Conselho Nacional de Desenvolvimento Científico e Tecnológico / Studies over recent years have highlighted the important role of creatine in health and in treating various neurological diseases. However, its role in secondary damage induced by traumatic brain injury (TBI) is not fully understood. The aim of this study was to evaluate the effect of creatine supplementation on the oxidative damage and susceptibility to seizures after TBI. For this, we used the model of fluid percussion injury (FPI) in rats, where brain damage is caused by a liquid column that causes a pressure on the dura intact of animal, which was previously exposed. Our results revealed that at 4 and 8 days after TBI, there was increased oxidative damage characterized by increased protein carbonylation and levels of species thiobarbituric acid reactive substances (TBARS), and also there was a reduction in Na+, K+ -ATPase activity. Statistical analysis (two way ANOVA) also revealed that creatine supplementation (300 mg / kg orally), beginning 30 minutes after TBI and continuing until 3, or 7 days after injury, reduced protein carbonylation and TBARS when analyzed at 4 and 8 days after injury. However, creatine supplementation did not protect the inhibition of Na+, K+-ATPase 4 and 8 days after TBI. Furthermore, the analysis electroencephalographic (EEG) showed that injection of a subconvulsant dose (35 mg / kg, intraperitoneally) of pentylenetetrazol (PTZ), 4 but not 8 days after TBI, decreased latency to the tonic- clonic seizures and increased the time spend in generalized seizure, when compared to the control group. Creatine supplementation had no effect on the convulsive parameters induced by PTZ injection. The experiments in this study suggest that in this experimental model of TBI, oxidative damage seems not to be directly involved in susceptibility to seizures after neuronal injury since the antioxidant capacity exerted by creatine does not protect against PTZ-induced seizures after TBI / Estudos realizados ao longo dos últimos anos têm destacado o importante papel da creatina na saúde bem como no tratamento de diversas doenças neurológicas. Entretanto, seu papel no dano secundário induzido por traumatismo cranioencefálico (TCE) não está totalmente compreendido. O objetivo de nosso estudo foi avaliar o efetio da suplementação com creatina sobre o dano oxidativo e suscetibilidade a convulsões após TCE. Para isto, utilizamos o modelo de lesão por percussão de fluido (LPF) em ratos, onde a lesão encefálica é provocada por uma coluna líquida que exerce uma pressão sobre a duramáter intacta dos animais, a qual foi previamente exposta. Nossos resultados revelaram que em 4 e 8 dias após TCE, houve o aumento do dano oxidativo caracterizado pelo aumento de carbonilação protéica e dos níveis de espécies reativas ao ácido tiobarbitúrico (TBARS) e, também, houve uma redução da atividade da enzima Na+, K+-ATPase. A análise estatística (ANOVA de duas vias) também revelou que a suplementação com creatina (300 mg/kg, via oral), iniciando 30 minutos após o TCE e prolongando-se até o 3º, ou 7º dia após a lesão, reduziu a carbonilação protéica e os níveis de TBARS, quando analisado no 4º e 8º dia após a injuria. Entretanto a suplementação com creatina não protegeu da inibição da enzima Na+, K+-ATPase 4 e 8 dias após a TCE. Além disso, a análise eletroencefalográfica (EEG) revelou que a injeção de uma dose subconvulsivante (35 mg/Kg, intraperitoneal) de pentilenotetrazol (PTZ), em 4, mas não em 8 dias após TCE, diminuiu a latência para as convulsões tônico-clônicas generalizadas e aumentou o tempo de sua duração, quando comparado ao grupo controle. A suplementação de creatina não exerceu qualquer efeito sobre os parâmetros convulsivos induzidos pela injeção de PTZ. Os experimentos realizados no presente estudo sugerem que, neste modelo experimental de TCE, o dano oxidativo parece não estar diretamente envolvido na suscetibilidade a convulsões após lesão neuronal uma vez que, a capacidade antioxidante exercida pela creatina não protege das crises convulsivas induzidas por PTZ após TCE.

OF DIPLOMA THESIS Author: Bc. Lenka Macková Supervisor: Mgr. Olga Marková Title: Evaluation of quality of life in patients with brain acquaired brain injury from the perspective of occupational therapy Abstract: Acquired brain injury is one of the most common causes of a reducing quality of life. The concept of quality of life is defined differently in different areas and there is no uniform definition. The theoretical part introduces the operationalization and conceptualization of concept of the quality of life and the use of evaluation of quality of life in occupational therapy in the Czech Republic and abroad. The aim of diploma thesis is to describe how acquired brain injury affects the quality of life, how to evaluate the quality of life in occupational therapy, and what quality of life areas are influenced after acquired brain injury and to evaluate subjectively the impact of occupational interventions on quality of life in these patients. The practical part contains 6 case studies of patients after acquired brain injury. Patients were assessed for quality of life through a WHODAS 2 subjective quality of life questionnaire and semi-structured interviews.This assessment was carried out before and after occupational intervention in patients after 2 months. The interviews and the results of the...

abstract: The objective of this small animal pre-clinical research project was to study quantitatively the long-term micro- and macro- structural brain changes employing multiparametric MRI (Magnetic Resonance Imaging) techniques. Two separate projects make up the basis of this thesis. The first part focuses on obtaining prognostic information at early stages in the case of Traumatic Brain Injury (TBI) in rat animal model using imaging data acquired at 24-hours and 7-days post injury. The obtained parametric T2 and diffusion values from DTI (Diffusion Tensor Imaging) showed significant deviations in the signal intensities from the control and were potentially useful as an early indicator of the severity of post-traumatic injury damage. DTI was especially critical in distinguishing between the cytotoxic and vasogenic edema and in identification of injury regions resolving to normal control values by day-7. These results indicate the potential of quantitative MRI as a clinical marker in predicting prognosis following TBI. The second part of this thesis focuses on studying the effect of novel therapeutic strategies employing dendritic cell (DC) based vaccinations in mice glioma model. The treatment cohorts included comparing a single dose of Azacytidine drug vs. mice getting three doses of drug per week. Another cohort was used as an untreated control group. The MRI results did not show any significant changes in between the two treated cohorts with no reduction in tumor volumes compared to the control group. The future studies would be focused on issues regarding the optimal dose for the application of DC vaccine. Together, the quantitative MRI plays an important role in the prognosis and diagnosis of the above mentioned pathologies, providing essential information about the anatomical location, micro-structural tissue environment, lesion volume and treatment response. / Dissertation/Thesis / Masters Thesis Bioengineering 2014

Submitted by Jean Medeiros (jeanletras@uepb.edu.br) on 2017-03-17T12:45:33Z No. of bitstreams: 1 PDF - Fábio Henrique Costa Ferreira.pdf: 13187089 bytes, checksum: d4ae565d43e98eb970955e2f76203929 (MD5) / Approved for entry into archive by Secta BC (secta.csu.bc@uepb.edu.br) on 2017-03-22T15:19:26Z (GMT) No. of bitstreams: 1 PDF - Fábio Henrique Costa Ferreira.pdf: 13187089 bytes, checksum: d4ae565d43e98eb970955e2f76203929 (MD5) / Made available in DSpace on 2017-03-22T15:19:26Z (GMT). No. of bitstreams: 1 PDF - Fábio Henrique Costa Ferreira.pdf: 13187089 bytes, checksum: d4ae565d43e98eb970955e2f76203929 (MD5) Previous issue date: 2016-11-03 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Objective: To identify the prevalence of traumatic brain injury (TBI) in traffic accident victims with motorcycle assisted in a hospital of emergency and trauma. Methods: Cross- sectional study with a probabilistic sample composed by 309 medical records of patients victims of traffic accidents involving motorcycles during the period from January to December 2014, attended in Hospital Dom Luiz Gonzaga Fernandes in Campina Grande - PB. The research instrument consisted of a form containing the following variables: gender, age, day and hospitalization time, presence and type of bone fracture, presence of TCE, helmet, Glasgow coma scale, Marshall classification and the occurrence of death. It was realized a descriptive analysis of data using SPSS software 18. For bivariate analyzes were used the chi - square test and Fisher's exact, considering the value of statistical significance (p <0.05). Results: The prevalence of traumatic brain injury in traffic accident victims with motorcycle was 24.3%. There was a predominance of male victims (79.6%) and the age group of 21-30 years. It was found that the highest frequency of hospital admissions were recorded on Sundays (31.1%) and Saturdays (15.9%), predominantly night shifts (36.9%) and afternoon (28.8%).It was found statistically significant differences in the associations between TCE and helmet use (p = 0.008) and TCE and death (p = 0.001). Conclusion: It was observed a high prevalence of TBI in motorcycles traffic accident victims. The non-use of the helmet was associated with a higher frequency of TBI and the victims with TBI had higher risk to progress to death. / Objetivo: Identificar a prevalência de trauma cranioencefálico (TCE) em vítimas de acidente de trânsito com motocicleta atendidas em um hospital de emergência e trauma. Métodos: Estudo transversal com amostra probabilística composta de 309 prontuários de pacientes vítimas de acidentes de trânsito com motocicletas, no período de Janeiro a Dezembro de 2014, atendidas no Hospital Regional de Emergência e Trauma Dom Luiz Gonzaga Fernandes, em Campina Grande – PB. O instrumento de pesquisa consistiu de um formulário contendo as seguintes variáveis: sexo, faixa etária, dia da semana e horário de internação, presença e tipo de fratura óssea, presença de TCE, uso de capacete, escala de coma de Glasgow, classificação de Marshall e ocorrência de óbito. Realizou-se análise descritiva dos dados através do software SPSS 18. Para análises bivariadas foram empregados os testes de Qui-Quadrado e Exato de Fisher, considerando-se o valor de significância estatística ( p < 0,05). Resultados: A prevalência de traumatismo cranioencefálico em vítimas de acidentes de trânsito com motocicleta foi de 24,3%. Houve predomínio de vítimas do sexo masculino (79,6%) e da faixa etária de 21-30 anos. Verificou-se que as maiores frequências de internações foram registradas aos domingos (31,1%) e sábados (15,9%), predominando os turnos da noite (36,9%) e tarde (28,8%). Observaram-se diferenças estatisticamente significantes para as associações entre TCE e uso de capacete (p = 0,008) e TCE e óbito (p = 0,001). Conclusão: Pôde-se observar uma elevada prevalência de TCE em vítimas de acidentes de trânsito com motocicletas. A não-utilização do capacete foi associada a uma maior frequência de TCE e as vítimas que apresentaram TCE apresentaram maior chance de evoluir para o óbito.

The consequences resulting from Traumatic brain injury (TBI) cause disabilities or physical disabilities (motor, visual, among others), cognitive (memory, attention, learning, among others) and or behavioral/emotional (loss of self-confidence, depression, anxiety, difficulty of Self-Control, irritability, aggression, among others) that can be temporary or permanent. The study aimed to perform the validation of content and clinical aspects of nursing diagnosis of ""Labile emotional control" in treated TBI outpatients. Methodological and descriptive study that used the model of Fehring for validation. The research was developed in two steps: Content validation and clinical validation. In the former, there was the participation of 31 experts to evaluate, by means of electronic questionnaire, the taxonomic structure of NANDA International concerning the diagnosis "Labile emotional control". The later was performed in the outpatient clinic of the University Hospital of the Federal University of Sergipe, between the months of August and September 2016 with a sample consisting of 40 patients in two distinct groups with mild TBI (n=20) and moderate TBI (n=20). For comparison of proportions among groups the z test (two groups) was used and with Bonferroni correction (3 groups). The results showed that the majority of experts considered the domain 05 (perception/cognition), Class 4 (cognition) and the wording (Labile emotional control) suitable for diagnosis, although they suggested modifications in the current definition of diagnosis Two of the defining characteristics were considered major (removal of the social situation and the expression of incoherent emotions with the triggering factor) and 11 secondary (removal of the professional situation, lack of contact with the eyes, crying without excessive feel sorrow, uncontrollable crying, involuntary crying, difficulty using facial expressions, embarrassment on the expression of emotions, tears, laughter in excess without feeling happiness, uncontrollable laughter and involuntary laughter. The total score of the diagnosis “Labile emotional control” was 0.69, considered valid. In the clinical validation, the characteristics that are considered important for the mild TBI were: professional situation leave, avoidance of social situation, embarrassment on the expression of emotions, expression of emotions would be inconsistent with the triggering factor and the secondary were absence of eye contact, excessive crying without feeling sadness, uncontrollable crying , involuntary crying, difficulty using facial expressions and tears and the irrelevant ones were laughter in excess without feeling happiness, uncontrollable laughters and involuntary laughter. In the moderate TBI group the following were identified as main characteristics: professional situation leaves, avoidance of social situation, excessive crying without feeling sadness, embarrassment on the expression of emotions, expression of emotions would be inconsistent with the triggering factor and the secondary were absence of eye contact, uncontrollable crying, involuntary crying, difficulty using facial expressions, tears, uncontrollable laughter and involuntary laughter. The total score was similar in both groups, 0.74, considered to be validated for the NANDA Taxonomy-I. It is concluded that almost all of the defining characteristics were considered valid for the diagnosis "Labile Emotional Control" in TBI. / As consequências advindas do Trauma Cranioencefálico (TCE) provocam deficiências ou incapacidades físicas (motora, visual, entre outras), cognitivas (memoria, atenção, aprendizagem, entre outras) e ou comportamentais/emocionais (perda de autoconfiança, depressão, ansiedade, dificuldade de autocontrole, irritabilidade, agressão, entre outras) que podem ser temporárias ou permanentes. O estudo objetivou realizar a validação de conteúdo e clínica do diagnóstico de Enfermagem “Controle emocional instável” em pacientes com TCE atendidos ambulatoriamente. Estudo metodológico e descritivo que utilizou o modelo de Fehring para a validação. Foi desenvolvido em duas etapas: validação de conteúdo e clínica. Na primeira, houve a participação de 31 experts para avaliar, por meio de questionário eletrônico, a estrutura taxonômica da NANDA International relativo ao diagnóstico “Controle emocional instável”. A segunda etapa foi realizada no ambulatório do Hospital Universitário da Universidade Federal de Sergipe, entre os meses de agosto e setembro de 2016 com uma amostra constituída por 40 pacientes em dois grupos distintos com TCE leve (n=20) e TCE moderado (n=20). Para comparação de proporções entre grupos foi utilizado o teste Z (dois grupos) e correção de Bonferroni (3 grupos). Os resultados apontaram que a maioria dos experts considerou o domínio 05 (Percepção/cognição), a Classe 4 (Cognição) e o enunciado (Controle emocional instável) adequados ao diagnóstico, embora tenham sugerido modificações na definição atual do diagnóstico. Duas características definidoras foram consideradas principais (afastamento da situação social e expressão de emoções incoerentes com o fator desencadeador) e 11 secundárias (afastamento da situação profissional, ausência de contato com o olhar, choro excessivo sem sentir tristeza, choro incontrolável, choro involuntário, dificuldade de usar expressões faciais, embaraço relativo à expressão das emoções, lágrimas, risadas em excesso sem sentir felicidade, risadas incontroláveis e risadas involuntárias. O escore total do diagnóstico “Controle emocional instável” foi de 0,69, considerado válido. Na validação clínica, as características consideradas principais para o grupo do TCE leve foram: afastamento da situação profissional, afastamento da situação social, embaraço relativo à expressão das emoções, expressão de emoções incoerentes com o fator desencadeador e as secundários foram ausência no contato pelo olhar, choro excessivo sem sentir tristeza, choro incontrolável, choro involuntário, dificuldade de usar expressões faciais e lágrimas e as irrelevantes concerne a risada em excesso sem sentir felicidade, risadas incontroláveis e risadas involuntárias. No grupo do TCE moderado foram identificadas como características principais o afastamento da situação profissional, afastamento da situação social, choro excessivo sem sentir tristeza, embaraço relativo à expressão das emoções, expressão de emoções incoerentes com o fator desencadeador e as secundárias foram ausência no contato pelo olhar, choro incontrolável, choro involuntário, dificuldade de usar expressões faciais, lágrimas, risadas incontroláveis e risadas involuntárias. O escore total foi semelhante nos dois grupos, 0,74, considerado validado para a Taxonomia da NANDA-I. Conclui-se que a quase totalidade das características definidoras foram consideradas válidas para o diagnóstico “Controle emocional instável” no TCE. / Aracaju, SE

En raison de la complexité de sa pathogenèse, le traumatisme crânien (TC) entraîne de nombreuses lésions cérébrales pour lesquelles il n’existe aucun traitement neuroprotecteur. Il est aujourd’hui clairement établi que la neuro-inflammation est fortement impliquée dans les conséquences post-traumatiques. Cette neuro-inflammation se manifeste entre autres par l’induction de la cyclo-oxygénase de type 2 (COX-2). Bien que plusieurs données soient en faveur d’un rôle délétère de cette enzyme au cours de ce processus dévastateur, l’implication de la COX-2 dans les lésions induites par le TC reste encore controversée. Dans un modèle du TC par percussion mécanique chez la souris, nous avons mis en évidence une augmentation précoce et transitoire du contenu cérébral en COX-2 à 6 et 12 heures après le trauma. Cette induction protéique était à l’origine d’une production accrue de la prostacycline. Cependant, l’inhibition préférentielle de COX-2 était sans effet sur l’œdème cérébral et le déficit neurologique, deux indicateurs de pertinence clinique. Ces données montrent que la COX-2 ne peut pas constituer à elle seule une cible intéressante pour le traitement des conséquences post-traumatiques malgré son induction et son activité après le trauma. Par ailleurs, nous avons montré un effet bénéfique induit par l’indométacine au niveau fonctionnel, ce qui est en faveur d’un rôle délétère des COXs dans le déficit neurologique post-traumatique. Cet effet bénéfique peut impliquer uniquement la COX-1 ou en association avec la COX-2. Ces données constituent un argument supplémentaire qui s’ajoute à plusieurs preuves récentes fournies par la littérature en faveur d’un rôle délétère de COX-1 dans la neuro-inflammation. Malheureusement, ce rôle ne pourra pas être confirmé dans notre modèle car les inhibiteurs sélectifs de COX-1 disponibles à ce jour sont inexploitables dans nos conditions expérimentales. Ce travail constitue une nouvelle piste pour évaluer l’intérêt de l’inhibition des COXs au cours de la phase précoce de la prise en charge du patient traumatisé crânien. La bonne tolérance de l’usage à court terme des inhibiteurs de COX, leur disponibilité sur le marché, leur prix abordable, leur simplicité d’administration, leurs caractéristiques pharmacocinétiques et pharmacodynamiques bien connus sont des facteurs suscitant un intérêt croissant d’élargir le spectre de leurs utilisations en clinique et de la mise en place de nouveaux essais thérapeutiques dans les années à venir. / Because of its complex pathology, Traumatic Brain Injury (TBI) leads to numerous cerebral lesions for which there is no neuroprotective treatment. It is clearly known nowadays that neuro-inflammation is highly involved in post-traumatic consequences. This devastating process is manifested among others by the induction of cyclo-oxygenase type 2 (COX-2). Although many data are in agreement with a deleterious role of COX-2 in neuro-inflammation, the implication of this isoform in the TBI-induced lesions is still controversial. In a mouse model of TBI induced by mechanical percussion, we have shown an early and a transitory increase in the cerebral content of COX-2 at 6 and 12 hours after trauma. This protein induction was the source of an increased production of prostacyclin. However, the preferential inhibition of COX-2 had no effect against cerebral œdema and neurological deficit, two indicators of high clinical relevance. These data show that COX-2 cannot be considered by itself as an interesting target for the treatment of post-traumatic consequences despite its induction and activity after trauma. Besides, we have shown a beneficial effect that was induced by indomethacin at the functional level. This effect highly suggests a deleterious role of COXs in the post-traumatic neurological deficit. This neuroprotection could solely involve COX-1 or both COX isoforms. In accordance with several proofs that were recently supplied by literature, our data constitute an additional argument suggesting a deleterious role of COX-1 in neuro-inflammation. Unfortunately, this hypothesis cannot be confirmed in our model of TBI because the selective inhibitors of COX-1 available this day cannot be exploited in our experimental conditions. This experimental work is a new indication to evaluate the potential interest of COXs inhibition during the early phase of clinical management of patients with TBI. The good tolerance of the short-term intake of COX inhibitors, their availability on the market, their affordable price, their simple way of administration, their well-known pharmacokinetic and pharmacodynamic characteristics increase the need to widen the spectrum of their therapeutic indications and to design new clinical trials during the upcoming years.

The thesis deals with the issue of executive functions in patients with acquired brain injury and possibilies of executive deficit detection in real life circumstances. The thesis is divided into theoretical and empirical part.The theoretical part consists of three chapters. In the first chapterthe definition, localization and different disorders of executive functions are mentioned. The second chapter presents some neuropsychological methods suitable for executive functions assessment and their limits. In the final chapter the Multiple Errands Test method and its various modifications are introduced. The main purpose of the empirical part was to evaluate the ability of the Multiple Errands Test method - hospital version (MET - HV) to detect deficits in executive functions related to daily life functioning. The research group consisted of patients with acquired brain injury (N = 20) and neurologically healthy adults (N = 20) hospitalized in the Rehabilitation Center Kladruby. The results proved the ability of the method MET - HV to distinguish well between patients with acquired brain damage and healthy adults. The second hypothesis concerning the ability of the method to distinguish between patients with frontal and nonfrontal injury wasn't confirmed. Another purpose of the empirical part was to...

This thesis deals with speech therapy for people with acquired brain injury. The theoretical part consists of three chapters that acquaint readers with the theoretical framework necessary to understand the range of problems examined. It approximates the issue of origin and effects of this disease and refers to attitude in therapy that can be realized to people with this impairment. The research part of the work puts a goal to analyze the possibilities of speech therapy of selected persons with aphasia. The resulting data agree on the fact that for effective speech therapy is necessary on the one hand an individual approach but also motivation of patient is very important. The thesis also includes creating a custom set of exercises which has confirmed the effectivness of the development of cognitive functions in persons with aphasia. The empirical part is based on the qualitative research which was realized by techniques of participant observing, interviewing, questionnaire survey, analysing progress and outcomes of activities, documentation and literature.

Les traumatismes crâniens (TC) représentent la première cause de décès ou de handicap avant l'âge de 45 ans, avec une incidence en Europe de 235/100 000 habitants. Chez les patients survivant à un TC, les séquelles sont fréquentes allant de l'état végétatif chronique au syndrome post-concussionnel compliquant principalement la réinsertion socio professionnelle et familiale des victimes. Cependant la nature des lésions cérébrales provoquées par un TC est encore mal connue et les thérapies susceptibles d'empêcher la progression des lésions neurologiques sont très limitées. Un TC provoque d'abord des lésions directement dues à l'impact (lésions primaires). D'autres mécanismes secondaires vont avoir lieu dès les premières minutes suivant le TC et peuvent évoluer sur plusieurs jours. Elles sont susceptibles d'être atténuées par une thérapeutique appropriée et sont donc l'objet de la plupart des efforts de recherche actuels. Néanmoins, notre connaissance de ces phénomènes d'agression primaires et secondaires, est incomplète et ne permet pas d'expliquer correctement l'évolution des TC. Les dépolarisations corticales envahissantes (DCE) ou cortical spreading depolarizations””sont un des évènements délétères contribuant aux lésions secondaires consécutives au TC. Les DCE sont des vagues de dépolarisation massive associées à un mauvais pronostic. Elles sont caractérisées par une dépression de l'activité electrocorticographique et une dépolarisation des neurones corticaux et des astrocytes qui se propagent sur le cortex. Les DCE s'accompagnent d'une augmentation des besoins métaboliques visant à restituer au tissu son état d'homéostasie neurochimique et de polarisation cellulaire. Les conséquences des DCE sur le métabolisme cérébral sont encore mal connues aussi bien sur un tissu sain qu'après agression cérébrale. Il existe des arguments pour penser que l'incidence, le nombre et la durée des DCE sont associés à un moins bon pronostic chez l'homme après agression cérébrale. Cependant, les mécanismes par lesquels ces DCE auraient une toxicité directe reposent encore sur des arguments le plus souvent indirects et sont mal compris. L'objectif principal de ce travail de thèse a été de caractériser les conséquences neurochimiques et micro-vasculaires des DCE afin de mieux comprendre leur physiopathologie dans un cortex sain ou agressé par un TC sévère / “Traumatic brain injury” (TBI) encompasses a heterogeneous group of physio-pathological phenomenon. Prognosis, clinical course evaluation and treatment of brain trauma remain challenging. Brain damage results from both the initial physical insult (primary injury), and also continues to occur in the ensuing hours to days because of secondary brain aggressions. Among secondary injuries following TBI, Cortical Spreading Depolarizations (CSD) have emerged since the mid-90s. CSD are waves of depolarization propagating along the cortex at a speed of 1-5 mm/min that induced a massive energetic demand to repolarize the cells. CSD are participating to prognosis because their occurrence and duration are related to outcome in different acute brain injuries (TBI, sub-arachnoid hemorrhage and ischemic stroke). During my thesis, our main goal was to determine whether the CSD reinforced neuronal death following brain trauma that can explain the poor prognosis. In a first study we delineated brain regions where neuronal death occurs following lateral fluid percussion injury (LFPI) in order to record CSDs in this area. Then, as we wanted to assess the energetic balance of this tissue during CSD using biosensors, we had primarily to check for the biosensor reliability to oxygen (O2) and temperature (To). As oxygen and temperature were different from bench (in vitro) to bedside (in vivo) monitoring, we developed algorithms to compute offline the in vivo values obtained for glucose, lactate or glutamate brain concentrations respecting the local O2 concentrations and To measured in the cortex. Finally, using the biosensors, we described the dynamic real time metabolic changes occurring after CSDs in 3 conditions: A healthy cortex, an injured cortex after LFPI, and when CSD occurred in cluster after LFPI. Although the normal brain displayed a hyper-glycolytic state following CSD (transient low glucose concentrations + prolonged elevated lactate concentrations), TBI tissue exhibited a different pattern that could be metabolic crisis (very low glucose concentrations + normal to low lactateconcentrations)

Abstract Traumatic brain injury (TBI) is an enormous health and economic problem. The proportion of alcohol involvement among subjects with TBI varies 34–51%. Acute alcohol intoxication increases the risk for head trauma compared with other parts of the body. Therefore, alcohol is a major, yet preventable risk factor for TBI. Alcohol taxes were reduced in 2004 and limits on tax-free imports from other EU countries were also removed. Within a year, total alcohol consumption increased by 10% in Finland. Alcohol-induced liver diseases and sudden deaths involving alcohol increased after the reduction. The effects of the reduction on the incidence and mortality of TBI were not known. Data on all TBI subjects admitted to Oulu University Hospital (1999, 2007) were gathered, as well as data on all fatal TBIs among the residents of Oulu Province (1999, 2006, and 2007). A cohort of subjects with head trauma admitted to Oulu University Hospital in 1999 was followed up until the end of 2009. Alcohol involvement was based on positive alcohol measurement or alcohol-related cause of death on death certificate or hospital chart notes made by health care providers. The incidence and mortality rates of moderate-to-severe TBI and alcohol involvement between the observation years were compared. Cumulative survival rates were calculated to demonstrate the effect of alcohol price reduction on the mortality of the head trauma cohort during a 10-year follow-up. The incidence of moderate-to-severe and fatal TBI was similar before and after the reduction of alcohol prices. After the reduction, the proportion of alcohol-related moderate-to-severe and fatal TBIs increased among middle-aged people, but decreased among young adults. The increase in TBIs among the middle-aged was mainly due to an increase in falls, whereas the decrease among young adults was due to a decreased number of suicides (particularly among young men). After the reduction of alcohol prices, harmful drinkers were significantly more likely to die than those who were not harmful drinkers. The overall incidence of moderate-to-severe and fatal TBIs did not increase after the reduction of alcohol prices, but the proportions of alcohol-related TBIs due to falls increased among middle-aged people. Our observations demonstrate that harmful drinkers and middle-aged people were the groups which suffered the most TBI-related harm after the reduction of alcohol prices. / Tiivistelmä Traumaattiset aivovammat aiheuttavat mittavia terveydellisiä ja taloudellisia ongelmia. Alkoholin vaikutuksen alaisena on vammautumishetkellä 34–51&#160;% aivovammapotilaista. Akuutti päihtymystila lisää riskiä saada pään alueen vamma verrattuna muihin vartalon osiin. Alkoholi on merkittävä ja estettävissä oleva aivovammojen riskitekijä. Vuonna 2004 toteutettiin merkittävä alkoholin veronalennus sekä poistettiin muista EU-maista tuotavien verottomien juomien rajoitukset. Alkoholin kulutus lisääntyi 10&#160;% vuoden aikana. Alkoholin aiheuttamat maksasairaudet sekä äkkikuolemat lisääntyivät alkoholin veronalennuksen jälkeen. Vaikutuksia traumaattisten aivovammojen ilmaantuvuuteen ja kuolleisuuteen ei ole vielä tutkittu. Tiedot kerättiin Oulun yliopistollisessa sairaalassa hoidetuista aivovammapotilaista (1999 ja 2007) sekä Oulun läänin alueella aivovammoihin kuolleista (1999, 2006 ja 2007) vainajista. Vuonna 1999 pään vamman vuoksi Oulun yliopistollisessa sairaalassa käyneitä potilaita seurattiin vuoden 2009 loppuun saakka. Tiedot alkoholin käytöstä perustuivat positiiviseen mitattuun alkoholipitoisuuteen sekä asiakirjamerkintöihin alkoholin käytöstä. Lievää vaikeampien traumaattisten aivovammojen ilmaantuvuutta, kuolleisuutta sekä alkoholiin liittyvien tapausten osuutta verrattiin tutkimusvuosien välillä. Vuonna 1999 päätään loukanneiden pitkäaikaisseurannassa tutkittiin alkoholin veronalennuksen vaikutusta kuolleisuuteen. Lievää vaikeampien aivovammojen ilmaantuvuus sekä aivovammakuolleisuus pysyivät samansuuruisina ennen ja jälkeen alkoholin veronalennuksen. Veronalennuksen jälkeen alkoholiin liittyvien aivovammojen osuus lisääntyi keski-ikäisillä mutta väheni nuorilla. Keski-ikäisillä havaittu alkoholi liitännäisten aivovammojen lisääntyminen johtui pääasiallisesti siitä että kaatumisvammoja tapahtui enemmän, kun taas nuorten kohdalla havaittu väheneminen johtui itsemurhien vähenemisestä. Alkoholin veronalennuksen jälkeen alkoholia haitallisesti käyttävien kuolleisuus lisääntyi merkittävästi verrattuna niihin, jotka eivät käyttäneet alkoholia haitallisesti. Lievää vaikeampien aivovammojen ilmaantuvuus sekä kuolleisuus eivät lisääntynyt alkoholin veronalennuksen jälkeen, mutta keski-ikäisten alkoholiin liittyvät kaatumistapaukset lisääntyivät. Havainnot osoittavat, että erityisesti haitallisesti alkoholia käyttävillä sekä keski-ikäisillä oli suurempi riski saada aivovammoihin liittyviä ongelmia veronalennuksen jälkeen.