La médecine de l’Antiquité voit l’individu malade et ne reconnaît pas le handicap. Les classifications C.I.H. et C.I.F. de l’O.M.S. ont modifié notre manière de voir le handicap. La loi du 11 février 2005 utilise les termes de limitation d’activité et de restriction de participation issus de la C.I.F. La grille G-MAP évalue les limitations d’activité et la restriction de participation par la mesure de l’interaction entre les dimensions individuelles et environnementales (facilitatrices / obstacles) et rend compte ainsi de la situation de handicap. Le type de travail, de formation, le fait de côtoyer au quotidien les personnes handicapées, sont les facteurs principaux modifiant les attitudes des professionnels ou des étudiants. L’évolution et la modification de l’organisation du travail limitent parfois négativement la participation des travailleurs handicapés à la vie de l’entreprise. Une ergonomie logicielle adaptée semble être une voie prometteuse pour faciliter l’insertion. L’accompagnement des professionnels d’un ESAT portant sur la compréhension des troubles cognitifs et comportementaux facilite la vie relationnelle au sein de l’entreprise adaptée. La vision socialisée et politique du handicap impulsée par la loi du 11 février 2005 a considérablement amélioré l’image de celui-ci dans l’ensemble de la population. Nous sommes peut-être, en 2012, dans la phase du balancier de l’histoire qui pointe surtout vers l’aspect social du handicap. Ce changement mérite d’être accompagné, mais il ne doit pas se faire au détriment de la prise en compte des problèmes de santé sous-jacents et plus particulièrement de ce qui concerne le handicap cognitif ou psychique. / The traditional medical model views patients as ‘illnesses’ and does not recognize disability. The WHO’s classifications of handicap (ICH) and function (ICF) have changed our understanding of disability. The Disability Discrimination law of 11th February 2005 introduced the concepts of activity and participation. G-MAP is an assessment tool that looks at the limitations of activity and participation by measuring the interaction between individual and environmental dimensions (facilitators/obstacles) that contribute to the handicap. The main factors that help modify the attitudes of professionals and students, are the nature of their work, training and being around people with disabilities in their daily lives. The evolution and development of an organisation sometimes negatively impacts on the participation of employees with a disability. Adapted software ergonomics seems to be a promising way forward, appearing to change the attitudes towards disabled employees. The use of specific work supporting activities for the professionals of an establishment that employs disabled people (ESAT) to develop an understanding of cognitive and behavioural disorders facilitates good employee relationships within the company. The socialised and political vision of disability engendered by the law of February 2005 has considerably improved the image of disabled people in the general population. This change has to be facilitated, but it should not be detrimental to the awareness of underlying health problems. In 2012 we are the point where the pendulum is starting to swing towards the social aspect of disability.

Le syndrome post-commotionnel (SPC) a été proposé comme un ensemble de symptômes qui peuvent apparaître après un traumatisme crânien léger (TCL) et perdurer des semaines, des mois, parfois jusqu’à un an, engendrant des conséquences importantes sur la vie quotidienne. Des débats entourent la définition et même l’existence du SPC. Ils portent notamment sur la spécificité des symptômes (qui peuvent apparaître dans d’autres conditions, ou chez des personnes non traumatisées), et sur la validité des outils diagnostiques qui restent très hétérogènes. La relation entre le SPC et le stress post-traumatique (SSPT) est également au cœur de ces questionnements. La cohorte PERICLES permet d’apporter un éclairage sur ces questions. Elle porte sur un groupe de patients TCL ainsi qu’un groupe de patients avec un traumatisme léger dont le siège n’est pas la tête. Dans un premier temps, nous avons étudié la spécificité des symptômes en comparant leur prévalence et évolution entre ces deux groupes de patients. Nous avons ensuite tenté de définir un critère diagnostique à partir des symptômes spécifiques à l’aide de tests de corrélations et analyse factorielle. Les facteurs prédictifs du SPC ont été évalués à partir de ce critère, à l’aide d’une régression logistique. Dans un deuxième temps, les facteurs prédictifs des SPC et SSPT ont été évalués et comparés, tout comme la proximité des symptômes des deux syndromes, à l’aide d’une analyse des correspondances multiples. Huit symptômes ont été sélectionnés comme spécifiques au TCL. Un critère diagnostique a pu être défini à partir de ces huit symptômes. Le TCL a été observé facteur prédictif du SSPT (OR = 4,47 [2,38 - 8,40]) mais pas du SPC. Enfin, les symptômes du SPC présentaient une forte proximité avec les variables de la dimension « hypervigilance » du SSPT. Ainsi, le SSPT apparaît être plus spécifique du TCL que le SPC. Les variables du SPC semblent être proches de celles du SSPT. Il semblerait que le stress lié au traumatisme joue un rôle plus important dans la persistance de symptômes à long terme que le mécanisme subi par le cerveau. / Postconcussion syndrome (PCS) has been proposed as a set of symptoms that may occur after mild traumatic brain injury (MTBI) and continue for weeks, months, sometimes up to a year, causing a significant impact on daily life. Debates surround the definition and even the existence of the PCS. They relate in particular to the specific symptoms (which may occur in other conditions or in people not traumatized), and the validity of diagnostical tools that are very heterogeneous. The relationship between the SPCS and post-traumatic stress disorder (PTSD) is also at the heart of these questions. The Pericles cohort can shed light on these issues. It focuses on a group of MTBI patients and a group of patients with mild trauma not related to the head (controls). At first we studied the specificity of symptoms by comparing their prevalence and evolution between these two groups of patients. We then attempted to define a diagnostical test based on specific symptoms using test correlations and factor analysis. Predictors of PCS were evaluated from this test, using logistic regression. In a second step, predictors of PCS and PTSD were assessed and compared, as well as the proximity between symptoms of both syndromes using a multiple correspondence analysis.Eight symptoms were selected as specific to MTBI. A diagnostic criterion has been defined from the eight symptoms. TCL was observed as a predictor of PTSD (OR = 4.47 [2.38 to 8.40]) but not of PCS. Finally PCS symptoms showed strong proximity with variables from "hypervigilance" PTSD dimension. Thus, PTSD appears to be more specific to MTBI than PCS. PCS variables appear to be similar to those of PTSD. It seems that the stress linked to the trauma plays a more important role in the persistence of long-term symptoms than the mechanism of the brain.

of diploma thesis: Objective In the Czech republic there is no normative data for Purdue pegboard test in any reprezentative group of people. First goal of this diploma thesis is to determine basic normative data Purdue pegboard test in not representative sample of people with traumatic brain injury at the age of 22-40 years in chronic phase. Second goal is to determine clinical utility of Purdue pegboard test in this clinical population group of people. The Student t-test and ambiguity proportion was used to statistic analyse the hypothesis. As a graphic processing was choosen the linear equation with the image of the Gaussian curve. There are analysed 3 case studies about people with traumatic brain injury to accomplish second goal. There is no significant difference in Purdue pegboard test score in employed and unemployed people with traumatic brain injury, equally to women and men with traumatic brain injury. There is evidence, that age influence score of Purdue pegboard test in men with traumatic brain injury, but not in women with traumatic brain injury. There are presented basic norms of Purdue pegboard test in people with traumatic brain injury in standard and percentile scale in this thesis. Normative data in people with traumatic brain injury makes easier to work with this clinical...

Previous studies have found that poor effort can significantly impact psychometric performance by Traumatic Brain Injury (TBI) patients. So far, this impact has been relatively well studied in attention and memory. However, this is not the case for visual perception functions. Thus, the goal of this study was to determine to what extent TBI severity affect visual perception after controlling for effort. Results showed that mild TBI good effort group did not differ from a demographically matched control group. In contrast, a mild TBI poor effort group, a moderate-severe TBI group and a right hemisphere cerebro-vascular (CVA) group performed worse than the mild TBI good effort group and the control group. The results suggest a dose response relationship between injury severity and visual perception performance. After controlling for effort, results indicated that moderate-severe TBI, but not mild TBI, has long lasting effects on visual perception. Clinical implications are discussed.

Prospective memory is very important for everyday life of all people. Patients with brain injury often have problems with their prospective memory, the ability to remember what they would like to do in the future and to remember that intention at the right time. Rehabilitation and prospective memory training differ in the literature as well as its efficacy results. The thesis deals with the issues of prospective memory and its rehabilitation with people with acquired brain injury. The aim of this work is to create a summary of existing knowledge about prospective memory, design and implementation of prospective memory training program with patiens with acquired brain injury. The theoretical part of the thesis summarizes basic information about prospective memory, its division and overview of theories. An important part of the thesis is an overview of methods for prospective memory diagnostics. The end of the theoretical part of thesis is about different ways of rehabilitation prospective memory. The empirical part presents the theoretical basis for the cognitive rehabilitation. On this basis a prospective memory training was developed and subsequently tested with patiens with acquired brain injury. The thesis also includes a detailed manual for prospective memory training. The effectivness of the...

<p>Intricate neural circuits underlie all brain functions. However, these neural circuits are highly dynamic. The ability to change, or the plasticity, of the brain has long been demonstrated at the level of isolated single synapses under artificial conditions. Circuit organization and brain function has been extensively studied by correlating neuronal activity with information input. The primary visual cortex has become an important model brain region for the study of sensory processing, in large part due to the ease of manipulating visual stimuli. Much has been learned from studies of visual cortex focused on understanding the signal-processing of visual inputs within neural circuits. Many of these findings are generalizable to other sensory systems and other regions of cortex. However, few studies have directly demonstrated the orchestrated neural-circuit plasticity occurring during behavioral experience. </p> <p>It is vital to measure the precise circuit connectivity and to quantitatively characterize experience-dependent circuit plasticity to understand the processes of learning and memory formation. Moreover, it is important to study how circuit connectivity and plasticity in neurological and psychiatric disease states deviates from that in healthy brains. By understanding the impact of disease on circuit plasticity, it may be possible to develop therapeutic interventions to alleviate significant neurological and psychiatric morbidity. In the case of neural trauma or ischemic injury, where neurons and their connections are lost, functional recovery relies on neural-circuit repair. Evaluating whether neurons are reconnected into the local circuitry to re-establish the lost connectivity is crucial for guiding therapeutic development.</p> <p>There are several major technical hurdles for studies aiming to quantify circuit connectivity. First, the lack of high-specificity circuit stimulation methods and second, the low throughput of the gold-standard patch-clamp technique for measuring synaptic events have limited progress in this area. To address these problems, we first engineered the patch-clamp experimental system to automate the patching process, increasing the throughput and consistency of patch-clamp electrophysiology while retaining compatibility of the system for experiments in <i>ex vivo </i>brain slices. We also took advantage of optogenetics, the technology that enables control of neural activity with light through ectopic expression of genetically encoded photo-sensitive channels in targeted neuronal populations. Combining optogenetic stimulation of pre-synaptic axonal terminals and whole-cell patch-clamp recording of post-synaptic currents, we mapped the distribution and strength of synaptic connections from a specific group of neurons onto a single cell. With the improved patch-clamp efficiency using our automated system, we efficiently mapped a significant number of neurons in different experimental conditions/treatments. This approach yielded large datasets, with sufficient power to make meaningful comparisons between groups.</p> <p>Using this method, we first studied visual experience-dependent circuit plasticity in the primary visual cortex. We measured the connectivity of local feedback and recurrent neural projections in a Fragile X syndrome mouse model and their healthy counterparts, with or without a specific visual experience. We found that repeated visual experience led to increased excitatory drive onto inhibitory interneurons and intrinsically bursting neurons in healthy animals. Potentiation at these synapses was absent or abnormal in Fragile X animals. Furthermore, recurrent excitatory input onto regular spiking neurons within the same layer remained stable in healthy animals but was depressed in Fragile X animals following repeated visual experience. These results support the hypothesis that visual experience leads to selective circuit plasticity which may underlie the mechanism of visual learning. This circuit plasticity process is impaired in a mouse model of Fragile X syndrome. </p> <p>In a separate study, in collaboration with the laboratory of Dr. Gong Chen, we applied the circuit-mapping method to measure the effect of a novel brain-repair therapy on functional circuit recovery following ischemic injury, which locally kills neurons and creates a glial scar. By directly reprogramming astrocytes into neurons within the region of the glial scar, this gene-therapy technology aims to restore the local circuit and thereby dramatically improve behavioral function after devastating neurological injury. We found that direct reprogramming converted astrocytes into neurons, and importantly, we found that these newly reprogrammed neurons integrated appropriately into the local circuit. The reprogramming also improved connections between surviving endogenous neurons at the injury site toward normal healthy levels of connectivity. Connections formed onto the newly reprogrammed neurons spontaneously remodeled, the process of which resembled neural development. By directly demonstrating functional connectivity of newly reprogrammed neurons, our results suggest that this direct reprogramming gene-therapy technology holds significant promise for future clinical application to restore circuit connectivity and neurological function following brain injury.</p>

O presente trabalho contempla o estudo das principais alterações macroscópicas e anatomopatológicas do sistema nervoso central (SNC) encontradas em animais que morreram em decorrência de traumatismo cranioencefálico (TCE). Além da determinação das lesões de golpe, contragolpe e padrão de lesão axonal difusa encontradas nesse tipo de trauma. Inicialmente realizou-se a necropsia dos animais com devido registro fotográfico, descrição das lesões macroscópicas e coleta de material para processamento histológico de rotina e confecção das lâminas coradas em hematoxilina-eosina (HE) para avaliação histopatológica. A imunohistoquímica foi realizada a partir dos mesmos segmentos utilizados nas lâminas de HE, com os anticorpos anti-proteína precursora do &#946;-amiloide (APP), para determinação da lesão axonal, e anti-GFAP e anti-vimentina para avaliação de respostas do tecido nervoso à injúria, como astrocitose e astrogliose. Macroscopicamente as principais lesões observadas caracterizaram-se por lesões focais decorrentes de traumatismo direto, com fraturas de ossos do crânio, laceração de neuroparênquima e contusões. No exame histopatológico as lesões principais caracterizaram-se por hemorragia subdural e em neuroparênquima, congestão, edema tecidual e necrose em variados graus de intensidade e regiões do encéfalo. A lesão axonal foi confirmada pela imunomarcação do &#946;APP que revelou marcação multifocal de axônios tumefeitos formando esferoides axonais, bulbos axonais ou axônios varicosos em alguns casos. Astrocitose, astrogliose e neovascularização foram observados na maioria dos casos através dos anticorpos GFAP e vimentina. Conclui-se no presente estudo que cães e gatos com TCE apresentaram lesões histologicamente caracterizadas por hemorragias multifocais em meninge e neuroparênquima em diversas regiões, além de edema, necrose e congestão, principalmente. A lesão axonal caracterizou-se pela formação de esferoides axonais, bulbos axonais e longos axônios varicosos. Esta característica foi observada em apenas 2 animais deste estudo, e destes apenas um animal (caso 6) apresentou um padrão de lesão axonal traumática difusa, confirmada pela presença de acentuada marcação pelo anticorpo &#946;APP. Adicionalmente, foi observada astrocitose e astrogliose em cinco animais, principalmente das áreas próximas às lesões, avaliadas pelos anticorpos GFAP e vimentina. / The present work contemplates the study of the main macroscopic and anatomopathological changes of the central nervous system (CNS) in animals that died due to traumatic brain injury (TBI). Besides the determination of the coup and countercoup and pattern of diffuse axonal injury in this type of trauma. Initially, the animals were necropsied and photographic recorded and macroscopic lesions were described and collect material for histological processing routine and the preparation of slides in hematoxylin-eosin (HE) staining for histopathological evaluation. Immunohistochemistry was performed from the same segments used in the HE slides, with anti-(&#946;-amyloid precursor protein antibodies (&#946;APP) for determination of axonal lesion, and anti-GFAP and anti-vimentin for evaluation of tissue responses to injury, such as astrocytosis and astrogliosis. Macroscopically, the main lesions observed were focal lesions due to direct trauma, such as skull fractures, neuroparenchyma laceration and contusions. In the histopathological evaluation, the main lesions were characterized by subdural hemorrhage and in neuroparenchyma, congestion, tissue edema and necrosis in varying degrees of intensity and regions of the encephalon. The axonal injury was confirmed by (&#946;APP immunostaining that revealed multifocal labeled of swellings axons forming axonal spheroids, axonal bulbs or varicose axons in some cases. Astrocytosis, astrogliosis and neovascularization were observed in most cases through the antibodies GFAP and vimentin. In conclusion the present study demonstrate that dogs and cats with TBI presented histologically lesions characterized by multifocal hemorrhage in meninge and neuroparenchyma in different areas, as well as edema, necrosis and congestion, mainly. Axonal injury was determined by axonal swelling, bulbs and varicosities. This characteristic was observed in only 2 animals in this study, and only one of those (case 6) presented pattern of diffuse traumatic axonal injury, confirmed by accentuated (&#946;APP labeling. Addiotionally, astrocytosis and astrogliosis was observed in five animals, mainly in areas close to lesions, evaluated by GFAP and vimentin antibodies.

Adenosine Triphosphate (ATP) can be released as a signal between cells in an autocrine and paracrine manner that binds purinergic receptors. Highly conserved, purinergic receptors expressed on the cell surface of neurons and astrocytes are capable of being activated across eight orders of magnitude from hundreds of nanomolar ATP to millimolar. Genetically encoded fluorescent protein biosensors have been used to detect ATP outside the cell, but a high affinity extracellular ATP sensor is required to study the ATP signaling dynamics from nanomolar to micromolar magnitudes. Previously, our lab developed a first generation sensor of extracellular ATP called ECATS1 (Conley et al.). To develop an improved sensor, we caried out site-directed mutagenesis of the sensor's ATP binding site and identified a mutant that exhibited a 4-fold increase in ATP binding affinity in solution. We then optimized the membrane-tethering of the sensor to achieve the 4-fold increase in extracellular ATP binding affinity when measured on live cell.s This second-generation sensor was dubbed ECATS2. As a proof-of-concept application, we sought to detect ATP release from cells using <i>in vitro</i> models of edema. We subjected HEK293A cells to hypo-osmotic shock (HOS), revealing ATP release at micromolar levels. Then we tested HOS in cultured cortical astrocytes, also revealing micromolar ATP release. However, when we tested neuron-astrocyte co-cultures, we no longer observed ATP release in response to HOS. Interestingly, this implies that co-culture either entirely prevented ATP release from astrocytes or dampened it into the nanomolar range below the limit of ECATS2 detection. Thus, we have validated the development of a higher affinity, second-generation sensor and used it to discover that ATP release from astrocytes after HOS can be affected by the presence of neurons. <br>

La cognition sociale, i.e. notre capacité à attribuer des états mentaux à autrui et à identifier ses émotions, est souvent perturbée dans certaines pathologies telles que le traumatisme crânien (TC). Cette capacité est traditionnellement évaluée à l’aide de tâches sous format « papier-crayon » n’impliquant pas le participant dans une situation d’interaction sociale. Pourtant, la cognition sociale est fondamentale dans nos interactions sociales car elle nous permet de comprendre le discours et le comportement d’autrui. Ainsi, dans ce travail de thèse, nous avons évalué les capacités d’attribution d’états mentaux et de reconnaissance émotionnelle de personnes ayant subi un TC à l’aide de tâches les impliquant activement dans une situation de communication (tâche de communication référentielle et tâche EViCog), ce qui n’a jamais été fait dans cette pathologie. La tâche EViCog (Evaluation de la cognition sociale en interaction virtuelle), créée pour cette étude, permet d’avoir des conversations audio-visuelles avec des humains virtuels, qui expriment des émotions et produisent du discours nécessitant d’inférer leurs états mentaux. Les résultats ont montré que les difficultés des personnes TC étaient encore plus importantes pour la tâche en situation d’interaction (tâche EViCog) par rapport à des tâches traditionnelles au format « papier-crayon ». Par ailleurs, en situation d’interaction, les performances de cognition sociale semblent dépendre en partie des capacités mnésiques (mémoire autobiographique et du contexte), ainsi que des fonctions exécutives, alors que pour les tâches traditionnelles, les performances ne seraient expliquées que par certaines capacités exécutives. / Social cognition, i.e. the ability to attribute mental states to others and to identify emotions, is often impaired in various pathologies, such as traumatic brain injury (TBI). This ability is traditionally assessed with “paper-and-pencil” tasks that do not involve the participant in a social interaction situation. However, social cognition is central in our daily social interactions, as it helps us understand others’ speech and behavior. Thus, in this study, we assessed mental state attribution and emotion recognition abilities of TBI participants, using tasks that involve the participant in a communication situation (referential communication task and EViCog task). The EViCog task (social cognition evaluation in virtual interaction), designed for this research, provides audio-visual conversations with virtual humans, which express emotions and produce speech requiring mental state inference. The results showed that the difficulties of the TBI participants were even more important for the task in interaction situation (EViCog task) compared to traditional tasks in paper-and-pencil format. Moreover, in interaction situation, social cognition performance seemed to rely on mnemonic abilities (autobiographical memory and context memory), and on executive functions, while for traditional tasks, performances were only explained by some executive abilities.

L’inhalation de monoxyde d’azote (NO) est l’une des thérapies les plus utilisées en réanimation néonatale. Cependant, peu de données sont disponibles sur l’impact de l’inhalation de NO sur le développement cérébral et le devenir des enfants prématurés. Nous avons étudié l’impact du monoxyde d’azote inhalé (iNO) sur le cerveau en développement chez le rongeur. Des portées et leur mère sont placés sous 5 à 20 ppm de NO de la naissance (P0) jusqu’au 7ème jour de vie postnatal (P7). Les animaux exposés au NO présentent une augmentation transitoire de l’angiogenèse et de la myélinisation, sans incidence sur les fonctions cognitives à l’âge adulte. L’exposition au NO est associée à une prolifération d’oligodendrocytes immatures et à une maturation anticipée des formes myélinisantes. Les rôles du NO endogène et du couple VEGF/VEGFR2 dans ces effets ont été évalués via l’injection d’antagonistes : LNAME pour inhiber les NOS, SU-5416 comme antagoniste du VEGFR2. Dans les deux cas, l’inhalation de NO corrige les anomalies de myélinisation et d’angiogenèse induites par ces inhibiteurs. Nous avons soumis des ratons à une agression excitotoxique par injection intracérébrale d’agonistes du glutamate. A P10 les rats exposés au iNO avant l’injection présentent des lésions moins importantes ; ainsi qu’un diminution de densité des microglies activées et des astrocytes. Cet effet neuroprotecteur est associé à une régulation de sous-unités des récepteurs au glutamate dès P5. Cet effet transcriptionnel semble lié à la modulation de la signalisation pCREB/Akt. Les effets à distance du iNO sont liés à un transport réversible endovasculaire du NO. In fine, du NO est delivré à la cellule et les concentrations intracellaires de cGMP augmentent d’un facteur 5. Plusieurs facteurs de transcription sont régulés : PDGFR-α, Sema3F, les sous-unités des récepteurs au glutamate, Thrombospondine-1. Cette dernière est un antagoniste naturel de la signalisation NO-cGMP. L’injection de ABT-510, agoniste de TSP-1, abolit les effets du iNO, confirmant l’hypothèse que les effets à distance reposent sur la signalisation NO-Guanylate Cyclase soluble-cGMP. Au total, nous avons démontré que le iNO est transporté de manière réversible et delivré au cerveau en développement. Il y exerce un effet pro-angiogénique et pro-myélinisant, via une signalisation cGMP, régulée par la thrombospondine-1. Plus encore, l’exposition prophylactique au iNO diminue l’impact d’une agression excitotoxique. Ce qui augure de propriétés neuroprotectrices prometteuses en néonatalogie, et au delà. / Inhaled nitric oxide (iNO) is one of the most promising therapies used in neonates, but littlei known about its effect on the developing brain. We explored the effects of iNO on developing brain in rodent pups, and pathway involved in iNO remote effects. Rat pups and their mothers were placed in a chamber containing 5 to 20 ppm of NO for 7 days after birth. Extensive serum analysis, immunochemistry, RT-PCR analysis, were performed Neonatal exposure to iNO was associated with a transient increase in central nervous system myelination and angiogenesis in rats, without any behavioral consequences in adulthood. Exposure to iNO was associated with a proliferative effect on immature oligodendrocytes and a subsequent promaturational effect. The role of endogenous NO in myelination was investigated in animals treated with the nitric oxides synthase inhibitor N-nitro-L- arginine methyl ester (L-NAME) in the neonatal period ; this led to protracted myelination defects and subsequent behavioral deficits in adulthood. These effects were reversed by rescuing L-NAME-treated animals with iNO. We challenged animals with intracranial injection of glutamate agonists. At P10, rat pups exposed to iNO exhibited a significant decrease of lesion size in both the white matter and cortical plate compared to controls. Microglia activation and astrogliosis were found significantly decreased in NO-exposed animals. This neuroprotective effect was associated with a significantdecrease of several glutamate receptor subunits expression at P5. iNO was associated with an early(P1) downregulation of pCREB/pAkt expression and induced an increase in pAkt proteinconcentration in response to excitotoxic challenge (P7) Those effects were related to a release of NOto the cells, and a rise of cGMP intracellular concentration. Several transcription factor wereregulated, namely PDGFR-α, Sema3F, TSP-1, glutamate receptors subunits, Thrombospondin-1. Thelatter was responsible for NO pathway regulation, and injection of TSP-1 agonist (AbT-510) abolishediNO remote effects. iNO remote effects are not associated VEGF concentration increase nor VEGFRstimulation, as VEGF-R antagonist SU54-16 failed to abolish iNO effects on angiogenesis andmyelination. Moreover iNO reverses severe myelination and angiogenesis defects induced by this SU-5416. Thus, we demonstrate transport and considerable remote effect of iNO on angiogenesis andmyelination in rodents. Those effects are related to an enhancement of cGMP pathway, regulated byTSP-1, and transcriptional effects. Moreover we described and investigated the neuroprotectiveeffect of iNO in neonatal excitotoxic-induced brain damage. These data point to potential newavenues for neuroprotection in human perinatal brain damage.