head, the decerebrate cat additionally does not have access to vestibular or visual inputs. Therefore, this result strongly implicates muscle receptors as the primary source of directional feedback. Finally to confirm that muscle receptors, specifically muscle spindles, are capable of generating feedback to drive the directionally tuning, we investigated the response properties of muscle spindles to horizontal support surface perturbations in the anesthetized cat. As previously stated, we hypothesized that muscle spindles provide the feedback necessary for properly directed muscular responses. We further hypothesized that muscle spindles can relay feedback about the perturbation parameters such as velocity and the initial stance condtion. Results confirmed that muscle spindle generate activation patterns remarkably similar to muscular activation patterns generated in the intact cat. This information, along the knowledge that cutaneous feedback does not substantially eliminate directional tuning, strongly suggests that muscle spindles contribute the critical directional feedback to drive muscular activation in response to support surface perturbations.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2009. / Härtill 4 uppsatser.