No description available.

La sclérose latérale amyotrophique (SLA) est une maladie neurodégénérative due à une dégénérescence des motoneurones. Plus de 40 mutations du gène TARDBP ont été identifiées chez des patients SLA. Les défauts biochimiques de ces mutations étant encore inconnus, les modèles animaux sont présentement la seule mesure possible d’un phénotype. Pour étudier les conséquences physiopathologiques d’une de ces mutations, nous avons développé deux lignées transgéniques de poisson zébré, exprimant le gène humain TARDBP soit de type sauvage, soit avec la mutation G348C liée à la SLA, sous le contrôle d’un promoteur de choc thermique. Ces lignées ont été étudiées sur trois générations, après avoir établi un protocole de choc thermique induisant une expression ubiquitaire du transgène. Les embryons transgéniques de la génération F2 de la lignée exprimant la mutation développent un phénotype moteur suite à un choc thermique de 38.5°C pendant 30 minutes lorsque les embryons sont à 18 heures post-fertilisation. 60% des embryons ont une réponse anormale au toucher. De plus, une réduction de 28% de la longueur de pré-branchement des axones des motoneurones est observée. Ces résultats indiquent que notre lignée exprimant la protéine mutante TDP-43 est un modèle génétique de la SLA prometteur, qui ouvre des perspectives pour la compréhension de la physiopathologie de la maladie et la découverte de molécules thérapeutiques. / Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease due to motoneurons degeneration. More than 40 mutations of the gene TARDBP, coding for the protein TDP-43 have been found in ALS patients. As the biochemical defects of these mutations are not known, in vivo models are currently the only windows onto the pathology. To study the pathophysiological consequences of one of these mutations, we have generated two stable zebrafish transgenic lines, expressing the human gene TARDBP, either the wild-type version, or the G348C mutated version linked to ALS, under the control of a heat shock promotor. These lines were studied for three generation, after establishing a heat shock protocol sufficient to induce a ubiquitous expression of the transgene. The transgenic embryos of the F2 generation of the line expressing the mutant protein develop a motor phenotype after a 38.5°C heat shock for 30 minutes when the embryos are 18 hours post-fertilization. 60% of these embryos have an abnormal touch escaped evoked response, and a 28% reduction of the pre-branching axonal length of the motoneurons axons. These results indicate that our line expressing the mutant TDP-43 protein is a promising genetic model of ALS, opening perspectives for the pathophysiological understanding of the disease, and the discovery of new therapeutics.

Orientador: Alexandre Leite Rodrigues de Oliveira / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-12T20:59:38Z (GMT). No. of bitstreams: 1 Zanon_RenataGraciele_D.pdf: 7966608 bytes, checksum: 79a55fb4c6226868859fa3daefc0adb2 (MD5) Previous issue date: 2009 / Resumo: O complexo de histocompatibilidade principal de classe I (MHC I) é uma molécula originalmente do Sistema Imunológico. A presença desses elementos no Sistema Nervoso Central (SNC) parece estar relacionada a diferentes funções, apresentando papel importante no refinamento sináptico durante o desenvolvimento do SNC e sendo fundamental no processo de eliminação sináptica após uma lesão nervosa no adulto. No intuito de investigarmos os processos de plasticidade sináptica e reatividade glial no microambiente da medula espinal foram utilizados dois imunomoduladores empregados no tratamento da Esclerose Múltipla, o interferon beta (IFN beta) e o acetato de glatirâmer (AG). O IFN beta, potencialmente capaz de influenciar a expressão de MHC I, foi utilizado in vivo, juntamente com axotomia periférica e in vitro, enquanto o AG foi utilizado para testes in vitro. Para tanto, camundongos C57BL/6J foram tratados com 10.000 UI de IFN beta durante 2 semanas, antes e depois da transecção unilateral do nervo isquiático. Os camundongos foram submetidos à eutanásia e suas medulas espinais lombares processadas para imunohistoquímica (anti-MHC I, sinaptofisina, GFAP - glial fibrillary acidc protein, ezrina e iba1), hibridação in situ (sondas para GFAP e microglobulina beta-2), Western blotting (GFAP e MHC I) e microscopia eletrônica de transmissão. Grupos axotomizados, placebo e não tratado foram utilizados como controles. Adicionalmente ao estudo in vivo, foram estabelecidas culturas purificadas de astrócitos para o tratamento com diferentes doses de IFN beta (0, 100, 500 ou 1000 UI/ml) ou AG (0, 1.2, 2.5 ou 5.0µg/ml) durante 5 dias. As culturas tratadas com IFN beta foram submetidas à imunohistoquímica para MHC I, ezrina, GFAP, enquanto nas culturas tratadas com AG foi realizado o estudo para verificar a reatividade e proliferação através da marcação anti-GFAP e DAPI (para identificação dos núcleos das células). In vivo, os resultados mostraram um aumento do RNAm e da expressão protéica para MHC I após axotomia, sendo que este incremento foi maior no grupo tratado com INF. Observou-se a intensificação da expressão das proteínas que expressam a reatividade astrocitária, GFAP e ezrina, concomitantemente à diminuição da imunomarcação para sinaptofisina, especialmente no grupo tratado. O tratamento realizado não influenciou a reatividade da microglia. A análise do material in vitro também mostrou, após o tratamento com IFN beta, um aumento da expressão de MHC I e GFAP, bem como de ezrina. As doses que mais estimularam a elevação da expressão dos marcadores estudados foram as de 500 e 1000 UI/ml. Dado que não ocorreu para o tratamento com o acetato de glatirâmer. Assim, o tratamento com AG não alterou o nível de reatividade astrocitária, apesar de estimular a proliferação celular. A ultraestrutura das sinapses mostrou uma intensa retração dos terminais pré-sinápticos em contato com os motoneurônios alfa, induzida pela axotomia mais o tratamento com IFN beta. Em conjunto, esses resultados reforçam a importância da expressão de moléculas de MHC I em resposta à lesão nervosa e seu papel como mecanismo de comunicação entre neurônio e glia, além de reafirmar que os astrócitos são elementos ativos no processo de plasticidade sináptica. / Abstract: The class I main histocompatibility complex (MHC I) is a molecule originally restricted to Immune System. The presence of such element in the Central Nervous System (CNS) may indicate other functions, including an important role in the synaptic refinement during the development of the CNS as well as in the synaptic elimination process after a peripheral nerve injury in the adult. To investigate the synaptic plasticity and glial reactivity in the spinal cord, two immunomodulators, widely used for treating Multiple Sclerosis, were applied, namely the Interferon beta (IFN beta) and the glatiramer acetate (GA). The IFN beta was used in order to upregulate the MHC I expression in vivo, after a peripheral axotomy, and also in vitro. GA treatment was only used for in vitro experiments. C57BL/6J mice were injected with 10,000 IU of IFN beta for 2 weeks, before and after the nerve transection. The animals were sacrificed and the lumbar spinal cords were processed for immunohistochemistry (MHC I, synapthophysin, GFAP, ezrin and Iba-1 antisera), in situ hybridization (beta 2 immunoglobulin, a component of the MHC I molecule, and GFAP), Western blotting (GFAP and MHC I) and transmission electron microscopy. Placebo and non-treated axotomized groups were used as controls. Additionally to the in vivo study, primary cultures of astrocytes were established and treated during five consecutive days with different doses of IFN beta (0, 100 IU, 500 IU and 1000 IU/ml). In this case, some cultures were treated with GA (0, 1.2, 2,5 and 5.0 µg/ml). INF treated cultures were processed for immunocitochemistry (MHC I, GFAP and ezrin antisera). GA treated cultures were evaluated with anti-GFAP antibody and cell proliferation was accessed with DAPI staining. In vivo, the results showed an upregulation of MHC I mRNA and protein expression after axotomy, that was stronger in the IFN treated group. We observed a greater GFAP and ezrin expression, coupled with a decrease of synapthophysin immunoreactivity. Such alterations were more evident in the IFN treated group. Interestingly, the IFN beta treatment did not interfere in the microglial reactivity. The in vitro analysis also showed a sharp upregulation of MHC I, GFAP and ezrin, mostly when the cultures were subjected to 500 and 1000 IU/ml of IFN beta. Regarding the GA treatment, the results showed that treatment did not change the level of astroglial reactivity despite stimulating cellular proliferation. The ultrastructural analysis of synapses showed a larger pruning of presynaptic terminals in contact with alpha motoneurons, induced by axotomy plus IFN beta treatment. Together, our results reinforce the importance of the MHC I expression as a response to nerve injury and its role as a communication mechanism between neurons and surrounding glial cells. Furthermore, the present data confirm that astrocytes are active elements during the synaptic plasticity process. / Doutorado / Anatomia / Biologia Celular e Estrutural

Made available in DSpace on 2014-07-29T15:08:23Z (GMT). No. of bitstreams: 1 dissertacao fabio b rodrigues.pdf: 2707992 bytes, checksum: 8e5e7c8d4e6f975bb6e22b0b760695a6 (MD5) Previous issue date: 2010-04-23 / From motoneurons models (MN) of complex geometry and structure, able to reproduce the characteristics of a real motoneuron, the aim of this work is to verify the functional differences between proximal and distal synapses, investigating the nonlinearities in passive equivalent dendrites of motoneuron models and to study the influence of persistent calcium channels type L (Cav1.3), present in the dendrites, in the synaptic amplification. The original models developed by Vieira and Kohn (2007), implemented in C++, were expanded. This allowed to accomplish tests in order to verify the functional differences of synapses that occur near the soma and along of the dendrites. Persistent channels of calcium (CaV1.3) were modeled in dendrites and the influence of these channels in the amplification of the synaptic currents along the dendrites was verified. Finally, the nonlinearities of responses degree in the dendritic tree for different synaptic activation was evaluated. In order to verify the functional differences between proximal and distal synapses pure sinusoids were injected in different dendritic compartments of the models. The results showed attenuation at higher frequencies and the cutoff frequency is smaller as we move along the dendrites far from the soma. The influence of persistent calcium channels was verified comparing the functional differences between proximal and distal synapses along of the soma, with and without them. The initial results showed a notable amplification of synaptic activation. Nonlinear interactions were evaluated using sinusoids synaptic inputs with different frequencies in two or more equivalent dendrites in different compartments. The frequency spectrum of the current between the initial segment and the soma was analyzed by comparing the peak amplitude of harmonics and spurious bands with the peak amplitude of the fundamental frequency of smaller amplitude: the smaller these differences were, greater was degree of nonlinearity between synaptic activation in different dendritic segments. The results showed a high degree of nonlinearity between the dendrites. The cases where the synaptic conductance was varied showed greater degree of nonlinearity in relation to the cases in which the synaptic current was varied. / A partir de modelos de motoneurônios (MN) de geometria e estrutura complexa e capacidade de reproduzir as características de um motoneurônio real, este trabalho tem como objetivos verificar as diferenças funcionais entre sinapses proximais e distais, investigar as interações não lineares de ativações sinápticas e estudar a influência dos canais persistentes de Ca2+ tipo L existentes nos dendritos na amplificação sináptica. Para isso, os modelos originais desenvolvidos por Vieira e Kohn (2007), implementados em C++, foram expandidos. Isso possibilitou a realização de testes que verificaram as diferenças funcionais de sinapses que ocorrem em segmentos dendríticos distintos. Foram modelados canais de cálcio tipo L (CaV1.3) nos dendritos, verificando a influência destes na amplificação das correntes sinápticas e avaliando o grau de não linearidade da arborização dendrítica para diferentes ativações sinápticas. A verificação das diferenças funcionais entre as sinapses proximais e distais foi realizada, pela injeção de senoides puras em diferentes compartimentos dendríticos do modelo. Os resultados mostraram atenuações mais intensas nas altas frequências e frequência de corte mais baixa em compartimentos dendríticos mais distantes do soma. A influência dos canais persistentes de cálcio foi verificada comparando as diferenças funcionais entre sinapses proximais e distais ao soma com e sem os canais de cálcio persistentes. Os resultados apontam amplificação da ativação sináptica. As interações não lineares foram avaliadas aplicando potenciais senoidais pós-sinápticos com frequências primas entre si, em dois ou mais dendritos equivalentes simultaneamente e em compartimentos dendríticos diferentes. O espectro de frequência da corrente efetiva foi analisado, comparando a amplitude do pico das harmônicas e das raias espúrias com a amplitude do pico da frequência fundamental de menor amplitude: quanto menores estas diferenças maior o grau de não linearidade entre as ativações sinápticas em segmentos dendríticos distintos. Os resultados sugerem um alto grau de não linearidade entre os dendritos. Notou-se que, nas situações, quando variou-se a condutância sináptica, maior foi o grau de não linearidade em relação aos casos em que variou-se a corrente sináptica, sugerindo influência do potencial de membrana que introduz não linearidades na somação de correntes sinápticas.

Submitted by Erika Demachki (erikademachki@gmail.com) on 2015-10-21T20:40:31Z No. of bitstreams: 2 Dissertação - Evlyn de Jesus Fernandes - 2014.pdf: 2834444 bytes, checksum: d4b45f976a00cc4ad236b991042227bc (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Erika Demachki (erikademachki@gmail.com) on 2015-10-21T20:41:42Z (GMT) No. of bitstreams: 2 Dissertação - Evlyn de Jesus Fernandes - 2014.pdf: 2834444 bytes, checksum: d4b45f976a00cc4ad236b991042227bc (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-10-21T20:41:42Z (GMT). No. of bitstreams: 2 Dissertação - Evlyn de Jesus Fernandes - 2014.pdf: 2834444 bytes, checksum: d4b45f976a00cc4ad236b991042227bc (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-12-01 / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / Mathematical motoneurons models are widely used to help researchers to understand the behavior of the neuromuscular system. This study aims to analyze the currents involved in the temporal summation process and in the location-dependent variability of the synaptic input (LDV), using models of type S and type FF motoneurons. The temporal summation was defined as the percentual increase of soma’s depolarization for a train of synaptic inputs. LDV is the variability of discharge patterns in soma for the same input pattern applied in a distal or proximal dendrite. The models developed were parameterized to motoneurons of cats and validated according to protocols described in literature. The dendritic branch was simulated in an active manner, simulating the presence of calcium –L channels in dendrites. A hyperpolarizing current has been identified as the responsible for the decrease of temporal summation in hyppocampal’s neurons, therefore, we also simulated these channels in order to detect their influence on temporal summation. Temporal summation was evaluated applying synaptic currents of 20 Hz, and also applying excitatory post-synaptic currents–shaped (EPSC-shaped) inputs in the dendrite of the model with a pseudo-random distance between each peak. Results indicated that the presence of a hyperpolarizing current, which turns off during membrane depolarization, can counteract the temporal summation effects introduced by the calcium-L channels, minimizing the location-dependent variability for high input values. Minimizing the effects of variability is interesting because similar input pattern applied in a proximal or distal dendrite will cause the same output in soma, standardizing the input/output relationship of the motorneuron. The hyperpolarizing current, however, greatly reduces the excitability of the cell so that it can lead to variability in the output if the distal or proximal input applied is very low, since the distal one will be unable to trigger an action potential. There may be an interaction between the calcium –L channels, the hyperpolarizing current channels and the monoamine levels which will modulate the input/output relationship of the motoneuron. / Modelos matemáticos de motoneurônios são utilizados para auxiliar a compreensão dos fenômenos do sistema neuromuscular. Este estudo tem como objetivo analisar as correntes envolvidas no processo de somação temporal e no fenômeno de variabilidade dependente da localização da entrada sináptica (Location-Dependent Variability - LDV), utilizando para isso modelos de motoneurônios do tipo S e do tipo FF. A somação temporal foi definida como o aumento percentual da despolarização do soma para um trem de entradas sinápticas. A LDV é a variabilidade dos padrões de disparos no soma para mesmos padrões de entrada aplicados em dendritos distais ou proximais. Os modelos construídos foram parametrizados para motoneurônios de gatos e validados de acordo com protocolos descritos na literatura. A arborização dendrítica foi simulada de maneira ativa, com a presença de canais de cálcio do tipo -L nos dendritos. Uma corrente hiperpolarizante tem sido apontada como a responsável pela diminuição da somação temporal em neurônios do hipocampo, de maneira que essa corrente também foi incluída de maneira a detectar sua influência na somação temporal. A somação temporal foi avaliada por meio da aplicação de correntes sinápticas de 20 Hz e também pela aplicação de correntes na forma de correntes excitatórias pós-sinápticas (EPSC – Excitatory Post-Synaptic Currents) nos dendritos dos modelos com espaçamento entre picos pseudo-aleatórios. Os resultados indicaram que a presença de uma corrente hiperpolarizante, que se desativa durante a despolarização da membrana, pode contrabalancear os efeitos da somação temporal introduzida pela corrente de cálcio do tipo -L, minimizando a variabilidade dependente de localização de entrada para valores de corrente de entrada altos. A minimização dos efeitos da variabilidade possibilita que padrões semelhantes de entrada aplicados em um dendrito proximal ou distal produzam uma mesma saída no soma, padronizando a relação entrada/saída do motoneurônio. A corrente hiperpolarizante, no entanto, diminui bastante a excitabilidade da célula, de maneira que pode levar a uma variabilidade entre a entrada distal e a proximal para valores de corrente de entrada muito baixos, já que a entrada distal pode não conseguir levar ao disparo. É possível que haja uma interação entre os canais de cálcio –L, os canais de corrente hiperpolarizante e os níveis de monoaminas que irá modular a relação de entrada/saída do motoneurônio.

No description available.

Les études basées sur l’utilisation de modèles murins de la Sclérose Latérale Amyotrophique (SLA) portent très souvent sur des stades symptomatiques ou pré-symptomatiques. Des données existent cependant montrant que des altérations morphologiques des motoneurones existent aux stades post-nataux, suggérant que la SLA pourrait être une maladie neurodéveloppementale. Dans ce travail de thèse basé sur l’utilisation du modèle murin SOD1G93A de la SLA, nous avons cherché à savoir si dès le développement des réseaux moteurs, des perturbations existaient notamment au niveau de la mise en place des inhibitions, c'est-à-dire au niveau de l’homéostasie chlorure. En effet, nous pensons qu’une mauvaise construction du réseau pendant la vie embryonnaire serait la cause des dysfonctionnements observés lors de la survenue de la SLA. Nos données mettent en évidence que la morphologie des motoneurones est modifiée chez les embryons SOD1G93A au stade de développement E17,5 par rapport aux embryons WT et que cette modification de morphologie induit une hyperexcitabilité. De plus, nous montrons une altération du potentiel d’équilibre des ions chlorure (ECl) due à une modification de l’équilibre de la balance des co-transporteurs NKCC1/KCC2. Enfin, nous avons cherché à savoir si une modification du ECl avait une conséquence fonctionnelle au niveau de la mise en place de l’activité locomotrice exprimée par le réseau spinal lombaire. En conclusion, les travaux de cette thèse démontrent pour la première fois un déficit développemental au niveau du modèle murin SOD1G93A et ouvre des perspectives sur la recherche des mécanismes de compensations opérant jusqu’à la survenue du phénotype de la maladie. / Most studies based on the use of Amyotrophic Lateral Sclerosis (ALS) mouse models focus on symptomatic or presymptomatic periods. However, morphological alterations of ALS motoneurons have been described in post-natal stages, suggesting that ALS could be a neurodevelopmental disease. In this PhD Thesis, based on the use of the SOD1G93A mouse model of ALS, we tried to know if during the embryonic development of the spinal motoneuronal networks, alterations occur particularly at the level of the maturation of GABA/Glycine inhibition, driven by the chloride homeostasis. Indeed, we believe that a wrong construction of the motor network during the embryonic life may be the cause of the troubles observed at the onset of ALS. Our data show that the morphology of motoneurons is altered in E17,5 SOD1G93A embryos compared to WT embryos and that this changes in morphology induced hyperexcitability. In addition, we show an alteration of the equilibrium potential of chloride ions (ECl) due to a modification of the balance of NKCC1/KCC2 chloride co-transporters. Finally, we tried to know if a modification of the ECl had functional consequences in the development of locomotor activity expressed by the lumbar spinal network. In conclusion, the work of this PhD Thesis demonstrates, for the first time, a developmental deficit in the SOD1G93A mouse model and opens new perspectives based on understanding compensatory mechanisms occuring until the appearance of the disease.

L’objectif de ce travail a été d’analyser les effets d’une préparation motrice sur l’activité des motoneurones (MN). Pour cela, des protocoles expérimentaux combinant l’enregistrement unitaire de l’activité des unités motrices des muscles extenseurs du poignet avec des paradigmes de préparation motrice de nature temporelle ont été utilisés chez l’Homme. L’analyse des caractéristiques de la décharge tonique des MN montre un allongement des intervalles inter-potentiels associé à une diminution de leur variabilité durant la période préparatoire, bien avant que la réponse motrice ne soit déclenchée. Ces changements démontrent clairement l’implication de mécanismes inhibiteurs spinaux au cours de la préparation motrice pouvant s’exercer au travers d’interneurones prémotoneuronaux. Il est montré que les modulations d’activité motoneuronales induites par la préparation motrice ne sont ni spécifiques au muscle effecteur de la réponse motrice ni prédictifs de la performance. Il est proposé que l’inhibition exercée sur les MN pendant la préparation motrice constitue un mécanisme généralisé de frein pour retenir le déclenchement prématuré de la réponse motrice, tandis que la diminution de variabilité dans la décharge serait un phénomène de compensation, permettant de produire des forces stables malgré la désactivation motoneuronale. L’implication du niveau motoneuronal dans la préparation motrice montre qu’une information au préalable influence l’état du système moteur jusqu’à son élément le plus périphérique, supportant ainsi le caractère hautement distribué des processus préparatoires. Ce travail a également conduit à proposer l’utilisation de l’entropie approximative pour l’analyse de l’activité motoneuronale, permettant d’éviter les écueils liés aux méthodes classiques d’analyse tout en respectant l’hypothèse d’un codage neuronal temporel. / The aim of this work was to analyze the effects of motor preparation on motoneuron (MN) activity. For this purpose, recordings of wrist extensor muscles motor unit activity were combined with time motor preparation paradigms in Human. Changes in the MN tonic discharge were found to occur during preparatory period, i.e. well before it is time to act. These changes were a lengthening of the mean inter-spike interval associated with a decrease of its variability. These data clearly demonstrate that spinal inhibitory mechanisms are activated during motor preparation and suggest the involvement of premotoneuronal interneurons. The modulations of motoneuronal activity induced by the motor preparation are neither specific to the agonist muscle involved in the motor response nor predictive of the performance. It is assumed that the inhibition acting on the MN during the motor preparation constitutes a general braking mechanism serving to prevent premature motor response, whereas the decrease of discharge variability would be a compensatory phenomenon, allowing to produce an efficient steady force in spite of lower motoneuronal activation. The involvement of the motoneuronal level in motor preparation demonstrates that advance information may influence the state of the motor system, including even the most peripheral motor neurons in the spinal cord, which supports the idea that motor preparation involves highly distributed functional processes. In addition, this work led us to argue in favor of the approximate entropy analysis as a suitable method for analyzing spike trains, allowing to detect changes in the regularity of the time-ordered inter-spikes intervals.

No description available.

La stimulation électrique directe (SED), pour une heure, améliore la régénération de nerfs périphériques chez le rat après la réparation. Cliniquement, ceci augmenterait le temps opératoire, rehaussant les risques de complications périopératoires. Objectif: Cette étude examine si la stimulation électrique transcutanée (SETC) est aussi efficace à améliorer la régénération de nerfs périphériques que la stimulation électrique directe. Méthode: Le nerf sciatique droit de 28 souris a été axotomisé. Une réparation par microsuture est effectuée. Quatre groupes sont étudiés : (1) sham; (2) suture seulement; (3) suture et SED; (4) suture et SETC. La stimulation est appliquée pour 1 heure à 20 Hz. Les souris sont étudiées pour un total de 12 semaines. La récupération sciatique est évaluée aux semaines 0, 1, 2 et aux 2 semaines par la suite par analyse de démarche sur la poutre. Résultats: La cinématique post-récupération démontre un index fonctionnel sciatique et angle de décollement significativement améliorés pour les groupes SED et SETC aux semaines 8, 10 et 12. Conclusions: 12 semaines après l’axotomie du nerf sciatique, la récupération fonctionnelle est significativement améliorée avec la SED et la SETC. Donc, la SETC est aussi bénéfique pour la promotion de la régénération nerveuse et réinnervation musculaire fonctionnelle que la SED. / Direct electrical stimulation (DES) for one hour increases the rate of peripheral nerve regeneration in rats after nerve repair. Clinically, this would lengthen surgery time, increasing risks of perioperative complications. Purpose: This study examines whether transcutaneous electrical stimulation (TCES) is as effective at improving peripheral nerve regeneration as direct electrical stimulation. Methods: The right sciatic nerve was axotomized in 28 mice. End-to-end microsuture repair was undertaken. Four groups were studied: (1) sham; (2) suture only; (3) suture and DES; (4) suture and TCES. Stimulation was applied for 1 hour, at 20 Hz. The mice were studied for a total of 12 weeks. Hind-limb recovery was evaluated at weeks 0, 1, 2 and then every 2 weeks by walking-track analysis. Results: Post recovery kinematic showed significantly improved functional sciatic index and foot-base angles at weeks 8, 10 and 12 for both DES and TCES groups. Conclusions: 12 weeks after sciatic nerve axotomy, functional recovery was improved significantly in both DES and TCES groups. Therefore, TCES is as beneficial in promoting nerve regeneration and functional muscle reinnervation as is DES.