Le traumatisme crânien (TC) est la première cause de visite aux urgences pour la population pédiatrique. Indépendamment du niveau de sévérité du TC, les patients pédiatriques souffrent sur le long-terme de troubles cognitifs et émotionnels, cependant les mécanismes moléculaires et cellulaires sous-jacents sont encore peu connus, et il n’existe pas de traitement efficace disponible à ce jour. L’unité neurovasculaire est composée de vaisseaux sanguins, neurones et astrocytes. Les astrocytes sont essentiels à une variété de fonctions physiologiques assurées par cette unité tels que l’homéostasie cérébrale et le couplage neurovasculaire. Suite à une lésion, les astrocytes deviennent « réactifs », et cette « astrocytopatie » peut impacter leur rôle physiologique et empirer les conséquences de la lésion.Nous avons étudié le rôle de l’astrocytopatie dans le TC juvénile et fait l’hypothèse que : (1) les astrocytes réactifs contribuent à la propagation de l’œdème via les jonctions serrées connexines après un TC juvénile modéré ; (2) l’astrocytopatie se développe également après un TC juvénile léger avec des changements calciques qui pourraient contribuer à (3) une altération de la réactivité vasculaire, tout cela impactant sur les conséquences comportementales qui font suite à la lésion.Nous avons montré que :(1) Réduire l’astrocythopatie en sous-régulant la connexine 43 permettait d’améliorer les conséquences comportementales après un TC modéré juvénile, mais n’impactait pas la propagation de l’œdème.(2) Les astrocytes devenaient réactifs et subissaient des changements morphologiques après un TC juvénile léger avec des perturbations dans les signaux purinergiques-calciques liés à des changements dans l’expression du canal aqueux aquaporine 4 (AQP4).(3) Une dysfonction vasculaire majeure s’était développée après le TC juvénile léger avec des changements fonctionnels et morphologiques des vaisseaux intraparenchymaux parallèles aux altérations comportementales et précédant les dommages axonaux après la lésion.Ce travail apporte un nouvel aperçu de la pathophysiologie du TC juvénile et ouvre des possibilités pour développer des thérapies ciblant l’astrocytopatie après une lésion. / Traumatic brain injury (TBI) is the first cause for emergency department visits in the pediatric population. Regardless of the severity of TBI, pediatric patients suffer long-term cognitive and emotional impairments but the underlying cellular and molecular mechanisms are still poorly understood and there are no effective treatments available. The neurovascular unit is composed by blood vessels, neurons and astrocytes. Astrocytes are crucial for various physiological functions of this unit such as brain homeostasis and neurovascular coupling. In injuries astrocytes become “reactive”, and this “astrocytopathy” can impact their physiological roles and worsen the outcome after injury.We investigated astrocytopathy in juvenile TBI and hypothesized that: (1) reactive astrocytes contribute to spread of edema through connexin gap junctions after juvenile moderate TBI; and that (2) astrocytopathy also develops after juvenile mild TBI with calcium changes that could contribute to (3) impaired vascular reactivity, all of which impacts the behavioral outcome after injury.We have shown that:(1) Reducing astrocytopathy by downregulating the gap junction protein connexin 43 improved the behavioral outcome after juvenile moderate TBI, but did not impact the spread of edema.(2) Astrocytes became reactive and underwent morphological changes after juvenile mild TBI with disturbances in purinergic-calcium signaling related to expression changes of the water channel aquaporin 4 (AQP4).(3) Major vascular dysfunction developed after juvenile mild TBI with functional and morphological changes of the intraparenchymal vessels that paralleled behavioral impairments and preceded axonal damage after injury.This work brings new insights in the pathophysiology of juvenile TBI and opens prospects for developing therapeutics targeting astrocytopathy after injury.

Le traumatisme crânien (TC) représente un des problèmes majeurs de santé publique, pour lequel à l’heure actuelle il n’existe aucun traitement. Le TC induit une neuro-inflammation délétère qui pourrait contribuer à l’apparition des lésions de la substance blanche (SB). Ces dernières sont à l’origine de lourdes conséquences neurologiques chez les patients victimes de TC. Néanmoins, très peu d’études se sont intéressées à ces lésions bien que plus sévères que les lésions de la substance grise. Ainsi une meilleure connaissance de leur évolution et des causes devient indispensable. L’hyperactivation de la poly(ADP ribose)polymérase (PARP) joue un rôle délétère dans les conséquences post-traumatiques, notamment sur la neuro-inflammation. Ainsi son inhibition pourrait être bénéfique le développement des lésions de la SB. Dans ce contexte, l’objectif de notre travail a été d’évaluer le rôle de la PARP dans les lésions de la SB dans un modèle expérimental de TC induit par impact cortical contrôlé chez la souris. Dans une première partie, nous avons étudié l’évolution de la démyélinisation dans le corps calleux, une structure riche en SB, entre 6 heures et 3 mois post-TC. Parallèlement, les évolutions de la lésion cérébrale, des déficits sensorimoteurs, de la neuro-inflammation et de l’œdème cérébral ont été étudiées. Le TC induit (1) une démyélinisation dès 7 jours et au moins jusqu’à 3 mois post-TC, précédée par (2) une lésion cérébrale entre 24 et 72 heures suivie par une cicatrisation, (3) une neuro-inflammation entre 6 heures et 7 jours et (4) un œdème cérébral entre 6 et 72 heures post-TC. De plus, le TC induit des déficits sensorimoteurs à 6 heures et 3 mois. Ces résultats montrent que ce modèle est adapté pour étudier les lésions de la SB post-TC, et que la neuro-inflammation et l’œdème cérébral pourrait être impliqués dans la démyélinisation. Dans une deuxième partie, nous avons étudié le rôle de la PARP dans les lésions de la SB suite à TC à l’aide de souris knockout (KO) et wild-type (WT) pour le gène de la PARP. Nous avons mis en évidence que les souris KO ne présentent pas de démyélinisation bilatérale du corps calleux après un TC par rapport aux souris WT à 7 jours post-TC, démontrant pour la première fois l’implication de cette enzyme dans les lésions de la SB consécutives à un TC. De plus, nous avons constaté que les souris KO non traumatisées présentent une diminution de myélinisation comparativement aux souris WT non traumatisées, suggérant un rôle de la PARP dans le processus physiologique de la myélinisation.En conclusion, l’ensemble de ce travail expérimental a permis (1) une meilleure caractérisation de la démyélinisation post-TC et des mécanismes potentiellement impliqués dans cette dernière, et (2) de démontrer pour la première fois le rôle délétère de la PARP dans la démyélinisation induite par un TC. Nos travaux suggèrent le potentiel de l’inhibition de la PARP comme stratégie thérapeutique pour la prévention des lésions de la SB post-traumatiques. / Traumatic brain injury (TBI) is a leading cause of death and disability for which there is no neuroprotective treatment up to date. It results in neuroinflammation that may participate in lasting motor and cognitive impairments accompanied by changes in white matter (WM) tracts. WM lesions, evidenced by demyelination, are associated with neurological disorders and in clinical studies are common consequences in patients with chronic TBI. Several studies suggest a contribution of an overactivation of the poly(ADP-ribose) polymerase (PARP) to the neuroinflammatory response which may lead to demyelination. The first part of this study was dedicated to a detailed in vivo assessment of the evolution over time of neurological disorders, cerebral lesion and edema, neuroinflammation and white matter injury induced by controlled cortical impact (CCI) between 6 hours and 12 weeks post-TBI. Notably in the corpus callosum, a significant demyelination starting at 7 days appeared to be a major consequence to post-traumatic neuroinflammation associated with motor dysfunctions. The second part of this study was dedicated to the evaluation of PARP’s role in WM lesions post-TBI, using PARP knockout (KO) mice. Our main findings reveal a diminished demyelination in the corpus callosum of TBI PARP KO as opposed to TBI PARP wildtype specimens. Hence, these data suggest for the first time PARP’s deleterious role in post-traumatic demyelination. In conclusion, taken together these data give an overall view of motor/sensorimotor deficits, neuroinflammation and demyelination in a CCI model of TBI that could help to validate pharmacological strategy for preventing post-traumatic WM injury. Notably, PARP’s inhibition seems to be a valid candidate as this enzyme participates in the establishment of a demyelinating process.

In der vorliegenden Arbeit wird die Erstellung eines computergestützten Systems zum multimodalen zerebralen Monitoring von Patienten mit schwerem Schädel-Hirn-Trauma beschrieben. Das multimodale zerebrale Monitoring dient der Erfassung, graphischen Darstellung und elektronischen Speicherung von physiologischen Meßdaten. Zur kontinuierlichen Überwachung der zerebralen Sauerstoffversorgung wurden die jugularvenöse Oxymetrie, die Hirngewebe-Sauerstoffpartialdruckmessung und die Nah-Infrarot-Spektroskopie hinsichtlich ihrer Stabilität und Sensitivität vergleichend getestet. Weiterhin erfolgte die prospektive Untersuchung der Inzidenz zerebraler hypoxischer Episoden, ihrer möglichen Ursachen, sowie des Einfluß der zerebralen Hypoxie auf das neurologische Outcome er Patienten mit schwerem Schädel-Hirn-Trauma. Zur kontinuierlichen Überwachung der zerebralen Oxygenierung ist gegenwärtig die Messung des lokalen Hirngewebe-pO2 am besten geeignet. Als häufigste Ursachen der zerebralen Hypoxie wurden die systemische Hypokapnie, ein verminderter zerebrale Perfusionsdruck und ein erhöhter intrakranieller Druck identifiziert. Das akkumulierte Auftreten zerebraler hypoxischer Episoden für mehr als 30 Minuten war mit einem signifikant schlechteren neurologischen Outcome der Patienten verbunden. Durch die Einführung weiterer Methoden zur invasiven und nicht-invasiven Überwachung von Patienten mit schwerem Schädel-Hirn-Trauma, wie zum Beispiel der zerebralen Mikrodialyse, können zukünftig die metabolischen Veränderungen durch eine zerebrale Hypoxie untersucht werden. / Cerebral hypoxia is considered the main cause of secondary damage to the vulnerable brain following severe traumatic brain injury, and critical care management is primarily focused on the prevention of cerebral hypoxic events. Goals of this study were: First, the development of a computerized multimodal cerebral monitoring system to continuously acquire, display, and record data from multiple monitoring devices. Second, the comparative study of different methods for monitoring of cerebral oxygenation, as there are jugular venous oxygen saturation, near-infrared spectroscopy, and brain tissue oxygen tension. Third, the prospective determination of a critical hypoxic threshold, the incidence of cerebral hypoxia, the influence of standard therapeutic maneuvres to treat intracranial hypertension on cerebral oxygenation, the significance of possible causes of cerebral hypoxia, and the influence of cerebral hypoxia on neurological outcome. The multimodal monitoring system was successfully established on a neurosurgical intensice care unit. Monitoring of local brain tissue pO2 was most appropriate for monitoring of cerebral oxygenation. The critical hypoxic threshold in brain tissue pO2 was 10 mmHg. Standard therapeutic maneuvres to treat elevated intracranial pressure were, in part, unsuccessful in improving cerebral oxygen delivery. Cerebral hypoxic episodes were predominantly associated with arterial hypocarbia and low cerebral perfusion pressure. Patients with a total of more than 30 minutes of cerebral hypoxic events had a significantly worse neurological outcome. Future investigations using cerebral microdialysis will help to further improve insight into pathophysiology and metabolic changes following traumatic brain injury.

The aim of this final thesis is to apply Feuerstein's instrumental enrichment program (FIE) to a person with traumatic brain injury (TBI). The theoretical part deals with the problematic of traumatic brain injury and Feuerstein's approach to the development of cognitive functions. The empirical part focuse on qualitative research to find out whether there has been an improvement in cognitive functions with three respondents with TBI after five months of intervention using the FIE program, or not. Respondents are young men aged between 23 and 32, about 10 years after the accident, who regularly rehabilitate and undergo reeducation at the Jedlička Institute and Schools (JÚŠ). The aim of the research is to compare whether the influence of the FIE program has improved cognitive functions. The comparison is achieved by objective assessment of cognitive functions using Klecanská opakovatelná neuropsychologická baterie (KONB; Klecany Repeatable Neuropsychological Battery). The results of the research are presented in structured case studies. These in addition to the results of the KONB examination and the description of several months of intervention, follows the respondents throughout their past from life before the accident, through the rehabilitation of the consequences of the accident to the present...

Les objectifs de cette thèse étaient de caractériser les corrélats neuronaux fonctionnels et structurels de l'abolition de la conscience observés pendant le coma et d'identifier les signatures neuronales précoces de la récupération neurologique à partir de cet état. Pour atteindre ce but, nous avons étudié des patients cérébrolésés, recrutés au stade aigu du coma, à l'aide de l'IRM fonctionnelle au repos et IRM structurale. Nos résultats indiquent une réorganisation topologique globale du cerveau des patients, reflétée par une dédifférenciation et une réduction de la résilience des réseaux fonctionnels au repos d'ordre élevé. Ces anomalies sont accompagnées d'une perte de connexions fronto-pariétales à longue distance. Au niveau régional, nous avons observé un schéma complexe de diminution et d'augmentation de la densité de connexion fonctionnelle entre le cortex postéromédial et le cortex préfrontal médial : régions précédemment décrites pour avoir un rôle critique dans la conscience. De manière intéressante, ces modifications de densité de connexion étaient significativement liées à la récupération des patients trois mois après le coma. Enfin, l'analyse multimodale a permis de démontrer une association significative entre la connectivité fonctionnelle et l'intégrité structurelle cérébrales antéro-postérieure, fournissant des informations importantes sur le lien structure/fonction au décours de ces troubles acquis de la conscience. / The aim of the present thesis was to characterize the functional and structural neural correlates of acute consciousness abolition induced by severe brain injury and identify early neural signatures of long-term neurological recovery. To do so, we studied brain-injured patients, recruited in the acute stage of coma, using resting-state functional and structural MRI. Our findings indicated a global topological brain reorganization in coma patients, reflected in dedifferentiated and less resilient high-order resting-state functional networks, paralleled with a loss of long-range fronto-parietal connections. On a regional level, we found a complex pattern of voxel-wise decrease and increase in functional connection density between the posteromedial cortex and the medial prefrontal cortex, regions previously described to have a critical role in conscious processing. These connection density patterns seemed to permit outcome prediction in patients, assessed three months post-coma. Furthermore, the multi-modal MRI analysis demonstrated a significant association between antero-posterior functional connectivity and structural integrity, providing further insights into the pathological underpinning of conscious processing.

Made available in DSpace on 2016-04-28T20:56:20Z (GMT). No. of bitstreams: 1 Silvia Cristina de Freitas Feldberg.pdf: 8472150 bytes, checksum: d1b62a4823332d0da7e9ca29e7af441c (MD5) Previous issue date: 2010-10-25 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / This study evaluated the mathematical performance of children and adolescents with congenital or acquired brain injuries, trying to identify whether (and how) the neuropsychological profile reflects in this performance. Since math learning is central to a successful school experience, it is important to identify whether the brain lesions necessarily promote, as claimed by teachers, learning difficulties, or whether, instead, the plasticity of the brain, combined with a good school, discredits that statement. The theoretical approach is based on the neuropsychology and the socio-historical conception of human development, considering the importance of the biological basis and, moreover, of the social world in which the process of learning and human development occurs. The study investigated 5 male adolescents diagnosed with brain damage. The boys were 12 to 15 years old and were attending series 6th to 9th in private schools in the state of Sao Paulo (BR). They answered a battery of tests, which included verification of their IQs, their performance in Math and also a neuropsychological evaluation. The procedures were applied individually, lasting three to four sessions of 90 minutes in average. The results were analyzed according to the standards required by each instrument. For performance in mathematics, qualitative and quantitative analyses of the tests were made. The results showed that, among the neuropsychological functions, the visual constructive and the executive one showed more pronounced problems. Regarding Math performance, the greatest difficulties were detected in skills related to Space and Form, Information Processing, Multiplication and Problems Resolution. However, since the participants are similar to the average Brazilian students in terms of IQ and mathematical performance, the inadequate functioning of their psychological functions seems to be due not to the brain damage but to the precarious teaching of that school discipline. Thus, the research findings defy simplistic analysis, which establish a causal relationship between learning difficulties and brain damage. The recommendation, once again, is to invest efforts in promoting teachers professional development so that they can offer to any student the necessary incentive, motivation, help and guidance to conquer what society expects and schools must deliver / O presente trabalho avaliou o desempenho matemático de crianças e adolescentes com lesões cerebrais congênitas ou adquiridas, tentando identificar se (e como) o perfil neuropsicológico se reflete neste desempenho. Como a aprendizagem da matemática é central para uma trajetória escolar bem-sucedida, convém identificar se as lesões encefálicas concorrem, como alegam os professores, para a presença de dificuldades de aprendizagem ou se, ao contrário, a plasticidade do cérebro, aliada a uma escola de boa qualidade, desacredita essa afirmação. O referencial teórico adotado apoia-se na neuropsicologia e na concepção sócio-histórica do desenvolvimento humano, considerando tanto a importância da base biológica como a do mundo social no processo de aprendizagem e desenvolvimento humano. Foram pesquisados cinco adolescentes com idades entre 12 e 15 anos, do sexo masculino, diagnosticados com lesão cerebral, cursando entre o sexto e o nono ano do ensino fundamental, em escolas privadas localizadas no Estado de São Paulo. Foi-lhes aplicada uma bateria de testes, que incluíam a verificação do coeficiente intelectual, o desempenho matemático e, ainda, uma avaliação neuropsicológica. Os procedimentos foram aplicados individualmente e levaram cerca de três ou quatro sessões, de duração média de 90 minutos. Os resultados da avaliação foram analisados conforme as normas requeridas em cada instrumento utilizado. Para o desempenho em matemática, foram feitas análises qualitativas e quantitativas dos testes empregados. Os resultados mostraram que, no âmbito neuropsicológico, as habilidades visoconstrutivas e funções executivas apresentavam os problemas mais acentuados. Em relação ao desempenho em matemática, maiores dificuldades foram detectadas nas competências relacionadas aos domínios Espaço e Forma e Tratamento da Informação, Multiplicação e Resolução de Problemas. No entanto, como os participantes não discrepavam da média dos alunos brasileiros em termos de QI e, inclusive, de desempenho matemático, as funções psicológicas deficitárias parecem ser devidas não às lesões cerebrais, e sim, à precariedade do ensino dessa disciplina. Dessa forma, os achados da pesquisa desafiam análises simplistas, que estabelecem uma relação causal entre dificuldades de aprendizagem e lesões cerebrais. A recomendação, mais uma vez, é a de se investir na formação profissional dos docentes, para que possam oferecer a todo e qualquer aluno ainda que mais a uns do que a outros, para cumprir o preceito da equidade estímulos, motivação, auxílio e guia para dominarem aquilo que a sociedade espera deles e que a escola tem por meta lhes ensinar

This thesis explores physiological changes occurring after acute brain injury. The first two chapters focus on traumatic brain injury (TBI), a significant cause of disability and death worldwide. I discuss the evidence behind current management of secondary brain injury with emphasis on partial brain oxygen tension (PbtO2) and intracranial pressure (ICP). The second chapter describes a subgroup analysis of the effect of hypothermia on ICP and PbtO2 in 17 patients enrolled to the Eurotherm3235 trial. There was a mean decrease in ICP of 4.1 mmHg (n=9, p < 0.02) and a mean decrease in PbtO2 (7.8 ± 3.1 mmHg (p < 0.05)) in the hypothermia group that was not present in controls. The findings support previous studies in demonstrating a decrease in ICP with hypothermia. Decreased PbtO2 could partially explain worse outcomes seen in the hypothermia group in the Eurotherm3235 trial. Further analysis of PbtO2 and ICP guided treatment is needed. The third chapter focuses on delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH), another form of acute brain injury that causes significant morbidity and mortality. I include a background of alpha-calcitonin gene-related peptide (αCGRP), a potential treatment of DCI, along with results from a systematic review and meta-analysis of nine experimental models investigating αCGRP. The meta-analysis demonstrates a 40.8 ± 8.2% increase in cerebral vessel diameter in those animals treated with αCGRP compared with controls (p < 0.0005, 95% CI 23.7 to 57.9). Neurobehavioural scores were reported in four publications and showed a Physiological responses to brain tissue hypoxia and blood flow after acute brain injury standardised mean difference of 1.31 in favour of αCGRP (CI -0.49 to 3.12). I conclude that αCGRP reduces cerebral vessel narrowing seen after SAH in animal studies but note that there is insufficient evidence to determine its effect on functional outcomes. A review of previous trials of αCGRP administration in humans is included, in addition to an original retrospective analysis of CSF concentrations of αCGRP in humans. Enzyme-linked immunosorbent assay of CSF (n = 22) was unable to detect αCGRP in any sample, which contrasts with previous studies and was likely secondary to study methodology. Finally, I summarise by discussing a protocol I designed for a dose-toxicity study involving the intraventricular administration of αCGRP to patients with aSAH and provide some recommendations for future research. This protocol was based upon the systematic review and was submitted to the Medical Research Council's DPFS funding stream during the PhD.

Les pathologies neurologiques sont souvent considérées comme les plus graves et provoquent régulièrement des perturbations cognitives jugées irréversibles. Cependant, certaines affections comme le traumatisme cranio-cérébral et l’accident vasculaire cérébral disposent d’un potentiel de récupération. Ces deux pathologies restent distinctes sur l’étiologie et la population affectée mais sont communes au niveau de la prise en charge et des séquelles existantes. Les différentes recherches effectuées sur la récupération des troubles phasiques et la mise en évidence de facteurs pronostics dans les perturbations langagières, nous ont conduits à effectuer une recherche longitudinale sur les variables de la récupération dans les traumatismes cranio-cérébraux. Compte tenu du potentiel de récupération des accidents vasculaires cérébraux, nous avons effectué une recherche comparative entre les deux pathologies. L’analyse des liens entre les états dépressifs, les états anxieux, l’estime de soi, le coping, la résilience, les performances cognitives, les soins dispensés et l’anosognosie nous a permis d’appréhender les facteurs de récupération présents dans les deux affections. Les résultats de cette étude révèlent des performances cognitives similaires entre les sujets cérébro-lésés ainsi que la possibilité d’une récupération pour chacune des pathologiques. Nos résultats ont également montré une récupération identique, indiquant ainsi que quelle que soit la pathologie, nos sujets récupèrent de la même manière. / Neurological pathologies are frequently considered as serious and generate cognitive disabilities irreversible. However some diseases as traumatic brain injury and stroke have a recovery potential. These pathologies are different concerning etiology and people who are suffer but similar about medical care and sequelae. The different researches related to the recovery of language disorders and prognostic variables exposure, led us to realize a longitudinal study on recovery variables on traumatic brain injury. Considering the potential recovery of stroke, we have effected a comparative research between both pathologies. Correlational analyses between depression, anxiety, self-esteem, resilience, coping, abilities cognitive, medical care and anosognosia have exposed the determinants of recovery in traumatic brain injury and stroke. The results of this study show identical cognitive performances between patients and also a recovery for both disease. Recovery was similar for patients, which means regardless pathologies, patients recover in same way.

L’objectif de ce travail de recherche consistait à utiliser la réalité virtuelle (simulateur de conduite) afin d'améliorer les capacités attentionnelles de personnes présentant une baisse d’efficience de ces aptitudes (en lien avec l’âge ou la survenue d’un traumatisme crânien) pouvant se répercuter sur la conduite automobile. En référence au modèle de l’attention de Van Zomeren et Brouwer (1994), quatre processus attentionnels (alerte phasique, vigilance, attention sélective et attention divisée) ont été entraînés sur simulateur de conduite lors d’un programme comprenant 9 sessions d’une heure. Un groupe contrôle a effectué un training plus conventionnel sur ordinateur. Les performances des participants (10 patients traumatisés crâniens et 16 personnes âgées de plus de 65 ans) ont été évaluées avant et après le training à partir de trois mesures : une évaluation neuropsychologique, une évaluation sur simulateur de conduite et une évaluation sur route réelle. Le bénéfice de l’entraînement sur les performances aux tests neuropsychologiques s’est avéré limité pour les deux groupes. Concernant l’évaluation sur simulateur, les résultats ont révélé une amélioration des performances plus importante pour les participants entraînés sur simulateur. En revanche, les participants ayant bénéficié du training sur ordinateur ont davantage progressé que ceux entraînés sur simulateur lors de l’évaluation sur route réelle. Les résultats ont été discutés en termes d’approche rééducative et d’automatisation des processus attentionnels. Ce travail permet de conclure quant à la nécessité de poursuivre et d’approfondir les recherches sur la réalité virtuelle et le transfert de l’apprentissage en situation de vie quotidienne / The aim of this research was to investigate the role of the virtual reality in the improvement of attentional processes and driving competence. A driving simulator was used in order to train people with attentional impairments, like Traumatic Brain Injury (TBI) patients or elderly people. The theoretical frame suggested by Van Zomeren and Brouwer (1994) was used in order to train four attentional processes (phasic alert, vigilance, selective attention and divided attention). Ten TBI patients and 16 elderly people entered a 3-week 9-hour training program in which they were randomly allocated to either an experimental (simulator-based training) or control (computer-based training) group. Performance in off-road evaluations (neuropsychological and driving simulator tests) and on-road test were used to assess the driving ability of subjects pre- and post-training. Both groups improved in many neuropsychological evaluations. Significant improvements in driving simulator test were found in favor of the experimental group. However, improvements were greater for the control group regarding the on-road test. Results were discussed in terms of rehabilitation approach and automatic vs control processing theory. This study offers future research possibilities concerning the improvement of knowledge on virtual reality and learning transfer in daily activities

O efeito devastador da hipotensão na mortalidade relacionada ao trauma de crânio é bem estabelecido. Este estudo avalia a resposta hemodinâmica sistêmica e cerebral à reposição volêmica com Solução de Ringer Lactato (RL) ou Salina Hipertônica a 3% (SSH 3%), o comportamento da liberação de prostanóides encefálicos, aspectos anátomo-patológicos encefálicos e aspectos neurológicos, durante a fase aguda do choque hemorrágico (CH) associado ao traumatismo craniencefálico (TCE). MÉTODOS: Quinze cães foram distribuidos em três grupos (n=5, cada), após randomização, de acordo com o protocolo de reposição volêmica, realizada após TCE (fluido-percussão cerebral, 4 atm) e balão epidural para induzir hipertensão intracraniana (HIC) a 20-25 mmHg e CH, induzido por remoção sanguínea até pressão arterial média (PAM) de 40 mmHg em 5 minutos: grupo CH+TCE+HSS 3% (8ml/kg), CH+TCE+RL (16ml/kg) e grupo CH+TCE (controle, sem tratamento). Simulamos o tratamento durante a fase pré-hospitalar e hospitalar precoce. Os grupos tratados receberam infusão sanguínea para atingir hematócrito de 30%. As medidas incluiram volume sanguíneo removido, volume de cristalóide infundido para restabelecer PAM, PAM, índice cardíaco (IC), pressão intracraniana (PIC), pressão de perfusão cerebral (PPC), lactato sistêmico e cerebral, taxas de extração de oxigênio, concentração plasmática de tromboxane e prostaciclina. Avaliamos o padrão pupilar dos animais e realizamos análise anátomo-patológica dos encéfalos. RESULTADOS: A reposição volêmica com RL ou SSH 3% promoveu maior benefício hemodinâmico que o grupo controle sem tratamento. A pressão de perfusão cerebral foi maior que no grupo controle e similar entre os grupos tratados; entretanto, a infusão de SSH 3% foi associada com valores mais baixos de PIC durante a fase \"hospitalar precoce\" e com maior osmolaridade e concentração de sódio plasmático. Não houve diferença nos valores da concentração venosa cerebral de prostaciclina e tromboxane. Os encéfalos do grupo tratado com SSH 3% não demonstraram edema e os hipocampos dos cães do grupo controle se mostraram isquêmicos em relação ao grupo tratado com SSH 3%. A reversão pupilar após alteração pupilar estabelecida ocorreu mais precocemente no grupo tratado com SSH 3% que RL. CONCLUSÕES: No evento de um trauma de crânio grave e choque hemorrágico, o uso de SSH 3% ou o dobro do volume de RL promoveram benefícios hemodinâmicos sistêmicos e cerebrais. Entretanto, valores mais baixos de PIC foram observados após SSH 3%. / The devastating effects of hypotension on head-trauma-related mortality are well known. This study evaluates the systemic and cerebral hemodynamic responses to volume replacement with 3% hypertonic saline (HSS) or lactated Ringer\'s solution (LR), during the acute phase of hemorrhagic shock (HS) associated with traumatic brain injury (TBI). METHODS: Fifteen mongrel dogs were assigned to one of three groups (n=5, each) according to the volume replacement protocol, infused after TBI (brain fluid percussion, 4atm) and epidural balloon to an intracranial pressure (ICP) higher than 20 mm Hg and HS, induced by blood removal to a mean arterial pressure (MAP) of 40 mm Hg in 5 minutes: Group HS+TBI+HSS (8 mL/kg of 3% HSS), HS+TBI+LR (16 mL/kg LR) and Group HS+TBI (controls, no fluids). We simulated treatment during prehospital and early hospital admission. Groups HS+TBI+HSS and HS+TBI+LR received shed blood infusion to a target hematocrit of 30%. Measurements included shed blood volume, fluid volume infused to restore MAP, MAP, cardiac output, cerebral perfusion pressure, cerebral and systemic lactate, and oxygen extraction ratios, tromboxane and prostaciclin. We evaluated the dog\'s pupil pattern and the anatomopathological study of the brain. RESULTS: Fluid replacement with HSS or LR promoted major hemodynamic benefits over control animals without fluids. Cerebral perfusion pressure was higher than controls and similar between treated groups; however, HSS infusion was associated with lower ICP during the \"early hospital phase\" and a higher serum sodium and osmolarity. There were no differences between groups in cerebral venous concentration of tromboxane and prostaciclin. There was no edema in brains of HSS group, the hypocampi of control\'s group showed ischemia comparing to HSS group. The pupils reverted early in HSS than LR group. CONCLUSION: In the event of severe head trauma and hemorrhagic shock, the use of HSS and larger volumes of LR promote similar systemic and cerebral hemodynamic benefits. However, a lower ICP was observed after HSS 3% than after LR.