Every year 1.4 million people will suffer from a traumatic brain injury (TBI). The Centers for Disease Control (CDC) estimates that there are over 5.3 million TBI survivors living in the United States, or about two percent of the population, living with long-term effects or in need of lifelong help. Estimations have been made that with both the direct and indirect costs of medical bills and productivity loss in the United States the total cost for TBI was 60 billion dollars in 2000. Sensory stimulation consists of visual, tactile, auditory, gustatory, and-olfactory stimuli that attempt to increase the levels of conscio-µsness in TBI patients by enhancing synaptic reinnervation in the brain. Sensory stimulation has been around since the 1980's and has been found to be beneficial for TBI patients, however, no guidelines have been created for nurses and other health care providers to perform this program. By making guidelines for nurses and other health care providers that outline the proper procedure of this treatment, the cost for care of TBI patients will decrease, therefore positively impacting the health care system.

Proper neuronal function requires the preservation of appropriate neural excitability. An adaptive increase in neural excitability after exposure to agents that depress neuronal signaling blunts the sedative drug effects upon subsequent drug exposure. This adaptive response to drug exposure leads to changes in drug induced behaviors such as tolerance, withdrawal and addiction. Here I use Drosophila melanogaster to study the cellular and neuronal components which mediate behavioral tolerance to the anesthetic benzyl alcohol. I demonstrate that rapid tolerance to benzyl alcohol is a pharmacodynamic mechanism independent of drug metabolism. Furthermore, tolerance is a cell autonomous response which occurs in the absence of neural signaling. Using genetic and pharmacological manipulations I find the synapse to play an important role in the development of tolerance. In addition, the neural circuits that regulate arousal and sleep also alter benzyl alcohol sensitivity. Beyond previously described transcriptional mechanisms I find a post-translational role of the Ca2+-activated K+-channel, slowpoke in the development of tolerance. Finally, I explore a form of juvenile onset tolerance, which may have origins that differ from rapid tolerance. The implications of this study go beyond tolerance in Drosophila melanogaster to benzyl alcohol and can shed light on human drug tolerance, withdrawal and addiction. / text

O sinal EEG, cujas informações descrevem o comportamento elétrico do córtex cerebral, apesar de ser bastante utilizado para diagnósticos, principalmente de patologias como epilepsia, no Brasil ainda não é usual o monitoramento contínuo em ambiente de UTI em hospitais públicos. Diante disso, e partindo do pressuposto que estudos sobre o EEG normal, registrado em pessoas sem problemas neurológicos, são escassos, a criação de uma base de registros de EEG normal e análise quantitativa da mesma se faz necessária para que, por meio dos resultados obtidos, padrões normais possam ser estabelecidos e por meio deles a identificação de parâmetros patológicos se torne mais eficaz. Nesse projeto foi elaborada uma base de dados de EEG, com total de 100 registros válidos, advindos de voluntários normais e saudáveis. E a partir desses registros a situação de vigília e olhos fechados foi analisada sob o aspecto de três quantificadores distintos, sendo eles, Porcentagem de Contribuição de Potência (PCP), Frequência Mediana (FM) e Coerência, ambos avaliando o sinal no domínio da frequência. A fim de obter comparações para os resultados obtidos pela análise dos dados do EEG normal, foram utilizados 128 registros de EEG em situação de coma, com diferentes tipos de etiologias e desfechos. Os ritmos que apresentaram maiores distinções entre normal e coma foram Delta e Alfa, principalmente para o quantificador FM. Notou-se que o PCP avaliou características de potência e portanto sintetizou as informações de energia de cada ritmo cerebral tanto em EEG normal quanto em EEG coma. Já FM traz informações de valores de frequências em que há maior concentração de potência, e por fim o quantificador coerência informa o grau de semelhança entre o hemisfério direito e o esquerdo do cérebro. Sendo assim não foi possível afirmar qual dos quantificadores apresentou melhores resultados, visto que cada um trata-se de uma características distintas. / The EEG signal, whose information describes the electrical behavior of the cerebral cortex, although it is widely used for diagnoses, mainly of pathologies such as epilepsy, in Brazil it is still not usual to monitor the ICU environment in public hospitals. Considering this, and assuming that studies on normal EEG, registered in people without neurological problems, are scarce, the creation of a base of normal EEG registers and quantitative analysis of it is necessary so that, through the obtained results, Normal patterns can be established and through them, the identification of pathological parameters becomes more effective. In this project, an EEG database was developed, with 100 valid records from normal and healthy volunteers. In addition, from these records, the waking and closed eyes situation was analyzed under the aspect of three distinct quantifiers, being: Power Contribution Percentage (PCP), Median Frequency (FM) and Coherence, both evaluating the signal in the frequency domain. In order to obtain comparisons for the results obtained by the analysis of the normal EEG data, 128 EEG records were used in coma, with different types of etiologies and outcomes. The rhythms that presented the highest distinctions between normal and coma were Delta and Alpha, mainly for the FM quantifier. It was noted that PCP evaluated power characteristics and therefore synthesized the energy information of each brain rhythm in both normal EEG and EEG coma. Already FM brings information of values of frequencies in which there is greater concentration of power, and finally the quantifier coherence informs the degree of similarity between the right and left hemisphere of the brain. Thus, it was not possible to say which of the quantifiers presented better results, since each one is a distinct characterization. / Dissertação (Mestrado)