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Sample records for axonal inducida por

  1. Osteomalacia inducida por tumor: hemangiopericitoma rinosinusal

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    Enriqueta M. Serafini

    2013-02-01

    Full Text Available La osteomalacia inducida por tumor es una rara enfermedad del metabolismo óseo caracterizada por el aumento en la excreción de fosfato a nivel renal seguido de hipofosfatemia. Es causada por agentes fosfatúricos producidos por determinados tumores. La resección total del tumor resulta en la completa reversión de las anormalidades bioquímicas, la desaparición de las manifestaciones clínicas y los hallazgos en los estudios por imágenes. Presentamos el caso de un varón de 61 años con cuadro clínico y laboratorio compatibles con osteomalacia oncogénica inducida por tumor mesenquimático de localización rinosinusal. En nuestro caso el diagnóstico histológico correspondió a una neoplasia de tipo vascular: hemangiopericitoma.

  2. Hipoglucemia inducida por carcinoma adrenal

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    Jimena Soutelo

    2013-08-01

    Full Text Available El carcinoma suprarrenal es una neoplasia maligna infrecuente y de mal pronóstico. La presentación clínica más común es originada por la producción hormonal excesiva, mientras que el desarrollo de hipoglucemia sintomática es excepcional. Presentamos el caso de una mujer de 37 años que ingresó al hospital por síntomas de hipoglucemias graves, hipertensión arterial, hipopotasemia y amenorrea secundaria. En el laboratorio se halló hipoglucemia con insulina inhibida y niveles de andrógenos en rango tumoral. La tomografía computarizada (TC de abdomen y pelvis mostró voluminosa formación heterogénea de aspecto sólido sin plano de clivaje con respecto al parénquima hepático e intenso realce con contraste. Luego de la extirpación de la masa retroperitoneal, evolucionó con valores de glucemia y potasemia normales, estabilizó la presión arterial y recuperó los ciclos menstruales.

  3. Alteraciones hepáticas inducidas por la nutrición parenteral

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    J Salas Salvado; A Recaséns Garica

    1993-01-01

    Liver disorders induced by parenteral nutrition Alteraciones hepáticas inducidas por la nutrición parenteral Liver disorders induced by parenteral nutrition Alteraciones hepáticas inducidas por la nutrición parenteral

  4. Agranulocitosis inducida por metimazol en pacientes con enfermedad de Graves

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    Manrique-Hurtado, Helard; Médico cirujano, especialista en Endocrinología, Servicio de Endocrinología, Hospital Nacional Arzobispo Loayza. Lima.; Pinto-Valdivia, Miguel; Médico cirujano, especialista en Endocrinología, Servicio de Endocrinología, Hospital Nacional Cayetano Heredia. Lima, Perú. Facultad de Medicina Alberto Hurtado, Universidad Peruana Cayetano Heredia. Lima.

    2013-01-01

    Objetivo: Describir las características clínicas y epidemiológicas de los pacientes con enfermedad de Graves que presentaron agranulocitosis inducida por metimazol. Material y métodos: Estudio retrospectivo, tipo serie de casos. Se revisaron las historias clínicas de todos los pacientes con diagnóstico de agranulocitosis inducida por metimazol, atendidos en el Hospital Nacional Arzobispo Loayza, entre enero 2002 y diciembre 2008. Se buscó asociación entre las variables demográficas y clínicas...

  5. Reacciones radicalarias de epoxicetonas insaturadas inducidas por titanoceno

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    Mateos Burón, Lydia

    2010-01-01

    [ES]Tesis doctoral sobre Reacciones radicalarias de epoxicetonas insaturadas inducidas por titanoceno, perteneciente al departamento de química orgánica [EN]Doctoral Thesis on the radical reactions induced by unsaturated titanocene epoxicetonas, from the organic chemistry´s departament

  6. Agranulocitosis inducida por metimazol en pacientes con enfermedad de Graves

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    Helard Manrique-Hurtado

    2013-04-01

    Full Text Available Objetivo: Describir las características clínicas y epidemiológicas de los pacientes con enfermedad de Graves que presentaron agranulocitosis inducida por metimazol. Material y métodos: Estudio retrospectivo, tipo serie de casos. Se revisaron las historias clínicas de todos los pacientes con diagnóstico de agranulocitosis inducida por metimazol, atendidos en el Hospital Nacional Arzobispo Loayza, entre enero 2002 y diciembre 2008. Se buscó asociación entre las variables demográficas y clínicas con la mortalidad y el tiempo de recuperación. Resultados: Treinta (0,60% pacientes con enfermedad de Graves fueron hospitalizados con el diagnóstico de agranulocitosis inducida por metimazol. La mediana de la edad fue 33,5 años y 86,67% fueron mujeres. Al ingreso, todos los pacientes presentaron fiebre y dolor de garganta. El manejo incluyó aislamiento invertido, suspensión del metimazol, administración de antibióticos y glucocorticoides. Doce (40% pacientes recibieron GM-CSF. El número de granulocitos se normalizó después de 10,59 días y cuatro (13,33% pacientes murieron por infecciones bacterianas y sepsis. En todos los casos, el tratamiento definitivo fue yodo radioactivo. No hubo diferencia significativa en la edad, sexo, dosis de metimazol, duración del tratamiento y uso de factor estimulante colonia, entre los pacientes fallecidos y los sobrevivientes. Además, el uso de factor estimulante de colonia no redujo el tiempo de recuperación de la agranulocitosis. Conclusión: La agranulocitosis inducida por metimazol es un evento adverso serio y potencialmente mortal. En este grupo de pacientes, la mortalidad fue elevada y el uso de factor estimulante de colonia no disminuyó el tiempo de recuperación.

  7. Vasculitis inducida por metimazol: Reporte de caso

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    Miguel Pinto

    2011-07-01

    Full Text Available Se reporta el caso de una paciente con enfermedad de Graves, que presentó vasculitis asociada al uso de metimazol. Mujer de 14 años, que acudió a consulta por presentar intolerancia al calor, tremor distal y palpitaciones. El examen físico mostró bocio difuso, y el perfil tiroideo, TSH suprimida y hormonas tiroideas elevadas. Los anticuerpos antiperoxidasa tiroidea fueron positivos. Se inició tratamiento con metimazol y beta bloqueadores. Después de 20 días, la paciente regresó por presentar malestar general, fiebre, poliartralgia, lesiones cutáneas maculopapulares y edema de miembros inferiores. Los anticuerpos antinucleares fueron negativos y los anticuerpos anticitoplasma de los neutrófilos (ANCA, positivos. Se suspendió el metimazol y se inició prednisona. Después de 10 días de tratamiento, las molestias desaparecieron y la paciente recibió I 131.Las vasculitis asociadas al uso de tionamidas son poco frecuentes, no dependen de la dosis y están asociadas a la presencia de anticuerpos tipo ANCA. Clásicamente, afectan a los vasos pequeños de la piel; sin embargo, también pueden afectar los riñones y pulmones. El cuadro clínico se caracteriza por artralgias y mialgias. En algunos casos puede ocurrir insuficiencia renal de grado variable. En la mayoría de casos, el cuadro remite con la suspensión de la droga; pero, en algunos se requiere el uso de glucocorticoides o inmunosupresores.(Rev Med Hered 2011;22:147-150.

  8. Osteoporosis secundaria y Osteoporosis inducida por glucocorticoides (OIG

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    Elías Forero Illera

    2006-01-01

    Full Text Available La osteoporosis es un problema de salud pública importante a nivel mundial, y su prevalencia está aumentando. La osteoporosis secundaria se puede producir por varias patologías y el uso de ciertos medicamentos. Los glucocorticoides son un grupo de fármacos usados extensamente en la práctica médica debido a su indiscutible utilidad. La osteoporosis inducida por glucocorticoides es un problema de salud pública. Aunque la patogénesis de la pérdida producida por los glucocorticoides en el hueso no se conoce totalmente, investigaciones recientes han proporcionado nuevas conocimientos en los mecanismos de estos fármacos a nivel celular y molecular. Diversas guías han sido propuestas por diversos grupos para el tratamiento de la OIG; desafortunadamente, las guías del tratamiento no se utilizan adecuadamente en los pacientes.

  9. Osteonecrosis de hueso maxilar inducida por bisfosfonatos

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    Vera Sempere, Francisco José

    2016-01-01

    Los bisfosfonatos son un grupo de fármacos, análogos de los pirofosfatos, utilizados en administración oral en el tratamiento de la osteoporosis, así como en formulaciones intravenosas para el tratamiento del dolor óseo y de la hipercalcemia ligada a la enfermedad tumoral metastasica (generalmente en el contexto de mieloma múltiple / cáncer de mama o próstata avanzados), actuando como un inhibidor de la reabsorción ósea, mediada por osteoclastos, así como de la apoptosis de los osteobl...

  10. EXCRECION FRACCIONAL DE UREA BAJA EN HIPONATREMIA INDUCIDA POR HIPOTIROIDISMO

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    Musso CG

    2005-02-01

    Full Text Available ABSTRACTHypothyroidism can cause disturbance of renal hemodinamics, kidney histology, water and electrolyte metabolism, being hyponatremia and glomerular filtration reduction their low prevalent but most significant consequences. All these changes are largely corrected by substitution of exogenous thyroid hormone.Fractional excretion of urea (FEU is a useful index in the evaluation of hyponatremia. However, it was not still reported in the literature the FEU value in hyponatremia induced by hypothyroidism. Because of that we presented a case report showing that the value of FEU and fractional excretion of sodium (FENa were low (FEU: 29% and high (FENa: 2.2 % respectively in a severe hypothyroid patient. Treatment based on thyroid hormone normalized both indeces.RESUMEN:El hipotiroidismo puede causar alteraciones del metabolismo del agua, los electrolitos, la hemodinamia e histología renales, siendo la hiponatremia y la reducción del filtrado glomerular sus consecuencias más significativas, pero poco prevalentes. Todos estos cambios son corregibles con el suministro de hormona tiroidea exógena.La excreción fraccional de urea (EFU es un índice útil en la evaluación de la hiponatremia, pero no se ha descripto aun el valor que este índice alcanza en la hiponatremia inducida por hipotiroidismo. En el presente reporte mostramos que la EFU y excreción fraccional de sodio (EFNa fueron baja (EFU: 29% y alta (EFNa: 2.2% respectivamente en un paciente que padecía hipotiroidismo severo. El tratamiento con hormona tiroidea normalizó el valor de ambos índices.

  11. Estrategias para el tratamiento de la disfunción sexual inducida por la medicación antidepresiva

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    Matthew J. Taylor

    2014-01-01

    Conclusiones de los autores: Las pruebas actualmente disponibles son muy limitadas. En los hombres con disfunción eréctil inducida por antidepresivos, el agregado de sildenafil o tadalafil parece ser una estrategia eficaz. En las mujeres con disfunción sexual inducida por antidepresivos, el agregado de bupropión a dosis mayores parece ser el enfoque más alentador estudiado hasta el presente.

  12. Prevalencia y severidad de la disfunción intestinal inducida por opioides

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    Gálvez, Rafael; Provencio, Mariano; Cobo, Manuel; Pérez, Cristina; Pérez, Concha; Canal, Jaume

    2014-01-01

    Objetivo: Analizar la prevalencia y severidad de los síntomas de disfunción intestinal inducida por opioides (DIO). Diseño: Estudio epidemiológico, observacional y transversal. Emplazamiento: Seis hospitales españoles. Participantes: Trescientos diecisiete pacientes en régimen ambulatorio con diagnóstico de dolor oncológico o dolor crónico no oncológico tratados con un único opioide mayor. Mediciones principales: La prevalencia de los síntomas de DIO y su severidad se midió usando...

  13. Insuficiencia renal aguda inducida por mordedura de serpiente Bothrops

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    Gustavo A. Aroca Martínez

    2014-01-01

    Full Text Available Mujer de 58 años de edad, remitida a urgencias por presentar cuadro clínico de insuficiencia renal aguda (IRA secundaria a mordedura de serpiente (Bothrops Atrox. Ingresa hipotensa con elevación de azoados e hiperkalemia, ecografía renal dentro de parámetros normales. Se maneja terapia dialítica con lo cual presenta mejoría clínica. En este reporte se detallan aspectos del diagnóstico, manejo clínico y posibles mecanismos fisiopatológicos que explican el daño renal.

  14. Corrosión inducida por microorganismos en la industria papelera

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    Blanco, A.

    1998-05-01

    Full Text Available Microbial deposits (slime or biofilm formation is one of the most important problems in the paper industry. Slime formation cause a reduction of the final product quality (spots, holes, odours, as well as in the production and equipment life, due to a greater number of web breaks, down time for cleaning and maintenance of the machinery, corrosion, etc. Microbiologically-induced corrosion cause an important economic losses due to the reduction of the equipment life. In microbially-induced corrosion studies is basic the rapid and precise determination of the evolution of slime growth on metallic surfaces. Thus, the goal of the present work have been the development of a methodology that leads to characterize the population of aerobic bacteria that compose the slimes of a board mill by means of multiparametric flow cytometry, using two different angles of light scattering and the total protein content as parameters, as first step of the studies of microbiologically-induced corrosion.

    De todos los problemas que aparecen en la industria de papel y cartón, la formación de depósitos microbiológicos (biofilm o slime es uno de los más importantes, ya que causa problemas tanto en la calidad del producto (suciedad, agujeros, olores como en el proceso (paradas no programadas, corrosión, malos olores, producción de gases tóxicos, etc.. La corrosión inducida por microorganismos en la industria papelera produce grandes pérdidas económicas debido a la necesidad de sustituir los materiales más frecuentemente. En los estudios de corrosión inducida por microorganismos (CIM es imprescindible determinar de una forma rápida y precisa la evolución del slime sobre las superficies metálicas. Por tanto, el objetivo de este trabajo ha sido el desarrollo de una metodología que permita caracterizar la población de bacterias de los slimes de una fábrica de cartón mediante citometría de flujo multiparamétrica, tomando

  15. HIPONATREMIA INDUCIDA POR OXCARBACEPINA: UNA HIPÓTESIS FISIOPATOLÓGICA

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    Musso CG

    2009-01-01

    Full Text Available La carbamazepina y la oxcarbazepina son drogas antiepilépticas potencialmente inductoras de hiponatremia, siendo este disturbio más frecuente con ésta última.En este reporte presentamos un caso de hiponatremia inducida por oxcarbazepina, y proponemos una potencial explicación fisiopatológica para esta entidad, a la cual se la considera consecuencia de un aumento a nivel de los túmulos colectores de la reabsorción de agua libre, de la pérdida urinaria de sodio, o de ambos fenómenos combinados.Además, postulamos que la mayor propensión a la aparición de hiponatremia con el uso de oxcarbazepina respecto del empleo de carbamazepina podría ser consecuencia de una mayor sensibilidad de los túmulos colectores a la primera de las drogas mencionadas.

  16. Cardiomiopatía inducida por estrés (Takotsubo en una paciente con anorexia nerviosa

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    Sabrina Vadalá

    2014-06-01

    Full Text Available Presentamos el caso de una mujer con diagnóstico de anorexia nerviosa que desarrolló cardiomiopatía de takotsubo precipitada por estrés emocional y alteraciones del medio interno. Evolucionó favorablemente con manejo conservador. Los casos de cardiomiopatía inducida por estrés, descriptos en pacientes con trastornos de la conducta alimentaria, suelen alcanzar mayor gravedad y se asocian con la prolongación del intervalo QT por desequilibrios electrolíticos, arritmias ventriculares e hipoglucemia. Se realiza una revisión del compromiso cardiovascular en pacientes con anorexia nerviosa.

  17. Cardiomiopatía inducida por estrés (Takotsubo) en una paciente con anorexia nerviosa

    OpenAIRE

    Sabrina Vadalá; Débora Pellegrini; María Fernanda Verdaguer; Marcela Schrappe; José Álvarez; Julio E. Bruetman

    2014-01-01

    Presentamos el caso de una mujer con diagnóstico de anorexia nerviosa que desarrolló cardiomiopatía de takotsubo precipitada por estrés emocional y alteraciones del medio interno. Evolucionó favorablemente con manejo conservador. Los casos de cardiomiopatía inducida por estrés, descriptos en pacientes con trastornos de la conducta alimentaria, suelen alcanzar mayor gravedad y se asocian con la prolongación del intervalo QT por desequilibrios electrolíticos, arritmias ventriculares e hipogluce...

  18. Capacidad antiteratogénica del resveratrol en diabetes inducida por estreptozotocina en ratas

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    Ninna Leslie Trejo-González

    Full Text Available Objetivos. Evaluar la capacidad antihiperglucémica y antiteratogénica del resveratrol en ratas inducidas a diabetes por estreptozotocina. Materiales y métodos. Estudio de tipo experimental. Se tuvieron tres grupos, de cinco ratas Wistar preñadas cada uno, dos de los cuales fueron tratados el cuarto día de gestación con una dosis de estreptozotocina de 50 mg/kg, disuelta en tampón de citratos, y el otro fue considerado como control, y solo se le administró el tampón de citratos. A uno de los grupos inducidos con estreptozotocina se le administró resveratrol a dosis de 100 mg/kg durante los días 8 al 12 de gestación, cuando sucede la neurulación. Los fetos se obtuvieron el día 19 de gestación y se les realizó un análisis morfológico, y en el hígado fetal se determinó la actividad de las enzimas depuradoras de especies reactivas catalasa, superóxido dismutasa y glutatión peroxidasa. Resultados. La administración de resveratrol (DM+R revierte los parámetros a valores similares a los del grupo control. Las actividades de catalasa y de glutatión peroxidasa, se vieron incrementadas en el grupo tratado con resveratrol con respecto al grupo diabético, en cuanto a la frecuencia de malformaciones en el grupo control y en el grupo tratado con resveratrol no presentaron malformaciones, mientras que en las ratas con diabetes inducida, se encontró una elevada frecuencia de malformaciones. Conclusiones. El resveratrol muestra propiedades antiteratogénicas a través de la disminución del estrés oxidativo que se presenta a causa de la hiperglucemia materna

  19. El aceite de pescado atenua las crisis convulsivas inducidas por hipertermia en ratas neonatas

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    Leopoldo E. Flores M.

    2008-01-01

    Full Text Available Un alto porcentaje (50-60% del cerebro en los mamíferos son principalmente grasas o lípidos, de éstos, el 35% son ácidos grasos esenciales, en particular los llamados omegas (O, como el Acido Docosahexanoico (DHA y el Eicosapentanoico (EPA llamados omega 3 (O-3. Diversos estudios han mostrado beneficios en la salud con la implementación de los O-3 como agentes terapéuticos en alteraciones cardiovasculares, renales, dérmicas, metabólicas, neurodegenerativas e inmunológicas. Evidencias experimentales sugieren un beneficio potencial del aceite de pescado (APE como neuroprotector debido al alto contenido de DHA y EPA. Sin embargo, es poco lo que se conoce en cuanto a los efectos que pudieran tener sobre alteraciones nerviosas, como las crisis convulsivas. En este contexto, se ha reportado que el tipo más común de trastorno epiléptico observado en los niños son las crisis convulsivas provocadas por fiebre (CF. La incidencia es de 3-5%, con ocurrencia entre los 5 meses y 5 años de edad, y se ha propuesto que esta alteración en la vida temprana pudiera tener efectos a largo plazo, manifestándose como un síndrome de epilepsia en la vida adulta. El objetivo del presente estudio fue evaluar el efecto del APE sobre las convulsiones inducidas por hipertermia experimental en un grupo de ratas Wistar macho de 5 días de edad (grupo SAPE cuyas madres consumieron una dieta base más un suplemento de APE (suministrado desde su infancia hasta la etapa de crianza. Este grupo se comparó con otro grupo de ratas de la misma edad y cepa (grupo SAPA cuyas madres consumieron una dieta base más un suplemento de aceite de palma (suministrado desde su infancia hasta la etapa de crianza, y con un tercer grupo de ratas (grupo CTRL cuyas madres consumieron la dieta base más agua bidestilada como suplemento. Las ratas tratadas con APE presentaron mayor resistencia a la elevación de la temperatura corporal inducida por la hipertermia, una menor frecuencia

  20. Efectividad de la ivermectina en un modelo de disquinesia tardía inducida por haloperidol en ratas

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    Mauricio Palacios; Hernán Pimienta

    2008-01-01

    Introducción: Los síntomas extrapiramidales y en especial las disquinesias tardías, son la mayor limitante de la terapia con antipsicóticos, debido a la frecuencia de aparición durante el tratamiento y la falta de recursos para controlar estas reacciones adversas, por lo cual es necesario investigar nuevos recursos para el manejo de las disquinesias tardías.Objetivo: Evaluar el efecto de la ivermectina sobre las disquinesias tardías inducidas por haloperidol en ratas.Métodos: En un modelo de ...

  1. Modificaciones del proteoma plasmático inducidas por el contenido graso y antioxidante de la dieta

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    Santos-González, Mónica

    2010-01-01

    Modificaciones del proteoma plasmático inducidas por el contenido graso Los ácidos grasos y otros componentes de la dieta como los antioxidantes, ejercen un papel muy importante en el desarrollo y progresión de enfermedades asociadas a la edad y constituyen la principal estrategia que en la actualidad disponemos para conseguir lo que denominamos un envejecimiento saludable. El objetivo de este trabajo es la identificación de biomarcadores plasmáticos que nos ayuden a entender el mecanismo ...

  2. Disfunción tiroidea inducida por amiodarona en la práctica clínica

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    José Luis Paz-Ibarra

    2011-01-01

    Full Text Available La amiodarona (AMD es una droga antiarrítmica potente (clase III usada en la práctica clínica para la profilaxis y el tratamiento de muchos disturbios del ritmo cardiaco, desde la fibrilación auricular paroxística hasta las taquiarritmias ventriculares que amenazan la vida. Frecuentemente causa cambios en las pruebas de función tiroidea principalmente relacionados a la inhibición de la actividad de la 5'-deiodinasa, resultando en una disminución de la generación de T3 desde T4 y el consecuente incremento en la producción de T3 reversa y una disminución de su aclaramiento. En 14 a 18% de pacientes tratados con AMD hay una disfunción tiroidea manifiesta, ya sea tirotoxicosis inducida por amiodarona (TIA o hipotiroidismo inducido por amiodarona (HIA. Tanto TIA como HIA pueden desarrollarse en glándulas aparentemente normales o en glándulas con anormalidades preexistentes clínicamente silentes. La TIA está primariamente relacionada a la síntesis de hormonas tiroideas inducida por el exceso de yodo en una glándula tiroidea anormal (TIA tipo 1 o a una tiroiditis destructiva relacionada a la amiodarona (TIA tipo 2, aunque frecuentemente ocurren formas mixtas. La tiroiditis de Hashimoto preexistente es un factor de riesgo definido para la ocurrencia de HIA. La patogenia del HIA es la falla para escapar del efecto agudo de Wolff-Chaikoff inducido por el yodo, debido a los defectos en la hormonogénesis tiroidea y, en pacientes con pruebas de autoanticuerpos tiroideos positivos, para tiroiditis de Hashimoto concomitante. La TIA es más común en zonas deficientes de yodo mientras que el HIA es usualmente visto en zonas suficientes en yodo. En contraste al HIA, la TIA es una condición difícil de diagnosticar y tratar, y usualmente se recomienda la descontinuación de la amiodarona. En esta revisión se analiza, de acuerdo a los datos actuales, las alteraciones en las pruebas de función tiroidea vistas en pacientes eutirodeos bajo

  3. Determination of forces induced by steam flow in turbines; Determinacion de fuerzas inducidas por flujo de vapor en turbinas

    Energy Technology Data Exchange (ETDEWEB)

    Garcia Castrejon, Juan Carlos

    2008-09-15

    blades, has a harmonic pattern. The pressure field variation as time function is uniform: the peaks and valleys across the axial clearance are always in phase. However the instant picture of the pressure field it's different: the peaks and valleys are not in phase and the number of peaks and valley changed across the clearance. In the case of the forces acting on blades, a Fourier on the forces calculated was used to determine the coefficients and frequency of a Fourier equation which can be used to calculate the alternating stresses on the blade in order to predict the useful life blades. [Spanish] Las vibraciones inducidas por flujo de vapor en turbinas representan uno de los problemas que enfrenta la operacion de turbinas de vapor cuya capacidad rebasa los 300 MW. Ademas estas constituyen uno de los limites tecnologicos para el desarrollo de turbinas de vapor de mas de 1 GW. Este tipo de fenomeno tiene su origen en la interaccion del rotor con el fluido que se encuentra en sus proximidades. El flujo de vapor dentro de la turbina es complejo, ya que es turbulento e inestable. A medida que el flujo pasa una etapa de estator o de rotor, se generan secundarios, vortices en los filos de salida, estelas con caracteristicas de flujo diferentes al flujo principal en los pasajes. Estas variaciones en el flujo son las que inducen vibraciones forzadas en los alabes. Ademas existen varios factores que contribuyen a la aplicacion de vibraciones en alabes inducidas por flujo como son: inestabilidad del flujo de vapor en los claros de los sellos, secuencia de apertura de las valvulas, estelas de las toberas, obstrucciones en algunas de las toberas y diferente espaciamiento en las toberas. Las vibraciones por flujo pueden ser peligrosas si su frecuencia coincide con la frecuencia natural del sistema, provocando efectos mas nocivos que las vibraciones por desbalance o por desalineamiento, pues tienen amplitudes mas grandes y provocan esfuerzos alternantes en los componentes del

  4. Osteoporosis inducida por Glucocorticoides: análisis de las guías internacionales de prevención y tratamiento

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    Brance, María Lorena; Plantalech, Luisa

    2017-01-01

    La osteoporosis inducida por glucocorticoides (OIG) es la segunda causa de osteoporosis luego de la osteoporosis posmenopáusica, y la más frecuente dentro de las causas secundarias. Previamente, diferentes sociedades científicas establecieron guías para el tratamiento de la OIG teniendo en cuenta dosis, tiempo de tratamiento de glucocorticoides (GC) y grados de pérdida ósea medidas por densitometría. En los últimos años las nuevas guías diseñadas por sociedades como American College of Rheuma...

  5. Arteriopatía periférica crónica inducida por cocaína

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    Sonia Pankl

    2012-02-01

    Full Text Available La trombosis periférica aguda inducida por cocaína ha sido descripta en la literatura, siendo una complicación poco común. Si bien existen comunicaciones que reflejan los efectos crónicos de la cocaína sobre el sistema arterial periférico, no hay casos publicados de tal complicación en ausencia de otros factores de riesgo. Se presenta el caso de una mujer de 22 años de edad con antecedentes de consumo de cocaína intranasal de 3 gramos por semana durante un año, que consultó por claudicación intermitente a los 200 metros asociada a dolor y parestesias en miembro inferior izquierdo de 2 meses de evolución. El ecodoppler arterial evidenció una estenosis mayor del 70% en la arteria femoral superficial izquierda. Se realizaron estudios complementarios descartando otras etiologías probables. Se inició tratamiento con ácido acetilsalicílico, cilostazol y ejercicio reglado, asociado a terapia de apoyo para mantenimiento del cese del consumo de cocaína, con buena respuesta. Se destaca la importancia de la difusión de información a los pacientes, dado que la mayoría de la población desconoce las complicaciones cardiovasculares de dicha adicción. Es indispensable indagar sobre el consumo de cocaína en pacientes jóvenes con arteriopatía sin factores de riesgo aparentes.

  6. El tratamiento con progesterona previene las alteraciones motoras inducidas por la intoxicación con semillas de cícada (Dioon spinulosum) en la rata macho

    OpenAIRE

    E Rivadeneyra-Domínguez; M Saavedra; JF Rodríguez-Landa

    2009-01-01

    El consumo crónico de semillas de cícadas ha sido asociado con enfermedades neurodegenerativas, las cuales predominan en el género masculino. En México, las semillas de cícada (Dioon spinulosum) son usadas como sustituto de maíz y a nivel experimental producen un déficit motor; probablemente causado por sus componentes neurotóxicos. En este sentido, la progesterona ejerce efectos neuroprotectores contra traumatismo cerebral, hipoxia, así como la muerte neuronal inducida por colchicina en el S...

  7. Detección y estudio mediante Fluorescencia Inducida por Láser de radicales libres formados por Disociación Multifotónica Infrarroja

    Science.gov (United States)

    Santos, M.; Díaz, L.; Torresano, J. A.; Rubio, L.; Samoudi, B.

    Una de las principales aplicaciones actuales de los procesos de disociación multifotónica inducidos por radiación láser infrarroja (DMI) es la producción de radiales libres, con el fin de estudiar sus propiedades cinéticas y espectroscópicas. La disociación de moléculas poliatómicas en el IR con láseres de CO2 tiene lugar desde la superficie de energía molecular mas baja y conduce generalmente a la formación de fragmentos en el estado electrónico fundamental, con diversos grados de excitación vibracional. En el Grupo de Procesos Multifotónicos del Instituto de Estructura de la Materia del C.S.I.C. hemos puesto a punto la técnica de Fluorescencia Inducida por Láser (LIF) para la detección y análisis en tiempo real de los fragmentos producidos en la DMI inducida mediante uno o dos campos láseres de diferentes longitudes de onda. Objetivos de nuestro trabajo han sido el estudio de los canales de disociación mayoritarios y de las especies transitoria producidas, así como de la distribución de energía interna con que éstas son generadas. En particular hemos detectado mediante LIF las especies: C2, CF, CH, SiH2, CF2, CH2, SiHCl, y CF3 a partir de la disociación de, entre otras, las siguientes moléculas: C2H3Br, C3F6, C4H8Si, C2H5ClSi y CH5ClSi. En este trabajo presentamos algunos de los resultados obtenidos mediante el estudio por LIF de estos radicales: estudio temporal de la señal LIF obtenida con determinación de tiempos de vida, espectros de excitación y fluorescencia, temperaturas vibracionales de formación, variación de la intensidad LIF con el tiempo de retraso entre los láseres de disociación y prueba, etc.

  8. Intervención multimodal en la fatiga inducida por el cáncer de mama mediante un programa de fisioterapia y ejercicio físico

    OpenAIRE

    Cantarero Villanueva, Irene

    2013-01-01

    La supervivencia a un cáncer de mama se ha incrementado cuantiosamente en estos años. Estas mujeres arrastran numerosas secuelas, entre las que destaca la fatiga, un síntoma de naturaleza multifactorial quemerma su calidad de vida. Con esta memoria de Tesis se persiguió mejorar la comprensión sobre la fatiga inducida por el cáncer de mama estudiando su relación con distintos factores, así como analizar la efectividad de un programa multimodal de ejercicio terapéutico.Las 95 participantes habí...

  9. Efecto antihipertensivo del extracto de Piper aduncum ‘matico’ sobre la hipertensión inducida por L-NAME en ratones

    OpenAIRE

    Jorge Arroyo; Renán Hañari; Aldo Tinco; Deyvis Baca; Lester Domínguez; Jesús Buendía

    2012-01-01

    Introducción: El Piper aduncum es una planta conocida como matico. Se le atribuye efectos antihipertensivo, antiinflamatorio, cicatrizante. Objetivos: Determinar el efecto antihipertensivo del extracto de Piper aduncum ‘matico’, sobre la hipertensión inducida por L-NAME, en ratones. Diseño: Experimental. Lugar: Facultades de Medicina y de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material biológico: Extracto etanólico de las hojas de Piper aduncum y ratas. I...

  10. Efecto antioxidante y hepatoprotector del Petroselinum sativum (perejil) en ratas, con intoxicación hepática inducida por paracetamol

    OpenAIRE

    Luzmila Troncoso; Emilio Guija

    2007-01-01

    Objetivo: Determinar el efecto antioxidante y hepatoprotector del perejil (Petroselinum sativum) en ratas con intoxicación hepática inducida por paracetamol. Lugar: Centro de Investigación de Bioquímica y Nutrición - "Laboratorio de Bioquímica Clínica y Nutricional "Leonidas Delgado Butrón" "Emilio Guija Poma" - Universidad Nacional Mayor de San Marcos. Lima, Perú. Diseño: Estudio analítico, transversal, prospectivo y cuasi-experimental. Material: Ratas albinas Holtzman machos adultas. Método...

  11. Mecanismos moleculares de la muerte celular inducida por privación de glucosa

    OpenAIRE

    Caro Maldonado, Alfredo

    2010-01-01

    La apoptosis es una forma de muerte controlada por unas proteasas llamadas caspasas. La activación de las caspasas lleva a la desintegración controlada de la célula y a su fagocitación por parte de macrófagos. La necrosis es una forma de muerte que no depende de caspasas, pero que sí que puede tener un control y ser homeostático. Buena parte de los tumores presentan la característica de tener un metabolismo glicolítico superior al de la mayoría de los tejidos. Además, esta gran dependencia en...

  12. Papel antioxidante de la vitamina E en la aterogénesis inducida por hiperfibrinogenemia

    Directory of Open Access Journals (Sweden)

    Mónica Moya

    2010-01-01

    Full Text Available Con el propósito de estudiar el efecto de la vitamina E sobre el estrés oxidativo desencade- nado por hiperfibrinogenemia (HF en un modelo experimental de aterogénesis y la posible normalización de los indicadores de estrés oxidativo, se evaluaron: óxido nítrico (NO, L-citrulina, superóxido dismutasa (SOD e involución de lesiones histopatológicas en la aorta torácica. El estudio se realizó en 36 ratas, cepa Wistar, que se dividieron en tres grupos (n = 12 cada uno: A, control; B, HF × 90 días; C, HF × 90 días + vitamina E. La HF se indujo mediante inyecciones de adrenalina (0,1 ml/día/rata por 90 días. La dosis de vitamina E fue de 2 mg/día/rata durante 75 días. Se dosaron en plasma los niveles de fibrinógeno (mg/dl, NO (uM y L-citrulina (mM y en lisado de glóbulos rojos, por espectrofotometría, se determinó la actividad de la SOD (U/ml. Se analizaron cortes de la aorta torácica por microscopia óptica (MO. Para el análisis estadístico se emplearon MANOVA y la prueba de Fisher; se estableció un nivel de significación de p < 0,05. Se observó un aumento significativo de fibrinógeno en el grupo B (407 ± 8,9 mg/dl en comparación con los grupos A (203 ± 9 mg/dl y C (191,58 ± 17,79 mg/dl (p < 0,001. El NO disminuyó significativamente en el grupo B (13,73 ± 1,76 uM frente a los grupos A (23,58 ± 0,08 uM y C (26,64 ± 3,65 uM (p < 0,001. La L-citrulina aumentó en forma significativa en los grupos B (4,99 ± 0,18 mM y C (6,60 ± 0,16 mM en comparación con el grupo A (3,03 ± 0,13 mM (p < 0,001. El SOD incrementó su actividad en los grupos B (251,67 ± 10,34 U/ml y C (304,75 ± 10,43 U/ml frente al grupo A (139,44 ± 4,74 U/ml (p < 0,001. La microscopia óptica mostró denudación endotelial, engrosamiento intimal y protrusión de la pared en el grupo B (90% y recuperación de la denudación endotelial y disminución del 50% del engrosamiento intimal en el grupo C (p < 0,001. Niveles aumentados de SOD ser

  13. SEÑALES DE CALCIO NUCLEAR INDUCIDAS POR IGF-1 EN CARDIOMIOCITOS: CARACTERIZACION Y MECANISMO FUNCINAL

    OpenAIRE

    IBARRA IRIBARREN; CRISTIAN ANDRES; IBARRA IRIBARREN; CRISTIAN ANDRES

    2010-01-01

    IGF-1 es un importante estímulo pro hipertrófico y antiapoptótico en los cardiomiocitos. Diversas vías de transducción de señales son activadas por IGF-1 en los cardiomiocitos y están involucradas sus efectos fisiopatológicos. En nuestro laboratorio hemos estudiado la participación del calcio intracelular en el sistema transduccional del IGF-1 . Encontramos que IGF-1 incrementa los niveles intracelulares de calcio de modo transitorio y con una cinética rápida a nivel de los núcleos celulares....

  14. SEÑALES DE CALCIO NUCLEAR INDUCIDAS POR IGF-1 EN CARDIOMIOCITOS: CARACTERIZACION Y MECANISMO FUNCIONAL

    OpenAIRE

    IBARRA IRIBARREN, CRISTIAN ANDRES

    2010-01-01

    IGF-1 es un importante estímulo pro hipertrófico y antiapoptótico en los cardiomiocitos. Diversas vías de transducción de señales son activadas por IGF-1 en los cardiomiocitos y están involucradas sus efectos fisiopatológicos. En nuestro laboratorio hemos estudiado la participación del calcio intracelular en el sistema transduccional del IGF-1. Encontramos que IGF-1 incrementa los niveles intracelulares de calcio de modo transitorio y con una cinética rápida a nivel de los núcleos celulare...

  15. Epitelización inducida por células troncales derivadas del tejido adiposo

    OpenAIRE

    M. Meruane; S. Benítez; M. Rojas; A. Sagredo; K. Marcelain; B. Villalobos

    2014-01-01

    El tratamiento de lesiones con pérdida de tejido cutáneo ha mejorado notablemente con el advenimiento de la bioingeniería tisular. Una alternativa en desarrollo es la utilización de sustitutos dérmicos combinados con células troncales derivadas del tejido adiposo autólogo. Estudios previos nos muestran que con esta técnica es posible optimizar la angiogénesis y la síntesis de colágeno, sin embargo potenciar la epitelización es un tema pendiente por resolver. En el presente estudio evaluamos l...

  16. EFECTO IN VITRO DE LA INSULINA SOBRE LA CAPACIDAD CONTRACTIL UTERINA INDUCIDA POR OXITOCINA

    OpenAIRE

    Figueroa D.,Horacio; Marusic B.,Elisa T.; González N.,Magdalena; Barcos M.,Francisca; Yungue V.,Paola

    2002-01-01

    La capacidad contráctil del útero puede ser evaluada in vitro por medio del método isométrico. El objetivo de este estudio fue comparar la efectividad de la administración simultánea de oxitocina e insulina en la contractilidad uterina. La comparación entre ambas hormonas se realizó en úteros aislados de dos modelos experimentales: ratas hembras adultas en diferentes fases del ciclo estral y ratas preñadas en fase final de preñez. Los úteros de estos animales fueron sometidos, in vitro, a la ...

  17. Muerte súbita debida a cardiotoxicidad aguda inducida por antraciclinas

    Directory of Open Access Journals (Sweden)

    Orlando D. Navarro-Ulloa

    2018-01-01

    Full Text Available Antraciclinas como la doxorrubicina, así como anticuerpos monoclonales, como el trastuzumab, y agentes alquilantes, como la ciclofosfamida, son compuestos muy útiles como quimioterapia citotóxica al reducir en forma significativa la mortalidad relacionada con el cáncer. Sin embargo, su potencial cardiotoxicidad es un efecto adverso mayor que puede presentarse en cualquier momento de su administración o posterior a la misma, en especial cuando se usan combinados. La toxicidad cardiovascular por doxorrubicina suele ser dependiente de dosis e irreversible, mientras la ocasionada por trastuzumab no lo es. Se han encontrado cambios electrocardiográficos habituales durante la administración de quimioterapia, independiente de la dosis acumulada; a estos cambios agudos se les ha dado poca importancia, aunque pueden suceder hasta en el 40% de los pacientes. A pesar de la aparición documentada de arritmias tanto en humanos como en modelos animales, la muerte súbita cardiaca durante o inmediatamente después de la infusión de quimioterapia no está bien descrita. Se presenta el caso de un adulto joven sin antecedentes cardiovasculares, con linfoma no-Hodgkin y corazón con imagen ecocardiográfica muy sugestiva de infiltración linfomatosa del ventrículo izquierdo, quien desarrolla alteraciones del ritmo cardiaco que condicionan muerte súbita tras la infusión endovenosa lenta de doxorrubicina y trastuzumab.

  18. Epitelización inducida por células troncales derivadas del tejido adiposo

    Directory of Open Access Journals (Sweden)

    M. Meruane

    2014-06-01

    Full Text Available El tratamiento de lesiones con pérdida de tejido cutáneo ha mejorado notablemente con el advenimiento de la bioingeniería tisular. Una alternativa en desarrollo es la utilización de sustitutos dérmicos combinados con células troncales derivadas del tejido adiposo autólogo. Estudios previos nos muestran que con esta técnica es posible optimizar la angiogénesis y la síntesis de colágeno, sin embargo potenciar la epitelización es un tema pendiente por resolver. En el presente estudio evaluamos la progresión y diferenciación epitelial en un período de tiempo prologando. Obtuvimos las células troncales a partir del tejido adiposo (ASC de la región inguinal de 4 ratas Sprague Dawley. Cultivamos las células frescas en una matriz de Integra® durante un período total de 48 horas, y las marcamos con un vector lentiviral-GFP (proteína fluorescente verde. Posteriormente, injertamos en las mismas ratas la matriz dérmica con células troncales y un implante contralateral sin células, como control. A las 4 semanas, evaluamos el avance epitelial mediante planimetría de superficie e histología. Los resultados macroscópicos muestran que el cierre de la herida por contracción de los bordes no tiene diferencias significativas (82,63% ± 3,4% vs. 80,66% ± 3,89%; p=0,08, pero el cierre por epitelización fue significativamente mayor en el lado intervenido con ASCs (93,47% ± 5,98% vs. 79,88% ± 6,28%; p=0,0028. Todas las muestras obtuvieron tinción positiva para el anticuerpo anti-citoqueratina 34βE12 y el avance epitelial lineal cuantificado por microscopía resultó significativamente mayor en el lado con ASCs (6408 ± 275μm vs. 5375 ± 250μm; p < 0,001. Identificamos las células GFP positivas formando parte de la dermis regenerada, no así en la epidermis. En conclusión, las células troncales derivadas del tejido adiposo autólogo sembradas en una matriz de Integra® aumentan la formación epitelial significativamente

  19. EFECTO PROTECTOR DE PEUMUS BOLDUS EN RATAS CON TOXICIDAD HEPÁTICA INDUCIDA POR PARACETAMOL

    Directory of Open Access Journals (Sweden)

    Christiam Ochoa

    2012-02-01

    Full Text Available Objetivo: Comprobar el efecto protector hepático del extracto acuoso de boldo (EAB (Peumus boldus al daño hepático inducido por acetaminofén (paracetamol. Diseño: Analítico, experimental, aleatorizado, completo – experimento verdadero. Realizado en el Instituto de Patología de la Facultad de Medicina de UNMSM. Material y método. 30 Ratas Holtzman macho de 250g y dos meses se dividieron en 5 grupos aleatoriamente, grupo blanco, control paracetamol 200mg/kg y 3 experimentales tratados con EAB a 80 mg/kg, 120 mg/kg y 160 mg/kg respectivamente. Se administró EAB de 80 mg/kg, 120 mg/kg y 160 mg/kg vía orogástrica. Luego de media hora se administró paracetamol 200mg/kg i.p. a los grupos control y experimentales. Este procedimiento se repitió por 5 días. Se tomó pruebas de transaminasas (TGP basal y final en sangre. Se utilizó la prueba de Kruskal-Wallis para analizar la data y un p<0.05 fue considerado significante. Se estudió la anatomopatología de los hígados y se tomaron muestras de tejido teñidas con HE. Resultados: Existe diferencia significativa en los niveles de transaminasas (TGP entre grupos (p<0.05. El control obtuvo 196.6 U/L +- 38.1 (TGP mientras que los experimentales como máximo 55.6 U/l. Las muestras control evidencian signos de lesión hepática, degeneración grasa, congestión sinusoidal y centrolobulillar, y necrosis celular. Sin embargo los grupos experimentales no presentan signos de lesión celular y hay ausencia de inflamación. Conclusiones: El boldo tiene un efecto protector hepático al daño inducido por paracetamol en ratas Holtzmann.

  20. Efecto Protector de Peumus Boldus en ratas con toxicidad hepática inducida por Paracetamol

    Directory of Open Access Journals (Sweden)

    Christiam Ochoa

    2008-01-01

    Full Text Available Objetivo: Comprobar el efecto protector hepático del extracto acuoso de boldo (EAB (Peumus boldus al daño hepático inducido por acetaminofén (paracetamol. Diseño: Analítico, experimental, aleatorizado, completo ¿ experimento verdadero. Realizado en el Instituto de Patología de la Facultad de Medicina de UNMSM. Material y método. 30 Ratas Holtzman macho de 250g y dos meses se dividieron en 5 grupos aleatoriamente, grupo blanco, control paracetamol 200mg/kg y 3 experimentales tratados con EAB a 80 mg/kg, 120 mg/kg y 160 mg/kg respectivamente. Se administró EAB de 80 mg/kg, 120 mg/kg y 160 mg/kg vía orogástrica. Luego de media hora se administró paracetamol 200mg/kg i.p. a los grupos control y experimentales. Este procedimiento se repitió por 5 días. Se tomó pruebas de transaminasas (TGP basal y final en sangre. Se utilizó la prueba de Kruskal-Wallis para analizar la data y un p<0.05 fue considerado significante. Se estudió la anatomopatología de los hígados y se tomaron muestras de tejido teñidas con HE. Resultados: Existe diferencia significativa en los niveles de transaminasas (TGP entre grupos (p<0.05. El control obtuvo 196.6 U/L +- 38.1 (TGP mientras que los experimentales como máximo 55.6 U/l. Las muestras control evidencian signos de lesión hepática, degeneración grasa, congestión sinusoidal y centrolobulillar, y necrosis celular. Sin embargo los grupos experimentales no presentan signos de lesión celular y hay ausencia de inflamación. Conclusiones: El boldo tiene un efecto protector hepático al daño inducido por paracetamol en ratas Holtzmann.

  1. EFECTO DEL DIMETILSULFÓXIDO EN UN MODELO ANIMAL DE NEFROTOXICIDAD INDUCIDA POR GENTAMICINA EN CONEJOS

    Directory of Open Access Journals (Sweden)

    Oscar Francisco López Núñez

    2013-01-01

    Full Text Available Objetivo: La utilidad clínica de la gentamicina se ve limitada por sus efectos deletéreos renales, causados principalmente por daño oxidativo. Dado que el dimetilsulfóxido posee propiedades antioxidantes, se plantea su uso como agente nefroprotector en un modelo animal. Métodos: Se distribuyeron de forma aleatoria 24 conejos en 3 grupos (A, B y C, se administró durante 5 días solución salina normal 0,9%(SSN para el grupo A, gentamicina más SSN par el grupo B y gentamicina más dimetilsulfóxido al 25% para el grupo C. Se determinaron los parámetros: creatinina sérica, actividad enzimática (n-acetyl-b-d-glucosaminidasa urinaria e histopatología renal. Resultados: La creatinina aumentó respecto al valor basal en los grupos B y C (p=0,009. La comparación del incremento entre grupo A vs C mostró significancia estadística (p=0,0194. La clasifica- ción para lesión renal aguda RIFLE fue del 25% y 50% en estadío Riesgo para los grupos C y B respectivamente y 12,5% en estadío Injuria para el grupo B. La actividad de n-acetyl-b-d-glucosaminidasa urinaria presentó incrementos en todas sus mediciones (p<0,05. La histopatología reveló necrosis mayor del 50% de los túbulos proximales en el 25% del grupo C y 87,5% del grupo B, así como necrosis total en 12,5% del grupo B. Se observaron diferencias entre el grupo A vs B (p<0,001 y C (p<0,05. Conclusiones: El modelo planteado induce nefrotoxicidad. El uso de dimetilsulfóxido no redujo el incremento en los niveles de creatinina y en actividad enzimática, mientras que la Lesión Renal Aguda (LRA por evaluación histopatológica presentó una leve mejoría que carece de respaldo estadístico.

  2. EFECTO DEL DIMETILSULFÓXIDO EN UN MODELO ANIMAL DE NEFROTOXICIDAD INDUCIDA POR GENTAMICINA EN CONEJOS

    Directory of Open Access Journals (Sweden)

    Oscar Francisco López Núñez

    2013-07-01

    Full Text Available Objetivo: La utilidad clínica de la gentamicina se ve limitada por sus efectos deletéreos renales, causados principalmente por daño oxidativo. Dado que el dimetilsulfóxido posee propiedades antioxidantes, se plantea su uso como agente nefroprotector en un modelo animal. Métodos: Se distribuyeron de forma aleatoria 24 conejos en 3 grupos (A, B y C, se administró durante 5 días solución salina normal 0,9%(SSN para el grupo A, gentamicina más SSN para el grupo B y gentamicina más dimetilsulfóxido al 25% para el grupo C. Se determinaron los parámetros: creatinina sérica, actividad enzimática (n-acetyl-b-d-glucosaminidasa urinaria e histopatología renal. Resultados: La creatinina aumentó respecto al valor basal en los grupos B y C (p=0,009. La comparación del incremento entre grupo A vs C mostró significancia estadística (p=0,0194. La clasificación para lesión renal aguda RIFLE fue del 25% y 50% en estadío Riesgo para los grupos C y B respectivamente y 12,5% en estadío Injuria para el grupo B. La actividad de n-acetyl-b-d-glucosaminidasa urinaria presentó incrementos en todas sus mediciones (p<0,05. La histopatología reveló necrosis mayor del 50% de los túbulos proximales en el 25% del grupo C y 87,5% del grupo B, así como necrosis total en 12,5% del grupo B. Se observaron diferencias entre el grupo A vs B (p<0,001 y C (p<0,05. Conclusiones: El modelo planteado induce nefrotoxicidad. El uso de dimetilsulfóxido no redujo el incremento en los niveles de creatinina y en actividad enzimática, mientras que la Lesión Renal Aguda (LRA por evaluación histopatológica presentó una leve mejoría que carece de respaldo estadístico. Palabras Clave: Dimetilsulfóxido, gentamicina, lesión renal aguda, radicales libres

  3. La fragmentación territorial inducida por el centralismo fiscal, Colombia (1984-2013

    Directory of Open Access Journals (Sweden)

    Oscar Alfredo Alfonso Roa

    2015-07-01

    Full Text Available Los debates a la organización del Estado en América Latina son inagotables, porque la universalización de los bienes públicos y la consecuente elevación del nivel de vida de los ciudadanos es un desafío inalcanzado. Los excesos de centralismo en Colombia limitan la eficacia del modelo territorial de Estado mientras que el avance de la corrupción es innegable y, por tanto, la necesidad de nuevas reglas de distribución del poder es inaplazable. Uno de los efectos más duraderos de ese tipo de intervención es la fragmentación territorial en heterogéneos regímenes espaciales que van más allá de la mera regionalización con criterios naturalistas o de contigüidad geográfica.

  4. Costo-efectividad de medios de contraste isoosmolales e hiposmolales en pacientes con alto riesgo de nefropatía inducida por medio de contraste

    Directory of Open Access Journals (Sweden)

    Liliana Alejandra Chicaíza-Becerra

    2012-06-01

    Full Text Available Introducción. Los medios de contraste pueden provocar falla renal aguda por toxicidad directa sobre las células tubulares e isquemia medular renal. Los pacientes diabéticos y los hospitalizados presentan mayor riesgo de desarrollar nefropatía inducida por medios de contraste que la población general. Objetivo. Establecer el costo-efectividad de los medios de contraste isosmolales e hiposmolales en pacientes con alto riesgo. Materiales and métodos. El análisis se basó en una revisión sistemática de la literatura científica, comparando los efectos nefrotóxicos de los medios isosmolales e hipoosmolales. Se consideraron sólo los costos directos, obtenidos del manual tarifario. Se calcularon las tasas del incremento del costoefectividad, las curvas de eficiencia y de aceptabilidad. Se hicieron análisis univariados de sensibilidad para costos y efectos, así como probabilísticos. Se aplicaron tasas de descuento de 0 y 3 % a losresultados. Se usó como umbral de costo-efectividad por año de vida ganado, el producto interno bruto per cápita. Resultados. Las alternativas con Iopamidol y Iodixanol dominan a las demás porque reducen el riesgo de nefropatía inducida por contraste a un menor costo. La razón del incremento del costo-efectividad del iodixanol comparado con el iopamidol es de US$ 14.660 por año de vida ganado que más que duplica el umbral. Conclusión. El medio de baja osmolalidad, iopamidol, parece ser costo-efectivo comparado con iohexol u otros medios hiposmolares (iopromide, iobitridol, iomeprol, iopentol y ioxilan, en pacientes con alto riesgo de nefropatía inducida por contraste. La elección del medio hiposmolar, depende de la disponibilidad a pagar o del costo por ampolleta.   doi: http://dx.doi.org/10.7705/biomedica.v32i2.367

  5. Diagnóstico erróneo de psicosis inducida por cocaína en una persona con esquizofrenia y masticadora de hojas de coca.

    OpenAIRE

    Revilla-Zúñiga, Joshep; Rivera-Encinas, María Teresa; Cruzado, Lizardo

    2016-01-01

    En el Perú existe una elevada prevalencia de trastornos por consumo de estimulantes y aunque no existen estadísticas precisas, puede asumirse la ocurrencia de múltiples casos de psicosis inducida por el consumo declorhidrato de cocaína o pasta básica de cocaína. Por otro lado, la masticación de hojas de coca constituye parte del acervo cultural e histórico de un gran segmento de la población peruana. A propósito de un caso de confusióndiagnóstica (un cuadro de esquizofrenia en un paciente mas...

  6. Efecto hipoglucemiante del extracto etanólico de Geranium ruizii Hieron. (pasuchaca en la hiperglucemia inducida por aloxano en ratas

    Directory of Open Access Journals (Sweden)

    Oscar Herrera-Calderon

    2015-04-01

    Full Text Available Introducción: Geranium ruizii (Pasuchaca es una planta medicinal utilizada tradicionalmente como hipoglucemiante en el departamento de Ancash, Perú. Objetivo: Evaluar el efecto hipoglucemiante del extracto etanólico de Geranium ruizii administrada en ratas con hiperglicemia inducida por aloxano. Diseño: Experimental. Institución: Laboratorio de Farmacología Experimental, Facultad de Medicina Humana, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material biológico: Planta entera de Geranium ruizii, ratas Holtzman hembras de ocho semanas con 200 ± 20 g de peso corporal. Intervenciones: La hiperglicemia fue inducida con aloxano. Las ratas incluidas en el estudio presentaron una glicemia > 200 mg/dL. Se formaron seis grupos de seis ratas cada uno. El grupo I recibió agua destilada 2 mL; los grupo II, III y IV recibieron Geranium ruizii 50 mg/kg; 150 mg/kg y 300 mg/kg, respectivamente (vía oral; al grupo V se administró glibenclamida 5 mg/kg y al grupo VI insulina 4UI/kg. Principales medidas de los resultados: Glucemia (mg/ dL, porcentaje de inhibición del radical DPPH, especies reactivas al ácido tiobarbitúrico (TBARS (nmoles/mL, estudio histológico de páncreas. Resultados: La dosis de 150 mg/kg de G. ruizii redujo 65,58% los valores de glicemia a las 2 h post administración (Kruskal Wallis; p< 0,001, redujo TBARS en 22,34% e inhibió el radical DPPH en 23,66%; el tejido pancreático se mantuvo en buen estado de conservación. Conclusiones: El extracto etanólico de Geranium ruizii (pasuchaca tuvo efecto hipoglicemiante en ratas con hiperglucemia inducida con aloxano.

  7. Efecto antihipertensivo del extracto de Piper aduncum ‘matico’ sobre la hipertensión inducida por L-NAME en ratones

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    Jorge Arroyo

    2012-10-01

    Full Text Available Introducción: El Piper aduncum es una planta conocida como matico. Se le atribuye efectos antihipertensivo, antiinflamatorio, cicatrizante. Objetivos: Determinar el efecto antihipertensivo del extracto de Piper aduncum ‘matico’, sobre la hipertensión inducida por L-NAME, en ratones. Diseño: Experimental. Lugar: Facultades de Medicina y de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material biológico: Extracto etanólico de las hojas de Piper aduncum y ratas. Intervenciones: Se utilizó seis grupos de seis ratones Muss musculus cada uno, uno sin hipertensión (control negativo y cuatro con hipertensión inducida por L-NAME: un control positivo y tres grupos para las dosis de 50, 150 y 300 mg/kg, respectivamente. El tratamiento se realizó por vía oral, una vez por día, durante 25 días. Las mediciones de la presión arterial sistólica (PAS, presión arterial diastólica (PAD y presión arterial media (PAM fueron realizadas dos veces por semana (martes y viernes y se consideró las mediciones entre los días 19 y 23 de iniciado el tratamiento. Principales medidas de resultados: Actividad antihipertensiva. Resultados: En los días 19 y 23 se observó los mejores niveles de presión arterial en el grupo control y los experimentales, correspondiendo a las mediciones 6 y 7. La eficacia antihipertensiva para enalapril fue 24,1 a 20,6%, respectivamente, seguida por matico, entre 24,9 y 13,7% (p<0,05. Conclusiones: En las condiciones experimentales, se demostró la actividad antihipertensiva del extracto etanólico de hojas de Piper aduncum ‘matico’.

  8. Papel del endotelio en hipertensión inducida por el embarazo: ¿alteraciones comunes a las de la aterosclerosis?

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    Patricio López-Jaramillo

    2014-10-01

    Full Text Available La hipertensión inducida por el embarazo, cuya forma proteinúrica es denominada preeclampsia (PE, es una alteración que ocurre en el segundo trimestre del embarazo, y se caracteriza por la presencia de hipertensión y proteinuria. Durante el embarazo normal ocurren cambios fisiológicos adaptativos que incluyen insulino-resistencia (IR, hiperlipidemia, hipercoagulabilidad, inflamación y un estado circulatorio hiperdinámico. Estos cambios se expresan de una forma exagerada en las mujeres que desarrollan PE, alteraciones que están presentes también en el clúster de factores de riesgo que conforman el denominado síndrome metabólico (SM, el cual es un factor de riesgo para el desarrollo de diabetes mellitus tipo 2 (DM2 y enfermedad cardiovascular (ECV. En la presente revisión proponemos que la disfunción endotelial es la alteración común que explica la presencia de estas dos enfermedades comunes en América Latina.

  9. Cardiopatía inducida por estrés (Tako-Tsubo. Nueva hipótesis fisiopatológica

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    Carlos E. Gadda

    2010-01-01

    Full Text Available RESUMENLa miocardiopatía inducida por estrés tiene como factor común su casi exclusiva apariciónen mujeres posmenopáusicas que acaban de sufrir una situación de estrés de gran envergaduray que clínicamente presentan un evento coronario agudo muy similar a un infartoagudo de miocardio. Al ser estudiadas de urgencia por cateterismo o ecocardiografía, en elventrículo izquierdo se observa un área de acinesia o discinesia focalizada habitualmente enla “punta”, pero con coronarias angiográficamente normales o, a lo sumo, mínimamentecomprometidas.Las coronarias pronunciadamente flexuosas también son habituales en mujeresposmenopáusicas y las arterias con estas características, al acodarse en forma extrema,pueden generar kinkings. Durante una crisis adrenérgica, estos kinkings llegan a estrangularla arteria y comprometer el flujo más allá de la sístole, lo cual, sumado a los efectos de lascatecolaminas, generaría la alteración focal y transitoria de la contractilidad que caracterizaal Tako-Tsubo.Queda claro que para afirmar esta hipótesis deben explorarse futuros pacientes en búsquedade este patrón anatómico.REV ARGENT CARDIOL 2010;78:43-45.

  10. El estrés oxidativo: detonante fisiopatológico en la cardiomiopatía dilatada inducida por doxorrubicina

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    Yanet Hernández Matos

    2011-10-01

    Full Text Available La cardiomiopatía dilatada inducida por doxorrubicina constituye uno de los principales efectos indeseables del tratamiento de pacientes con tumores malignos. El estrés oxidativo constituye uno de los mecanismos fisiopatológicos que desempeñan un papel fundamental en la instauración de la enfermedad causada por este antibiótico del grupo de las antraciclinas. La comprensión de estos mecanismos fisiopatológicos resulta de vital importancia para llevar a cabo estrategias de intervención farmacológica y nutricional para contribuir a palear los efectos nocivos de este antineoplásico. En el presente trabajo se realizó una actualización bibliográfica sobre el tema y se proponen ideas que pueden ser útiles para la comunidad científica que está enfrascada en el tratamiento de esta enfermedad crónica, y que se propone mejorar la calidad de vida de los pacientes que la padecen.

  11. Efectos en ratas de los alcoholes de cera de abejas (D-002 sobre la colitis ulcerativa inducida por sulfato de dextrano y etanol

    Directory of Open Access Journals (Sweden)

    Vivian Molina-Cuevas

    Full Text Available RESUMEN Objetivos. Investigar los efectos del D-002, mezcla de seis alcoholes alifáticos primarios de alto peso molecular, obtenida de la cera de abejas (Apis mellifera, sobre la colitis ulcerativa (CU inflamatoria severa inducida por sulfato de dextrano (DSS y etanol en ratas (Ratus ratus. Materiales y métodos. Las ratas se distribuyeron aleatoriamente en seis grupos: un control cero al que no se provocó daño, y cinco a los que se les indujo la CU: un control negativo (vehículo, tres tratados con D-002 (25, 100 y 400 mg/kg y un control positivo con sulfazalacina (200 mg/kg (sustancia de referencia. Se cuantificaron las manifestaciones clínicas (variación del peso corporal, presencia de diarrea y de sangrado rectal, el puntaje de daño macroscópico e histológico, y la actividad de mieoloperoxidasa (MPO. Resultados. El tratamiento oral con D-002 (25, 100 y 400 mg/kg previno significativamente la disminución del peso corporal. La dosis de 400 mg/kg redujo la presencia de diarreas y sangrado rectal, aunque su comparación con el control negativo solo alcanzó significación estadística sobre las diarreas. El D-002 (25, 100 y 400 mg/kg redujo significativamente el puntaje de las lesiones macroscópicas (40,0; 43,3 y 47,2% de inhibición, respectivamente, el puntaje de daño histológico (31,5; 53,7 y 67,1% de inhibición, respectivamente y la actividad de MPO (73,2; 83,6 y 85,0% de inhibición, respectivamente, comparado con el grupo control negativo. La sulfazalacina redujo significativamente todas las variables estudiadas. Conclusiones. El D-002 (25, 100 y 400 mg/kg protegió significativamente la mucosa colónica en ratas con CU inflamatoria severa inducida por DSS y etanol.

  12. Efectos en ratas de los alcoholes de cera de abejas (D-002 sobre la colitis ulcerativa inducida por sulfato de dextrano y etanol

    Directory of Open Access Journals (Sweden)

    Vivian Molina-Cuevas

    Full Text Available Objetivos. Investigar los efectos del D-002, mezcla de seis alcoholes alifáticos primarios de alto peso molecular, obtenida de la cera de abejas (Apis mellifera, sobre la colitis ulcerativa (CU inflamatoria severa inducida por sulfato de dextrano (DSS y etanol en ratas (Ratus ratus. Materiales y métodos. Las ratas se distribuyeron aleatoriamente en seis grupos: un control cero al que no se provocó daño, y cinco a los que se les indujo la CU: un control negativo (vehículo, tres tratados con D-002 (25, 100 y 400 mg/kg y un control positivo con sulfazalacina (200 mg/kg (sustancia de referencia. Se cuantificaron las manifestaciones clínicas (variación del peso corporal, presencia de diarrea y de sangrado rectal, el puntaje de daño macroscópico e histológico, y la actividad de mieoloperoxidasa (MPO. Resultados. El tratamiento oral con D-002 (25, 100 y 400 mg/kg previno significativamente la disminución del peso corporal. La dosis de 400 mg/kg redujo la presencia de diarreas y sangrado rectal, aunque su comparación con el control negativo solo alcanzó significación estadística sobre las diarreas. El D-002 (25, 100 y 400 mg/kg redujo significativamente el puntaje de las lesiones macroscópicas (40,0; 43,3 y 47,2% de inhibición, respectivamente, el puntaje de daño histológico (31,5; 53,7 y 67,1% de inhibición, respectivamente y la actividad de MPO (73,2; 83,6 y 85,0% de inhibición, respectivamente, comparado con el grupo control negativo. La sulfazalacina redujo significativamente todas las variables estudiadas. Conclusiones. El D-002 (25, 100 y 400 mg/kg protegió significativamente la mucosa colónica en ratas con CU inflamatoria severa inducida por DSS y etanol.

  13. Disminución del daño oxidativo y efecto hipoglicemiante de la maca (Lepidium meyenii Walp en ratas con diabetes inducida por streptozotocina

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    María Elena Rodrigo

    2011-01-01

    Full Text Available Introducción: La maca es consumida desde tiempos ancestrales como parte de la dieta. Se le ha atribuido propiedades medicinales y se encuentra incluida en la medicina tradicional peruana. Estudios recientes describen que la admistración de maca reduce la glicemia en animales normoglicémicos, pero los mecanismos involucrados no están muy claros. Objetivos: Determinar el efecto hipoglicemiante y antioxidante de la harina de maca (Lepidium meyenii Walp del ecotipo amarillo, en ratas con diabetes inducida por estreptozotocina. Diseño: Experimental. Institución: Centro de Investigación de Bioquímica y Nutrición, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material biológico: Harina de maca amarilla y ratas albinas Holtzmann machos con diabetes inducida. Intervenciones: Se administró la harina de maca amarilla a las ratas distribuidas en 4 grupos: grupo I control (solo dieta; II, harina de maca 4 g/día; III, harina de maca 6 g/día; y IV, dieta + glibenclamida 10 mg/kg de peso; el experimento duró 46 días. Se evaluó diariamente la glicemia y el peso; al final del experimento se determinó en sangre los niveles de insulina, parámetros de daño oxidativo (vitamina C y se midió la peroxidación lipídica (TBARS, como indicador del proceso oxidativo. Principales medidas de los resultados: Modificación de los niveles de glicemia, insulina, vitamina C y formación del complejo MDA-TBARS. Resultados: La administración de harina de maca en la dieta (4 a 6 g/día de animales diabéticos redujo la glicemia en 50%, incrementó los niveles de insulina 22% y mejoró los niveles de vitamina C respecto al grupo control. La administración de maca 4 g/día disminuyó el daño oxidativo, pues redujo la formación del complejo MDA-TBARS en 54% con respecto al grupo control. Conclusiones: La administración de harina de maca amarilla a animales diabéticos mejoró el metabolismo de la glucosa, regulando la glicemia y

  14. Estudio de la función de la desaminasa inducida por activación en la diversificación de anticuerpos y en la generación de lesiones linfomagénicas

    OpenAIRE

    Vidal Sernández, Isora

    2011-01-01

    La Desaminasa Inducida por Activación inicia las reacciones de Hipermutación Somática (SHM) y Cambio de Isotipo (CSR), responsables de la diversificación secundaria de anticuerpos. Además, AID promueve la generación de translocaciones cromosómicas con potencial linfomagénico. Por ello, el estudio de la regulación de esta enzima es de vital importancia. En primer lugar, realizamos un análisis exhaustivo de las consecuencias de una reducción en los niveles de AID in vivo e in vitro utilizando a...

  15. El estrés oxidativo: detonante fisiopatológico en la cardiomiopatía dilatada inducida por doxorrubicina

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    Ronal Aroche Aportela

    2011-12-01

    Full Text Available

    La cardiomiopatía dilatada inducida por doxorrubicina constituye uno de los principales efectos indeseables del tratamiento de pacientes con tumores malignos. El estrés oxidativo constituye uno de los mecanismos fisiopatológicos que desempeñan un papel fundamental en la instauración de la enfermedad causada por este antibiótico del grupo de las antraciclinas. La comprensión de estos mecanismos fisiopatológicos resulta de vital importancia para llevar a cabo estrategias de intervención farmacológica y nutricional para contribuir a palear los efectos nocivos de este antineoplásico. En el presente trabajo se realizó una actualización bibliográfica sobre el tema y se proponen ideas que pueden ser útiles para la comunidad científica que está enfrascada en el tratamiento de esta enfermedad crónica, y que se propone mejorar la calidad de vida de los pacientes que la padecen.

    Oxidative Stress: Pathophysiologic Trigger in Doxorubicin-induced Dilated Cardiomyopathy

    Doxorubicin-induced dilated cardiomyopathy is one of the main adverse effects in the treatment of patients with malignant tumours. Oxidative stress is one of the pathophysiological mechanisms that play a key role in the establishment of the disease caused by this anthracycline-type antibiotic. Understanding these pathophysiologic mechanisms becomes of vital importance in order to carry out pharmacological and nutritional intervention strategies to help paddling the harmful effects of this antineoplastic. As part of this research we conducted an updating literature review on the subject and provided ideas that can be useful for the scientific community engaged in the treatment of this chronic disease, which aims to improve the life quality of patients suffering from it.

  16. Diabetes insípida nefrogénica inducida por litio: el papel de las aquoporinas

    OpenAIRE

    Mauricio J. De Castro-Pretelt

    2005-01-01

    La diabetes insípida nefrogénica es una entidad caracterizada por un cuadro de poliuria, polidipsia, baja osmolaridad urinaria y osmolaridad sérica aumentada por un daño en la capacidad concentradora renal, debido a lo cual se produce un cuadro de deshidratación por depleción de volumen que puede llegar a ser mortal. Dentro de las múltiples causas de diabetes insípida nefrogénica se encuentra la toxicidad por litio. Este es el reporte de un caso de una paciente que llegó a l...

  17. Arteriopatía periférica crónica inducida por cocaína Chronic peripheral arterial disease induced by cocaine

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    Sonia Pankl

    2012-02-01

    Full Text Available La trombosis periférica aguda inducida por cocaína ha sido descripta en la literatura, siendo una complicación poco común. Si bien existen comunicaciones que reflejan los efectos crónicos de la cocaína sobre el sistema arterial periférico, no hay casos publicados de tal complicación en ausencia de otros factores de riesgo. Se presenta el caso de una mujer de 22 años de edad con antecedentes de consumo de cocaína intranasal de 3 gramos por semana durante un año, que consultó por claudicación intermitente a los 200 metros asociada a dolor y parestesias en miembro inferior izquierdo de 2 meses de evolución. El ecodoppler arterial evidenció una estenosis mayor del 70% en la arteria femoral superficial izquierda. Se realizaron estudios complementarios descartando otras etiologías probables. Se inició tratamiento con ácido acetilsalicílico, cilostazol y ejercicio reglado, asociado a terapia de apoyo para mantenimiento del cese del consumo de cocaína, con buena respuesta. Se destaca la importancia de la difusión de información a los pacientes, dado que la mayoría de la población desconoce las complicaciones cardiovasculares de dicha adicción. Es indispensable indagar sobre el consumo de cocaína en pacientes jóvenes con arteriopatía sin factores de riesgo aparentes.Cocaine induced acute peripheral thrombosis, though a rare complication, has been described in the literature. Although there are reports describing the chronic effects of cocaine on the peripheral arterial system, there are no published cases of this complication when other risk factors are lacking. We report on a 22 year old female patient, with intranasal consumption of 3 grams of cocaine per week for a year, who consulted for intermittent claudication at 200 meters, associated to left lower limb pain and paresthesiae for the last two months. Arterial Doppler ultrasonography showed a stenosis greater than 70% in the superficial left femoral artery. Other

  18. Mecanismo de la apoptosis inducida por el inhibidor de quinasas sorafenib en células de mieloma humano

    OpenAIRE

    Ramírez Labrada, Ariel Gaspar; Naval Iraberri, Javier; Marzo Rubio, María Isabel

    2013-01-01

    El mieloma múltiple (MM) es la segunda neoplasia hematológica más frecuente, después del linfoma no Hodgkin y constituye, aproximadamente, el 10% de todas las neoplasias hematológicas, y el 1% de todos los cánceres y causa el 2% de las muertes por cáncer. El sorafenib es un inhibidor de múltiples quinasas diseñado originalmente como inhibidor de la vía de las MAPK. Debido que la actividad de ERK es esencial para la proliferación de las células de mieloma múltiple mediada por la IL-6, se anal...

  19. Reacciones de fotodegradación de tirosina, histidina, metionina y hormona estimulante de los melanocitos inducidas por pterina

    OpenAIRE

    Castaño Espinal, Diana Carolina

    2016-01-01

    El principal objetivo de este trabajo de Tesis Doctoral es identificar los mecanismos implicados en la degradación fotosensibilizada de aminoácidos libres (tirosina (Tyr), histidina (His), metionina (Met)) y péptidos con importancia biológica (α-MSH) por compuestos pterínicos (pterina (Ptr)) en solución acuosa, bajo irradiación UV-A (320 – 400 nm). A continuación se presentan los objetivos específicos con los cuales se dirigió el desarrollo de esta tesis: - Estudiar los procesos fot...

  20. Evaluación del efecto de duloxetina y pregabalina en un modelo de fibromialgia inducida por reserpina en rata

    OpenAIRE

    González Soler, Eva María

    2017-01-01

    INTRODUCCIÓN El síndrome de fibromialgia (FMS) es una enfermedad que se caracteriza principalmente por dolor muscular crónico generalizado o multifocal de origen desconocido, y la co-existencia de otras manifestaciones clínicas, como las alteraciones del estado de ánimo, los trastornos del sueño, la fatiga, la rigidez matutina, las disfunciones cognitivas, la ansiedad, los dolores de cabeza recurrentes, los mareos, el síndrome de colon irritable y/o el dolor urogenital. La alta prevalencia...

  1. Transiciones microestructurales inducidas por cizalla en sistemas acuosos de un tensioactivo catiónico tipo esterquat

    OpenAIRE

    Calero, Nuria; Alfaro, Mª; Lluch, Mª; Berjano, M.; Muñoz, J.

    2010-01-01

    Se presenta un estudio basado en técnicas reológicas y de microscopía electrónica de barrido de bajas temperaturas (cryo-SEM) sobre los cambios de microestructura provocados por el flujo en cizalla de dispersiones acuosas de un tensioactivo catiónico tipo esterquat. Se comparan micrografías de cryo-SEM y las respuestas bajo cizalla oscilatoria de dispersiones sin y con cloruro de calcio. Esta última no presenta zona de comportamiento viscoelástico lineal, apuntando su respuesta no lineal a un...

  2. Transiciones microestructurales inducidas por cizalla en sistemas acuosos de un tensioactivo catiónico tipo esterqua

    OpenAIRE

    Calero Romero, Nuria; Alfaro Rodríguez, María del Carmen; Lluch, M. Ángeles; Berjano Núñez, Manuel; Muñoz García, José; Muñoz García, José (Coordinador)

    2010-01-01

    Se presenta un estudio basado en técnicas reológicas y de microscopía electrónica de barrido de bajas temperaturas (cryo-SEM) sobre los cambios de microestructura provocados por el flujo en cizalla de dispersiones acuosas de un tensioactivo catiónico tipo esterquat. Se comparan micrografías de cryo-SEM y las respuestas bajo cizalla oscilatoria de dispersiones sin y con cloruro de calcio. Esta última no presenta zona de comportamiento viscoelástico lineal, apuntando su respuesta no lineal a un...

  3. Evaluación de la reacción acrosomal en espermatozoides humanos inducida por oligosacáridos

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    Angela Cadavid

    2004-02-01

    Full Text Available

    La capacitación es un proceso necesario que debe sufrir el espermatozoide para poder llevar a cabo la fertilización del ocito. Este evento se da durante su paso a través del tracto reproductor femenino, donde ocurre la interacción entre los espermatozoides y las células del epitelio oviductal, la cual es dependiente de carbohidratos. Adicionalmente, el espermatozoide necesita interactuar con una serie de moléculas presentes en la zona pelúcida, que permiten un reconocimiento específico entre el espermatozoide y el oocito. La interacción entre gametos es específica de especie; ésto indica que la zona pelúcida posee ligandos que son reconocidos por los espermatozoides y que éstos poseen receptores que le permiten la unión al oocito (1.

     

     

  4. Programación temprana de alteraciones en el sistema del óxido nítrico renal y vascular inducidas por la deficiencia de cinc

    Directory of Open Access Journals (Sweden)

    María A. Costa

    2008-01-01

    Full Text Available Resumen:IntroducciónNumerosos estudios mostraron que la deficiencia nutricional durante la vida fetal y posnatal predisponen al desarrollo de patologías en la vida adulta, como la hipertensión arterial y las enfermedades renales. La distribución ubicua del cinc y sus propiedades químicas determinan su esencialidad en los sistemas biológicos.ObjetivosEvaluar si las alteraciones renales y cardiovasculares en la vida adulta inducidas por la restricción moderada de cinc durante la vida fetal, la lactancia y/o el crecimiento se asocian con cambios en el sistema del óxido nítrico.Material y métodosRatas Wistar hembra recibieron durante la preñez hasta el destete de las crías una dieta control o una baja en cinc. Luego del destete, las crías macho se asignaron al azar a dos grupos que recibieron una dieta control o una baja en cinc durante 60 días.ResultadosLos resultados mostraron que el aporte insuficiente de cinc durante el crecimiento previo y/o posterior al destete indujo un aumento de la presión arterial y una disminución del volumen de filtrado glomerular en la vida adulta, asociados con una disminución del sistema del óxido nítrico renal y vascular. Además, el bajo aporte de este mineral durante la vida fetal indujo un peso menor al nacer, que se correlacionó en forma negativa con la presión arterial en la vida adulta.ConclusionesEste trabajo brinda evidencias importantes que sugieren que el aporte inadecuado de cinc durante el crecimiento prenatal y posnatal constituye un factor de riesgo cardiovascular y renal, dado que induce alteraciones en la regulación de la presión arterial y en la función renal en el individuo adulto.REV ARGENT CARDIOL 2008;76:459-464.

  5. Lactancia masculina inducida

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    Joaquín Román Lafont

    Full Text Available Para crear el mundo que se vislumbra en la Declaración del Milenio, aprobada en las Naciones Unidas, es esencial la igualdad entre los géneros. En las mujeres, que son las cuidadoras primarias de los niños, cada día es más preocupante el abandono parcial -o total- de la lactancia natural. En la etapa embrionaria el desarrollo de las estructuras que forman los tejidos mamarios es el mismo para ambos sexos. Las tetillas en los varones, que son el equivalente de las mamas en la mujer, por mucho tiempo fueron consideradas un misterio, pues aparentemente no cumplen con ninguna función biológica y cuya presencia plantea un problema para la teoría de la evolución. Sin embargo, de diferentes latitudes del planeta se reportan hombres que han logrado una lactancia inducida con solo la succión frecuente y prolongada del bebé. Si esto ha ocurrido en hombres con mamas subdesarrolladas, ¿cómo es posible que las mujeres, que están mejor preparadas para este fin, abandonen la lactancia? Ante la interrogante de ¿puede el hombre lactar?, se realizó una búsqueda sobre lactancia masculina online a través de Infomed e Internet, visitas a Bibliotecas especializadas y al Hospital Universitario “Calixto García” de la capital. El resultado de la búsqueda es sorprendente…, hasta en Cuba hubo un camagüeyano que lactó a su hija durante 22 meses.

  6. Efecto antioxidante y hepatoprotector del Petroselinum sativum (perejil en ratas, con intoxicación hepática inducida por paracetamol

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    Luzmila Troncoso

    2007-12-01

    Full Text Available Objetivo: Determinar el efecto antioxidante y hepatoprotector del perejil (Petroselinum sativum en ratas con intoxicación hepática inducida por paracetamol. Lugar: Centro de Investigación de Bioquímica y Nutrición - "Laboratorio de Bioquímica Clínica y Nutricional "Leonidas Delgado Butrón" "Emilio Guija Poma" - Universidad Nacional Mayor de San Marcos. Lima, Perú. Diseño: Estudio analítico, transversal, prospectivo y cuasi-experimental. Material: Ratas albinas Holtzman machos adultas. Métodos: Se utilizó 40 ratas de 2 meses de edad, con pesos entre 280 y 320 g, distribuidas aleatoriamente en cuatro grupos de 10 animales cada uno. Todos los grupos recibieron la misma dieta y agua ad libitum, además de los respectivos tratamientos, los cuales fueron administrados por vía oral diariamente, durante 5 días: paracetamol (administrado en una dosis de 200 mg/kg de peso corporal para inducir la intoxicación hepática y, al mismo tiempo, un hepatoprotector, ya fuera farmacológico (fármaco hepatoprotector (FHP: Purinor® o natural (perejil; además, un grupo de paracetamol solo y otro de control. Al término del período experimental, los animales fueron sacrificados. En suero sanguíneo se determinó aspartato aminotransferasa (AST, alanina aminotransferasa (ALT, gamma glutamil transferasa (GGT, grupos sulfhidrilo, proteínas totales y albúmina sérica; y en el homogenizado citosólico de hígado, fracción posmitocondrial, se determinó superóxido dismutasa, catalasa, glucosa-6-fosfato deshidrogenasa, grupos sulfidrilo, especies reactivas al ácido tiobarbitúrico (TBARS o radicales libres y proteínas. Además, se realizó el estudio histopatológico del hígado, para identificar signos de necrosis y signos de regeneración posnecrótica. Principales medidas de resultados: Efecto antioxidante y hepatoprotector del perejil. Resultados: El perejil mostró un mejor efecto hepatoprotector que el FHP, frente a la acción nociva del

  7. Modificaciones hematológicas inducidas por eritropoyetina frente a hipoxia normobárica intermitente Hematologic changes induced by erythropoietin versus intermittent normobaric hypoxia

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    F. Sanchis-Gomar

    2010-12-01

    Full Text Available

    Publicaciones recientes reflejan la preocupación de las autoridades antidopaje por el uso de sistemas simuladores de altitud y la posibilidad de considerarlos métodos dopantes. El objetivo de nuestro estudio fue el de comparar las modificaciones hematológicas inducidas por dos tratamientos con eritropoyetina recombinante humana (rHuEpo a diferentes dosis, frente a un protocolo de hipoxia normobárica intermitente (HNI en un modelo animal.
    Veinticuatro ratas Wistar macho jóvenes fueron divididas en 3 grupos experimentales: grupo sometido a HNI (12h pO2 12% /12h pO2 21% (n=8; grupo tratado con una dosis de 300 UI de rHuEpo (n=8 y grupo tratado con 500 UI de rHuEpo (n=8. Se extrajeron dos muestras de sangre a cada uno de los grupos experimentales (antes y después de los tratamientos. Nuestros resultados muestran incrementos muy similares, y estadísticamente significativos, en los valores de hemoglobina, de hematocrito y de reticulocitos, tanto en el grupo HNI como en el grupo tratado con 300 UI de rHuEpo tras los 15 días de tratamiento. El tratamiento con 500 UI de rHuEpo produjo un incremento significativamente mayor.
    La principal conclusión de nuestro estudio es que las modificaciones de los parámetros hematológicos obtenidas mediante un protocolo de HNI son similares a las obtenidas con un tratamiento con 300 UI de rHuEpo.
    Palabras clave: Hemoglobina, hematocrito, reticulocitos, dopaje

    Recent publications reflect the anti-doping authorities’ concern about the use of altitude simulator systems, since these technologies could be considered as doping methods. The major aim of our study was to compare the effect of two different rHuEpo treatments with a normobaric intermittent hypoxic (NIH protocol regarding the modifications of hemoglobin, hematocrit and reticulocytes values in an animal model. Although these hematological parameters are of secondary nature, some international sport federations

  8. Efectos del policosanol en los modelos de pleuresía inducida por carragenina y granuloma por algodón

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    Daisy Carbajal Quintana

    Full Text Available Introducción: el policosanol, mezcla de alcoholes alifáticos primarios superiores purificada de la cera de caña, inhibe la actividad de la cicloxigenasa-1 (COX-1 in vitro, efecto que pudiera sustentar su acción antiagregante plaquetaria. Sin embargo, sus posibles efectos en modelos experimentales de inflamación no se habían investigado. Objetivo: determinar el efecto antinflamatorio in vivo del policosanol en un modelo de inflamación aguda (pleuresía por carragenina y crónico (granuloma por algodón. Métodos: se distribuyeron las ratas Sprague Dawley en siete grupos para el modelo de inflamación aguda: un control negativo (vehículo y seis a los que se les indujo la inflamación: un control positivo (vehículo, cuatro tratados con policosanol (50-800 mg/kg y uno con aspirina (100 mg/kg. Se cuantificaron a las 5 h el volumen de exudado pleural, la concentración de proteínas y actividad de la enzima mieloperoxidasa. Se distribuyeron las ratas en seis grupos para el modelo crónico: un control (vehículo, cuatro tratados con policosanol (50-800 mg/kg y uno con aspirina (100 mg/kg. Se extrajo el granuloma para determinar los pesos húmedo y seco seis días después de implantado el pellet. Resultados: dosis orales únicas de policosanol (200, 400 y 800 mg/kg redujeron significativa y moderadamente el volumen, la actividad de la enzima mieloperoxidasa (» 12 % y la concentración de proteínas (» 20 % del exudado pleural, mientras la aspirina redujo estos indicadores en un 35,3, 19,9 y 19,1%, respectivamente. La administración oral de policosanol (400 y 800 mg/kg durante 6 días disminuyó significativa y moderadamente el peso húmedo del granuloma (16,4 y 16,2 %, y el peso seco (28,4 y 34,4 %. La aspirina 100 mg/kg redujo estas variables en un 18,5 % (peso húmedo y 34,4 % (peso seco. Ambos tratamientos produjeron mayores reducciones del peso seco que del peso húmedo del granuloma. Conclusiones: la administración oral de policosanol

  9. Funciones inducidas conexas

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    Sergio A. Pérez

    2013-12-01

    Full Text Available Se dice que una función f : X → Y definida entre espacios topológicos es conexa si la gráfica Γ(f = {(x, f(x : x ∈ X} es conexa. Dado un continuo X, se consideran los hiperespacios: 2 X, la colección de todos los subconjuntos cerrados no vacíos de X; C(X, el conjunto de todos los subcontinuos de X; y Fn(X, los subconjuntos no vacíos de a lo más n puntos de X. Además, dada una función f : X → Y entre continuos, consideramos las funciones inducidas 2 f : 2X → 2 Y definidas por 2 f (A = f(A para cada A ∈ 2 X; Fn(f: Fn(X → Fn(Y , la función restricción Fn(f = 2f |Fn(X ; y si f es una función de Darboux débil, definimos C(f: C(X → C(Y por C(f = 2f |C(X . En este artículo estudiamos las relaciones entre las siguientes cinco afirmaciones: 1 f es conexa; 2 C(f es conexa; 3 Fn(f es conexa, para algún n ≥ 2; 4 Fn(f es conexa, para todo n ≥ 2; 5 2 f es conexa. Abstract. A function between topological spaces f : X → Y is said to be connected provided that the graph Γ(f = {(x, f(x : x ∈ X} is connected. Given a continuum X, some hyperspaces are considered: 2 X, the collection of all non-empty closed subsets of X; C(X, the set of all subcontinua of X, and Fn(X the set of nonempty subsets of at most n points of X. Moreover, given f : X → Y a function between continua, consider the induced functions: 2 f : 2X → 2 Y , defined by 2 f (A = f(A for each A ∈ 2 X; Fn(f: Fn(X → Fn(Y , the restriction function Fn(f = 2f |Fn(X ; and, if f is a weak Darboux function, we define C(f: C(X → C(Y by C(f = 2f |C(X . In this paper we study the relationships between the following five statements: 1 f is connected; 2 C(f is connected; 3 Fn(f is connected, for some n ≥ 2; 4 Fn(f is connected, for all n ≥ 2; 5 2 f is connected.

  10. Mecanismos involucrados en la promoción de crecimiento axonal por la glia envolvente del bulbo olfatorio

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    Vilma C. Muñetón-Gómez

    2001-06-01

    Full Text Available La actividad que promueve el crecimiento de axones por la glia envolvente (GE del bulbo olfatorio depende de la expresión de diversas moléculas durante el desarrollo, la vida adulta y la reparación de lesiones nerviosas. Diversas moléculas tales como las neurotrofinas y sus receptores, los factores de crecimiento, las moléculas de adhesión celular, las moléculas de matriz extracelular y las moléculas asociadas con la mielinización son producidas por la glia del sistema olfatorio durante el desarrollo. Su expresión sostenida durante la vida adulta parece estar asociada con el reemplazo celular y la alta plasticidad de este sistema. A su vez, su expresión se involucra en procesos de reparación de lesiones mediados por trasplantes de glia. La migración de la GE, que acompaña axones en crecimiento, se observa durante el desarrollo y en procesos de regeneración luego de una lesión. Los trasplantes de,GE permiten la navegación de brotes regenerantes a través del tejido gliótico inhibidor formado luego de una lesión del sistema nervioso central. El propósito de esta revisión es profundizar en los mecanismos de actividad promotora de crecimiento axonal.

  11. Estudio de la influencia del Cu y Ni en la cinética de transformación martensítica inducida por deformación en fundiciones nodulares austemperadas

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    Guzmán, D.

    2013-06-01

    Full Text Available The objective of this work was to study the influence of copper and nickel on the kinetics of strain-induced martensite in austempered ductile cast iron. The austempered ductile cast irons were obtained from two ductile cast irons with different copper and nickel contents by means of austempering treatment. The deformation was carried out using a rolling mill. The quantification of the phases was obtained by means of X ray diffraction, while the microstructural characterization was carried out using optical and scanning electron microscopy. It was proved that the kinetics of strain-induced martensite in austempered ductile cast iron can be modeled using the equations proposed by Olson- Cohen and Chang et al. Based on the results obtained from these analyses, it is possible to conclude that the nickel and copper complicate the martensite transformation because these elements increase the staking fault energy of the austenite and its thermodynamic stability.El objetivo de este trabajo fue estudiar el efecto del cobre y níquel en la cinética de la transformación martensítica inducida por deformación en fundiciones nodulares austemperadas. Las fundiciones utilizadas se fabricaron mediante austemperado, a partir de dos fundiciones nodulares, con diferentes contenidos de cobre y níquel. La deformación se realizó en un laminador de rodillo. La cuantificación de las fases se realizó mediante difracción de rayos X, mientras que la caracterización microestructural se efectuó utilizando microscopía óptica y electrónica de barrido. Se comprobó que la cinética de transformación martensítica inducida por deformación en fundiciones nodulares austemperadas puede ser modelada mediante los modelos de Olson-Cohen y Chang et al. Basándose en los resultados obtenidos de estos ajustes, se concluye que tanto el níquel como el cobre dificultan la transformación martensítica debido a que estos elementos aumentan la energía de falla de

  12. Asma inducida por el ejercicio y la clase de Educación Física : ¿qué aspectos ha de tener en cuenta el profesor durante la clase de E. Física enfocada al desarrollo de la resistencia en niños con AIE?

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    López Torres, Jesús

    2014-01-01

    El asma inducida por el ejercicio es una manifestación de la enfermedad asmática. La prevalencia está en aumento y una de las zonas dentro de España con más casos es Andalucía. De este modo existe una gran probabilidad de que un maestro se encuentre con este tipo de alumnos. El problema es el gran desconocimiento por parte del profesorado sobre este tipo de enfermedad. Esto es debido a que existe una gran desinformación sobre qué aspectos hay que tener en cuenta con este tipo de alumnado. Por...

  13. PROFILAXIS DE LA NEFROPATÍA INDUCIDA POR CONTRASTE EN PACIENTES DE ALTO RIESGO CON SÍNDROME CORONARIO AGUDO SIN ELEVACIÓN DEL SEGMENTO ST / Prophylaxis of contrast-induced nephropathy in high risk patients with non-ST-segment elevation acute coronary syndrome

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    Pilar Portero Pérez; Tatiana Matajira Chia; Ramón Bascompte Claret; Pilar Artero Bello; Antonela Lukic; Jose A. Linares Vicente; Pablo Revilla Martí; Jose R. Ruiz Arroyo

    2012-01-01

    ResumenIntroducción y objetivos: La eficacia de la administración conjunta de suero salino isotónico y N-acetilcisteína presenta resultados dispares en la prevención de la nefropatía por contraste yodado. Nuestro objetivo fue valorar la posible eficacia de esta estrategia combinada en pacientes con alto riesgo de desarrollar nefropatía inducida por contraste, ingresados y sometidos a intervencionismo coronario percutáneo por síndrome coronario agudo sin elevación del segmento ST en nuestro ce...

  14. El coactivador de receptores nucleares RAC3 tiene un rol protector de la Apoptosis inducida por distintos estímulos RAC3 nuclear receptor co-activator has a protective role in the apoptosis induced by different stimuli

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    Georgina P. Coló

    2007-10-01

    Full Text Available RAC3 pertenece a la familia de coactivadores de receptores nucleares p160, y se encuentra sobreexpresado en varios tumores. Demostramos previamente que RAC3 es coactivador del factor de transcripción anti-apoptótico NF-kapa;B. En este trabajo investigamos su rol en la apoptosis inducida por H2O2 en una línea celular no tumoral derivada de riñón embrionario humano (HEK293, y por el ligando inductor de apoptosis relacionado a TNF (TRAIL en una línea de leucemia mieloide crónica humana (K562, naturalmente resistente a la muerte por este estímulo. Observamos que las células tumorales K562 poseen niveles altos de RAC3 comparados con las células no tumorales HEK293. La sobreexpresión normal de coactivador o por transfección, inhibe la apoptosis mediante una disminución de la activación de caspasas, translocación del factor inductor de apoptosis (AIF al núcleo, aumento de la actividad de NF-kapa;B y las quinasas AKT y p38 y disminución de la quinasa ERK. Lo opuesto fue observado por disminución de RAC3 mediante la técnica de ARN interferente (RNAi en K562, aumentando así la apoptosis inducida por TRAIL. Estas evidencias sugieren que una sobreexpresión de RAC3 contribuye al desarrollo de tumores, participando en las cascadas que controlan la muerte celular por mecanismos no estrictamente dependientes de hormonas esteroideas y/o de acetilación, constituyendo esto un posible blanco de ataque para el tratamiento de tumores.RAC3 belongs to the family of p160 nuclear receptors coactivators and it is over-expressed in several tumors. We have previously shown that RAC3 is a NF-kappa;B coactivator. In this paper, we investigated the role of RAC3 in cell-sensitivity to apoptosis, using H2O2 in the human embryonic kidney cell line (HEK293, and tumor necrosis factor-related apoptosis inducing ligand (TRAIL in a human chronic myeloid leukemia cell line (K562 naturally resistant to TRAIL. We observed that the tumoral K562 cells have high levels

  15. Mitogen activated protein kinases blockade improves lipopolysaccharide-induced ileal motor disturbances El bloqueo de las proteínas cinasas activadas por mitógenos mejora las alteraciones motoras inducidas por el lipopolisacárido en íleon

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    Sergio Gonzalo

    2012-06-01

    Full Text Available Background: several diseases such as sepsis can affect the ileum. Lipopolysaccharide (LPS, an endotoxin present in the cell wall of gram negative bacteria, is a causative agent of sepsis. Objectives: the aims of this study were: a to investigate the role of mitogen activated protein kinases (MAPKs in the effect of LPS on the acetylcholine-induced contractions of rabbit ileum; and b to study the localization of MAPKs in the ileum. Material and methods: ileal contractility was studied in an organ bath and MAPKs were localized by immunohistochemistry. Results: acetylcholine-induced contractions decreased with LPS. SB203580, SP600125 and U0126 blocked the effect of LPS on the acetylcholine-induced contractions. Phosphorylated p38 and ERK were detected in neurons of myenteric plexus and phosphorylated p38 and JNK in smooth muscle cells of ileum. Conclusion: we can suggest that p38, JNK, and ERK MAPKs are involved in the mechanism of action of LPS in the ileum.Introducción: varias enfermedades como la sepsis pueden afectar al íleon. El lipopolisacárido (LPS, una endotoxina presente en la pared celular de las bacterias gram-negativas, es un agente causal de la sepsis. Objetivos: los objetivos del presente estudio fueron: a investigar el papel de las proteína cinasas activadas por mitógenos (MAPKs en los efectos del LPS en las contracciones inducidas por acetilcolina en el íleon de conejo; y b estudiar la localización de las MAPKs en el íleon. Material y métodos: la contractilidad ileal se estudió en un baño de órganos y las MAPKs se localizaron mediante inmunohistoquímica. Resultados: el LPS disminuyó las contracciones inducidas por acetilcolina. El SB203580, el SP600125 y el U0126 bloquearon los efectos del LPS sobre las contracciones inducidas por acetilcolina. La p38 y la ERK fosforiladas se detectaron en las neuronas del plexo mientérico y la p38 y la JNK fosforiladas en las células del músculo liso del íleon. Conclusi

  16. Estudio de la enteropatía inducida por péptidos de gliadinas y ligandos de la inmunidad innata en modelos experimentales

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    Araya, Romina Elizabeth

    2015-01-01

    La Enfermedad Celíaca (EC) es una enteropatía crónica de base inmune desencadenada por la ingestión de gluten en pacientes con predisposición genética. Se caracteriza por cambios histológicos severos en la mucosa duodenal definidos por atrofia vellositaria, infiltrado linfocitario e hiperplasia de criptas. Es una patología de alta prevalencia (estimada en un 1% de la población) con una sintomatología variada que puede estar asociada a complicaciones severas. Esta enfermedad ha sido ...

  17. Actividad inducida por androsterona y hemisuccinato de androsterona sobre la presión de perfusión y la resistencia vascular

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    Lauro Figueroa

    2009-12-01

    Conclusiones. Los efectos inducidos por androsterona y hemisuccinato de androsterona sobre la presión de perfusión y la resistencia vascular pueden depender de su estructura química. En el caso de la actividad ejercida por el análogo de androsterona, podría involucrar la interacción del esteroide-receptor androgénico e, indirectamente, la activación del canal de calcio y, consecuentemente, inducir variaciones en la presión de perfusión.

  18. Estudio de la osteoporosis inducida por la deprivación androgénica en pacientes con cáncer de próstata

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    Abascal Junquera, José María

    2009-01-01

    Consultable des del TDX Títol obtingut de la portada digitalitzada INTRODUCCIÓN: La supresión androgénica (SA) en el contexto global del manejo terapéutico del cáncer de próstata (CAP), ocupa un lugar cada vez más relevante, por el gran volumen de pacientes que son sometidos a este tipo de tratamiento y su larga duración. El hipogonadismo inducido por la SA prolongada es una de las causas principales de osteoporosis (OP) secundaria en el varón. La pérdida de masa ósea es un efecto secun...

  19. Actividad inotrópica inducida por el derivado carbamacepina-alquino en un modelo de corazón aislado y perfundido a flujo constante

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    Lauro Figueroa-Valverde

    2011-03-01

    Conclusiones. La actividad ejercida por el derivado carbamacepina-alquino sobre la presión de perfusión, la resistencia vascular y la presión intraventricular, involucra la activación del canal de calcio de tipo L, lo que trae como consecuencia indirecta cambios en los niveles de calcio intracelular y, subsecuentemente, induce un efecto inotrópico positivo.

  20. Reacción posquirúrgica del lecho vascular inducida por el campo magnético de ultra-alta frecuencia

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    Armando Hidalgo de Paz

    1995-06-01

    Full Text Available En 82 ratas blancas adultas se estudió el efecto posoperatorio del campo magnético de ultra- -alta frecuencia (CMUAF sobre el volumen del lecho intramuscular, durante el período de formación de colaterales. El CMUAF se aplicó con el aparato portátil UVCHE-30, con frecuencia de 40,68 MHz y potencias fijas de salida de 15 y 30 W. Luego de seccionar quirúrgicamente las arterias femorales, se aplicó el campo magnético por 2, 6, 10 y 16 semanas. En estos plazos se inyectó mezcla de tinta china-gelatina en el lecho vascular y se obtuvieron cortes micrométricos que se transparentaron y fueron posteriormente leídos por microfotometría. Se observó un marcado aumento del volumen del lecho vascular intramuscular por acción del CMUAF, particularmente en los períodos de 2 y 6 semanas posteriores al inicio del tratamiento. También se evidenció mayor reacción vascular a la acción del CMUAF con potencia de 15 W, en comparación con los resultados en 30 W

  1. Compactación inducida por el tránsito vehicular sobre un suelo en producción hortícola Induced compaction by the vehicular traffic in a soil for horticultural crop production

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    Antonino Marcelo Terminiello

    2000-01-01

    Full Text Available Se realizaron ensayos en campo con el objeto de caracterizar el estado de compactación de un suelo en producción hortícola inducida por el tránsito, luego del desarrollo del ciclo de un cultivo de repollo (Brassica oleracea L. grupo capitata y su incidencia sobre el rendimiento. Se efectuaron determinaciones de resistencia a la penetración, densidad aparente y humedad gravimétrica sobre el suelo y biomasa aérea al finalizar el ciclo del cultivo en los sectores de mayor y menor número de pasajes de vehículos. Los valores de resistencia a la penetración fueron de 1,7 y 1,3 MPa, significativamente mayores para el tratamiento de más de 7 y 3 pasadas respectivamente en el rango de profundidad de 0-100 mm . No se manifestaron diferencias en el parámetro densidad aparente en la totalidad del perfil. Se encontraron diferencias estadísticamente significativas en biomasa aérea, para el tratamiento de 3 pasadas (1902.6 g planta-1, en relación al de mas de 7 pasadas (1447,9 g planta-1. El pasaje repetido sobre los surcos originan incrementos en la resistencia a la penetración a nivel superficial. El peso fresco y la materia seca del cultivo son afectados por el número de pasadas de los tractores y máquinas agrícolas.Field test were carried out with the objective of characterizing the state of compaction in horticultural soil induced by traffic, after the development of a cabbage crop (Brassica oleracea L. group capitata cycle, and its incidence on yield. Measurements of penetration resistance, bulk density, and moisture content in soil were made and aeread biomass at the end of the cycle crop in sectors with larger and smaller number of vehicles passes. Values of penetration resistance of 1.7 and 1.3 MPa were found for treatment with more than 7 passes and 3 passes respectively in the depth range of 0-100 mm. No significant differences were found in bulk density parameter in the entire soil profile. Statistically significant differences

  2. Estudio de la apoptosis inducida por la inhibición de la vía de la PI3K/AKT

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    Vázquez de la Torre Cervera, Aurelio

    2013-01-01

    [spa] Una de las vías que se postula que tienen una mayor importancia en las enfermedades neurodegenerativas es la de los inositoles fosfato. Para el estudio de esta vía se ha utilizado un inhibidor farmacológico de la fosfoinositol 3 cinasa (PI3K), el LY294002, en un modelo in vitro de células granulares de cerebelo de rata (CGC). Al tratar las CGC con una dosis de 30μM de LY294002 se produce una muerte celular por apoptosis que es independiente de calpaínas y dependiente de caspasas, además...

  3. Efecto antioxidante del extracto acuoso de propóleos sobre la hepatotoxicidad inducida por el octilfenol en ratas macho Antioxidant effect of aqueous extract of propolis on hepatotoxicity induced by octylphenol in male rats

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    Eman M Saleh

    2012-12-01

    Full Text Available El 4-terc-octilfenol (4-terc-OP es un alquilfenol que afecta a la salud humana mediante la estimulación de la producción de radicales libres. El extracto acuoso de propóleos es un producto natural rico en favonoides que tienen actividad antioxidante. Este estudio fue diseñado para investigar la capacidad del extracto de propóleos de reducir la hepatotoxicidad inducida por el 4-terc-OP en ratas macho. Los animales fueron asignados a 5 grupos y tratados durante 6 semanas. Grupo 1: control; grupo 2: 100 mg de 4-terc-OP/kg/día; grupo 3: 100 mg de extracto de propóleos/kg/día; grupo 4: 100 mg de 4-terc-OP/ kg/día más 100 mg de extracto de propóleos/kg/día, grupo 5: 100 mg de 4-terc-OP/kg/día durante 6 semanas, seguidos de 100 mg de extracto de propóleos/kg/día durante 6 semanas. El grupo 4-terc-OP mostró niveles signifcativamente elevados de AST, ALT, ALP, GGT, bilirrubina, creatinina, urea, lípidos totales, colesterol total, triglicéridos, LDL-C y MDA, con una disminución signi-fcativa de proteínas totales, albúmina, globulina, HDL-C, la capacidad antioxidante total, SOD, CAT y GST, en comparación con el grupo control. La administración de extracto de propóleos, ya sea solo o combinado con 4-terc-OP redujo la hepatotoxicidad inducida por 4-terc-OP. Los estudios de fragmentación del ADN apoyan el efecto deletéreo observado por el tratamiento con 4-terc-OP y el efecto protector del extracto de propóleos, sobre las proteínas y las enzimas celulares hepáticas. Los resultados histopatológicos revelaron la hepatotoxicidad por 4-terc-OP y efecto protector inducido por el extracto de propóleos. En conclusión, el extracto de propóleos podría reducir el daño hepático y los efectos celulares de toxicidad en las células del hígado inducidos por 4-terc-OP.4-tertiary-octylphenol (4-tert-OP is an alkylphenol that affects human health by stimulating free radical production. Aqueous propolis extract is a natural product rich in

  4. Prevención, diagnóstico y tratamiento de la cardiotoxicidad inducida por quimioterapia: ¿qué estamos haciendo?

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    Lázaro de la Cruz Avilés

    2012-09-01

    Full Text Available Las enfermedades del corazón y los tumores malignos constituyen las dos primeras causas de muerte en Cuba, con tasas de mortalidad de 197,5 y 193,6 por 100 000 habitantes, respectivamente, en el año 2011. En Cienfuegos los tumores malignos fueron la primera causa de muerte con una tasa de 115,2 seguida de las enfermedades del corazón con 102,6 por 100 000 habitantes. Las mejoras alcanzadas en la detección y el tratamiento del cáncer han dado origen a una nueva cohorte de pacientes que alcanzan una supervivencia suficiente para que puedan aparecer complicaciones cardíacas derivadas del tratamiento. Lamentablemente, el abundante conocimiento sobre las vías bioquímicas involucradas en el tratamiento dirigido del cáncer no se ha visto acompañado de un conocimiento paralelo de las consecuencias cardíacas de su modulación.

  5. Aspergilosis pulmonar secundaria a neutropenia inducida por metimazol: reporte de un caso Pulmonary aspergillosis due to methimazole-induced neutropenia: a case report

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    Miguel E. Pinto

    2012-06-01

    Full Text Available Se reporta el caso de una paciente de 48 años de edad con diagnóstico reciente de enfermedad de Graves, quien acudió a emergencia por presentar fiebre, palpitaciones y dolor faríngeo. Su tratamiento regular incluía metimazol. Al ingreso, los análisis mostraron TSH suprimido, T4 libre elevado y neutropenia. La paciente fue hospitalizada, se administraron antibióticos y factor estimulante de colonia. Después de diez días de tratamiento, la paciente presentó leucocitosis, fiebre y hemoptisis. La tomografía de tórax mostró una cavidad con múltiples nódulos en el lóbulo superior derecho. Los cultivos fueron positivos a Aspergillus fumigatus y Aspergillus flavus. Se inició tratamiento con anfotericina B y luego se cambió a voriconazol, a pesar de lo cual no hubo mejoría del cuadro. La paciente falleció por falla multiorgánica.A 48-year old woman with a recent diagnosis of Graves’ disease arrived at the emergency room with fever, palpitations, and a sore throat. Her regular treatment included methimazole. On admission, laboratory results showed suppressed TSH, elevated free thyroxine, and neutropenia. She was admitted and started on antibiotics and granulocyte-macrophage colony stimulating factor (gm-csf. After ten days, the patient developed leukocytosis, fever, and hemoptysis. Chest CT scan showed a lung cavity with multiple nodules in the upper right lobe. Cultures from a lung biopsy were positive for Aspergillus Fumigatus and Aspergillus Flavus. Amphotericin B was started but then switched to voriconazole, with both treatments failing to result in clinical improvement. The patient died of multi-organ failure.

  6. Osteonecrosis de los maxilares inducida por bifosfonatos: prevención y actitud terapéutica Bisphosphonate induced osteonecrosis of the jaws: prevention and therapeutic approach

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    F.J. Barrientos Lezcano

    2007-10-01

    Full Text Available Introducción. La osteonecrosis maxilar o mandibular por bifosfonatos puede convertirse en una epidemia debido a la amplia difusión de estos fármacos entre la población. Material y método. Se muestra un protocolo para la prevención y el tratamiento de esta enfermedad. Se presentan tres casos de osteonecrosis maxilar/mandibular. Resultados. Es difícil lograr una curación completa; sin embargo es posible detener la progresión de la enfermedad. Discusión. La cirugía y la suspensión de la terapia con bifosfonatos han demostrado poca utilidad. Los antibióticos y los enjuagues con clorhexidina son las únicas medidas eficaces. Conclusiones. Es imprescindible una planificación adecuada previa a la instauración del tratamiento con bifosfonatos. Ante una osteonecrosis establecida, la actitud debe ser conservadora.Introduction. Bisphosphonate-induced osteonecrosis of the jaws might reach epidemic proportions due to the widespread use of this therapy. Materials and methods. A protocol for prevention and treatment of this pathology is shown. Three clinical cases are reported. Results. It is quite difficult to reach restitutio ad integrum, but stopping the progress of the disease is possible. Discussion. Surgical treatment and cessation of bisphosphonate therapy are of no use. Only antibiotics and oral chlorhexidine have shown some benefits. Conclusions. An accurate preventive attitude is mandatory prior to undergoing bisphosphonate therapy. If osteonecrosis of the jaws is present, management should be conservative.

  7. PROFILAXIS DE LA NEFROPATÍA INDUCIDA POR CONTRASTE EN PACIENTES DE ALTO RIESGO CON SÍNDROME CORONARIO AGUDO SIN ELEVACIÓN DEL SEGMENTO ST / Prophylaxis of contrast-induced nephropathy in high risk patients with non-ST-segment elevation acute coronary syndrome

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    Pilar Portero Pérez

    2012-07-01

    Full Text Available ResumenIntroducción y objetivos: La eficacia de la administración conjunta de suero salino isotónico y N-acetilcisteína presenta resultados dispares en la prevención de la nefropatía por contraste yodado. Nuestro objetivo fue valorar la posible eficacia de esta estrategia combinada en pacientes con alto riesgo de desarrollar nefropatía inducida por contraste, ingresados y sometidos a intervencionismo coronario percutáneo por síndrome coronario agudo sin elevación del segmento ST en nuestro centro. Método: Se aplicó esta estrategia en los pacientes referidos, con al menos un factor de alto riesgo para desarrollar la nefropatía inducida por contraste: mayores de 80 años, diabetes mellitus, creatinina basal mayor de 1,5 mg/dl o alto volumen de contraste (mayor de 400 ml. El protocolo se aplicó durante 12 meses (pacientes que recibieron el protocolo de prevención y se comparó con similares pacientes en los 12 meses previos que no recibieron profilaxis. Resultados: Un total de 30 pacientes (24 % desarrollaron nefropatía inducida por contraste. El porcentaje fue significativamente mayor en el grupo que no recibió profilaxis: 35,9 % vs. 11,5 % (p = 0.003. Conclusiones: La combinación de N-acetilcisteína por vía oral e hidratación parenteral en pacientes de alto riesgo, con síndrome coronario agudo sin elevación de ST, podría ser beneficiosa para evitar la aparición de la nefropatía inducida por contraste. /Abstract Introduction and Objectives: The effectiveness of the administration of isotonic saline solution and N-acetylcysteine shows different results in the prevention of iodine contrast nephropathy. Our objective was to assess the potential effectiveness of this combined strategy in patients at high risk for contrast-induced nephropathy, who were admitted in our center for percutaneous coronary intervention due to non-ST-segment elevation acute coronary syndrome. Method: This strategy was applied in the patients

  8. Tiroiditis autoinmune inducida por interferón en pacientes con infección por virus de la hepatitis C. Interferon-induced autoimmune thyroiditis in a patient with hepatitis C virus infection

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    José L. Pinto

    2011-06-01

    Full Text Available Se reporta el caso de un varón de 43 años de edad, sin antecedentes patológicos de importancia, que acudió por elevación asintomática de la alanino aminotransferasa (ALT. El paciente negó ser bebedor crónico de alcohol. Se hizo el diagnóstico serológico de infección activa por hepatitis C y la biopsia de hígado reveló inflamación crónica activa. Con estos resultados, se inició tratamiento con interferón-alfa y ribavirina. Durante el tratamiento de 48 semanas, el paciente presentó anticuerpos antitiroideos positivos con variaciones en sus niveles de tirotropina (TSH y hormonas tiroideas. En el seguimiento postratamiento, el paciente continuó con hipertiroidismo por enfermedad de Graves. La tiroiditis autoinmune es una complicación frecuente del uso de interferón en pacientes con hepatitis C. En algunos casos se presenta como hipertiroidismo por enfermedad de Graves. Se debe evaluar la función tiroidea y los anticuerpos antitiroideos antes y durante el tratamiento con interferón.A 43 year old man presented with asymptomatic elevation of alanine aminotransferase (ALT and no relevant past history. The patient denied being a chronic alcohol drinker. Work-up revealed an active hepatitis C, and liver biopsy showed active inflammation. Treatment was started with interferon-alfa and ribavirin. During the 48 weeks of treatment, the patient developed positive thyroid antibodies with varying level of thyrotropin (TSH and thyroid hormones. At follow-up after treatment, the patient continued with hyperthyroidism due to Graves’ disease. Autoimmune thyroiditis is a common complication of using interferon in patients with hepatitis C. In some cases, it is presented as hyperthyroidism because of Graves’ disease. Thyroid function and thyroid antibodies should be evaluated before and during treatment with interferon.

  9. Papel de la proteína supresora de la señalización por citocinas-3 (SOCS 3 en la resistencia a la hormona de crecimiento inducida por malnutrición.

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    Adriana Umaña

    2003-09-01

    Full Text Available La nutrición es un regulador importante de las acciones de la hormona de crecimiento (GH. Se ha demostrado que el déficit de nutrientes induce un estado de resistencia a la hormona, en el cual están involucrados, entre otros factores, alteraciones post-receptor en la vía de señalización, pero se desconocen los mecanismos responsables. En este trabajo se investigó la participación de algunos miembros de la familia de proteínas supresoras de la señalización por citocinas (SOCS en la resistencia causada por malnutrición, que inhibe la activación de la señalización a través de Janus cinasa 2/transductor de señal y activador de la transcripción 5 (JK2/STAT5. Se estudiaron los cambios en la expresión génica del receptor de GH (RGH, IGF-I y SOCS3 en el hígado de ratas alimentadas con una dieta baja en proteína (8% y estimuladas con GH. La restricción en el consumo de proteína disminuyó significativamente (p

  10. Cuidando de paciente com câncer de mama e osteonecrose mandibular induzida por bisfostonato: relato de experiência Cuidando de pacientes con cáncer de mama y osteonecrosis mandibular inducida por bisfosfonatos: relato de experiencia Providing care for patients with breast cancer and mandible ostheonecrosis induced by bisphosphonates: an experience report

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    Verônica Paula Torel de Moura

    2009-02-01

    Full Text Available OBJETIVO: Descrever as ações desenvolvidas pela enfermeira junto a uma paciente com câncer de mama e metástase óssea que apresentou necrose mandibular induzida pelo uso de bisfosfonato. RESULTADOS: As intervenções de enfermagem incluíram o ensino e reforço das orientações sobre higiene oral, destacando a escovação adequada, bochechos com solução antisséptica sem álcool, bem como sobre o controle da dor. CONCLUSÃO: Destaca-se a importância da atuação multiprofissional e da consulta de enfermagem no seguimento dessas pacientes para detecção precoce e controle dessa complicação.OBJETIVO: Describir las acciones de enfermería implementadas por la enfermera a una paciente con cáncer con metástasis ósea que presentó necrosis mandibular inducida por el uso de bisfosfonatos. RESULTADOS: Las intervenciones de enfermería incluyeron la enseñanza y el refuerzo de las orientaciones sobre la higiene oral, dando destaque al adecuado cepillado de los dientes, gárgaras con solución antiséptica sin alcohol y al control del dolor. CONCLUSIÓN: Es destacada el importancia de la actuación multiprofesional y de la consulta de enfermería en el seguimiento de esas pacientes, visando la detección temprana y el control de esa complicación.OBJECTIVE: To describe a nurse experience in providing care for a patient with cancer of the breast and bone metastasis who presented mandibular ostheonecrosis induced by the use of bisphosphonates. RESULTS: Nursing interventions included the re-enforcement of the guidelines for oral hygiene, highlighting the appropriate teeth-brushing technique, gargling with antiseptic solution without alcohol, as approach to pain management. CONCLUSION: There is a need for multidisciplinary and nursing consultations for early detection and control of potential complications.

  11. Papel de la fosfolipasa A2 citosólica de grupo IVA en la diferenciación adipocítica y en el desarrollo de obesidad inducida por dieta alta en grasa

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    Peña, Lucía

    2014-01-01

    Tesis Doctoral presentada por María Lucía Peña Moreno para optar al grado de Doctor por la Universidad de Valladolid, Facultad de Medicina (Departamento de Bioquímica y Biología y Fisiología); Instituto de Biología y Genética Molecular (IBGM).-- Sujeta a Licencia Creative Commons.

  12. Há uma associação entre anti-inflamatórios não-esteroides e nefropatia induzida por contraste? ¿Hay una asociación entre antiinflamatorios no esteroides y nefropatía inducida por contraste? Is there an association between non-steroidal anti-inflammatory drugs and contrast nephropathy?

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    Luciano Passamani Diogo

    2010-12-01

    Full Text Available FUNDAMENTO: A associação entre o uso de anti-inflamatórios não-esteroides (AINEs e insuficiência renal aguda ou crônica é bem documentada, mas evidências sobre a associação entre AINEs e nefropatia induzida por contraste (NIC não são encontradas na literatura. OBJETIVO: Avaliar uma possível associação entre AINEs e NIC. MÉTODOS: Em um estudo de coorte, através da entrevista clínica de pacientes que foram submetidos à cateterização cardíaca, analisamos o uso de AINEs e sua associação com desenvolvimento de NIC, através da alteração dos níveis de creatinina sérica ou taxa de filtração glomerular em 48 ou 72 horas. RESULTADOS: No período de julho de 2005 a julho de 2006, 236 pacientes foram incluídos no estudo, dos quais 29 foram posteriormente excluídos. A incidência de NIC foi 10,37% (20 de 207 e 42% dos pacientes estavam recebendo AINEs até o momento da avaliação. Não houve associação entre o uso de AINEs e o desenvolvimento de NIC com OR de 1,293; IC95% (0,46-4,2. O estudo detectou fatores de risco conhecidos para o desenvolvimento de NIC, tais como diabete, com OR de 2,77; IC95% (1,05-7,47 e insuficiência renal crônica com OR de 3,48; IC95% (1,1-11,07 e também sugeriu uma ação protetora da hidratação com solução salina com OR de 0,166; IC95% (0,03-0,92. CONCLUSÃO: Com base nos dados obtidos, concluímos que não houve associação entre NIC e uso prévio de AINEs, pelo menos com um OR > 2,85, o qual nossa amostra detectou.FUNDAMENTO: La asociación entre el uso de antiinflamatorios no esteroides (AINEs e insuficiencia renal aguda o crónica está bien documentada, pero evidencias sobre la asociación entre AINEs y nefropatía inducida por contraste (NIC no son encontradas en la literatura. OBJETIVO: Evaluar una posible asociación entre AINEs y NIC. MÉTODOS: En un estudio de cohorte, a través de la entrevista clínica de pacientes que fueron sometidos a cateterismo cardíaco, analizamos el

  13. Clonidina por via venosa na técnica de hipotensão arterial induzida para timpanoplastias Clonidina por vía venosa en la técnica de hipotensión inducida para timpanoplastias Intravenous clonidine in the induced arterial hypotension technique for tympanoplasty

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    Renato Mestriner Stocche

    2003-08-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A hipotensão arterial induzida é uma técnica eficaz para diminuir o sangramento durante atos cirúrgicos. A clonidina é um a2-agonista de ação central que já se mostrou segura em anestesia. O objetivo deste estudo foi verificar a eficiência da clonidina por via venosa como droga principal na hipotensão arterial controlada. MÉTODO: Participaram do estudo prospectivo e duplamente encoberto, 36 pacientes de ambos os sexos, estado físico ASA I e II, divididos aleatoriamente em três grupos de 12 pacientes que receberam medicação pré-anestésica: clonidina 3 µg.kg-1 (C3, clonidina 5 µg.kg-1 (C5 ou solução fisiológica a 0,9% (Controle 15 minutos antes da indução anestésica. A manutenção anestésica foi feita com isoflurano até a concentração máxima de 2%. Foram anotados a PA e a FC antes, com 1 e 5 minutos após a indução e a cada 5 minutos de anestesia. Pacientes há mais de 15 minutos recebendo isoflurano a 2% e que não apresentaram PAS menor que 80 mmHg receberam nitroprussiato de sódio para indução da hipotensão arterial. RESULTADOS: Três pacientes (25% no grupo C3 , um (8% no grupo C5 e oito (66% no grupo controle necessitaram de nitroprussiato de sódio. A dose total de nitroprussiato para se induzir hipotensão arterial no grupo controle foi maior do que nos grupos C3 e C5 (p JUSTIFICATIVA Y OBJETIVOS: A hipotensión arterial inducida es una técnica eficaz para diminuir el sangramiento durante actos quirúrgicos. La clonidina es un a2-agonista de ación central que ya se mostró segura en anestesia. El objetivo de este estudio fue verificar la eficiencia de la clonidina por vía venosa como droga principal en la hipotensión arterial controlada. MÉTODO: Participaron del estudio prospectivo y duplamente encubierto, 36 pacientes de ambos sexos, estado físico ASA I y II, divididos aleatoriamente en tres grupos de 12 pacientes que recibieron medicación pre-anestésica: clonidina 3

  14. Estimulación de la actividad péptica del jugo gástrico, inducida por látex de Croton palanostigma (sangre de grado

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    Miguel Sanvodal

    2008-09-01

    Full Text Available Objetivo: Determinar si la administración del látex de Croton palanostigma (sangre de grado, vía digestiva, modifica la actividad péptica de la secreción gástrica. Diseño: Estudio experimental. Institución: Centro de Investigación de Bioquímica y Nutrición Alberto Guzmán Barrón, Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Material biológico: Ratas albinas machos adultos y sangre de grado. Métodos: Se usó 50 ratas albinas machos adultos, entre 200 y 250 g de peso, que fueron distribuidas aleatoriamente en 5 grupos, a los que se administró por vía oro-gástrica, y en dosis única, como sigue: grupo I: 0,8 mL/kg de sangre de grado; grupo II: 0,8 mL/kg de sangre de grado neutralizada; grupo III: ranitidina 50 mg/kg; grupo IV: control, con solución salina 0,9 g% (sin histamina; grupo V: control con solución salina 0,9 g%. Se realizó ligadura pilórica, por laparotomía, con anestesia de éter etílico. Se utilizó histamina, aplicada por vía subcutánea, para estimular la secreción, excepto al grupo IV. Cuatro horas después, se extrajo el jugo gástrico, se midió el volumen, el pH por potenciometría y la actividad de la pepsina, por el método de Anson modificado, expresado como µg de tirosina/mL. Principales medidas de resultados: Modificación de la actividad péptica de la secreción gástrica. Resultados: El volumen del jugo gástrico fue significativamente menor en los grupos II y III; que en los otros, entre los que no hubo diferencia estadística. El pH del grupo III (con ranitidina fue significativamente mayor que los otros, demostrando el efecto del fármaco. La actividad péptica fue: con sangre de grado 5,34+1,04; sangre de grado neutralizada 2,69+1,27; grupo ranitidina 2,57+0,88; el control sin histamina 3,29+0,94 y control con histamina 3,58+1,18. La actividad péptica fue significativamente mayor (+49,2% en el grupo con sangre de grado (p<0,01 que en los otros grupos. Conclusiones

  15. Estudio de las alteraciones metabólicas inducidas por la dieta mediante técnicas de proteómica. Efecto del consumo de ácidos grasos omega-3 de origen marino

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    Méndez López, Lucía

    2016-01-01

    Las enfermedades cardiovasculares y la diabetes tipo 2 se han convertido en el principal problema de salud de los países desarrollados como consecuencia del consumo de dietas hipercalóricas y un estilo de vida sedentario. Estos problemas de salud están frecuentemente precedidos por el desarrollo de un grupo de alteraciones metabólicas que incluyen obesidad, resistencia a insulina, tolerancia a la glucosa deteriorada, dislipidemia e hipertensión, las cuales están interconectadas y caracterizan...

  16. 57. El menor número de células progenitoras endoteliales en la sangre periférica de pacientes coronarios no está relacionado con una disfunción in vitro inducida por su plasma

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    A. González Rocafort

    2010-01-01

    Conclusiones: Los pacientes coronarios tienen un menor nivel preoperatorio de EPC que los valvulares. La disfunción en cultivo de las EPC de pacientes ateroscleróticos no se observa en EPC cultivadas obtenidas de donantes sanos tras la incubación con plasma de pacientes coronarios, y, por lo tanto, podría ser debida más a factores intrínsecos de estas células en su procedencia de la médula ósea que a factores del medio.

  17. Prevention, Diagnosis and Treatment of Chemotherapy-Induced Cardiotoxicity: what Are we Doing about it? Prevención, diagnóstico y tratamiento de la cardiotoxicidad inducida por quimioterapia: ¿qué estamos haciendo?

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    Lázaro de la Cruz Avilés

    2012-11-01

    Full Text Available Heart disease and malignant tumors are the two leading causes of death in Cuba, with mortality rates of 197,5 and 193,6 per 100 000, respectively, in 2011. In Cienfuegos, malignant tumors were the leading cause of death with a rate of 115,2 followed by heart disease with 102,6 per 100 000 inhabitants. The improvements in the detection and treatment of cancer have led to a new cohort of patients achieving such a long survival that cardiac complications may appear. Unfortunately, the wide knowledge on biochemical pathways involved in cancer targeted therapy has not been accompanied by a parallel understanding of cardiac consequences of their modulation.Las enfermedades del corazón y los tumores malignos constituyen las dos primeras causas de muerte en Cuba, con tasas de mortalidad de 197,5 y 193,6 por 100 000 habitantes, respectivamente, en el año 2011. En Cienfuegos los tumores malignos fueron la primera causa de muerte con una tasa de 115,2 seguida de las enfermedades del corazón con 102,6 por 100 000 habitantes. Las mejoras alcanzadas en la detección y el tratamiento del cáncer han dado origen a una nueva cohorte de pacientes que alcanzan una supervivencia suficiente para que puedan aparecer complicaciones cardíacas derivadas del tratamiento. Lamentablemente, el abundante conocimiento sobre las vías bioquímicas involucradas en el tratamiento dirigido del cáncer no se ha visto acompañado de un conocimiento paralelo de las consecuencias cardíacas de su modulación.

  18. LA EXTENSION DE RAMAS COLATERALES LUEGO DE UNA LESION A LA MEDULA ESPINAL ES GATILLADA POR LA DEGENERACION AXONAL Y DEPENDE DE LA EXPRESION DEL RECEPTOR DE NEUROTROFINAS P75

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    COLLYER SAAVEDRA, EILEEN TEHANI; COLLYER SAAVEDRA, EILEEN TEHANI

    2013-01-01

    Las lesiones a la médula espinal (LME) presentan un pronóstico de recuperación prácticamente nulo debido a la baja capacidad regenerativa que tiene el sistema nervioso central (SNC) de los mamíferos. Este hecho estaría determinado por factores restrictivos microambientales que impiden la regeneración y no por una incapacidad intrínseca regenerativa de las neuronas del SNC. A pesar de que los axones del SNC que han sido dañados no son capaces de regenerar, luego de una LME parcial se observ...

  19. Necrolisis epidérmica tóxica inducida por fármacos: Caso clínico Toxical epidermal necrolysis related to the use of drugs: Case report

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    L. Melloni Magnelli

    2008-12-01

    Full Text Available El Síndrome de Stevens Johnson (SSJ ha sido definido como un eritema multiforme vesiculobulloso de la piel y de otros órganos y se considera que es la etapa inicial de una reacción dérmica cuya forma más severa de presentación es la Necrolisis Epidérmica Tóxica (NET. Se manifiesta como una reacción sistémica inflamatoria aguda que involucra más del 30 % de la superficie corporal. Etiológicamente está relacionada con el uso de fármacos e un 60 % de los casos, sin embargo el herpes simple, infecciones por micoplasma y algunos factores genéticos, están considerados también como posibles desencadenantes. El SSJ presenta un pródromos catarral de entre 1 a 14 días de duración; el hallazgo clínico más importante son las lesiones máculo-papilares que se extienden centrípetamente y evolucionan a vesículas confluentes, afectando por lo general a la mucosa oral, conjuntival y al área genital. El SSJ evoluciona ocasionalmente a NET, que se caracteriza por dolor intenso y pérdida de la superficie epitelial, comprometiendo las funciones vitales del organismo, ocasionando un desequilibrio hidroelectrolítico, un compromiso renal y ocular, un gran catabolismo y un riesgo potencial de sepsis. Presentamos el caso de un menor de 3 años de edad, con antecedentes de cuadro viral; la hipertermia le ocasionó crisis convulsivas que fueron tratadas con Difenilhidantonína. Durante su hospitalización desarrolló un cuadro de SSJ/NET al cual sobrevivió. Enfatizamos la etiología multifactorial del síndrome en la que se combinaron sinergicamente medicamentos e infección como factores predisponentes del proceso.Stevens Johnson Syndrome (SJS has been defined as a vesiculobullous multiform erythema of the skin and other organs. It´s considered as initial stage of a dermal reaction in which the most severe form of presentation is Toxic Epidermal Necrolysis (TEN. This is an acute systemic inflammatory disease that involves more than 30% of

  20. Rutas de señalización celular involucradas en la plasticidad post-sináptica inducida por la activación de los canales de glutamato tipo NMDA en el hipocampo

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    Sebastián Patrón Saade

    2005-01-01

    Full Text Available La apertura de los canales de glutamato tipo NMDA, gracias a la acción concomitante de las neuronas pre-sináptica y post-sináptica a nivel de las espinas dendríticas, induce a modificaciones de la fuerza y eficacia sinápticas en éstas, fenómeno mejor conocido como plasticidad sináptica. Las dos formas conocidas de plasticidad sinápticas son la potenciación a largo plazo (LTP y la depresión a largo plazo (LTD. Subyacen a ambos tipos de plasticidad modificaciones covalentes sobre las distintas proteínas que componen la densidad post-sináptica y, en caso de que la LTP se prolongue, una regulación activa de la transcripción y traducción de material genético. Así, la regulación activa de la fuerza y eficacia sináptica se debe al control activo sobre la tasa de inserción y remoción de los receptores de glutamato tipo AMPA, receptores encargados de la excitación rápida en el cerebro. Lo significativo de dicho evento en el hipocampo se debe a que éste está relacionado de manera estrecha con la memoria declarativa de los individuos, su memoria de reconocimiento y la memoria espacial, esta última mediada por la activación precisa y coordinada de las células de lugar que se encuentran en él.

  1. Evolución de la precipitación inducida por la deformación en aceros microaleados con Nb y V, e influencia sobre las propiedades mecánicas

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    Quispe, A.

    2004-04-01

    Full Text Available By means of hot torsion tests and applying the “Back Extrapolation” method, the static recrystallization kinetics in V and Nb-microalloyed steels has been determined and the recrystallization-precipitation-time-temperature (RPTT diagrams have also been plotted. The RPTT diagrams graphically show the Recristalization-Precipitation interaction and simultaneously the determination of the static recrystallization critical temperature (SRCT. The mentioned temperature represents the limit between the two phases, before and after of the precipitation. The activation energy for static recrytallization of the austenite before and after precipitation has also been determined. The present study is completed with the determination of the precipitate size distribution diagrams by means of TEM analysis.

    Mediante ensayos de torsión y haciendo uso del método conocido como “Back Extrapolation” se ha determinado la cinética de recristalización estática de dos aceros microaleados con V y Nb, respectivamente, y a partir de las mismas ha sido posible dibujar los diagramas recristalización-precipitación-tiempo-temperatura (RPTT. Los diagramas RPTT muestran gráficamente la interacción Recristalización- Precipitación y simultáneamente permiten la determinación de la Temperatura Crítica de Recristalización Estática (SRCT. Dicha temperatura crítica representa el límite entre las dos fases, antes y después de la precipitación. También se ha determinado la energía de activación de la recristalización estática de la austenita antes y después de la precipitación. El presente estudio es completado con la determinación de los diagramas de distribución del tamaño de los precipitados a través del análisis por TEM.

  2. Resistance exercise-induced microinjuries do not depend on 1or 3 minutes rest time interval between series. (Las microlesiones inducidas por el entrenamiento con cargas no dependen de los intervalos de descanso entre series de 1 o 3 minutos.

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    Rafael Pereira

    2008-10-01

    Full Text Available AbstractIn order to examine the effects of different rest intervals between sets on the muscle fiber integrity, 14 male subjects volunteered to participate in randomized crossover design methodology. All subjects completed 2 experimental training sessions. Both sessions consisted of 3 sets of 10 repetitions with 10 repetition maximum resistance bench press, cable pulldowns, military press, biceps curl, triceps curl, leg press, leg extension, and lying leg curls. The 2 experimental sessions differed only in the length of the rest period between sets and exercises: 1 session with a 1-minute and the other with a 3-minute rest period. the mechanical stress caused by the proposed training session cause similar damage in the muscle fibers do not depend of the 1 or 3 minutes of rest interval between series. ResumenEl propósito de ese estudio fue comparar los efectos de 2 diferentes períodos de descanso durante una sesión de entrenamiento con cargas en la integridad de la fibra muscular. Participaron de forma voluntaria 14 hombres en un estudio con diseño cruzado aleatorio. Todos los sujetos realizaron 2 sesiones de entrenamiento con cargas. Durante cada sesión, los sujetos completaban 3 series de 10 repeticiones máximas de press de banca, jalón en polea alta para dorsal, press militar, curl de bíceps con barra, extensión de tríceps trasnuca con mancuerna, prensa de piernas en máquina, extensión de rodillas en máquina, y flexión de rodillas en máquina. Las 2 sesiones experimentales diferían sólo en la longitud del período de descanso entre las series y los ejercicios: una sesión con 1 minuto y la otra con 3 minutos en los períodos de descanso. La tensión mecánica causada por las sesiones puede causar daños similares en las fibras musculares y no dependen de hacer 1 o 3 minutos de intervalo de descanso entre las series.

  3. Exercício físico previne alterações cardiometabólicas induzidas pelo uso crônico de glicocorticóides Ejercicio físico previene alteraciones cardiometabólicas inducidas por el uso crónico de glucocorticoides Exercise prevents cardiometabolic alterations induced by chronic use of glucocorticoids

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    Carlos Hermano da Justa Pinheiro

    2009-10-01

    , diabetes, dislipidemia, esteatosis hepática e hipertensión arterial. OBJETIVOS: Evaluar el efecto de la práctica regular de ejercicio físico aeróbico sobre las alteraciones cardiometabólicas inducidas por administración crónica de dexametasona (Dex - 0,5 mg/kg/día i.p en ratones. MÉTODOS: Se dividieron ratones Wistar machos (n = 24 en cuatro grupos: Grupo control; Grupo entrenado; Grupo tratado con Dex y Grupo tratado con Dex y entrenado. El entrenamiento físico (iniciado 72 horas después de la primera dosis de Dex se realizó 3 veces por semana, hasta el final del tratamiento. Al final de ese período, se realizaron las siguientes evaluaciones bioquímicas: glicemia en ayunas, test de tolerancia a la glucosa y análisis del perfil lipídico en sangre que incluyó colesterol total (CT, LDL-c, HDL-c, VLDL-c y triglicéridos (TG. También se evaluaron, el peso del músculo gastrocnemio, análisis histopatológico del hígado y los índices cardiometabólicos (CT/HDL-c, LDL-c/HDL-c y TG/HDL-c. RESULTADOS: Se observó hiperglicemia, menor tolerancia a la glucosa, elevación de CT, LDL-c, VLDL-c y TG, disminución del HDL-c, presencia de esteatosis hepática, hipotrofia muscular y elevación de los índices CT/HDL-c, LDL-c/HDL-c y TG/HDL-c en los animales tratados con Dex. El ejercicio físico redujo la hiperglicemia, mejoró la tolerancia a la glucosa, redujo la dislipidemia y previno la esteatosis hepática, la hipotrofia muscular y redujo los índices CT/HDL-c, LDL-c/ HDL-c ye TG/HDL-c. Con todo, no hubo efecto significativo del entrenamiento físico sobre el HDL-c. CONCLUSIÓN: El ejercicio físico aeróbico tiene efecto protector con las alteraciones cardiometabólicas inducidas por el uso crónico de glucocorticoides.BACKGROUND: Chronically, glucocorticoids induce adverse cardiometabolic alterations including insulin resistance, diabetes, dyslipidemia, liver steatosis and arterial hypertension. OBJECTIVES: To evaluate the effect of regular practice of aerobic

  4. MODELO EXPERIMENTAL DE GLOMERULONEFRITIS MEMBRANOSA INDUCIDA CON ALBUMINA BOVINA

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    Fontenla M

    2013-07-01

    Full Text Available El objetivo del presente trabajo fue diseñar un modelo experimental de Glomerulonefritis Membranosa (GM en ratas Wistar, inducida con Seroalbúmina Bovina (BSA, y validarlo mediante la determinación de parámetros bioquímicos, histológicos, ultraestructurales y detección de inmunocomplejos por inmunofluorescencia (IF. Los animales del grupo experimental fueron inmunizados por vía subcutánea, con dosis de 3 mg c/u de BSA/PBS con adyuvante de Freund. Se efectuaron diferentes esquemas de inmunización. Cuando el título de anticuerpos fue ≥1/2, comenzó la administración diaria de 2 mg, por vía endovenosa de BSA/PBS, durante 15 días. Se evaluó la funcionalidad renal por la proteinuria; después de la 5° semana, desde su aparición, se determinó: depuración (clearance de creatinina, uremia, proteinemia y perfil lipídico. Los dos riñones se usaron para estudios histológicos, ultraestructurales y detección de inmunocomplejos por IF. Los resultados mostraron que la inmunización fue efectiva con 5 R E S U M E N inoculaciones c/15 días. En los animales nefróticos la proteinuria, depuración (clearance de creatinina, proteinemia , uremia y el perfil lipídico presentaron alteraciones significativas (p<0.0001. Al microscopio óptico se observó hipercelularidad, engrosamiento difuso de las membranas basales de los capilares glomerulares y diferentes grados de atrofia, esclerosis e hialinización de los glomérulos. Por IF se detectó inmunocomplejos IgG en el 100 % de los glomérulos. Ultraestructuralmente, se observaron depósitos subepiteliales electrodensos en la membrana basal engrosada, compatibles con inmunocomplejos . Se encontraron alteraciones en la estructura de los podocitos. En conclusión, los estudios bioquímicos, estructurales y ultraestructurales permitieron inferir la inducción de un síndrome nefrótico experimental. Concluimos que el protocolo utilizado tiene validez para la inducción de una glomerulonefritis

  5. Expression of Early Light Induced Protein in Grapevine and Pea, under Different Conditions and its Relation with Photoinhibition Expresión de una Proteína inducida Tempranamente por Luz en Vid y Arveja Bajo Diferentes Condiciones y su Relación con la Fotoinhibición

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    Maritza Berti

    2012-09-01

    Full Text Available Early light induced proteins (ELIP are a type of proteins which are expressed before than other chloroplast proteins in the presence of light. These proteins have been studied in a large number of annual species such as pea (Pisum sativum L., barley (Hordeum vulgare L. and Arabidopsis sp. In perennials plants the studies about ELIPs are very scarce. The possible photoprotective function of the ELIPs has motivated the interest in investigating the presence of this type of proteins in a perennial plant such as grapevine (Vitis vinifera L. and if their characteristics differ from those found in annual plants. In this paper a comparative study was conducted on the ELIPs expression in grapevine and pea to investigate whether there are differences regarding to temperature and light intensity conditions necessary for maximum ELIP expression in each species and for studying in each case the relationship between ELIP expression and photoinhibition degree. The results of this study showed that the maximum ELIPs expression was reached from 25 °C and 1000 µmol PAR m-2 s-1 in both species. Above these values the expression remained constant. Regarding the temperature and light intensity effect on the photoinhibition degree, it was observed that temperature produced inverse relation in grapevine but no relation with pea. On the other hand, the light intensity produced direct relation in both grapevine and pea. The light intensity effect on ELIP expression suggests that these proteins may have a photorepairing role of the photosynthetic system, but the effect of temperature on the ELIP expression in short-term stress may be associated rather to the optimum conditions for their synthesis.Las proteínas tempranamente inducidas por luz (ELIP se expresan antes que otras proteínas del cloroplasto en presencia de luz. Estas proteínas han sido estudiadas en un gran número de especies anuales tales como arveja (Pisum sativum L., cebada (Hordeum bulgare L. y

  6. Alterações em variáveis motoras e metabólicas induzidas pelo treinamento durante um macrociclo em jogadores de handebol Alteraciones en las variables motoras y metabólicas inducidas por el entrenamiento durante un macro ciclo en jugadores de balonmano Changes in metabolic and motor performance variables induced by training in handball players

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    Juvenilson de Souza

    2006-06-01

    Full Text Available A monitoração do treinamento é uma prática comum no desporto. Essa monitoração deve ser baseada em testes específicos e que reflitam as adaptações às diversas etapas de treinamento, permitindo, assim, ajustes no programa deste. Assim, este estudo teve como objetivo analisar as alterações em variáveis motoras e metabólicas induzidas pelo treinamento durante um macrociclo em jogadores de handebol. Os atletas foram submetidos a um programa de preparação fundamentado no modelo de periodização proposto por Verkhoshanski(7 e adaptado por Oliveira(8. Foram estudados 11 jogadores de handebol, que realizaram treinamentos diários, na faixa etária de 20 a 32 anos, massa corporal média de 89,5 ± 10,4kg (70,2 a 105,1kg, e estatura média de 184,4 ± 6,7cm (171,8 a 198cm, filiados à equipe "UniFil/Londrina" do município de Londrina - PR. Os handebolistas foram submetidos a duas baterias de testes: a primeira no início do segundo macrociclo de treinamento e a segunda após 16 semanas, antecedendo o início da liga nacional. Para análise dos dados foi utilizado teste t para medidas repetidas com p La monitorización del entrenamiento es una práctica común en el deporte. Esa monitorización debe basarse en pruebas específicas y que reflejen las adaptaciones a las diversas etapas del entrenamiento, permitiendo así, ajustes en el programa del mismo. Así, este estudio ha tenido como objetivo analizar las alteraciones en las variables motoras y metabólicas inducidas por el entrenamiento durante un macro ciclo en jugadores de balonmano. Los atletas fueron sometidos a un programa de preparación basado en el modelo de periodicidad propuesto por Verkhoshanski(7 y adaptado por Oliveira(8. Fueron estudiados 11 jugadores de balonmano que realizaron entrenamiento diario, con edades entre 20 y 32 años, masa corporal media de 89,5 ± 10,4 kg (70,2 y 105,1 kg, y estatura media de 184,4 ± 6,7 cm (171,8 y 198 cm, afiliados al equipo "Uni

  7. Alteração da relação testosterona: cortisol induzida pelo treinamento de força em mulheres Alteración de la relación testosterona: cortisol inducida por el entrenamiento de fuerza en mujeres Alteration of testosterone: cortisol ratio induced by resistance training in women

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    Marco Carlos Uchida

    2004-06-01

    Full Text Available A razão entre a concentração de testosterona e cortisol (T:C é freqüentemente utilizada como indicativo do nível de estresse imposto pelo exercício. Alterações na concentração destes hormônios são responsáveis por modular diversas respostas induzidas pelo treinamento, como hipertrofia e ganho de força. O objetivo do presente estudo foi examinar a influência do protocolo de treinamento de força, conhecido como múltiplas-séries (MS, sobre o ganho de força, de resistência muscular localizada e a relação entre a concentração de hormônios catabólicos (cortisol e anabólicos (testosterona. Para testar esta hipótese cinco jovens do sexo feminino com um ano de experiência em treinamento de força foram submetidas ao protocolo MS. As amostras de sangue foram coletadas antes e imediatamente após o exercício, no primeiro dia e após oito semanas de treinamento. Os testes de 1-RM e de repetições máximas foram realizados também no início e ao final das oito semanas de treinamento de força. Não foram observadas alterações na massa corporal, no IMC, na percentagem de massa gorda e na força máxima (1-RM no supino, no agachamento e na rosca direta. O número de repetições máximas a 50% de 1-RM foi aumentado apenas para o supino (p La razón entre testosterona y cortisol (T:C es frecuentemente utilizada como indicador del nivel de stress impuesto por el ejercicio. Las alteraciones de las concentraciones de estas hormonas son las responsables por modular diversas respuestas inducidas por el entrenamiento, como son la hipertrofia y el aumento de la fuerza. El objetivo del presente estudio fué examinar la influencia del protocolo de entrenamiento de fuerza, conocido como series multiples (MS, sobre la ganancia de fuerza, la resistencia muscular localizada y la relación entre las concentraciones de las hormonas catabólicas (cortisol y anabólicas (testoterona. Para testar esta hipótesis, cinco jovenes del sexo feminino

  8. Reação cutânea grave induzida por carbamazepina no tratamento da neuralgia pós-herpética: relato de caso Reacción cutánea grave inducida por la carbamazepina en el tratamiento de la neuralgia postherpética: relato de caso Severe carbamazepine-induced cutaneous reaction in the treatment of post-herpetic neuralgia: case report

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    João Batista Santos Garcia

    2010-08-01

    da carbamazepina, que deve sempre ser supervisionado, especialmente em idosos.JUSTIFICATIVA Y OBJETIVOS: El herpes zoster tiene como principal complicación la neuralgia postherpética (NPH. Para su tratamiento se usa la carbamazepina (CBZ, un anticonvulsivo bien tolerado, pero que sin embargo está a menudo asociado a reacciones cutáneas graves, como por ejemplo, el síndrome de Stevens-Johnson (SSJ y la necrólisis epidérmica tóxica (NET. El objetivo de este trabajo es relatar un caso de SSJ/NET secundario al uso de CBZ en paciente con NPH. RELATO DEL CASO: Paciente del sexo femenino, con dolor continuo e intenso en la región torácica y dorso, ardor, punzada, descarga eléctrica, alteración de fuerza del miembro superior ipsilateral y sudoración. Presentaba lesiones de postillas y eritemas en la región dorsal del tórax, con alodinia y disestesias en el dermatoma acometido. Se inició CBZ 300 mg.día-1, amitriptilina (AMT12,5 mg por la noche e infiltración con anestésico local en la región afectada. Después de 15 días, el paciente decía sentir un fuerte malestar, fiebre, dolores musculares y artralgias con rash cutáneo ligero e inespecífico. Se le retiró la carbamazepina inmediatamente. Una semana después fue ingresado con urticaria y exantema generalizados, erupciones cutáneas eritematosas, burbujas y marcas purpúricas por todo el cuerpo. La impresión era de SSJ/NET inducida por carbamazepina. Hubo un progresivo empeoramiento del cuadro, con aumento del número y del tamaño de las lesiones cutáneas, además de rash eritematoso macular generalizado, áreas de necrosis y erosiones simétricas de la epidermis en la cara, cuello, tórax, dorso y miembros, llegando a más del 50% del área de superficie, además de la involucración de la mucosa bucal, conjuntival y genital con erosiones vesiculares. Presentó un empeoramiento funcional progresivo, evolucionando con choque séptico y fracaso multiorgánico, lo que produjo finalmente su deceso

  9. Desarrollo de métodos para la evaluación integrada de propiedades mecánicas y superficiales inducidas en materiales metálicos mediante tratamiento superficial por ondas de choque generadas por láser

    OpenAIRE

    Ruiz de Lara de Luis, Leonardo

    2016-01-01

    El tratamiento superficial por ondas de choque generadas por láser, LSP, es una técnica cuyo principal objetivo es el de la modificación del estado tensional de las primeras micras en profundidad de materiales metálicos. En sus comienzos está técnica fue empleada para inducir tensiones residuales de compresión en superficie, pero mientras se avanzaba en su desarrollo se empezaron a observar otros efectos. Profundizando en ellos se llega a la conclusión de que existe una fuerte relación entre ...

  10. Rabdomiólise induzida por exercício e risco de hipertermia maligna: relato de caso Rabdomiólisis inducida por ejercicio y riesgo de hipertermia maligna: relato de caso Exercise-induced rhabdomyolysis and risk for malignant hyperthermia: case report

    OpenAIRE

    Ricardo Barreira Uchoa; Cláudia Regina Fernandes

    2003-01-01

    JUSTIFICATIVA E OBJETIVOS: Rabdomiólise é a lesão do músculo esquelético com liberação dos constituintes da célula para o plasma. Exercício exaustivo e extenuante, especialmente em homens não condicionados, pode resultar em morbidade maior com hiperpotassemia, acidose metabólica, coagulação intravascular disseminada, síndrome do desconforto respiratório agudo e rabdomiólise. Tem sido sugerido que hipertermia maligna, choque térmico e rabdomiólise induzida por exercício são síndromes fortement...

  11. Características clínicas y epidemiológicas de los pacientes con intoxicación inducida e intencional atendidos en un hospital general, año 2006.

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    Jaime Wilfredo Zegarra Piérola

    2009-10-01

    Full Text Available Objetivo: Determinar las características clínicas y epidemiológicas de los pacientes con intoxicación inducida e intencional, atendidos en un hospital general. Material y métodos: Se incluyeron pacientes con intoxicación inducida e intencional; de ambos sexos, mayores de 14 años. La información se obtuvo de la historia clínica de ingreso, entrevista personal, test de Hamilton y evaluación toxicológica en orina en los intoxicados inducidos. Resultados: De marzo a diciembre del 2006 hubo 45 pacientes con intoxicación inducida y 382 pacientes con intoxicación intencional, de estos últimos se tuvo información completa en 104. Los pacientes con intoxicación inducida en comparación a los intoxicados intencionales fueron varones (p=0,001; de mayor edad (31,62 ± 9,38 vs 26,85 ± 12,18 años (p=0,011, mayor nivel de instrucción (p=0,04, empleados (p=0,01 y mayor nivel socioeconómico (p=0.01; los intencionales fueron mayormente estudiantes (34,62%, amas de casa (19,23% y pobres no extremos (p=0,02. Los pacientes con intoxicación inducida a diferencia de los intencionales ingresaron a Emergencia los días domingos (p=0,001, trasladados por la Policía Nacional (p=0,001; los intencionales ingresaron trasladados por la madre (p=0,001. Los pacientes inducidos a diferencia de los intencionales estuvieron expuestos al alcohol (p=0,001, relacionados con amigos (33,33%, taxistas (28,89% ó desconocidos (33,33%, ingresaron en estado de estupor (p=0,001, con Glasgow > 8 y 13 (0,001, y con depresión mayor (p=0,001.Conclusión: Los pacientes con intoxicación inducida a diferencia de los intencionales fueron varones, con nivel de instrucción superior, empleados, no pobres, ingresaron los días domingo, trasladados por la Policía Nacional y en estado de estupor, y los intoxicados intencionales fueron mujeres, estudiantes o amas de casa, ingresaron trasladados por la madre, con síntomas y signos colinérgicos, y con depresión mayor. (Rev Med

  12. Detección de anticuerpos antiplasmodium por ELISA en donantes de sangre

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    Patricia Olaya de Morales

    1982-06-01

    Full Text Available La malaria, una enfermedad transmitida por mosquitos del genero anopheles, puede ser inducida a través de transfusiones de sangre infectada con alguna de las especies de Plasmodium que afectan al hombre. Con el objeto de determinar el riesgo potencial de infección inducida por transfusiones, se analizaron durante 9 meses y mediante la técnica de E.L.I.S.A., las muestras de suero tomadas a los donantes de sangre del Hospital Militar Central de Bogotá. El 8.6 por mil de las 3114 muestras analizadas, resultaron positivas para anticuerpos antimaláricos y durante el tiempo del estudio fueron detectados 3 casos de malaria inducida por transfusiones.

  13. Acute nutritional axonal neuropathy.

    Science.gov (United States)

    Hamel, Johanna; Logigian, Eric L

    2018-01-01

    This study describes clinical, laboratory, and electrodiagnostic features of a severe acute axonal polyneuropathy common to patients with acute nutritional deficiency in the setting of alcoholism, bariatric surgery (BS), or anorexia. Retrospective analysis of clinical, electrodiagnostic, and laboratory data of patients with acute axonal neuropathy. Thirteen patients were identified with a severe, painful, sensory or sensorimotor axonal polyneuropathy that developed over 2-12 weeks with sensory ataxia, areflexia, variable muscle weakness, poor nutritional status, and weight loss, often with prolonged vomiting and normal cerebrospinal fluid protein. Vitamin B6 was low in half and thiamine was low in all patients when obtained before supplementation. Patients improved with weight gain and vitamin supplementation, with motor greater than sensory recovery. We suggest that acute or subacute axonal neuropathy in patients with weight loss or vomiting associated with alcohol abuse, BS, or dietary deficiency is one syndrome, caused by micronutrient deficiencies. Muscle Nerve 57: 33-39, 2018. © 2017 Wiley Periodicals, Inc.

  14. Respuesta del sistema antioxidante en varones sanos, frente a hiperglicemia aguda inducida

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    Raquel Oré

    2009-09-01

    Full Text Available Objetivo: determinar la respuesta del sistema antioxidante en varones sanos, frente a la hiperglicemia aguda inducida. Diseño: estudio prospectivo, descriptivo, longitudinal, experimental. Lugar: Instituto Nacional de Biología Andina, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material biológico: Sangre y suero de sujetos aparentemente sanos. Intervenciones: A 13 sujetos adultos clínicamente sanos, entre 20 y 41años, después de 10 horas de ayuno, se administró glucosa vía endovenosa, mediante el método de clamp hiperglicémico, a 125 mg/dL por encima del valor basal, durante 120 minutos. Se realizó mediciones de la glicemia a 0, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110 y 120 minutos. Se tomó la muestra sanguínea con anticoagulante EDTA y otra de sangre total, para obtención de suero, para las pruebas bioquímicas a los 0, 60 y 120 minutos. Principales medidas de resultados: Modificaciones de la glicemia y lipoperoxidación en suero, glutatión y actividad superóxido dismutasa en glóbulos rojos lisados e índices de estrés oxidativo. Resultados: El nivel de glucosa durante el clamp hiperglicémico, luego de alcanzar el ‘equilibrio’, fue 197±17,58 mg/dL. La lipoperoxidación aumentó de 2,54 + 0,51 a 2,90 + 0,58 umol/L, de 0 a 60 minutos, y a 2,66 + 0,55 umol/L a los 120 minutos. El glutatión se redujo en 8,10% a la hora, aumentando 7,08% a los 120 minutos. La actividad superóxido dismutasa se elevó 0,54% a los 60 minutos y 5,66% a los 120 minutos, sobre el basal. Los índices de valoración del estrés oxidativo tuvieron correlación r Pearson positiva, en nivel alto a muy alto. Conclusiones: la hiperglicemia aguda inducida hasta 2 horas elevó el estrés oxidativo, promoviendo generación de defensa antioxidante, con síntesis de glutatión reducido de novo y mayor actividad de la superóxido dismutasa.

  15. Efeito da perda ponderal induzida pela cirurgia bariátrica sobre a prevalência de síndrome metabólica Efecto de la pérdida ponderal inducida por la cirugía bariátrica sobre la prevalencia de síndrome metabólico Effects of weight loss induced by bariatric surgery on the prevalence of metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Francisco das Chagas Monteiro Júnior

    2009-06-01

    Full Text Available FUNDAMENTO: A síndrome metabólica (SM está frequentemente ligada ao excesso de peso e melhora com a perda ponderal, sendo esperado que essa melhora seja proporcional à intensidade dessa perda. OBJETIVO: Avaliar o impacto da perda ponderal induzida pela cirurgia bariátrica (CB sobre a prevalência da SM, em médio prazo. MÉTODOS: Foram analisados 35 pacientes submetidos à cirurgia de by-pass gastrojejunal em Y de Roux, no período de outubro de 2001 a outubro de 2005, em nosso HU, sendo 88,5% do sexo feminino, com uma média de idade de 37,8±11,1 anos e um IMC médio de 45,0±6,2 kg/m². Na primeira etapa da pesquisa, foram obtidos dados demográficos e clínico-antropométricos antes da realização da CB, incluindo os critérios para o diagnóstico da SM, de acordo com as diretrizes do NCEP dos Estados Unidos. Na segunda etapa, os pacientes operados foram reavaliados ambulatorialmente quanto à prevalência da SM. RESULTADOS:Antes da cirurgia, a SM foi diagnosticada em 27 pacientes (77,1%. Em reavaliação 34,4±15 meses após a cirurgia, observou-se uma queda do IMC médio para 28,3±5,0 kg/m² e a SM foi detectada em apenas dois pacientes (5,7% (pFUNDAMENTO: El síndrome metabólico (SM frecuentemente está vinculado al exceso de peso y mejora con la pérdida ponderal, esperándose que esta mejora sea proporcional a la intensidad de esa pérdida. OBJETIVO: Evaluar el impacto de la pérdida ponderal inducida por la cirugía bariátrica (CB sobre la prevalencia de la SM, a medio plazo. MÉTODOS: Se estudiaron 35 pacientes sometidos a cirugía de bypass gastroyeyunal en Y de Roux, en el período de octubre de 2001 a octubre de 2005, en nuestro HU, siendo el 88,5% del sexo femenino, con un promedio de edades de 37,8±11,1 años y un IMC promedio de 45,0±6,2 Kg/m². En la primera etapa de la investigación, se obtuvieron datos demográficos y clínico antropométricos antes de la realización de la CB, incluyendo los criterios para el

  16. Caracterización farmacológica y funcional de los receptores nicotínicos de las células cromafines de la médula adrenal de la rata: plasticidad inducida por un modelo de estrés crónico

    OpenAIRE

    Bustillo Merino, Diego

    2015-01-01

    Las células cromafines de la médula adrenal son bien conocidas por su participación en la clásica respuesta de lucha o huida frente a los estímulos estresantes mediante la liberación de catecolaminas al torrente sanguíneo. La activación de los receptores nicotínicos (nAChRs) de la membrana de las células cromafines constituye el primer eslabón de la cadena de procesos que bajo la denominación de acoplamiento excitación-secreción traduce la liberación de acetilcolina por las terminaciones del ...

  17. Respuesta de poblaciones microbianas que lideran el crecimiento en raíces y resistencia sistémica inducida

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    Hayron Fabricio Canchignia Martínez

    2016-01-01

    Full Text Available Las rizobacterias lideran una serie de mecanismo en el sistema radículas en plantas que favorecen en aspectos fisiológicos como: desarrollo radicular por la producción de auxinas y promueven el mecanismo de defensa a nivel sistémico. Las rizobacterias del género Pseudomonas spp reportan tener capacidad de producir ácido indolil-3-acetico (AIA, en presencia del precursor Triptófano, bajo condiciones in vitro. La rizobacterias Promotoras de Crecimiento en Plantas  (PGPR, en contacto con las raíces de la planta, estas rizobacterias utilizan los exudados de aminoácidos proteinogénico triptófano precursor para síntesis de AIA, esto incrementa la producción del fitoregulador que favorecen el desarrollo y proliferación de la biomasa radicular adventicias. Se rescata la importancia del empleo de PGPR, como efectores en el mecanismo en defensa sensu stricto para la Resistencia Sistémica Inducida (RSI, que activa el estado de prealerta en la planta antes y después de ser sometida al agente patogénico. La RSI se activa por la ruta dependiente al jasmonato (JA y etileno (ET.

  18. Signal propagation along the axon.

    Science.gov (United States)

    Rama, Sylvain; Zbili, Mickaël; Debanne, Dominique

    2018-03-08

    Axons link distant brain regions and are usually considered as simple transmission cables in which reliable propagation occurs once an action potential has been generated. Safe propagation of action potentials relies on specific ion channel expression at strategic points of the axon such as nodes of Ranvier or axonal branch points. However, while action potentials are generally considered as the quantum of neuronal information, their signaling is not entirely digital. In fact, both their shape and their conduction speed have been shown to be modulated by activity, leading to regulations of synaptic latency and synaptic strength. We report here newly identified mechanisms of (1) safe spike propagation along the axon, (2) compartmentalization of action potential shape in the axon, (3) analog modulation of spike-evoked synaptic transmission and (4) alteration in conduction time after persistent regulation of axon morphology in central neurons. We discuss the contribution of these regulations in information processing. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Theorical and experimental study of the induced forces by the mixed, divergent, convergent and straight labyrinth of seal systems on the steam turbines, gas turbines and compressor rotors; Estudio teorico-experimental de las fuerzas inducidas por los sistemas de sellos de laberinto rectos, convergentes, divergentes y mixtos sobre los rotores de turbinas de vapor, turbinas de gas y compresores

    Energy Technology Data Exchange (ETDEWEB)

    Salazar San Andres, Octavio Ramon

    1991-12-31

    demuestran que el modelo es capaz de dar una vision cualitativa y cuantitativa de las fuerzas y los coeficientes de rigidez y amortiguamiento de los sellos de laberinto con las geometrias antes mencionadas, tanto para el rotor estatico como en operacion. Por otra parte se recomienda llevar a cabo mas experimentacion con equipo instalado en plantas termoelectricas y en especial en turbinas de vapor con capacidades iguales o superiores a los 300 MW, donde las altas presiones y los sellos localizados en la parte superior de los alabes, vuelven mas susceptibles a las maquinas para autoinducir vibraciones subsincronas.

  20. Efecto protector en cirrosis hepática inducida en ratas del extracto etanólico de las hojas de Piper aduncum comparado con silimarina

    Directory of Open Access Journals (Sweden)

    Jorge Arroyo

    2012-04-01

    Full Text Available Objetivos: Evaluar la eficacia protectora del extracto etanólico de hojas de Piper aduncum (matico y su fitomedicamento en cápsulas, en la cirrosis hepática inducida en ratas. Diseño: Experimental. Lugar: Facultad Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material biológico: Hojas de Piper aduncum, y Rattus norvegicus, cepa Holtzman. Intervenciones: Las hojas fueron recolectadas en el distrito de Huariaca, departamento de Pasco. El fitomedicamento en cápsulas se preparó a partir del extracto etanólico de la planta. La cirrosis fue inducida con fenobarbital 0,5 mg/mL, diluida en el agua de beber por 15 días, y luego, tetracloruro de carbono 0,2mL/kg en aceite de oliva 1:1, oralmente por 7 días. Se colectó una muestra de sangre para determinar perfil hepático y malondialdehído; los animales fueron sacrificados extrayéndose el hígado para estudio histopatológico. Los datos fueron evaluados mediante técnicas multivariadas, con valor p < 0,05. Principales medidas de resultados: Grado de lesión hepática, marcadores bioquímicos, estrés oxidativo. Resultados: El extracto y el fitomedicamento a 200 mg/kg disminuyeron los valores de TGP (p < 0,621, bilirrubina total (p < 0,385 y bilirrubina directa (p < 0,283 e incrementaron las proteínas totales (p < 0,539 y albúmina (p < 0,114, similar al grupo silimarina. El colágeno, la fibrosis y el nivel de daño hepático se vieron aumentados con tetracloruro de carbono; estos indicadores se redujeron con los diferentes tratamientos y la silimarina. El marcador de estrés oxidativo se redujo con los tratamientos aplicados (p < 0,002. Conclusiones: El extracto etanólico de las hojas de Piper aduncum (matico y su fitomedicamento ejercieron efecto protector de la cirrosis inducida en ratas, comparativamente con la silimarina.

  1. Efeitos da fadiga muscular induzida por exercícios no tempo de reação muscular dos fibulares em indivíduos sadios Efectos de la fatiga muscular inducida por ejercicios sobre el tiempo de reacción muscular peronea en individuos sanos Effects of the exercise-induced muscular fatigue on the time of muscular reaction of the fibularis in healthy individuals

    Directory of Open Access Journals (Sweden)

    Bruno Araújo Rego Santos Silva

    2006-04-01

    Full Text Available A fadiga muscular (FM é um fenômeno comum nas atividades esportivas e diárias, resultando numa piora da performance motora. Ela é considerada um dos fatores causadores de lesões músculo-esqueléticas. A entorse de tornozelo é um exemplo: a FM afetaria tanto o sistema aferente quanto o eferente. Vários estudos têm analisado a influência da FM no controle neuromuscular (CNM; entretanto, existe pouca pesquisa sobre essa influência na velocidade de reação dos músculos. O objetivo deste estudo foi verificar os efeitos da FM no tempo de reação muscular (TRM dos músculos fibulares, que são os primeiros a responder a um estresse em inversão do tornozelo. Foram estudados 14 indivíduos saudáveis masculinos (idade: 20-35 anos, que tiveram seus TRM avaliados por meio de eletromiografia (EMG de superfície. O início da atividade muscular foi definido como a média de repouso + 3x o desvio-padrão (DP. O TRM dos fibulares foi mensurado após uma inversão súbita de 20º realizada numa plataforma. A inversão súbita foi realizada antes e depois da fadiga muscular, que foi induzida por exercícios localizados dos fibulares até a exaustão. Os resultados mostraram que houve um aumento significativo do tempo de reação muscular após a fadiga (p La fatiga muscular (FM es un fenómeno común en las actividades diarias, produciendo un empeoramiento de la actuación. Se la considera una de las causas de factores lesionantes musculares de esqueleto. El esguince del tobillo es un ejemplo: La FM afectaría tanto el sistema aferente cuanto el eferente. Varios estudios han estado analizando la influencia de FM en el comando neuromuscular (CNM, sin embargo, la existen pocas investigaciones sobre la influencia en la velocidad de reacción de los músculos. El objetivo de ese estudio era verificar los efectos de FM en el tiempo de reacción muscular (TRM de los músculos peroneos, que son los primeros en responder a una tensión en la inversi

  2. Efecto del extracto del fruto de Physalis peruviana "tomatillo" en Mus musculus var. swis con hiperlipidemia inducida.

    Directory of Open Access Journals (Sweden)

    Julio Campos Florián

    2011-01-01

    Full Text Available El objetivo de la presente i nvestigación fue determinar la actividad hipolipidémica del fruto de Physalis peruviana “tomatillo” en un modelo de hiperlipidemia aguda inducida con tritón. Se utilizaron Mus musculus var. swis machos como animales de experimentación. Se trabajó con cuatro grupos de ratones, el grupo blanco recibió agua destilada por vía oral y solución salina fisiológica por vía intraperitoneal, el grupo control recibió agua destilada por vía oral y tritón por vía intraperitoneal, el grupo problema 1 recibió por vía oral 0.05g/100g del extracto de Physalis peruviana y tritón por vía intraperitoneal y el grupo problema 2 recibió por vía oral 0.2g/100g del extracto de Physalis peruviana y tritón por vía intraperitoneal. Luego de 24 horas de administrar los tratamientos se re alizaron las mediciones en suero de las concentraciones de colesterol y triglicéridos. Los niveles promedio de colesterol (mg/dL fueron: 58.87±11.54 (blanco, 121.71±15.00 (control, 58.08±9. 21 (problema 1 y 66.78±16.77 (problema 2. Los niveles promedio de triglicéridos (g/L fueron: 0.48±0.07 (blanco, 1.84±0.18 (control, 0.34±0.10 (problema 1 y 0.94±0.25 (problema 2. Se encontró reducciones significativas (p<0.000, tanto de las concentraciones de colesterol como de triglicéridos en relación a las o btenidas en el grupo tratado sólo con tritón.

  3. Chromosomal aberrations induced by alpha particles; Aberraciones cromosomicas inducidas por particulas {alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero C, C.; Brena V, M. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)]. e-mail: cgc@nuclear.inin.mx

    2005-07-01

    The chromosomal aberrations produced by the ionizing radiation are commonly used when it is necessary to establish the exposure dose of an individual, it is a study that is used like complement of the traditional physical systems and its application is only in cases in that there is doubt about what indicates the conventional dosimetry. The biological dosimetry is based on the frequency of aberrations in the chromosomes of the lymphocytes of the individual in study and the dose is calculated taking like reference to the dose-response curves previously generated In vitro. A case of apparent over-exposure to alpha particles to which is practiced analysis of chromosomal aberrations to settle down if in fact there was exposure and as much as possible, to determine the presumed dose is presented. (Author)

  4. Estudio morfométrico de las malformaciones craneofaciales experimentales inducidas por ácido retinoico

    Directory of Open Access Journals (Sweden)

    T. González

    2003-10-01

    Full Text Available Objetivo: El ácido retinoico es un metabolito activo de la vitamina A que administrado en grandes cantidades tiene efecto teratógeno sobre la embriogénesis de los mamíferos. Hemos investigado los efectos de la exposición temprana de embriones de rata sobre las estructuras craneofaciales. Diseño: Cuarenta y cinco ratas Sprague-Dawley gestantes fueron tratadas con 125 mg/kg de ácido all-trans-retinoico el día 10 de gestación. Las 20 ratas controles fueron tratadas con aceite. Los fetos de ambos grupos se extrajeron el día antes de llegar a término y fueron sometidos a un estudio morfológico y otro estudio morfométrico, analizando las malformaciones craneofaciales. Resultados: Ninguno de los fetos controles presentó malformaciones. El 100% de los embriones tratados con retinoico presentaron defectos craneofaciales, incluyendo fisuras faciales, exoftalmos, malformaciones e inserción baja de los pabellones auriculares, apéndices faciales y anomalías nasales. El análisis morfométrico reveló un incremento de la distancia entre los poros nasales (pObjective: Retinoic acid is an active metabolite of Vitamin A that is teratogenic when present in excess during mammalian embriogenesis. We have investigated the effects of early exposure of rat embryos to retinoic acid on craniofacial structures. Design: Treatment of 45 pregnant Sprague-Dawley rats with 125mg./Kg all-trans-retinoic acid on pregnancy day 10 was performed. Twenty controls were treated only with oil. The fetuses were recovered the day before term, and both morphologic and morphometric analyses of the craniofacial structures were performed. Results: None of the control fetuses had malformations. Craniofacial defects were observed in 100% of the retinoic embryos including facial clefts, proptosis, abnormalities and inferior placement of the pinnae, skin tags, and nasal anomalies. Morphometric analyses revealed an increased distance between nasal pores (p<0,01 and between both eyes (p<0,05 in retinoic embryos. A reduced distance of the maxilla (p<0,01 and the mandible (p<0,01 were also noted. Conclusions: Morphologic and morphometric studies confirm the hypothesis that retinoic acid disturbs normal craniofacial development when administered during a critical period. Hindrance of migration of the cranial neural crest cells may be a main reason to explain these events.

  5. Respuesta inmune mucosal inducida por proteoliposoma y cocleato derivados de N. meningitidis serogrupo B

    Directory of Open Access Journals (Sweden)

    Judith del Campo

    2009-08-01

    Full Text Available Mucosal vaccination offers attractive advantages to conventional systemic vaccination. Most pathogens enter or establish infection at mucosal surfaces. This represents an enormous challenge for vaccine development. Nevertheless, the availability of safe and effective adjuvants that function mucosally is the major limitation. Therefore, we investigated the impact of mucosal immunization with the Neisseria meningitidis B proteoliposome (AFPL1, Adjuvant Finlay Proteoliposome 1 and its-derived cochleate (Co, AFCo1. They contain multiple PAMPs as immunopotentiators and have delivery system ability as well as Th1 polarization activity. Groups of female mice were immunized by nasal, oral, intravaginal, or intramuscular routes with three doses with AFPL1/AFCo1 alone or containing ovalbumin or glycoprotein (g D2 from Herpes Simplex Virus type 2 (HSV-2. High levels of specific IgG antibodies were detected in sera of mice vaccinated with either route. However, specific IgA antibodies were produced in saliva and vaginal wash only following mucosal delivering. The polarization to a Th1 pattern was confirmed by testing the induction of IgG2a/IgG2c antibody, positive delayed-type hypersensitivity reactions, and gIFN production. Additionally, AFCo1gD2 showed practically no vaginal HSV-2 replication and 100% protection against lethal vaginal HSV-2 challenge. In conclusion, the results support the use of AFCo1 as potent Th1 adjuvant for mucosal vaccines, particularly for nasal route.

  6. Muerte celular inducida por condiciones ambientales adversas en Calibrachoa parviflora (Petunia

    Directory of Open Access Journals (Sweden)

    Daniela Montes Berrueta

    2012-03-01

    Full Text Available Se ha descrito que condiciones ambientales extremas tales como altas temperaturas, luz ultravioleta y el efecto invernadero, alteran la tasa de crecimiento de las plantas. En este trabajo se investigó el efecto agudo de dos condiciones ambientales extremas tales como la limitación de nutrientes y la acidificación del suelo con ácido sulfúrico, un compuesto comúnmente depositado en los suelos como consecuencia de la llamada lluvia ácida, sobre la tasa de muerte y proliferación celular en petunias (Calibrachoa parviflora. Para tales efectos, grupos de petunias fueron sometidas a tres condiciones diferentes: grupo A o control, mantenida en condiciones óptimas y de suministro de nutrientes, grupo B en ausencia de nutrientes y de luz natural, y grupo C expuestas a agua acidificada con ácido sulfúrico. En un seguimiento hasta 72 horas, se analizaron muestras de pétalos, hojas y tallos de cada una de las plantas y, posterior a la extracción de los núcleos, estos fueron teñidos con ioduro de propidio, un agente intercalante del ADN, y analizados mediante citometría de flujo y microscopía de fluorescencia. Los resultados muestran que ambas condiciones extremas generan un desbalance en el proceso de muerte/sobrevida de las petunias, pero a diferencia de las plantas del grupo B, las plantas del grupo C no incrementaron la tasa de proliferación celular. Estos resultados sugieren que las plantas que crecen en suelos ácidos pierden la capacidad compensatoria ante la señal de estrés que se genera a consecuencia de la exposición aguda a concentraciones tóxicas de ácido sulfúrico. Cell death induced by adverse environmental conditions in Calibrachoa parviflora (petunia Abstract It has been previously reported that extreme environmental conditions such as high temperatures, ultraviolet light and the greenhouse effect, alter the rate of growth in plants. In this study we investigated the acute effect of two extreme environmental conditions: nutrient deprivation and soil acidification with sulfuric acid, a compound commonly deposited in the soil, as a result of acid rain, on the rate of death and cell proliferation in petunias (Calibrachoa parviflora. For this purpose, a group of petunias was subjected to three different conditions: group A or control, kept in optimum conditions and nutrient supply, group B in the absence of nutrients and natural light and group C, exposed to water acidified with sulfuric acid. In continuous observations for up to 72 hours, samples from petals, leaves and stems of each plant were analyzed and after nuclei extraction; these were treated with propidium iodide, a DNA intercalator compound, and analyzed by flow cytometry and fluorescence microscopy. The results show that both extreme conditions generate an imbalance in the process of death/survival of petunias, but unlike plants from group B, plants in group C, did not increase their rate of cell proliferation. These results suggest that plants growing in acid soils lose their ability to compensate the stress signal generated as a result of acute exposure to toxic concentrations of sulfuric acid.

  7. Posible papel protector de la melatonina frente a la toxicidad neuroendocrina inducida por cadmio

    OpenAIRE

    A Romero; T Cabaleiro; A Caride; A Lafuente

    2008-01-01

    El cadmio es un agente químico tóxico importante debido a su creciente nivel en el medio ambiente como resultado de prácticas industriales y agrícolas. Como perturbador endocrino, el cadmio modifica la secreción de hormonas hipofisarias. Los efectos indirectos del cadmio provocan la generación de especies reactivas de oxígeno y reducen la actividad de las proteínas implicadas en las defensas antioxidantes. La melatonina es conocida como un potente antioxidante, scavenger ...

  8. Polymerization of sodium methacrylate induced by irradiation; Polimerizacion del metacrilato de sodio inducida por la irradiacion

    Energy Technology Data Exchange (ETDEWEB)

    Galvan S, A. [Instituto Nacional de Investigaciones Nucleares, Gerencia de Ciencias Basicas, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    1998-07-01

    This work has two objectives, first: it is pretended to localize the lines of carbon links in its IR spectra, and second: following the polymerization of sodium methacrylate according to that it is irradiated with gamma rays. (Author)

  9. ALERGIA EN EL HUMANO INDUCIDA POR LA SALIVA DE INSECTOS DE LA FAMILIA CULICIDAE

    Directory of Open Access Journals (Sweden)

    Ligia Inés Moncada Álvarez

    2011-04-01

    Full Text Available Se hace una revisión de las moléculas que inoculan los insectos de la familia Culicidae al momento de la picadura y los mecanismos que muestran sus hospederos para contrarrestarlos y cómo algunas de esas moléculas, especialmente las enzimas se convierten en alérgenos que inducen una respuesta de amplio espectro, que va desde una pápula al momento de la picadura hasta una reacción anafiláctica. De la misma manera se analizan las posibilidades de diagnóstico con moléculas silvestres y antígenos recombinantes, lo mismo que pautas de tratamiento.

  10. Prevalencia y severidad de la disfunción intestinal inducida por opioides

    Directory of Open Access Journals (Sweden)

    Rafael Gálvez

    2014-01-01

    Conclusiones: En pacientes con tratamiento opioide se constata una elevada frecuencia de trastornos gastrointestinales posiblemente relacionados con la DIO, lo que subraya la necesidad de nuevas estrategias para su tratamiento.

  11. HIPONATREMIA INDUCIDA POR PERDIDA URINARIA DE SODIO EN EL ANCIANO BAJO DIETA HIPOSODICA

    Directory of Open Access Journals (Sweden)

    Luis S. Algranati L

    2006-04-01

    Full Text Available ABSTRACTHyponatremia is an electrolyte disorder which consist of a relative increase in body free water content respect to sodium one. Free water retention or sodium loss are its possible mechanisms, being the former more frequent than the latter. However, since urinary sodium loss is increased in healthy elderly, sodium depletion can be a frequent etiology of hyponatremia in this people when they have been on a low sodium diet for a long period.In this report a case of hyponatremia that solved with sodium restitution instead of water restriction is presented, and the name of senile sodium leakage hyponatremia is proposed for this entity. It is also analyzed the low reliability that fractional excretion of urea seems to have in the evaluation of this syndrome. RESUMENLa hiponatremia es un desorden electrolítico que consiste en un aumento relativo a nivel corporal del contenido acuoso respecto del salino.La retención de agua libre o la pérdida de sodio son sus mecanismos causales principales, siendo el primero de ellos el más frecuente. Sin embargo, dado que los ancianos normales poseen un aumento en la excreción urinaria de sodio respecto de los jóvenes, pueden desarrollar hiponatremia secundaria a deplección salina cuando han estado en forma prolongada bajo una dieta hiposódica.En este reporte presentamos un caso de hiponatremia que fue resuelto mediante la restitución de sodio y no mediante la restricción hídrica. Analizamos también la baja confiabilidad de la excreción fraccional de urea en la interpretación de la etiología de la hiponatremia en los ancianos.

  12. Efecto hepatoprotector del extracto hidroetanólico atomizado del maíz morado (Zea mays L. en lesiones hepáticas inducidas en ratas

    Directory of Open Access Journals (Sweden)

    Renán Hañari-Quispe

    2015-04-01

    Full Text Available Objetivos: Evaluar el efecto hepatoprotector del extracto hidroetanólico atomizado de Zea mays variedad morado sobre lesiones hepáticas inducidas en ratas. Diseño: Experimental. Institución: Laboratorio de Farmacología Experimental, Facultad de Medicina Humana, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material biológico: Extracto hidroetanólico atomizado de maíz morado (EAM. Intervenciones: Se formó seis grupos de ratas machos (n=10, por cada grupo, se les administró fenobarbital a concentración de 0,5 g/L en agua potable ad líbitum por 15 días; posteriormente se administró tetracloruro de carbono (CCl a una dosis de 0,2 mL/kg, por vía oral. El diseño experimental fue el siguiente: G1: suero fisiológico (SSF; G2: CCl0,2 mL/kg (T;4G3: T+ 4 silimarina 25 mg/kg; G4: T + EAM 500 mg/kg; G5: T + EAM 1 000 mg/kg; G6: T + EAM 2 000 mg/kg. Principales medidas de resultados: Perfil hepático, especies reactivas al ácido tiobarbitúrico (TBARS en suero, índice hepático, observación histológica. Resultados: Se observó aumento significativo (p<0,05 en la actividad de alanina amino transferasa (ALT entre el grupo G2 y los grupos G3 y G4 (p<0,001. Hubo disminución significativa (p<0,05 de fosfatasa alcalina (FAL en el grupo G2 con respecto G1. El nivel de TBARS fue menor en el grupo que recibió 1 000 mg/kg de EAM con respecto al control. Las actividades de HDL-C y triglicéridos no mostraron diferencias significativas. Se ha observado la reducción de 60% de la lesión hepática, evidenciado con menor daño del hepatocito al estudio histológico. Conclusiones: El extracto hidroetanólico atomizado de maíz morado a la dosis de 1 000 mg/kg disminuyó las lesiones hepáticas inducidas en ratas.

  13. Terapia de restricción inducida en afasia

    OpenAIRE

    Galindo Rojas, Edna Jeannet

    2012-01-01

    El presente trabajo monográfico fue desarrollado a través de un abordaje conceptual que pretendía aportar proposiciones teóricas desde diferentes perspectivas científicas al campo de las neurociencias del lenguaje y por ende al área de rehabilitación de desordenes de la comunicación humana. Este documento de trabajo contiene una revisión sistemática de tópicos novedosos relacionados con modelos explicativos en neurociencias, principios neurobiológicos del lenguaje, aportes en neuroplasti...

  14. Terapia de restricci?n inducida en afasia

    OpenAIRE

    Galindo Rojas, Edna Jeannet

    2012-01-01

    El presente trabajo monogr?fico fue desarrollado a trav?s de un abordaje conceptual que pretend?a aportar proposiciones te?ricas desde diferentes perspectivas cient?ficas al campo de las neurociencias del lenguaje y por ende al ?rea de rehabilitaci?n de desordenes de la comunicaci?n humana. Este documento de trabajo contiene una revisi?n sistem?tica de t?picos novedosos relacionados con modelos explicativos en neurociencias, principios neurobiol?gicos del lenguaje, aportes en neuroplasti...

  15. CSPGs inhibit axon branching by impairing mitochondria-dependent regulation of actin dynamics and axonal translation.

    Science.gov (United States)

    Sainath, Rajiv; Ketschek, Andrea; Grandi, Leah; Gallo, Gianluca

    2017-04-01

    Chondroitin sulfate proteoglycans (CSPGs) inhibit the formation of axon collateral branches. The regulation of the axonal cytoskeleton and mitochondria are important components of the mechanism of branching. Actin-dependent axonal plasticity, reflected in the dynamics of axonal actin patches and filopodia, is greatest along segments of the axon populated by mitochondria. It is reported that CSPGs partially depolarize the membrane potential of axonal mitochondria, which impairs the dynamics of the axonal actin cytoskeleton and decreases the formation and duration of axonal filopodia, the first steps in the mechanism of branching. The effects of CSPGs on actin cytoskeletal dynamics are specific to axon segments populated by mitochondria. In contrast, CSPGs do not affect the microtubule content of axons, or the localization of microtubules into axonal filopodia, a required step in the mechanism of branch formation. It is also reported that CSPGs decrease the mitochondria-dependent axonal translation of cortactin, an actin associated protein involved in branching. Finally, the inhibitory effects of CSPGs on axon branching, actin cytoskeletal dynamics and the axonal translation of cortactin are reversed by culturing neurons with acetyl-l-carnitine, which promotes mitochondrial respiration. Collectively these data indicate that CSPGs impair mitochondrial function in axons, an effect which contributes to the inhibition of axon branching. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419-437, 2017. © 2016 Wiley Periodicals, Inc.

  16. The axonal cytoskeleton : from organization to function

    NARCIS (Netherlands)

    Kevenaar, Josta T|info:eu-repo/dai/nl/338771042; Hoogenraad, Casper C|info:eu-repo/dai/nl/227263502

    The axon is the single long fiber that extends from the neuron and transmits electrical signals away from the cell body. The neuronal cytoskeleton, composed of microtubules (MTs), actin filaments and neurofilaments, is not only required for axon formation and axonal transport but also provides the

  17. Slowing of axonal regeneration is correlated with increased axonal viscosity during aging

    Directory of Open Access Journals (Sweden)

    Heidemann Steven R

    2010-10-01

    Full Text Available Abstract Background As we age, the speed of axonal regeneration declines. At the biophysical level, why this occurs is not well understood. Results To investigate we first measured the rate of axonal elongation of sensory neurons cultured from neonatal and adult rats. We found that neonatal axons grew 40% faster than adult axons (11.5 µm/hour vs. 8.2 µm/hour. To determine how the mechanical properties of axons change during maturation, we used force calibrated towing needles to measure the viscosity (stiffness and strength of substrate adhesion of neonatal and adult sensory axons. We found no significant difference in the strength of adhesions, but did find that adult axons were 3 times intrinsically stiffer than neonatal axons. Conclusions Taken together, our results suggest decreasing axonal stiffness may be part of an effective strategy to accelerate the regeneration of axons in the adult peripheral nervous system.

  18. Manifestaciones reumáticas de la infección por el virus de inmunodeficiencia humana (VIH

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    Gloria María Vásquez Duque

    2005-02-01

    Full Text Available Con la aparición del VIH/SIDA se ha puesto de manifiesto un espectro de manifestaciones clínicas reumáticas. El compromiso articular incluye las artralgias, la artritis por VIH, el síndrome de Reiter, la artritis psoriásica y la espondiloartropatía indiferenciada. También se ha documentado una miopatía inducida por el VIH en cuyo diagnóstico diferencial se deben tener en cuenta la miopatía inducida por zidovudina y la debida a toxoplasmosis, cuya presentación clínica es más parecida a la miopatía inducida por el VIH que a otras afecciones musculares. El síndrome de linfocitosis con infiltración difusa es una entidad parecida al síndrome de Sjögren, que es exclusiva de los pacientes VIH positivos, con algunas diferencias en la presentación clínica e inmunológica. Por último, es frecuente la presencia de fenómenos autoinmunes el más común de los cuales es la hipergamaglobulinemia policlonal. También se han descrito diferentes tipos de vasculitis como parte de esta enfermedad.

  19. Frecuencia espontánea e inducida de micronúcleos transplacentarios en ratones Balb/c

    Directory of Open Access Journals (Sweden)

    Daniel Francisco Arencibia Arrebola

    2011-01-01

    Full Text Available Introducción: El ensayo de micronúcleos transplacentario, ha sido desarrollado con el objetivo de evaluar el potencial genotóxico en la descendencia y demostrar la capacidad de un agente de causar daños cromosómicos durante el período prenatal. Éste realiza el registro de aberraciones cromosómicas, demostrando si una sustancia determinada puede ser clastogénica o aneugénica en el feto, a través de la exposición materna. Objetivo: Por lo cual en el presente trabajo se tuvo como objetivo determinar la frecuencia espontánea e inducida de micronúcleos transplacentarios en ratones de la línea Balb/c. Pretendiendo vincular de esta forma el efecto genotóxico y reproductivo de una droga a evaluar por esta metodología. Materiales y métodos: Se formaron 4 grupos experimentales, el primero un control negativo (simulacro, el segundo control solvente NaCl (0,9%, en el tercero se utilizo la ciclofosfamida en dosis de 50 mg/kg, y el cuarto se utilizó la bleomicina en dosis de 20 mg/kg. Todos los grupos se administraron por vía intraperitoneal los días 14, 15 y 16 de la gestación y 24 h después de la última inoculación se procedió al sacrificio de las gestantes por dislocación cervical. Obteniéndose las muestras de médula ósea materna e hígado fetal. Resultados: Se obtuvo como resultado los valores espontáneos e inducidos de los índices de citotoxicidad y de genotoxicidad, así como el total de micronúcleos divididos según niveles de daños.Discusión y conclusiones: Se observo mayor inducción de daño en células hepáticas fetales que en médula ósea materna. Además se demostró que la ciclofosfamida es capaz de inducir mayor citotoxicidad y genotoxicidad que la bleomicina tanto en células de la médula ósea materna como en células hepáticas fetales. Por tanto se demostró el poder clastogénico transplacentario de ambos mutágenos vinculando este ensayo de genotoxicidad a la reproducción. Además estos resultados se

  20. Cell intrinsic control of axon regeneration

    Science.gov (United States)

    Mar, Fernando M; Bonni, Azad; Sousa, Mónica M

    2014-01-01

    Although neurons execute a cell intrinsic program of axonal growth during development, following the establishment of connections, the developmental growth capacity declines. Besides environmental challenges, this switch largely accounts for the failure of adult central nervous system (CNS) axons to regenerate. Here, we discuss the cell intrinsic control of axon regeneration, including not only the regulation of transcriptional and epigenetic mechanisms, but also the modulation of local protein translation, retrograde and anterograde axonal transport, and microtubule dynamics. We further explore the causes underlying the failure of CNS neurons to mount a vigorous regenerative response, and the paradigms demonstrating the activation of cell intrinsic axon growth programs. Finally, we present potential mechanisms to support axon regeneration, as these may represent future therapeutic approaches to promote recovery following CNS injury and disease. PMID:24531721

  1. El género afecta las propiedades contráctiles del músculo sóleo en diabetes inducida experimentalmente en ratas

    Directory of Open Access Journals (Sweden)

    Adolfo Virgen Ortiz

    2015-06-01

    Full Text Available Ratas hembras y machos, de tres meses de edad, fueron separados en dos grupos: no diabéticas (ND, peso corporal, 274 ± 9 g; nivel de glucosa en la sangre, 4,94 ± 0,22 mmol/L; n = 16 y diabéticas (D; peso corporal, 207 ± 8 g; nivel de glucosa en sangre, 28,39 ± 0,94 mmol/L; n = 16. La diabetes fue inducida por una sola dosis de 60 mg/Kg de estreptozotocina administrada intraperitonealmente. Las ratas ND recibieron el mismo volumen de vehículo. Después de 4 semanas los animales fueron considerados diabéticos si su nivel de glucosa era ≥ 20 mmol/L. La masa y la contracción del músculo sóleo fueron mayores en machos ND que en las hembras ND. En las ratas macho D disminuyó su masa muscular en un 34% y la fuerza de contracción disminuyó en un 33%; mientras que en las hembras D disminuyeron 15% y 10% respectivamente.

  2. Sorting of Dendritic and Axonal Vesicles at the Pre-axonal Exclusion Zone

    Directory of Open Access Journals (Sweden)

    Ginny G. Farías

    2015-11-01

    Full Text Available Polarized sorting of newly synthesized proteins to the somatodendritic and axonal domains of neurons occurs by selective incorporation into distinct populations of vesicular transport carriers. An unresolved issue is how the vesicles themselves are sorted to their corresponding neuronal domains. Previous studies concluded that the axon initial segment (AIS is an actin-based filter that selectively prevents passage of somatodendritic vesicles into the axon. We find, however, that most somatodendritic vesicles fail to enter the axon at a more proximal region in the axon hillock, herein referred to as the pre-axonal exclusion zone (PAEZ. Forced coupling of a somatodendritic cargo protein to an axonally directed kinesin is sufficient to drive transport of whole somatodendritic vesicles through the PAEZ toward the distal axon. Based on these findings, we propose that polarized sorting of transport vesicles occurs at the PAEZ and depends on the ability of the vesicles to acquire an appropriately directed microtubule motor.

  3. Radial glia phagocytose axonal debris from degenerating overextending axons in the developing olfactory bulb.

    Science.gov (United States)

    Amaya, Daniel A; Wegner, Michael; Stolt, C Claus; Chehrehasa, Fatemeh; Ekberg, Jenny A K; St John, James A

    2015-02-01

    Axon targeting during the development of the olfactory system is not always accurate, and numerous axons overextend past the target layer into the deeper layers of the olfactory bulb. To date, the fate of the mis-targeted axons has not been determined. We hypothesized that following overextension, the axons degenerate, and cells within the deeper layers of the olfactory bulb phagocytose the axonal debris. We utilized a line of transgenic mice that expresses ZsGreen fluorescent protein in primary olfactory axons. We found that overextending axons closely followed the filaments of radial glia present in the olfactory bulb during embryonic development. Following overextension into deeper layers of the olfactory bulb, axons degenerated and radial glia responded by phagocytosing the resulting debris. We used in vitro analysis to confirm that the radial glia had phagocytosed debris from olfactory axons. We also investigated whether the fate of overextending axons was altered when the development of the olfactory bulb was perturbed. In mice that lacked Sox10, a transcription factor essential for normal olfactory bulb development, we observed a disruption to the morphology and positioning of radial glia and an accumulation of olfactory axon debris within the bulb. Our results demonstrate that during early development of the olfactory system, radial glia play an important role in removing overextended axons from the deeper layers of the olfactory bulb. © 2014 Wiley Periodicals, Inc.

  4. Action Potential Dynamics in Fine Axons Probed with an Axonally Targeted Optical Voltage Sensor.

    Science.gov (United States)

    Ma, Yihe; Bayguinov, Peter O; Jackson, Meyer B

    2017-01-01

    The complex and malleable conduction properties of axons determine how action potentials propagate through extensive axonal arbors to reach synaptic terminals. The excitability of axonal membranes plays a major role in neural circuit function, but because most axons are too thin for conventional electrical recording, their properties remain largely unexplored. To overcome this obstacle, we used a genetically encoded hybrid voltage sensor (hVOS) harboring an axonal targeting motif. Expressing this probe in transgenic mice enabled us to monitor voltage changes optically in two populations of axons in hippocampal slices, the large axons of dentate granule cells (mossy fibers) in the stratum lucidum of the CA3 region and the much finer axons of hilar mossy cells in the inner molecular layer of the dentate gyrus. Action potentials propagated with distinct velocities in each type of axon. Repetitive firing broadened action potentials in both populations, but at an intermediate frequency the degree of broadening differed. Repetitive firing also attenuated action potential amplitudes in both mossy cell and granule cell axons. These results indicate that the features of use-dependent action potential broadening, and possible failure, observed previously in large nerve terminals also appear in much finer unmyelinated axons. Subtle differences in the frequency dependences could influence the propagation of activity through different pathways to excite different populations of neurons. The axonally targeted hVOS probe used here opens up the diverse repertoire of neuronal processes to detailed biophysical study.

  5. AxonSeg: Open Source Software for Axon and Myelin Segmentation and Morphometric Analysis.

    Science.gov (United States)

    Zaimi, Aldo; Duval, Tanguy; Gasecka, Alicja; Côté, Daniel; Stikov, Nikola; Cohen-Adad, Julien

    2016-01-01

    Segmenting axon and myelin from microscopic images is relevant for studying the peripheral and central nervous system and for validating new MRI techniques that aim at quantifying tissue microstructure. While several software packages have been proposed, their interface is sometimes limited and/or they are designed to work with a specific modality (e.g., scanning electron microscopy (SEM) only). Here we introduce AxonSeg, which allows to perform automatic axon and myelin segmentation on histology images, and to extract relevant morphometric information, such as axon diameter distribution, axon density and the myelin g-ratio. AxonSeg includes a simple and intuitive MATLAB-based graphical user interface (GUI) and can easily be adapted to a variety of imaging modalities. The main steps of AxonSeg consist of: (i) image pre-processing; (ii) pre-segmentation of axons over a cropped image and discriminant analysis (DA) to select the best parameters based on axon shape and intensity information; (iii) automatic axon and myelin segmentation over the full image; and (iv) atlas-based statistics to extract morphometric information. Segmentation results from standard optical microscopy (OM), SEM and coherent anti-Stokes Raman scattering (CARS) microscopy are presented, along with validation against manual segmentations. Being fully-automatic after a quick manual intervention on a cropped image, we believe AxonSeg will be useful to researchers interested in large throughput histology. AxonSeg is open source and freely available at: https://github.com/neuropoly/axonseg.

  6. Regulating Axonal Responses to Injury: The Intersection between Signaling Pathways Involved in Axon Myelination and The Inhibition of Axon Regeneration

    Science.gov (United States)

    Rao, Sudheendra N. R.; Pearse, Damien D.

    2016-01-01

    Following spinal cord injury (SCI), a multitude of intrinsic and extrinsic factors adversely affect the gene programs that govern the expression of regeneration-associated genes (RAGs) and the production of a diversity of extracellular matrix molecules (ECM). Insufficient RAG expression in the injured neuron and the presence of inhibitory ECM at the lesion, leads to structural alterations in the axon that perturb the growth machinery, or form an extraneous barrier to axonal regeneration, respectively. Here, the role of myelin, both intact and debris, in antagonizing axon regeneration has been the focus of numerous investigations. These studies have employed antagonizing antibodies and knockout animals to examine how the growth cone of the re-growing axon responds to the presence of myelin and myelin-associated inhibitors (MAIs) within the lesion environment and caudal spinal cord. However, less attention has been placed on how the myelination of the axon after SCI, whether by endogenous glia or exogenously implanted glia, may alter axon regeneration. Here, we examine the intersection between intracellular signaling pathways in neurons and glia that are involved in axon myelination and axon growth, to provide greater insight into how interrogating this complex network of molecular interactions may lead to new therapeutics targeting SCI. PMID:27375427

  7. Axonal interferon responses and alphaherpesvirus neuroinvasion

    Science.gov (United States)

    Song, Ren

    Infection by alphaherpesviruses, including herpes simplex virus (HSV) and pseudorabies virus (PRV), typically begins at a peripheral epithelial surface and continues into the peripheral nervous system (PNS) that innervates this tissue. Inflammatory responses are induced at the infected peripheral site prior to viral invasion of the PNS. PNS neurons are highly polarized cells with long axonal processes that connect to distant targets. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which include type I interferon (e.g. IFNbeta) and type II interferon (i.e. IFNgamma). IFNbeta can be produced by all types of cells, while IFNgamma is secreted by some specific types of immune cells. And both types of IFN induce antiviral responses in surrounding cells that express the IFN receptors. The fundamental question is how do PNS neurons respond to the inflammatory milieu experienced only by their axons. Axons must act as potential front-line barriers to prevent PNS infection and damage. Using compartmented cultures that physically separate neuron axons from cell bodies, I found that pretreating isolated axons with IFNbeta or IFNgamma significantly diminished the number of HSV-1 and PRV particles moving from axons to the cell bodies in an IFN receptor-dependent manner. Furthermore, I found the responses in axons are activated differentially by the two types of IFNs. The response to IFNbeta is a rapid, axon-only response, while the response to IFNgamma involves long distance signaling to the PNS cell body. For example, exposing axons to IFNbeta induced STAT1 phosphorylation (p-STAT1) only in axons, while exposure of axons to IFNgamma induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated IFNgamma-, but not IFNbeta-mediated antiviral effects. Proteomic analysis of IFNbeta- or IFNgamma-treated axons identified several differentially regulated proteins. Therefore

  8. Torsional Behavior of Axonal Microtubule Bundles

    Science.gov (United States)

    Lazarus, Carole; Soheilypour, Mohammad; Mofrad, Mohammad R.K.

    2015-01-01

    Axonal microtubule (MT) bundles crosslinked by microtubule-associated protein (MAP) tau are responsible for vital biological functions such as maintaining mechanical integrity and shape of the axon as well as facilitating axonal transport. Breaking and twisting of MTs have been previously observed in damaged undulated axons. Such breaking and twisting of MTs is suggested to cause axonal swellings that lead to axonal degeneration, which is known as “diffuse axonal injury”. In particular, overstretching and torsion of axons can potentially damage the axonal cytoskeleton. Following our previous studies on mechanical response of axonal MT bundles under uniaxial tension and compression, this work seeks to characterize the mechanical behavior of MT bundles under pure torsion as well as a combination of torsional and tensile loads using a coarse-grained computational model. In the case of pure torsion, a competition between MAP tau tensile and MT bending energies is observed. After three turns, a transition occurs in the mechanical behavior of the bundle that is characterized by its diameter shrinkage. Furthermore, crosslink spacing is shown to considerably influence the mechanical response, with larger MAP tau spacing resulting in a higher rate of turns. Therefore, MAP tau crosslinking of MT filaments protects the bundle from excessive deformation. Simultaneous application of torsion and tension on MT bundles is shown to accelerate bundle failure, compared to pure tension experiments. MAP tau proteins fail in clusters of 10–100 elements located at the discontinuities or the ends of MT filaments. This failure occurs in a stepwise fashion, implying gradual accumulation of elastic tensile energy in crosslinks followed by rupture. Failure of large groups of interconnecting MAP tau proteins leads to detachment of MT filaments from the bundle near discontinuities. This study highlights the importance of torsional loading in axonal damage after traumatic brain injury

  9. IMP2 axonal localization, RNA interactome, and function in the development of axon trajectories

    DEFF Research Database (Denmark)

    Preitner, Nicolas; Quan, Jie; Li, Xinmin

    2016-01-01

    RNA-based regulatory mechanisms play important roles in the development and plasticity of neural circuits and neurological disease. Developing axons provide a model well suited to the study of RNA-based regulation, and contain specific subsets of mRNAsthat are locally translated and have roles...... to strong defects in commissural axon trajectories at the midline intermediate target. These results reveal a highly distinctive axonal enrichment of IMP2, show that it interacts with a network of axon guidance-related mRNAs, and reveal that it is required for normal axon pathfinding during vertebrate...

  10. Squid Giant Axons Synthesize NF Proteins.

    Science.gov (United States)

    Crispino, Marianna; Chun, Jong Tai; Giuditta, Antonio

    2018-04-01

    Squid giant axon has been an excellent model system for studying fundamental topics in neurobiology such as neuronal signaling. It has been also useful in addressing the questions of local protein synthesis in the axons. Incubation of isolated squid giant axons with [ 35 S]methionine followed by immunoprecipitation with a rabbit antibody against all squid neurofilament (NF) proteins demonstrates the local synthesis of a major 180 kDa NF protein and of several NF proteins of lower molecular weights. Their identification as NF proteins is based on their absence in the preimmune precipitates. Immunoprecipitates washed with more stringent buffers confirmed these results. Our data are at variance with a recent study based on the same experimental procedure that failed to visualize the local synthesis of NF proteins by the giant axon and thereby suggested their exclusive derivation from nerve cell bodies (as reported by Gainer et al. in Cell Mol Neurobiol 37:475-486, 2017). By reviewing the pertinent literature, we confute the claims that mRNA translation is absent in mature axons because of a putative translation block and that most proteins of mature axons are synthesized in the surrounding glial cells. Given the intrinsic axonal capacity to synthesize proteins, we stress the glial derivation of axonal and presynaptic RNAs and the related proposal that these neuronal domains are endowed with largely independent gene expression systems (as reported by Giuditta et al. in Physiol Rev 88:515-555, 2008).

  11. Ascending Midbrain Dopaminergic Axons Require Descending GAD65 Axon Fascicles for Normal Pathfinding

    Directory of Open Access Journals (Sweden)

    Claudia Marcela Garcia-Peña

    2014-06-01

    Full Text Available The Nigrostriatal pathway (NSP is formed by dopaminergic axons that project from the ventral midbrain to the dorsolateral striatum as part of the medial forebrain bundle. Previous studies have implicated chemotropic proteins in the formation of the NSP during development but little is known of the role of substrate-anchored signals in this process. We observed in mouse and rat embryos that midbrain dopaminergic axons ascend in close apposition to descending GAD65-positive axon bundles throughout their trajectory to the striatum. To test whether such interaction is important for dopaminergic axon pathfinding, we analyzed transgenic mouse embryos in which the GAD65 axon bundle was reduced by the conditional expression of the diphtheria toxin. In these embryos we observed dopaminergic misprojection into the hypothalamic region and abnormal projection in the striatum. In addition, analysis of Robo1/2 and Slit1/2 knockout embryos revealed that the previously described dopaminergic misprojection in these embryos is accompanied by severe alterations in the GAD65 axon scaffold. Additional studies with cultured dopaminergic neurons and whole embryos suggest that NCAM and Robo proteins are involved in the interaction of GAD65 and dopaminergic axons. These results indicate that the fasciculation between descending GAD65 axon bundles and ascending dopaminergic axons is required for the stereotypical NSP formation during brain development and that known guidance cues may determine this projection indirectly by instructing the pathfinding of the axons that are part of the GAD65 axon scaffold.

  12. Dynamics of mitochondrial transport in axons

    Directory of Open Access Journals (Sweden)

    Robert Francis Niescier

    2016-05-01

    Full Text Available The polarized structure and long neurites of neurons pose a unique challenge for proper mitochondrial distribution. It is widely accepted that mitochondria move from the cell body to axon ends and vice versa; however, we have found that mitochondria originating from the axon ends moving in the retrograde direction never reach to the cell body, and only a limited number of mitochondria moving in the anterograde direction from the cell body arrive at the axon ends of mouse hippocampal neurons. Furthermore, we have derived a mathematical formula using the Fokker-Planck equation to characterize features of mitochondrial transport, and the equation could determine altered mitochondrial transport in axons overexpressing parkin. Our analysis will provide new insights into the dynamics of mitochondrial transport in axons of normal and unhealthy neurons.

  13. The Genetics of Axon Guidance and Axon Regeneration in Caenorhabditis elegans

    Science.gov (United States)

    Chisholm, Andrew D.; Hutter, Harald; Jin, Yishi; Wadsworth, William G.

    2016-01-01

    The correct wiring of neuronal circuits depends on outgrowth and guidance of neuronal processes during development. In the past two decades, great progress has been made in understanding the molecular basis of axon outgrowth and guidance. Genetic analysis in Caenorhabditis elegans has played a key role in elucidating conserved pathways regulating axon guidance, including Netrin signaling, the slit Slit/Robo pathway, Wnt signaling, and others. Axon guidance factors were first identified by screens for mutations affecting animal behavior, and by direct visual screens for axon guidance defects. Genetic analysis of these pathways has revealed the complex and combinatorial nature of guidance cues, and has delineated how cues guide growth cones via receptor activity and cytoskeletal rearrangement. Several axon guidance pathways also affect directed migrations of non-neuronal cells in C. elegans, with implications for normal and pathological cell migrations in situations such as tumor metastasis. The small number of neurons and highly stereotyped axonal architecture of the C. elegans nervous system allow analysis of axon guidance at the level of single identified axons, and permit in vivo tests of prevailing models of axon guidance. C. elegans axons also have a robust capacity to undergo regenerative regrowth after precise laser injury (axotomy). Although such axon regrowth shares some similarities with developmental axon outgrowth, screens for regrowth mutants have revealed regeneration-specific pathways and factors that were not identified in developmental screens. Several areas remain poorly understood, including how major axon tracts are formed in the embryo, and the function of axon regeneration in the natural environment. PMID:28114100

  14. Meninges-derived cues control axon guidance.

    Science.gov (United States)

    Suter, Tracey A C S; DeLoughery, Zachary J; Jaworski, Alexander

    2017-10-01

    The axons of developing neurons travel long distances along stereotyped pathways under the direction of extracellular cues sensed by the axonal growth cone. Guidance cues are either secreted proteins that diffuse freely or bind the extracellular matrix, or membrane-anchored proteins. Different populations of axons express distinct sets of receptors for guidance cues, which results in differential responses to specific ligands. The full repertoire of axon guidance cues and receptors and the identity of the tissues producing these cues remain to be elucidated. The meninges are connective tissue layers enveloping the vertebrate brain and spinal cord that serve to protect the central nervous system (CNS). The meninges also instruct nervous system development by regulating the generation and migration of neural progenitors, but it has not been determined whether they help guide axons to their targets. Here, we investigate a possible role for the meninges in neuronal wiring. Using mouse neural tissue explants, we show that developing spinal cord meninges produce secreted attractive and repulsive cues that can guide multiple types of axons in vitro. We find that motor and sensory neurons, which project axons across the CNS-peripheral nervous system (PNS) boundary, are attracted by meninges. Conversely, axons of both ipsi- and contralaterally projecting dorsal spinal cord interneurons are repelled by meninges. The responses of these axonal populations to the meninges are consistent with their trajectories relative to meninges in vivo, suggesting that meningeal guidance factors contribute to nervous system wiring and control which axons are able to traverse the CNS-PNS boundary. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Developmental downregulation of LIS1 expression limits axonal extension and allows axon pruning

    Directory of Open Access Journals (Sweden)

    Kanako Kumamoto

    2017-07-01

    Full Text Available The robust axonal growth and regenerative capacities of young neurons decrease substantially with age. This developmental downregulation of axonal growth may facilitate axonal pruning and neural circuit formation but limits functional recovery following nerve damage. While external factors influencing axonal growth have been extensively investigated, relatively little is known about the intrinsic molecular changes underlying the age-dependent reduction in regeneration capacity. We report that developmental downregulation of LIS1 is responsible for the decreased axonal extension capacity of mature dorsal root ganglion (DRG neurons. In contrast, exogenous LIS1 expression or endogenous LIS1 augmentation by calpain inhibition restored axonal extension capacity in mature DRG neurons and facilitated regeneration of the damaged sciatic nerve. The insulator protein CTCF suppressed LIS1 expression in mature DRG neurons, and this reduction resulted in excessive accumulation of phosphoactivated GSK-3β at the axon tip, causing failure of the axonal extension. Conversely, sustained LIS1 expression inhibited developmental axon pruning in the mammillary body. Thus, LIS1 regulation may coordinate the balance between axonal growth and pruning during maturation of neuronal circuits.

  16. Dynamics of target recognition by interstitial axon branching along developing cortical axons.

    Science.gov (United States)

    Bastmeyer, M; O'Leary, D D

    1996-02-15

    Corticospinal axons innervate their midbrain, hindbrain, and spinal targets by extending collateral branches interstitially along their length. To establish that the axon shaft rather than the axonal growth cone is responsible for target recognition in this system, and to characterize the dynamics of interstitial branch formation, we have studied this process in an in vivo-like setting using slice cultures from neonatal mice containing the entire pathway of corticospinal axons. Corticospinal axons labeled with the dye 1,1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (or Dil) were imaged using time-lapse video microscopy of their pathway overlying the basilar pons, their major hindbrain target. The axon shaft millimeters behind the growth cone exhibits several dynamic behaviors, including the de novo formation of varicosities and filopodia-like extensions, and a behavior that we term "pulsation," which is characterized by a variable thickening and thining of short segments of the axon. An individual axon can have multiple sites of branching activity, with many of the branches being transient. These dynamic behaviors occur along the portion of the axon shaft overlying the basilar pons, but not just caudal to it. Once the collaterals extend into the pontine neuropil, they branch further in the neuropil, while the parent axon becomes quiescent. Thus, the branching activity is spatially restricted to specific portions of the axon, as well as temporally restricted to a relatively brief time window. These findings provide definitive evidence that collateral branches form de novo along corticospinal axons and establish that the process of target recognition in this system is a property of the axon shaft rather than the leading growth cone.

  17. Cargo distributions differentiate pathological axonal transport impairments.

    Science.gov (United States)

    Mitchell, Cassie S; Lee, Robert H

    2012-05-07

    Axonal transport is an essential process in neurons, analogous to shipping goods, by which energetic and cellular building supplies are carried downstream (anterogradely) and wastes are carried upstream (retrogradely) by molecular motors, which act as cargo porters. Impairments in axonal transport have been linked to devastating and often lethal neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis, Huntington's, and Alzheimer's. Axonal transport impairment types include a decrease in available motors for cargo transport (motor depletion), the presence of defective or non-functional motors (motor dilution), and the presence of increased or larger cargos (protein aggregation). An impediment to potential treatment identification has been the inability to determine what type(s) of axonal transport impairment candidates that could be present in a given disease. In this study, we utilize a computational model and common axonal transport experimental metrics to reveal the axonal transport impairment general characteristics or "signatures" that result from three general defect types of motor depletion, motor dilution, and protein aggregation. Our results not only provide a means to discern these general impairments types, they also reveal key dynamic and emergent features of axonal transport, which potentially underlie multiple impairment types. The identified characteristics, as well as the analytical method, can be used to help elucidate the axonal transport impairments observed in experimental and clinical data. For example, using the model-predicted defect signatures, we identify the defect candidates, which are most likely to be responsible for the axonal transport impairments in the G93A SOD1 mouse model of ALS. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Estrategias para el tratamiento de la disfunción sexual inducida por la medicación antidepresiva

    OpenAIRE

    Taylor, Matthew J.; Rudkin, Lisa; Bullemor-Day, Philippa; Lubin, Jade; Chukwujekwu, Christopher; Hawton, Keith

    2014-01-01

    Antecedentes: La disfunción sexual (que incluye alteración en el deseo sexual, disfunción orgásmica y eyaculatoria, problemas con la erección y otros) es un efecto secundario relativamente frecuente de la medicación antidepresiva. Estos efectos secundarios sexuales pueden comprometer el estilo de vida de los pacientes y dar lugar a una falta de cumplimiento con el antidepresivo prescrito en detrimento de la salud mental del paciente. Para abordar este problema, está disponible un amplio rango...

  19. Lesiones en órganos de cerdos posdestete, inducidas por el lipopolisacárido de E. coli

    Directory of Open Access Journals (Sweden)

    Cristian Gutiérrez V.

    2013-08-01

    Full Text Available Objetivo. Evaluar el efecto de la ingestión de varios niveles de Lipopolisacárido (LPS de E. coli sobre las manifestaciones clínicas y lesiones en órganos de cerdos recién destetados. Materiales y métodos. El trabajo de campo se realizó en el Centro San Pablo, perteneciente a la Universidad Nacional de Colombia. El estudio se realizó con 52 cerdos destetados (6.5±0.5 kg a los 21 días de edad. Los animales fueron alimentados durante 10 días con una dieta basal compuesta de leche y algunos de sus derivados, adicionada con cuatro niveles de LPS (0, 0.3, 0.5 y 1.0 μg/ml de alimento. Los cerdos se sacrificaron escalonadamente los días 1, 5, 7 y 10 posdestete y se tomaron muestras de intestino delgado, estómago, hígado, páncreas, corazón, pulmón, riñón y bazo. El monitoreo clínico y paraclínico se realizó diariamente durante la investigación. Para determinar la ganancia de peso, los animales fueron pesados el día del destete y el día del sacrificio. Resultados. Hubo diferencia (p<0.01 en las variables peso de los órganos y ganancia de peso, donde los animales que consumieron el mayor nivel de LPS presentaron los menores valores, llegando a su mínimo nivel el día 10 posdestete. Las variables presentación de: lesiones macroscópicas, diarreas, y temperatura rectal, aumentaron con el nivel de inclusión de LPS en la dieta, llegando a su máximo nivel el día 10 posdestete (p<0.01. Conclusiones. El LPS de E. coli provoca la inhibición del crecimiento corporal y de los órganos en estudio y una alta incidencia de diarreas.

  20. Efecto neuroprotector del sildenafilo frente a la isquemia química inducida por la toxina mitocondrial malonato

    OpenAIRE

    Barros-Miñones, L. (Lucía); Aguirre, N. (Norberto)

    2014-01-01

    Phosphodiesterase 5 inhibitors (PDE5i) have recently been reported to exert beneficial effects against ischemia-reperfusion injury in several organs but their neuroprotective effects in brain stroke models are scarce. The present study was undertaken to assess the effects of sildenafil against cell death caused by intrastriatal injection of malonate, an inhibitor of succinate dehydrogenase; which produces both energy depletion and lesions similar to those seen in cerebral ischemia. Our data d...

  1. La administración de Carditrofina-1 mejora la colitis ulcerosa inducida por dextrano sulfato de sodio

    OpenAIRE

    Prieto Vicente, Vanessa

    2016-01-01

    [ES] La enfermedad inflamatoria intestinal crónica (EIIC) surge de la interacción entre las bacterias de la luz intestinal y la mucosa y comprende la colitis ulcerosa (CU), la enfermedad de Crohn (EC) y la colitis inclasificable (CI) . Aunque la etiopatogenia de la EIIC no ha sido claramente dilucidada, se atribuye a una compleja interacción entre factores genéticos, ambientales, microbianos y diversos factores inmunes que incluyen péptidos quimiotácticos y citocinas proinflamatorias. La dis...

  2. Genetics Home Reference: giant axonal neuropathy

    Science.gov (United States)

    ... connect the brain and spinal cord (central nervous system) to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. However, axons in the central nervous system are affected as well. The signs and symptoms ...

  3. Drug therapy for chronic idiopathic axonal polyneuropathy

    NARCIS (Netherlands)

    Vrancken, A. F. J. E.; van Schaik, I. N.; Hughes, R. A. C.; Notermans, N. C.

    2004-01-01

    BACKGROUND: Chronic idiopathic axonal polyneuropathy is an insidiously progressive sensory or sensorimotor polyneuropathy that affects elderly people. Although severe disability or handicap does not occur, it reduces quality of life. OBJECTIVES: To assess whether drug therapy for chronic idiopathic

  4. Efecto del extracto metanólico de Jatropha macrantha Müll. Arg., en la disfunción eréctil inducida en ratas

    Directory of Open Access Journals (Sweden)

    Aldo Tinco

    2011-07-01

    Full Text Available Objetivos: Determinar el efecto del extracto metanólico de Jatropha macrantha Müll. Arg. ‘huanarpo macho’ en la disfunción eréctil inducida en ratas. Diseño: Experimental. Institución: Laboratorio de Farmacología, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú; Laboratorio de Farmacia, Universidad Nacional de San Cristóbal de Huamanga, Ayacucho, Perú. Material biológico: Extracto metanólico de Jatropha macrantha Müll Arg. ‘huanarpo macho’; ratas wistar de 300+/-50 g. Intervenciones: La obtención de la muestra se realizó en la Provincia de Vilcas Huamán - Ayacucho. Se evaluó el comportamiento sexual y la concentración de óxido nítrico y el efecto vasorrelajante en el cuerpo cavernoso aislado de pene de ratas, siendo los grupos de estudio: grupo 1 agua 10 mL/kg; grupo 2 sildenafilo 5 mg/kg; grupos 3, 4 y 5 extracto metanólico 100, 200 y 300 mg/kg. Se aisló órganos en los grupos de 50, 100 y 300 ug/mL de extracto, L- arginina 300 uM, acetilcolina 30uM, epinefrina u/mL y sildenafilo (3,2 × 10-5 mg/mL. Principales medidas de resultados: Flavonoides aislados, comportamiento sexual de ratas, niveles plasmáticos de óxido nítrico y relajación del músculo cavernoso. Resultados: Por cromatografía se encontró estructuras tipo flavonas, y mediante espectroscopia UV y reacciones de desplazamiento se identificó 6-hidroxi-4’,5,7-trimetoxi flavona, 4’,7-dihidroxi-5,6-dimetoxiflavona, 7-hidroxi-3’,4’,5’,5,8 pentametoxiflavona, 4’,7-dihidroxi-3’,5,6-trimetoxiflavona, DL50 1357 mg/kg. El comportamiento sexual fue dosis dependiente; la administración de 300 mg/kg de la planta por vía oral incrementó la frecuencia de monta en 75% y elevó los niveles de óxido nítrico en 85%, en tanto que la dosis de 200 mg/kg lo hizo en 71,1% y 32,4%, respectivamente (p<0,05. Conclusiones: En ratas con disfunción eréctil inducida, el extracto metanólico de Jatropha macrantha Müll Arg.

  5. Reproducción inducida de Pimelodus pictus con extracto de hipófisis de carpa (EHC y Ovaprim®

    Directory of Open Access Journals (Sweden)

    Elizabeth Aya B

    2011-04-01

    Full Text Available Objetivo. Comparar la respuesta a la maduración final de las ova y la tasa de ovulación usando dos tratamientos hormonales en hembras de Pimelodus pictus. Materiales y métodos. Hembras maduras recién capturadas fueron superestimuladas con Extracto de Hipófisis de Carpa (EHC y mezcla del análogo de la hormona liberadora de la gonadotropina de salmón más domperidona, Ovaprim®. Se utilizaron dosis totales de 5.5 y 7.7 mg/kg, y 0.5 y 1 ml/kg respectivamente, dividida en dos dosis, e inyectadas con un intervalo de 12 h (10% de la dosis total en la primera inyección y 90% en la segunda. Resultados. Con tiempo de latencia de 6 h 30±20 min a 27.4±0.2°C. Las hembras en todos los tratamientos respondieron por sobre el 50%, siendo mayor la respuesta en ambos protocolos para EHC (p<0.05. El diámetro ovocitario durante y después de los tratamientos aumentó en todos los casos, siendo mayor y diferente (p<0.05, para los tratamientos con Ovaprim®. La fecundidad se registró entre 818 a 1185 óvulos/hembra. Conclusiones. Se demuestra las posibilidades de reproducción inducida con dos inductores hormonales, siendo EHC superior a Ovaprim®.

  6. EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment

    Czech Academy of Sciences Publication Activity Database

    Eva, R.; Koseki, H.; Kanamarlapudi, V.; Fawcett, James

    2017-01-01

    Roč. 130, č. 21 (2017), s. 3663-3675 ISSN 0021-9533 Institutional support: RVO:68378041 Keywords : axon regeneration * axon transport * neuronal polarisation Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 4.431, year: 2016

  7. Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy

    NARCIS (Netherlands)

    Kole, Maarten H. P.; Letzkus, Johannes J.; Stuart, Greg J.

    2007-01-01

    Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action

  8. Axonal cleaved caspase-3 regulates axon targeting and morphogenesis in the developing auditory brainstem

    Directory of Open Access Journals (Sweden)

    Sarah E Rotschafer

    2016-10-01

    Full Text Available Caspase-3 is a cysteine protease that is most commonly associated with cell death. Recent studies have shown additional roles in mediating cell differentiation, cell proliferation, and development of cell morphology. We investigated the role of caspase-3 in the development of chick auditory brainstem nuclei during embryogenesis. Immunofluorescence from embryonic days E6-13 revealed that the temporal expression of cleaved caspase-3 follows the ascending anatomical pathway. Expression is first seen in the auditory portion of VIIIth nerve including central axonal regions projecting to nucleus magnocellularis (NM, then later in NM axons projecting to nucleus laminaris (NL, and subsequently in NL dendrites. To examine the function of cleaved caspase-3 in chick auditory brainstem development, we blocked caspase-3 cleavage in developing chick embryos with the caspase-3 inhibitor Z-DEVD-FMK from E6 to E9, then examined NM and NL morphology and NM axonal targeting on E10. NL lamination in treated embryos was disorganized and the neuropil around NL contained a significant number of glial cells normally excluded from this region. Additionally, NM axons projected into inappropriate portions of NL in Z-DEVD-FMK treated embyros. We found that the presence of misrouted axons was associated with more severe NL disorganization. The effects of axonal caspase-3 inhibition on both NL morphogenesis and NM axon targeting suggest that these developmental processes are coordinated, likely through communication between axons and their targets.

  9. Increased mitochondrial content in remyelinated axons: implications for multiple sclerosis

    Science.gov (United States)

    Zambonin, Jessica L.; Zhao, Chao; Ohno, Nobuhiko; Campbell, Graham R.; Engeham, Sarah; Ziabreva, Iryna; Schwarz, Nadine; Lee, Sok Ee; Frischer, Josa M.; Turnbull, Doug M.; Trapp, Bruce D.; Lassmann, Hans; Franklin, Robin J. M.

    2011-01-01

    Mitochondrial content within axons increases following demyelination in the central nervous system, presumably as a response to the changes in energy needs of axons imposed by redistribution of sodium channels. Myelin sheaths can be restored in demyelinated axons and remyelination in some multiple sclerosis lesions is extensive, while in others it is incomplete or absent. The effects of remyelination on axonal mitochondrial content in multiple sclerosis, particularly whether remyelination completely reverses the mitochondrial changes that follow demyelination, are currently unknown. In this study, we analysed axonal mitochondria within demyelinated, remyelinated and myelinated axons in post-mortem tissue from patients with multiple sclerosis and controls, as well as in experimental models of demyelination and remyelination, in vivo and in vitro. Immunofluorescent labelling of mitochondria (porin, a voltage-dependent anion channel expressed on all mitochondria) and axons (neurofilament), and ultrastructural imaging showed that in both multiple sclerosis and experimental demyelination, mitochondrial content within remyelinated axons was significantly less than in acutely and chronically demyelinated axons but more numerous than in myelinated axons. The greater mitochondrial content within remyelinated, compared with myelinated, axons was due to an increase in density of porin elements whereas increase in size accounted for the change observed in demyelinated axons. The increase in mitochondrial content in remyelinated axons was associated with an increase in mitochondrial respiratory chain complex IV activity. In vitro studies showed a significant increase in the number of stationary mitochondria in remyelinated compared with myelinated and demyelinated axons. The number of mobile mitochondria in remyelinated axons did not significantly differ from myelinated axons, although significantly greater than in demyelinated axons. Our neuropathological data and findings in

  10. Guidance of retinal axons in mammals.

    Science.gov (United States)

    Herrera, Eloísa; Erskine, Lynda; Morenilla-Palao, Cruz

    2017-11-26

    In order to navigate through the surrounding environment many mammals, including humans, primarily rely on vision. The eye, composed of the choroid, sclera, retinal pigmented epithelium, cornea, lens, iris and retina, is the structure that receives the light and converts it into electrical impulses. The retina contains six major types of neurons involving in receiving and modifying visual information and passing it onto higher visual processing centres in the brain. Visual information is relayed to the brain via the axons of retinal ganglion cells (RGCs), a projection known as the optic pathway. The proper formation of this pathway during development is essential for normal vision in the adult individual. Along this pathway there are several points where visual axons face 'choices' in their direction of growth. Understanding how these choices are made has advanced significantly our knowledge of axon guidance mechanisms. Thus, the development of the visual pathway has served as an extremely useful model to reveal general principles of axon pathfinding throughout the nervous system. However, due to its particularities, some cellular and molecular mechanisms are specific for the visual circuit. Here we review both general and specific mechanisms involved in the guidance of mammalian RGC axons when they are traveling from the retina to the brain to establish precise and stereotyped connections that will sustain vision. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Estudio de la influencia de la refrigeracion con aire de forma natural e inducida en el comportamiento de instalaciones fotovoltaicas

    Science.gov (United States)

    Mazon Hernandez, Rocio

    panels are analysed to compare and select the best configuration. The presented research provides a deep knowledge of how they work as well as information and results for an improvement in future designs of building integrated photovoltaic systems. Este estudio se centra en analizar la influencia negativa de la temperatura en la produccion electrica de paneles fotovoltaicos al estar emplazados sobre cubierta de acero, como sucede en naves industriales y sobre un invernadero. Se estudian diferentes configuraciones que permitan refrigerar los paneles, reduciendo su temperatura y mejorar su rendimiento. Para abordar este problema, se han construido dos instalaciones experimentales, fieles a plantas solares en funcionamiento. Una instalacion engloba dos paneles fotovoltaicos sobre estructura fija al suelo. Uno de los paneles esta integrado sobre una superficie paralela y metalica. Entre ambas superficies existe un espacio que posibilita circular aire, permitiendo refrigerar el panel por conveccion natural, o conveccion forzada impulsando el aire con un ventilador. El otro panel, libre por su cara posterior y se ha considerado de referencia. Se ha estudiado el comportamiento del panel integrado sobre cubierta para diferentes secciones de aire y velocidades inducidas, comparandolo con el panel de referencia. Se ha desarrollado un modelo experimental que nos permite determinar la temperatura del panel en funcion de las variables que influyen en su refrigeracion. Adicionalmente, se han analizado los datos de una planta solar en funcionamiento, con paneles de igual caracteristicas, obteniendo correlaciones entre la temperatura del panel y las variables electricas y comparandolos con las obtenidas en la instalacion experimental. La segunda instalacion experimental reproduce parte de una instalacion solar sobre un invernadero, formada por cuatro paneles fotovoltaicos colocados sobre el plastico del invernadero, existiendo un canal divergente entre ambas superficies. Se estudia la

  12. The effect of myelinating Schwann cells on axons.

    Science.gov (United States)

    Martini, R

    2001-04-01

    Myelinating Schwann cells control the number of neurofilaments and elevate the phosphorylation state of neurofilaments in the axon, eventually leading to the typical large axon caliber. Conversely, absence of myelin leads to lower amounts of neurofilaments, reduced phosphorylation levels, and smaller axon diameters. In addition, myelinating Schwann cells mediate the spacing of Na(+) channel clusters during development of the node of Ranvier. When axons are associated with mutant Schwann cells in inherited neuropathies, their calibers are reduced and their neurofilaments are less phosphorylated and more closely spaced. Also, axonal transport is reduced and axons degenerate at the distal ends of long nerves. Myelin-associated glycoprotein may mediate some aspects of Schwann cell-axon communication, but much remains to be learned about the molecular bases of Schwann cell-axon communication. Copyright 2001 John Wiley & Sons, Inc.

  13. Modeling molecular mechanisms in the axon

    Science.gov (United States)

    de Rooij, R.; Miller, K.E.; Kuhl, E.

    2016-01-01

    Axons are living systems that display highly dynamic changes in stiffness, viscosity, and internal stress. However, the mechanistic origin of these phenomenological properties remains elusive. Here we establish a computational mechanics model that interprets cellular-level characteristics as emergent properties from molecular-level events. We create an axon model of discrete microtubules, which are connected to neighboring microtubules via discrete crosslinking mechanisms that obey a set of simple rules. We explore two types of mechanisms: passive and active crosslinking. Our passive and active simulations suggest that the stiffness and viscosity of the axon increase linearly with the crosslink density, and that both are highly sensitive to the crosslink detachment and reattachment times. Our model explains how active crosslinking with dynein motors generates internal stresses and actively drives axon elongation. We anticipate that our model will allow us to probe a wide variety of molecular phenomena–both in isolation and in interaction–to explore emergent cellular-level features under physiological and pathological conditions. PMID:28603326

  14. Macrophages Promote Axon Regeneration with Concurrent Neurotoxicity

    NARCIS (Netherlands)

    Gensel, J.C.; Nakamura, S.; Guan, Z.; Rooijen, van N.; Ankeny, D.P.; Popovich, P.G.

    2009-01-01

    Activated macrophages can promote regeneration of CNS axons. However, macrophages also release factors that kill neurons. These opposing functions are likely induced simultaneously but are rarely considered together in the same experimental preparation. A goal of this study was to unequivocally

  15. Mitochondria Localize to Injured Axons to Support Regeneration.

    Science.gov (United States)

    Han, Sung Min; Baig, Huma S; Hammarlund, Marc

    2016-12-21

    Axon regeneration is essential to restore the nervous system after axon injury. However, the neuronal cell biology that underlies axon regeneration is incompletely understood. Here we use in vivo, single-neuron analysis to investigate the relationship between nerve injury, mitochondrial localization, and axon regeneration. Mitochondria translocate into injured axons so that average mitochondria density increases after injury. Moreover, single-neuron analysis reveals that axons that fail to increase mitochondria have poor regeneration. Experimental alterations to axonal mitochondrial distribution or mitochondrial respiratory chain function result in corresponding changes to regeneration outcomes. Axonal mitochondria are specifically required for growth-cone migration, identifying a key energy challenge for injured neurons. Finally, mitochondrial localization to the axon after injury is regulated in part by dual-leucine zipper kinase 1 (DLK-1), a conserved regulator of axon regeneration. These data identify regulation of axonal mitochondria as a new cell-biological mechanism that helps determine the regenerative response of injured neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Diffuse Axonal Injury and Oxidative Stress: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Alessandro Frati

    2017-12-01

    Full Text Available Traumatic brain injury (TBI is one of the world’s leading causes of morbidity and mortality among young individuals. TBI applies powerful rotational and translational forces to the brain parenchyma, which results in a traumatic diffuse axonal injury (DAI responsible for brain swelling and neuronal death. Following TBI, axonal degeneration has been identified as a progressive process that starts with disrupted axonal transport causing axonal swelling, followed by secondary axonal disconnection and Wallerian degeneration. These modifications in the axonal cytoskeleton interrupt the axoplasmic transport mechanisms, causing the gradual gathering of transport products so as to generate axonal swellings and modifications in neuronal homeostasis. Oxidative stress with consequent impairment of endogenous antioxidant defense mechanisms plays a significant role in the secondary events leading to neuronal death. Studies support the role of an altered axonal calcium homeostasis as a mechanism in the secondary damage of axon, and suggest that calcium channel blocker can alleviate the secondary damage, as well as other mechanisms implied in the secondary injury, and could be targeted as a candidate for therapeutic approaches. Reactive oxygen species (ROS-mediated axonal degeneration is mainly caused by extracellular Ca2+. Increases in the defense mechanisms through the use of exogenous antioxidants may be neuroprotective, particularly if they are given within the neuroprotective time window. A promising potential therapeutic target for DAI is to directly address mitochondria-related injury or to modulate energetic axonal energy failure.

  17. Diffuse Axonal Injury and Oxidative Stress: A Comprehensive Review.

    Science.gov (United States)

    Frati, Alessandro; Cerretani, Daniela; Fiaschi, Anna Ida; Frati, Paola; Gatto, Vittorio; La Russa, Raffaele; Pesce, Alessandro; Pinchi, Enrica; Santurro, Alessandro; Fraschetti, Flavia; Fineschi, Vittorio

    2017-12-02

    Traumatic brain injury (TBI) is one of the world's leading causes of morbidity and mortality among young individuals. TBI applies powerful rotational and translational forces to the brain parenchyma, which results in a traumatic diffuse axonal injury (DAI) responsible for brain swelling and neuronal death. Following TBI, axonal degeneration has been identified as a progressive process that starts with disrupted axonal transport causing axonal swelling, followed by secondary axonal disconnection and Wallerian degeneration. These modifications in the axonal cytoskeleton interrupt the axoplasmic transport mechanisms, causing the gradual gathering of transport products so as to generate axonal swellings and modifications in neuronal homeostasis. Oxidative stress with consequent impairment of endogenous antioxidant defense mechanisms plays a significant role in the secondary events leading to neuronal death. Studies support the role of an altered axonal calcium homeostasis as a mechanism in the secondary damage of axon, and suggest that calcium channel blocker can alleviate the secondary damage, as well as other mechanisms implied in the secondary injury, and could be targeted as a candidate for therapeutic approaches. Reactive oxygen species (ROS)-mediated axonal degeneration is mainly caused by extracellular Ca 2+ . Increases in the defense mechanisms through the use of exogenous antioxidants may be neuroprotective, particularly if they are given within the neuroprotective time window. A promising potential therapeutic target for DAI is to directly address mitochondria-related injury or to modulate energetic axonal energy failure.

  18. Efecto terapéutico del extracto etanólico de Erythroxylum coca spp. en anemia ferropénica inducida en ratas Holtzman macho

    Directory of Open Access Journals (Sweden)

    Evelyn F. Gonzales-Carazas

    2013-01-01

    Full Text Available Introducción: La hoja de coca ha sido usada tradicionalmente con fines medicinales y contiene altos niveles de hierro. Objetivos: Determinar el efecto del extracto etanólico de Erythroxylum coca spp. frente a anemia ferropénica inducida por dieta deficiente en hierro, en ratas Holtzman macho. Diseño: Experimental. Lugar: Laboratorio del Instituto de Patología, Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Material biológico: Dieciocho ratas Holtzman macho de 16 días de edad recién destetadas. Intervenciones: Se formó tres grupos de seis ratas cada uno: a grupo hierro suficiente (HS, recibió 25 g/d de alimento balanceado durante 7 semanas; b grupo hierro deficiente (HD, recibió 25 g/d de dieta ferropénica durante 7 semanas; y, c el grupo hierro deficiente - extracto E. coca (HD-EC, recibió 25 g/d de dieta ferropénica durante 7 semanas y a partir de la semana 5 se agregó 18 g/d de extracto de E. coca. Principales medidas de resultados: Nivel sérico de hemoglobina, peso y talla. Resultados: Al finalizar el tratamiento, se observó aumento significativo de la hemoglobina en el grupo HD-EC (p=0,04. Se encontró diferencia significativa en los niveles séricos de hemoglobina entre los grupos HD-EC y HD (p=0,0062. No se encontró diferencia significativa en los valores de hemoglobina entre los grupos HD-EC y HS (p= 0,06. No se evidenció diferencia en el peso y la talla entre los grupos HD y HD-EC (p=0,20 y p=0,23, respectivamente. Conclusiones: E. coca presenta efecto antianémico experimental, sustentado en los resultados de los niveles de hemoglobina.

  19. Axon degeneration: make the Schwann cell great again

    Directory of Open Access Journals (Sweden)

    Keit Men Wong

    2017-01-01

    Full Text Available Axonal degeneration is a pivotal feature of many neurodegenerative conditions and substantially accounts for neurological morbidity. A widely used experimental model to study the mechanisms of axonal degeneration is Wallerian degeneration (WD, which occurs after acute axonal injury. In the peripheral nervous system (PNS, WD is characterized by swift dismantling and clearance of injured axons with their myelin sheaths. This is a prerequisite for successful axonal regeneration. In the central nervous system (CNS, WD is much slower, which significantly contributes to failed axonal regeneration. Although it is well-documented that Schwann cells (SCs have a critical role in the regenerative potential of the PNS, to date we have only scarce knowledge as to how SCs 'sense' axonal injury and immediately respond to it. In this regard, it remains unknown as to whether SCs play the role of a passive bystander or an active director during the execution of the highly orchestrated disintegration program of axons. Older reports, together with more recent studies, suggest that SCs mount dynamic injury responses minutes after axonal injury, long before axonal breakdown occurs. The swift SC response to axonal injury could play either a pro-degenerative role, or alternatively a supportive role, to the integrity of distressed axons that have not yet committed to degenerate. Indeed, supporting the latter concept, recent findings in a chronic PNS neurodegeneration model indicate that deactivation of a key molecule promoting SC injury responses exacerbates axonal loss. If this holds true in a broader spectrum of conditions, it may provide the grounds for the development of new glia-centric therapeutic approaches to counteract axonal loss.

  20. Motor axon excitability during Wallerian degeneration

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Alvarez, Susana; Krarup, Christian

    2008-01-01

    Axonal loss and degeneration are major factors in determining long-term outcome in patients with peripheral nerve disorders or injury. Following loss of axonal continuity, the isolated nerve stump distal to the lesion undergoes Wallerian degeneration in several phases. In the initial 'latent' phase...... at ankle distal to axotomy were monitored by 'threshold-tracking'. The plantar compound muscle action potentials (CMAPs) were recorded under anesthesia in three animal models: 8-week-old wild-type mice, 8-week-old slow Wallerian degeneration mutant mice and 3-year-old cats. We found that the progressive...... decrease in CMAP following crush injury was associated with slowing of conduction and marked abnormalities in excitability: increased peak threshold deviations during both depolarizing and hyperpolarizing threshold electrotonus, enhanced superexcitability during the recovery cycle and increased rheobase...

  1. B-RAF kinase drives developmental axon growth and promotes axon regeneration in the injured mature CNS

    Science.gov (United States)

    O’Donovan, Kevin J.; Ma, Kaijie; Guo, Hengchang; Wang, Chen; Sun, Fang; Han, Seung Baek; Kim, Hyukmin; Wong, Jamie K.; Charron, Jean; Zou, Hongyan; Son, Young-Jin; He, Zhigang

    2014-01-01

    Activation of intrinsic growth programs that promote developmental axon growth may also facilitate axon regeneration in injured adult neurons. Here, we demonstrate that conditional activation of B-RAF kinase alone in mouse embryonic neurons is sufficient to drive the growth of long-range peripheral sensory axon projections in vivo in the absence of upstream neurotrophin signaling. We further show that activated B-RAF signaling enables robust regenerative growth of sensory axons into the spinal cord after a dorsal root crush as well as substantial axon regrowth in the crush-lesioned optic nerve. Finally, the combination of B-RAF gain-of-function and PTEN loss-of-function promotes optic nerve axon extension beyond what would be predicted for a simple additive effect. We conclude that cell-intrinsic RAF signaling is a crucial pathway promoting developmental and regenerative axon growth in the peripheral and central nervous systems. PMID:24733831

  2. Sensory axonal dysfunction in cervical radiculopathy.

    Science.gov (United States)

    Sung, Jia-Ying; Tani, Jowy; Hung, Kuo-Sheng; Lui, Tai-Ngar; Lin, Cindy Shin-Yi

    2015-06-01

    The aim of this study was to evaluate changes in sensory axonal excitability in the distal nerve in patients with cervical radiculopathy. The patients were classified by the findings of cervical MRI into two subgroups: 22 patients with C6/7 root compression and 25 patients with cervical cord and root compression above/at C6/7. Patients were investigated using conventional nerve conduction studies (NCS) and nerve excitability testing. Sensory nerve excitability testing was undertaken with stimulation at the wrist and recording from digit II (dermatome C6/7). The results were compared with healthy controls. Both preoperative and postoperative tests were performed if the patient underwent surgery. Sensory axonal excitability was significantly different in both cohorts compared with healthy controls, including prolonged strength-duration time constant, reduced S2 accommodation, increased threshold electrotonus hyperpolarisation (TEh (90-100 ms)), and increased superexcitability. The changes in these excitability indices are compatible with axonal membrane hyperpolarisation. In five patients who underwent surgery, the postoperative sensory excitability was tested after 1 week, and showed significant changes in TE (TEh (90-100 ms) and TEh slope, pcervical radiculopathy. These findings suggest that the hyperpolarised pattern might be due to Na(+)-K(+) ATPase overactivation induced by proximal ischaemia, or could reflect the remyelinating process. Distal sensory axons were hyperpolarised even though there were no changes in NCS, suggesting that nerve excitability testing may be more sensitive to clinical symptoms than NCS in patients with cervical radiculopathy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Unidirectional ephaptic stimulation between two myelinated axons.

    Science.gov (United States)

    Capllonch-Juan, Miguel; Kolbl, Florian; Sepulveda, Francisco

    2017-07-01

    Providing realistic sensory feedback for prosthetic devices strongly relies on an accurate modelling of machine-nerve interfaces. Models of these interfaces in the peripheral nervous system usually neglect the effects that ephaptic coupling can have on the selectivity of stimulating electrodes. In this contribution, we study the ephaptic stimulation between myelinated axons and show its relation with the separation between fibers and the conductivity of the medium that surrounds them.

  4. Multifunctional Silk Nerve Guides for Axon Outgrowth

    Science.gov (United States)

    Tupaj, Marie C.

    Peripheral nerve regeneration is a critical issue as 2.8% of trauma patients present with this type of injury, estimating a total of 200,000 nerve repair procedures yearly in the United States. While the peripheral nervous system exhibits slow regeneration, at a rate of 0.5 mm -- 9 mm/day following trauma, this regenerative ability is only possible under certain conditions. Clinical repairs have changed slightly in the last 30 years and standard methods of treatment include suturing damaged nerve ends, allografting, and autografting, with the autograft the gold standard of these approaches. Unfortunately, the use of autografts requires a second surgery and there is a shortage of nerves available for grafting. Allografts are a second option however allografts have lower success rates and are accompanied by the need of immunosuppressant drugs. Recently there has been a focus on developing nerve guides as an "off the shelf" approach. Although some natural and synthetic guidance channels have been approved by the FDA, these nerve guides are unfunctionalized and repair only short gaps, less than 3 cm in length. The goal of this project was to identify strategies for functionalizing peripheral nerve conduits for the outgrowth of neuron axons in vitro . To accomplish this, two strategies (bioelectrical and biophysical) were indentified for increasing axon outgrowth and promoting axon guidance. Bioelectrical strategies exploited electrical stimulation for increasing neurite outgrowth. Biophysical strategies tested a range of surface topographies for axon guidance. Novel methods were developed for integrating electrical and biophysical strategies into silk films in 2D. Finally, a functionalized nerve conduit system was developed that integrated all strategies for the purpose of attaching, elongating, and guiding nervous tissue in vitro. Future directions of this work include silk conduit translation into a rat sciatic nerve model in vivo for the purpose of repairing long

  5. Synaptic Democracy and Vesicular Transport in Axons

    Science.gov (United States)

    Bressloff, Paul C.; Levien, Ethan

    2015-04-01

    Synaptic democracy concerns the general problem of how regions of an axon or dendrite far from the cell body (soma) of a neuron can play an effective role in neuronal function. For example, stimulated synapses far from the soma are unlikely to influence the firing of a neuron unless some sort of active dendritic processing occurs. Analogously, the motor-driven transport of newly synthesized proteins from the soma to presynaptic targets along the axon tends to favor the delivery of resources to proximal synapses. Both of these phenomena reflect fundamental limitations of transport processes based on a localized source. In this Letter, we show that a more democratic distribution of proteins along an axon can be achieved by making the transport process less efficient. This involves two components: bidirectional or "stop-and-go" motor transport (which can be modeled in terms of advection-diffusion), and reversible interactions between motor-cargo complexes and synaptic targets. Both of these features have recently been observed experimentally. Our model suggests that, just as in human societies, there needs to be a balance between "efficiency" and "equality".

  6. Axonal branching patterns of nucleus accumbens neurons in the rat.

    Science.gov (United States)

    Tripathi, Anushree; Prensa, Lucía; Cebrián, Carolina; Mengual, Elisa

    2010-11-15

    The patterns of axonal collateralization of nucleus accumbens (Acb) projection neurons were investigated in the rat by means of single-axon tracing techniques using the anterograde tracer biotinylated dextran amine. Seventy-three axons were fully traced, originating from either the core (AcbC) or shell (AcbSh) compartment, as assessed by differential calbindin D28k-immunoreactivity. Axons from AcbC and AcbSh showed a substantial segregation in their targets; target areas were either exclusively or preferentially innervated from AcbC or AcbSh. Axon collaterals in the subthalamic nucleus were found at higher than expected frequencies; moreover, these originated exclusively in the dorsal AcbC. Intercompartmental collaterals were observed from ventral AcbC axons into AcbSh, and likewise, interconnections at pallidal and mesencephalic levels were also observed, although mostly from AcbC axons toward AcbSh targets, possibly supporting crosstalk between the two subcircuits at several levels. Cell somata giving rise to short-range accumbal axons, projecting to the ventral pallidum (VP), were spatially intermingled with others, giving rise to long-range axons that innervated VP and more caudal targets. This anatomical organization parallels that of the dorsal striatum and provides the basis for possible dual direct and indirect actions from a single axon on either individual or small sets of neurons. Copyright © 2010 Wiley-Liss, Inc.

  7. Axonal and Transynaptic Spread of Prions

    Science.gov (United States)

    Shearin, Harold

    2014-01-01

    ABSTRACT Natural transmission of prion diseases depends upon the spread of prions from the nervous system to excretory or secretory tissues, but the mechanism of prion transport in axons and into peripheral tissue is unresolved. Here, we examined the temporal and spatial movement of prions from the brain stem along cranial nerves into skeletal muscle as a model of axonal transport and transynaptic spread. The disease-specific isoform of the prion protein, PrPSc, was observed in nerve fibers of the tongue approximately 2 weeks prior to PrPSc deposition in skeletal muscle. Initially, PrPSc deposits had a small punctate pattern on the edge of muscle cells that colocalized with synaptophysin, a marker for the neuromuscular junction (NMJ), in >50% of the cells. At later time points PrPSc was widely distributed in muscle cells, but PrPSc deposition at the NMJ, suggesting additional prion replication and dissemination within muscle cells. In contrast to the NMJ, PrPSc was not associated with synaptophysin in nerve fibers but was found to colocalize with LAMP-1 and cathepsin D during early stages of axonal spread. We propose that PrPSc-bound endosomes can lead to membrane recycling in which PrPSc is directed to the synapse, where it either moves across the NMJ into the postsynaptic muscle cell or induces PrPSc formation on muscle cells across the NMJ. IMPORTANCE Prion diseases are transmissible and fatal neurodegenerative diseases in which prion dissemination to excretory or secretory tissues is necessary for natural disease transmission. Despite the importance of this pathway, the cellular mechanism of prion transport in axons and into peripheral tissue is unresolved. This study demonstrates anterograde spread of prions within nerve fibers prior to infection of peripheral synapses (i.e., neuromuscular junction) and infection of peripheral tissues (i.e., muscle cells). Within nerve fibers prions were associated with the endosomal-lysosomal pathway prior to entry into

  8. Incidencia del conflicto territorial por la soberanía de las islas Kuriles en las relaciones políticas entre Rusia y Japón (2006-2011)

    OpenAIRE

    Garzón Mejía, Ana Milena

    2013-01-01

    Este estudio examina las dinámicas de las relaciones políticas bilaterales- entre Rusia y Japón, influenciadas por el conflicto territorial por las islas Kuriles, entre el año 2006 al 2011.Todo con el propósito de identificar el papel del conflicto sobre dichas relaciones. Bajo el concepto de interés nacional, Rusia inducida por éste y sus capacidades militares ha mantenido el conflicto ignorando las reclamaciones de Japón. Lo anterior ha llevado a Japón a tener reacciones enérgicas tales co...

  9. Can injured adult CNS axons regenerate by recapitulating development?

    Science.gov (United States)

    Hilton, Brett J; Bradke, Frank

    2017-10-01

    In the adult mammalian central nervous system (CNS), neurons typically fail to regenerate their axons after injury. During development, by contrast, neurons extend axons effectively. A variety of intracellular mechanisms mediate this difference, including changes in gene expression, the ability to form a growth cone, differences in mitochondrial function/axonal transport and the efficacy of synaptic transmission. In turn, these intracellular processes are linked to extracellular differences between the developing and adult CNS. During development, the extracellular environment directs axon growth and circuit formation. In adulthood, by contrast, extracellular factors, such as myelin and the extracellular matrix, restrict axon growth. Here, we discuss whether the reactivation of developmental processes can elicit axon regeneration in the injured CNS. © 2017. Published by The Company of Biologists Ltd.

  10. Regulation and dysregulation of axon infrastructure by myelinating glia.

    Science.gov (United States)

    Pan, Simon; Chan, Jonah R

    2017-12-04

    Axon loss and neurodegeneration constitute clinically debilitating sequelae in demyelinating diseases such as multiple sclerosis, but the underlying mechanisms of secondary degeneration are not well understood. Myelinating glia play a fundamental role in promoting the maturation of the axon cytoskeleton, regulating axon trafficking parameters, and imposing architectural rearrangements such as the nodes of Ranvier and their associated molecular domains. In the setting of demyelination, these changes may be reversed or persist as maladaptive features, leading to axon degeneration. In this review, we consider recent insights into axon-glial interactions during development and disease to propose that disruption of the cytoskeleton, nodal architecture, and other components of axon infrastructure is a potential mediator of pathophysiological damage after demyelination. © 2017 Pan and Chan.

  11. Active polysomes in the axoplasm of the squid giant axon.

    Science.gov (United States)

    Giuditta, A; Menichini, E; Perrone Capano, C; Langella, M; Martin, R; Castigli, E; Kaplan, B B

    1991-01-01

    Axons and axon terminals are widely believed to lack the capacity to synthesize proteins, relying instead on the delivery of proteins made in the perikaryon. In agreement with this view, axoplasmic proteins synthesized by the isolated giant axon of the squid are believed to derive entirely from periaxonal glial cells. However, squid axoplasm is known to contain the requisite components of an extra-mitochondrial protein synthetic system, including protein factors, tRNAs, rRNAs, and a heterogeneous family of mRNAs. Hence, the giant axon could, in principle, maintain an endogenous protein synthetic capacity. Here, we report that the squid giant axon also contains active polysomes and mRNA, which hybridizes to a riboprobe encoding murine neurofilament protein. Taken together, these findings provide direct evidence that proteins (including the putative neuron-specific neurofilament protein) are also synthesized de novo in the axonal compartment.

  12. Axon-glia interaction and membrane traffic in myelin formation

    OpenAIRE

    White, Robin; Krämer-Albers, Eva-Maria

    2014-01-01

    In vertebrate nervous systems myelination of neuronal axons has evolved to increase conduction velocity of electrical impulses with minimal space and energy requirements. Myelin is formed by specialized glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarization followed by targeted myelin membrane expansion and compaction. Thereby, a myelin sheath of complex subdomain structure is...

  13. Schwann Cell Glycogen Selectively Supports Myelinated Axon Function

    Science.gov (United States)

    Brown, Angus M; Evans, Richard D; Black, Joel; Ransom, Bruce R

    2012-01-01

    Objectives Interruption of energy supply to peripheral axons is a cause of axon loss. We determined if glycogen was present in mammalian peripheral nerve, and if it supported axon conduction during aglycemia. Methods We used biochemical assay and electron microscopy to determine the presence of glycogen, and electrophysiology to monitor axon function. Results Glycogen was present in sciatic nerve, its concentration varying directly with ambient [glucose]. Electron microscopy detected glycogen granules primarily in myelinating Schwann cell cytoplasm and these diminished after exposure to aglycemia. During aglycemia, conduction failure in large myelinated axons (A fibers) mirrored the time-course of glycogen loss. Latency to CAP failure was directly related to nerve glycogen content at aglycemia onset. Glycogen did not benefit the function of slow-conducting, small diameter unmyelinated axons (C fibers) during aglycemia. Blocking glycogen breakdown pharmacologically accelerated CAP failure during aglycemia in A fibers, but not in C fibers. Lactate was as effective as glucose in supporting sciatic nerve function, and was continuously released into the extracellular space in the presence of glucose and fell rapidly during aglycemia. Interpretation Our findings indicated that glycogen is present in peripheral nerve, primarily in myelinating Schwann cells, and exclusively supports large diameter, myelinated axon conduction during aglycemia. Available evidence suggests that peripheral nerve glycogen breaks down during aglycemia and is passed, probably as lactate, to myelinated axons to support function. Unmyelinated axons are not protected by glycogen and are more vulnerable to dysfunction during periods of hypoglycemia. PMID:23034913

  14. Concepts for regulation of axon integrity by enwrapping glia

    Directory of Open Access Journals (Sweden)

    Bogdan eBeirowski

    2013-12-01

    Full Text Available Long axons and their enwrapping glia (Schwann cells and oligodendrocytes form a unique compound structure that serves as conduit for transport of electric and chemical information in the nervous system. The peculiar cytoarchitecture over an enormous length as well as its substantial energetic requirements make this conduit particularly susceptible to detrimental alterations. Degeneration of long axons independent of neuronal cell bodies is observed comparatively early in a range of neurodegenerative conditions as a consequence of abnormalities in Schwann cells and oligodendrocytes. This leads to the most relevant disease symptoms and highlights the critical role that these glia have for axon integrity, but the underlying mechanisms remain elusive. The quest to understand why and how axons degenerate is now a crucial frontier in disease-oriented research. This challenge is most likely to lead to significant progress if the inextricable link between axons and their flanking glia in pathological situations is recognized. In this review I compile recent advances in our understanding of the molecular programs governing axon degeneration, and mechanisms of enwrapping glia’s non-cell autonomous impact on axon-integrity. A particular focus is placed on emerging evidence suggesting that enwrapping glia nurture long axons by virtue of their intimate association, release of trophic substances, and neurometabolic coupling. The correction of defects in these functions has the potential to stabilize axons in a variety of neuronal diseases in the peripheral and central nervous system.

  15. Axonal branching patterns of ventral pallidal neurons in the rat.

    Science.gov (United States)

    Tripathi, Anushree; Prensa, Lucía; Mengual, Elisa

    2013-09-01

    The ventral pallidum (VP) is a key component of the cortico-basal ganglia circuits that process motivational and emotional information, and also a crucial site for reward. Although the main targets of the two VP compartments, medial (VPm) and lateral (VPl) have already been established, the collateralization patterns of individual axons have not previously been investigated. Here we have fully traced eighty-four axons from VPm, VPl and the rostral extension of VP into the olfactory tubercle (VPr), using the anterograde tracer biotinylated dextran amine in the rat. Thirty to fifty percent of axons originating from VPm and VPr collateralized in the mediodorsal thalamic nucleus and lateral habenula, indicating a close association between the ventral basal ganglia-thalamo-cortical loop and the reward network at the single axon level. Additional collateralization of these axons in diverse components of the extended amygdala and corticopetal system supports a multisystem integration that may take place at the basal forebrain. Remarkably, we did not find evidence for a sharp segregation in the targets of axons arising from the two VP compartments, as VPl axons frequently collateralized in the caudal lateral hypothalamus and ventral tegmental area, the well-known targets of VPm, while VPm axons, in turn, also collateralized in typical VPl targets such as the subthalamic nucleus, substantia nigra pars compacta and reticulata, and retrorubral field. Nevertheless, VPl and VPm displayed collateralization patterns that paralleled those of dorsal pallidal components, confirming at the single axon level the parallel organization of functionally different basal ganglia loops.

  16. Differences in excitability properties of FDI and ADM motor axons.

    Science.gov (United States)

    Bae, Jong Seok; Sawai, Setsu; Misawa, Sonoko; Kanai, Kazuaki; Isose, Sagiri; Kuwabara, Satoshi

    2009-03-01

    The first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles are innervated by the same ulnar nerve, but studies have shown that the former is much more severely affected in amyotrophic lateral sclerosis. In this study, threshold tracking was used to investigate whether membrane properties differ between FDI and ADM motor axons. In 12 normal subjects, compound muscle action potentials were recorded from FDI and ADM after ulnar nerve stimulation at the wrist. The strength-duration time constant was significantly longer in the FDI axons than in the ADM axons, and latent addition studies showed greater threshold changes at the conditioning-test stimulus of 0.2 ms in FDI than in ADM axons. These findings suggest that nodal persistent sodium conductances are more prominent in FDI axons than in ADM axons, and therefore excitability is physiologically higher in FDI axons. Even in the same nerve at the same sites, membrane properties of FDI and ADM motor axons differ significantly, and thus their axonal/neuronal responses to disease may also differ.

  17. Death Receptor 6 Promotes Wallerian Degeneration in Peripheral Axons.

    Science.gov (United States)

    Gamage, Kanchana K; Cheng, Irene; Park, Rachel E; Karim, Mardeen S; Edamura, Kazusa; Hughes, Christopher; Spano, Anthony J; Erisir, Alev; Deppmann, Christopher D

    2017-03-20

    Axon degeneration during development is required to sculpt a functional nervous system and is also a hallmark of pathological insult, such as injury [1, 2]. Despite similar morphological characteristics, very little overlap in molecular mechanisms has been reported between pathological and developmental degeneration [3-5]. In the peripheral nervous system (PNS), developmental axon pruning relies on receptor-mediated extrinsic degeneration mechanisms to determine which axons are maintained or degenerated [5-7]. Receptors have not been implicated in Wallerian axon degeneration; instead, axon autonomous, intrinsic mechanisms are thought to be the primary driver for this type of axon disintegration [8-10]. Here we survey the role of neuronally expressed, paralogous tumor necrosis factor receptor super family (TNFRSF) members in Wallerian degeneration. We find that an orphan receptor, death receptor 6 (DR6), is required to drive axon degeneration after axotomy in sympathetic and sensory neurons cultured in microfluidic devices. We sought to validate these in vitro findings in vivo using a transected sciatic nerve model. Consistent with the in vitro findings, DR6 -/- animals displayed preserved axons up to 4 weeks after injury. In contrast to phenotypes observed in Wld s and Sarm1 -/- mice, preserved axons in DR6 -/- animals display profound myelin remodeling. This indicates that deterioration of axons and myelin after axotomy are mechanistically distinct processes. Finally, we find that JNK signaling after injury requires DR6, suggesting a link between this novel extrinsic pathway and the axon autonomous, intrinsic pathways that have become established for Wallerian degeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Age-related changes in axonal transport.

    Science.gov (United States)

    Frolkis, V V; Tanin, S A; Gorban, Y N

    1997-01-01

    In rats the rate of axonal transport (AT) or radiolabeled material decreased in the ventral roots of the spinal cord and the vagal and hypoglossal nerves with aging. A maximum AT deceleration in old age was observed in the vagus. The uncoupling of oxidative phosphorylation, inhibition of glycolysis and hypoxia induced a greater AT deceleration in old rats as compared to adults. Small doses of sodium fluoride accelerated AT, and this correlated with a rise in cAMP levels in ventral roots. High doses of sodium fluoride decelerated AT more markedly in old rats. It was shown that anabolic hormones (sex steroids and thyroxine) accelerated AT in both adult and old rats, whereas insulin induced a rise in AT rate in only adults. The catabolic steroid, hydrocortisone decelerated AT. In old rats castration diminished AT, while thyroidectomy had no effect. It was also shown that hydrocortisone and testosterone were transported along axons, reached fibers of the skeletal muscles, and hyperpolarized the plasma membrane. In old age the latent period was extended. Following 73 to 74 days of irradiation, AT slowed down in all the nerves studied in both adult and old rats. Following irradiation hormonal effects on AT changed, for example, the stimulatory effect of estradiol became weak, especially in old rats. Changes in AT could be an important mechanism of disordering the growth of neurons and innervated cells in old age.

  19. Is action potential threshold lowest in the axon?

    NARCIS (Netherlands)

    Kole, Maarten H. P.; Stuart, Greg J.

    2008-01-01

    Action potential threshold is thought to be lowest in the axon, but when measured using conventional techniques, we found that action potential voltage threshold of rat cortical pyramidal neurons was higher in the axon than at other neuronal locations. In contrast, both current threshold and voltage

  20. Protein-synthesizing machinery in the axon compartment.

    Science.gov (United States)

    Koenig, E; Giuditta, A

    1999-03-01

    Contrary to the prevailing view that the axon lacks the capacity to synthesize proteins, a substantial body of evidence points to the existence of a metabolically active endogenous translational machinery. The machinery appears to be largely localized in the cortical zone of the axon, where, in vertebrate axons, it is distributed longitudinally as intermittent, discrete domains, called periaxoplasmic plaques. Studies, based on translation assays and probes of RNA transcripts in axon models such as the squid giant axon and selected vertebrate axons, provide evidence of locally synthesized proteins, most of which appear to be constituents of the slow axoplasmic transport rate groups. Metabolic and molecular biological findings are consistent with the view that the synthesis of proteins undergoing local turnover in the axonal compartment of macroneurons depends on the activity of an endogenous translational machinery. The documented presence of a metabolically active machinery in presynaptic terminals of squid photoreceptor neurons is also described. Finally, potential sources of axoplasmic RNAs comprising the machinery, which may include the ensheathing cell of the axon, as well as the cognate cell body, are also discussed.

  1. Wnts guide longitudinal axon tracts in the brain

    NARCIS (Netherlands)

    Prasad, A.A.

    2011-01-01

    The human brain contains more than 10 billion neurons that form over 10 trillion connections. The establishment of these connections during development requires axons to extend through the extracellular environment to their synaptic targets. This process of axon guidance is mediated by molecular

  2. SnoN facilitates axonal regeneration after spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Jiun L Do

    Full Text Available Adult CNS neurons exhibit a reduced capacity for growth compared to developing neurons, due in part to downregulation of growth-associated genes as development is completed. We tested the hypothesis that SnoN, an embryonically regulated transcription factor that specifies growth of the axonal compartment, can enhance growth in injured adult neurons. In vitro, SnoN overexpression in dissociated adult DRG neuronal cultures significantly enhanced neurite outgrowth. Moreover, TGF-β1, a negative regulator of SnoN, inhibited neurite outgrowth, and SnoN over-expression overcame this inhibition. We then examined whether SnoN influenced axonal regeneration in vivo: indeed, expression of a mutant form of SnoN resistant to degradation significantly enhanced axonal regeneration following cervical spinal cord injury, despite peri-lesional upregulation of TGF-β1. Thus, a developmental mechanism that specifies extension of the axonal compartment also promotes axonal regeneration after adult CNS injury.

  3. Motor Axonal Regeneration After Partial and Complete Spinal Cord Transection

    Science.gov (United States)

    Lu, Paul; Blesch, Armin; Graham, Lori; Wang, Yaozhi; Samara, Ramsey; Banos, Karla; Haringer, Verena; Havton, Leif; Weishaupt, Nina; Bennett, David; Fouad, Karim; Tuszynski, Mark H.

    2012-01-01

    We subjected rats to either partial mid-cervical or complete upper thoracic spinal cord transections and examined whether combinatorial treatments support motor axonal regeneration into and beyond the lesion. Subjects received cAMP injections into brainstem reticular motor neurons to stimulate their endogenous growth state, bone marrow stromal cell grafts in lesion sites to provide permissive matrices for axonal growth, and brain-derived neurotrophic factor (BDNF) gradients beyond the lesion to stimulate distal growth of motor axons. Findings were compared to several control groups. Combinatorial treatment generated motor axon regeneration beyond both C5 hemisection and complete transection sites. Yet despite formation of synapses with neurons below the lesion, motor outcomes worsened after partial cervical lesions and spasticity worsened after complete transection. These findings highlight the complexity of spinal cord repair, and the need for additional control and shaping of axonal regeneration. PMID:22699902

  4. Effect of rofecoxib on colon chemical carcinogenesis at colonic anastomotic area in the rat Influencia del rofecoxib en la carcinogénesis cólica perianastomótica inducida en ratas

    Directory of Open Access Journals (Sweden)

    J. F. Noguera Aguilar

    2005-06-01

    durante 18 semanas y se analizaron los tumores cólicos inducidos en la semana 20 del postoperatorio. El principal parámetro evaluado fue el porcentaje de tejido cólico neoplásico, que relaciona la superficie tumoral con la superficie del colon. Resultados: el rofecoxib a dosis de 0,0058 ppm redujo significativamente la carcinogénesis cólica inducida en ratas, tanto a nivel perianastomótico como en el resto del colon (p < 0,01. A nivel extraanastomótico, el rofecoxib a dosis de 2,5 mg/kg fue significativamente superior en su efecto inhibidor al rofecoxib a dosis de 1,2 mg/kg o 0,0027 ppm (p < 0,005. Conclusiones: el rofecoxib produce una disminución en la carcinogénesis cólica farmacológicamente inducida en ratas. Este efecto se mantiene en el área perianastomótica, por lo que puede ser interesante investigar su implicación en el cáncer colorrectal intervenido con riesgo de recidiva locorregional.

  5. Estudio de daño genético inducido en esperma de Drosophila melanogaster : análisis de letales recesivos ligados al sexo inducidos por neutrones de 3 MEV.

    OpenAIRE

    Muñoz, Enzo Ruben

    1992-01-01

    En esperma de Drosophila melanogaster la frecuencia de mutaciones letales recesivas ligadas al sexo inducida por neutrones o por rayos X crece linealmente, lo que significa que cada letal es el resultado de un impacto. A pesar de ésto hay evidencias conflictivas según las cuales a igualdad de dosis los neutrones serían menos eficientes o más eficientes que los rayos x en la inducción de este tipo de daño. Es decir que se encontraron Eficiencias Biológicas Relativas (RBE) (dosis de rayos x/dos...

  6. Plasticity of the Axon Initial Segment

    DEFF Research Database (Denmark)

    Petersen, Anders Victor; Cotel, Florence; Perrier, Jean François

    2017-01-01

    undergo important modifications during development. The development of the AIS is governed by intrinsic mechanisms. In addition, surrounding neuronal networks modify its maturation. As a result, neurons get tuned to particular physiological functions. Neuronal activity also influences the morphology......The axon initial segment (AIS) is a key neuronal compartment because it is responsible for action potential initiation. The local density of Na+ channels, the biophysical properties of K+ channels, as well as the length and diameter of the AIS determine the spiking of neurons. These parameters...... of the mature AIS. When excitatory neurons are hyperactive, their AIS undergo structural changes that decrease their excitability and thereby maintain the activity within a given range. These slow homeostatic regulatory mechanisms occur on a time scale of hours or days. In contrast, the activation...

  7. Prolyl Isomerase Pin1 Regulates Axon Guidance by Stabilizing CRMP2A Selectively in Distal Axons

    Czech Academy of Sciences Publication Activity Database

    Balaštík, Martin; Zhou, X.Z.; Alberich-Jorda, Meritxell; Weissová, Romana; Žiak, Jakub; Pazyra-Murphy, M.F.; Cosker, K.E.; Machoňová, Olga; Kozmiková, Iryna; Chen, CH.; Pastorino, L.; Asara, J.M.; Cole, A.; Sutherland, C.; Segal, R. A.; Lu, K.P.

    2015-01-01

    Roč. 13, č. 4 (2015), s. 812-828 ISSN 2211-1247 R&D Projects: GA MŠk(CZ) LK11213; GA MŠk LK21307; GA ČR GA15-03796S; GA MŠk LO1419 Institutional support: RVO:68378050 Keywords : Pin1 * axon guidance * Semaphorin 3A Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.870, year: 2015

  8. Axon tension regulates fasciculation/defasciculation through the control of axon shaft zippering

    Czech Academy of Sciences Publication Activity Database

    Šmít, Daniel; Fouquet, C.; Pincet, F.; Zápotocký, Martin; Trembleau, A.

    2017-01-01

    Roč. 6, Apr 19 (2017), č. článku e19907. ISSN 2050-084X R&D Projects: GA ČR(CZ) GA14-16755S; GA MŠk(CZ) 7AMB12FR002 Institutional support: RVO:67985823 Keywords : biophysics * cell adhesion * coarsening * developmental biology * mathematical model * mechanical tension * axon guidance Subject RIV: BO - Biophysics OBOR OECD: Biophysics Impact factor: 7.725, year: 2016

  9. Neuron Morphology Influences Axon Initial Segment Plasticity.

    Science.gov (United States)

    Gulledge, Allan T; Bravo, Jaime J

    2016-01-01

    In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation.

  10. El dipéptido de glutamina administrado por vía oral promueve la recuperación de glucemia aguda en ratas sometidas a hipoglucemia por insulina durante largo tiempo

    OpenAIRE

    García, Rosángela F.; Gazola, Vilma A. F. G.; Hartmann, Eduardo M.; Barrena, Helenton C.; Obici, Simoni; Nascimento, Kátia F.; Bazotte, Roberto B.

    2008-01-01

    Fue comparado el efecto agudo de la administración oral (100 mg/kg) del dipéptido de glutamina (L-alanil-L-glutamina, AGP), L-alanina (ALA) y L-glutamina (GLN) en la recuperación de la glucemia (RG) en los casos de hipoglucemia inducida por insulina (IIH) durante largo tiempo. Se comparó el comportamiento de ratas en ayuno de 24 h que recibieron insulina regular por vía intraperitoneal (1,0 U/kg) y luego de 165 min AGP, ALA, GLN o solución salina por vía oral. La glucemia fue evaluada a los 1...

  11. Efectos del cultivo hipóxico sobre la reprogramación de fibroblastos humanos a células madre pluripotentes inducidas

    OpenAIRE

    Questa, María

    2015-01-01

    Las células somáticas pueden ser reprogramadas a células pluripotentes denominadas Células Madre Pluripotentes Inducidas (CMPi) y éstas, a su vez, pueden diferenciarse a cualquier tipo celular adulto. Esto es de gran importancia en los campos de la medicina regenerativa, las pruebas farmacológicas in vitro y la investigación de trastornos genéticos, dado que pueden obtenerse células pluripotentes sin enfrentar la barrera ética de la manipulación de embriones y con el valor agregado de ser gen...

  12. Les activités de gestion d’alerte épidémiologique : les transformations induites par l’utilisation d’un système de surveillance en temps réel Alert Management Activity: Cognitive and team activity modifications due to the use of an early warning system Las actividades de gestión de alerta epidemiológica : las transformaciones inducidas por la utilización de un sistema de vigilancia en tiempo real

    Directory of Open Access Journals (Sweden)

    Charlotte Gaudin

    2012-05-01

    dinámico puesto que las epidemias evolucionan y se propagan rápidamente si ninguna acción es emprendida para controlarlas. Más precisamente dos tipos de situaciones son analizadas : (1 la actividad tradicional de gestión de alerta y (2 esta misma actividad cuando es asistida por un sistema informático, en el caso el sistema ASTER (o Alerta y Supervisión en Tiempo Real. Luego, los resultados obtenidos son discutidos a nivel cognitivo y a nivel de las actividades colectivas consecutivamente a la introducción y a la utilización de un sistema técnico.

  13. Procesos de corrosión debidos a corrientes alternas inducidas (60 Hz

    Directory of Open Access Journals (Sweden)

    Vera, E.

    1996-10-01

    Full Text Available The phenomenon by which a sinusoidal a.c. signal damages a steel in contact with an aggressive electrolite was determined. Thus, a series of electrochemical tests was carried out, when a signal of the previously mentioned characteristics is present in the metal-electrolite interphase, both with cathodic protection and without it. The results allowed to postulate an empirical relationship that determines the corrosive process kinetics exerted by the action of an alternating signal. The phenomenon by which the AC signal generates a corrosion state over a probe was determined from the physical point of view.

    Se determinó el fenómeno por el que una señal de c.a. de tipo sinusoidal genera fenómenos de corrosión en un acero en contacto con un electrólito agresivo. Para ello, se realizaron pruebas electroquímicas cuando una señal de las anteriores características está presente en la interfase metal-electrólito, con y sin protección catódica. Los resultados permitieron postular una relación empírica que determina la cinética del proceso corrosivo ejercido por la acción de la señal alterna. Se determinó, desde un punto de vista físico, el fenómeno por el cual la señal de c.a. genera un estado de corrosión sobre la probeta.

  14. EFECTO DE Tropaeolum tuberosum FRENTE A LA HIPERPLASIA PROSTÁTICA BENIGNA INDUCIDA EN RATAS HOLTZMAN

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    Gioliana Aire-Artezano

    2013-01-01

    Full Text Available Objetivo: Evaluar el efecto de Tropaeolum tuberosum(mashua frente a la Hiperplasia Prostática Benigna (HPB y compararlo con finasterida. Métodos: Estudio experimental completo. Se emplearon 30 ratas Holtzman macho de 12 semanas de edad, aleatorizadas y divididas en seis gru- pos: grupo blanco; grupo testosterona; grupo finasterida (0.33mg/kg/rata; y tres grupos dosis, dosis 1 (300mg/kg/rata, dosis 2 (500mg/kg/rata y dosis 3 (800mg/kg/rata tratados con Tropaeolum tuberosum. Se realizó una medición basal del volumen prostático mediante una ecografía transabdominal. La inducción de HPB se realizó con enantato de testosterona (0,083mg/Kg/rata en los grupos dosis, finasterida y testosterona, el día uno y siete. Paralelamente, se administró liofilizado de Tropaeolum tuberosum y finasterida durante 21 días. Para el diagnóstico, se realiza- ron estudios por imágenes, anatomopatológicos e histopatológicos. Resultados: El estudio por imágenes, en relación al incremento del volumen prostático,no arrojó diferencia significativa entre dosis 2 y finasterida; mientras que en relación con la ecogenicidad, dosis 3 presentó similitud cualitativa al finasterida. En el estudio anatomopatológico, no hubo diferencia significativa entre el grupo dosis 3 y el grupo finasterida. Histo- patológicamente, dosis 3 se asemejó cuantitativamente al finasterida. Conclusiones: Se evidenció disminución de la HPB histológicamente y en el estudio por imágenes; sin embargo, ninguna de las dosis mostró efecto superior al finasterida.

  15. Axonal Regulation of Central Nervous System Myelination: Structure and Function.

    Science.gov (United States)

    Klingseisen, Anna; Lyons, David A

    2018-02-01

    Approximately half of the human brain consists of myelinated axons. Central nervous system (CNS) myelin is made by oligodendrocytes and is essential for nervous system formation, health, and function. Once thought simply as a static insulator that facilitated rapid impulse conduction, myelin is now known to be made and remodeled in to adult life. Oligodendrocytes have a remarkable capacity to differentiate by default, but many aspects of their development can be influenced by axons. However, how axons and oligodendrocytes interact and cooperate to regulate myelination in the CNS remains unclear. Here, we review recent advances in our understanding of how such interactions generate the complexity of myelination known to exist in vivo. We highlight intriguing results that indicate that the cross-sectional size of an axon alone may regulate myelination to a surprising degree. We also review new studies, which have highlighted diversity in the myelination of axons of different neuronal subtypes and circuits, and structure-function relationships, which suggest that myelinated axons can be exquisitely fine-tuned to mediate precise conduction needs. We also discuss recent advances in our understanding of how neuronal activity regulates CNS myelination, and aim to provide an integrated overview of how axon-oligodendrocyte interactions sculpt neuronal circuit structure and function.

  16. Regeneration of axons in the mouse retina after injury.

    Science.gov (United States)

    McConnell, P; Berry, M

    1982-01-01

    It is generally accepted that most axons in the mammalian CNS show only transient growth in response to injury, and numerous hypotheses have been advanced to account for this phenomenon. Detailed knowledge of the time-course and extent of this so-called 'abortive regeneration' is, however, surprisingly lacking. The retina of the adult albino mouse provides a convenient system in which to quantify the response of central axons to injury, since the retina can be prepared as a whole mount, allowing silver-impregnated axons to be followed along their entire course. Using this experimental model, sprouting of injured axons was observed as early as 14 h post lesion (hpl) with rapid growth (20 micrometers/day on average) continuing until 10 dpl. Thereafter, a decline in the overall growth rate was observed, presumably regenerated sprouts began to degenerate. However, not all axons showed this abortive response: numerous unfasciculated axons continued in random growth until at least 100 dpl. One possible interpretation of these results is that the concept of abortive regeneration of injured axons is untenable in regions of the CNS which are lacking in myelin.

  17. Axonal and presynaptic RNAs are locally transcribed in glial cells.

    Science.gov (United States)

    Giuditta, Antonio; Chun, Jong Tai; Eyman, Maria; Cefaliello, Carolina; Bruno, Anna Paola; Crispino, Marianna

    2007-01-01

    In the last few years, the long-standing opinion that axonal and presynaptic proteins are exclusively derived from the neuron cell body has been substantially modified by the demonstration that active systems of protein synthesis are present in axons and nerve terminals. These observations have raised the issue of the cellular origin of the involved RNAs, which has been generally attributed to the neuron soma. However, data gathered in a number of model systems indicated that axonal RNAs are synthesized in the surrounding glial cells. More recent experiments on the perfused squid giant axon have definitively proved that axoplasmic RNAs are transcribed in periaxonal glia. Their delivery to the axon occurs by a modulatory mechanism based on the release of neurotransmitters from the stimulated axon and on their binding to glial receptors. In additional experiments on squid optic lobe synaptosomes, presynaptic RNA has been also shown to be synthesized locally, presumably in nearby glia. Together with a wealth of literature data, these observations indicate that axons and nerve terminals are endowed with a local system of gene expression that supports the maintenance and plasticity of these neuronal domains.

  18. Propagation of action potentials in inhomogeneous axon regions.

    Science.gov (United States)

    Ramón, F; Joyner, R W; Moore, J W

    1975-04-01

    Described are studies of propagation of action potentials through inhomogenous axon regions through experiments performed on squid giant axons and by computer simulations. The initial speed of propagation of the action potential is dependent upon the stimulus waveform. For a rectangular pulse of current, the action potential travel initally at a high speed that declines over the distance, reaching a constant speed of propagation at about 1-5 resting length constants; this distance depends on the stimulus strength. additional experiments studied the effects of changing the axon diameter and of introducing a temperature step. It was found that the propagated action potential suffers profound modification in shape and velocity as it reaches the region of transition. In both cases, it was possible to obtain reflected action potentials. A region of increased effective diameter was produced experimentally in the squid giant axon by insertion of an axial wire as usually employed in voltage clamps. It was found that the action potential, at the axial wire tip region, undergoes shape changes similar to those obtained tn simulations of a region of increased diameter as in a junction with the axon and soma in motor neurons. It is conducluded that the gaint axon can be used to reproduce simple electrical behaviors in other structures.-Ramón, F., R. W. Joyner and J.W. Moore. Propagation of action potentials in inhomogeneous axon regions.

  19. Mitotic motors coregulate microtubule patterns in axons and dendrites.

    Science.gov (United States)

    Lin, Shen; Liu, Mei; Mozgova, Olga I; Yu, Wenqian; Baas, Peter W

    2012-10-03

    Microtubules are nearly uniformly oriented in the axons of vertebrate neurons but are non-uniformly oriented in their dendrites. Studies to date suggest a scenario for establishing these microtubule patterns whereby microtubules are transported into the axon and nascent dendrites with plus-ends-leading, and then additional microtubules of the opposite orientation are transported into the developing dendrites. Here, we used contemporary tools to confirm that depletion of kinesin-6 (also called CHO1/MKLP1 or kif23) from rat sympathetic neurons causes a reduction in the appearance of minus-end-distal microtubules in developing dendrites, which in turn causes them to assume an axon-like morphology. Interestingly, we observed a similar phenomenon when we depleted kinesin-12 (also called kif15 or HKLP2). Both motors are best known for their participation in mitosis in other cell types, and both are enriched in the cell body and dendrites of neurons. Unlike kinesin-12, which is present throughout the neuron, kinesin-6 is barely detectable in the axon. Accordingly, depletion of kinesin-6, unlike depletion of kinesin-12, has no effect on axonal branching or navigation. Interestingly, depletion of either motor results in faster growing axons with greater numbers of mobile microtubules. Based on these observations, we posit a model whereby these two motors generate forces that attenuate the transport of microtubules with plus-ends-leading from the cell body into the axon. Some of these microtubules are not only prevented from moving into the axon but are driven with minus-ends-leading into developing dendrites. In this manner, these so-called "mitotic" motors coregulate the microtubule patterns of axons and dendrites.

  20. Carbonatogénesis inducida en un perfil de suelo tropical

    Directory of Open Access Journals (Sweden)

    Yamile Valencia González

    2014-01-01

    Full Text Available En los suelos puede generarse un proceso común en la naturaleza denominado “biomineralización”o “bioprecipitación”, mediante el cual los organismos vivos presentes en él forman precipitados minerales cristalinos o amorfos. Este proceso es muy importante para la ingeniería geotécnica, ya que los minerales precipitados pueden llenar los vacíos o ligar las partículas de suelo mejorando las propiedades geológico-geotécnicas del material; sin embargo, el proceso demora muchísimos años para ocurrir de forma natural. Es por eso, que con esta investigación se buscó inducir en pocos días (15 días la precipitación de minerales de carbonato de calcio, a partir de la adición de un nutriente precipitador sobre las bacterias nativas existentes en un perfil de suelo tropical, mejorando sus propiedades ingenieriles por medio de la disminución del índice de vacíos, la retracción, la permeabilidad, el colapso, la erodabilidad y la degradación, y del aumento de la cohesión y la fricción, causando menor impacto ambiental que otras técnicas usadas comúnmente en la ingeniería.

  1. Axonal Membranes and Their Domains: Assembly and Function of the Axon Initial Segment and Node of Ranvier

    Directory of Open Access Journals (Sweden)

    Andrew D. Nelson

    2017-05-01

    Full Text Available Neurons are highly specialized cells of the nervous system that receive, process and transmit electrical signals critical for normal brain function. Here, we review the intricate organization of axonal membrane domains that facilitate rapid action potential conduction underlying communication between complex neuronal circuits. Two critical excitable domains of vertebrate axons are the axon initial segment (AIS and the nodes of Ranvier, which are characterized by the high concentrations of voltage-gated ion channels, cell adhesion molecules and specialized cytoskeletal networks. The AIS is located at the proximal region of the axon and serves as the site of action potential initiation, while nodes of Ranvier, gaps between adjacent myelin sheaths, allow rapid propagation of the action potential through saltatory conduction. The AIS and nodes of Ranvier are assembled by ankyrins, spectrins and their associated binding partners through the clustering of membrane proteins and connection to the underlying cytoskeleton network. Although the AIS and nodes of Ranvier share similar protein composition, their mechanisms of assembly are strikingly different. Here we will cover the mechanisms of formation and maintenance of these axonal excitable membrane domains, specifically highlighting the similarities and differences between them. We will also discuss recent advances in super resolution fluorescence imaging which have elucidated the arrangement of the submembranous axonal cytoskeleton revealing a surprising structural organization necessary to maintain axonal organization and function. Finally, human mutations in axonal domain components have been associated with a growing number of neurological disorders including severe cognitive dysfunction, epilepsy, autism, neurodegenerative diseases and psychiatric disorders. Overall, this review highlights the assembly, maintenance and function of axonal excitable domains, particularly the AIS and nodes of

  2. La formación de la imagen turística inducida: un modelo conceptual

    Directory of Open Access Journals (Sweden)

    Raquel Camprubí

    2009-01-01

    más influyentes para la competitividad de los destinos turísticos, el principal objetivo de este artículo es construir un marco conceptual que muestre la influencia de la red relacional del destino en su imagen emitida. En este contexto, se asume que la imagen turística es una construcción social resultante de la interacción de los distintos agentes que intervienen en el destino turístico (administraciones públicas, instituciones locales, empresas turísticas, etc.; y se propone un modelo teórico para mostrar los efectos de la red relacional del destino turístico en la calidad de la imagen turística creada en términos de conocimiento generado y, por tanto, en su competitividad.

  3. Mutagénesis inducida en microbulbos de Allium sativum L.

    Directory of Open Access Journals (Sweden)

    Adriana Pardo Roldán

    2015-07-01

    Full Text Available Se estableció un protocolo de mutagénesis en microbulbos de ajo (Allium sativum L. clon Boconó cultivado in vitro. Para el efecto se realizaron dos ensayos, uno de radiosensibilidad para establecer la dosimetría apropiada de radiación gamma y otro de mutagénesis para determinar el comportamiento de los materiales hasta la etapa de almacenamiento. En el primero los microbulbos fueron tratados con cuatros dosis de radiación gamma (6, 8, 10 y 12 Krad, más un control. Para establecer la dosis óptima se consideró la sobrevivencia del 50% de los microbulbos (DL50. Se empleó un diseño de bloques al azar con cinco tratamientos y 20 repeticiones por tratamiento. En el ensayo mutagénico los microbulbos fueron irradiados con 8 y 10 Krad y almacenados durante 45 días a 10 °C en condiciones de oscuridad En este caso se utilizó un diseño de bloques al azar con tres tratamientos (0, 8 y 10 Krad y 20 repeticiones por tratamiento. En ambos ensayos, los microbulbos irradiados con 8 y 10 Krad registraron los mayores promedios para peso y diámetro, lo cual permite concluir que estas dosis son adecuadas para favorecer la producción de mutantes con características agronómicas deseables en el clon Boconó

  4. Evaluación de la reproducción inducida del blanquillo ( Sorubim cuspicaudus Littmann, Burr Nass, 2000 con ovaprim®.

    Directory of Open Access Journals (Sweden)

    Víctor Atencio G

    2003-01-01

    Full Text Available El blanquillo ( Sorubim suspicaudus Littmann, Burr &Nass, 2000 presenta características de importanciapara la acuicultura, destacándose la calidad de sucarne y el alto valor comercial. No se reproduce enconfinamiento, por lo que es necesario sureproducción inducida con sustancias hormonales.Responde bien a la inducción con extracto de pituitariade capa (EPC; sin embargo, no se ha evaluado suinducción con extracto de análogos deGonodotropine Releasing Hormone de salmón(sGnRH-a y domperidone en un vehículo inerte. Porlo tanto, entre mayo y noviembre/02, se evaluó eldesempeño reproductivo del blanquillo inducido condiferentes dosificaciones de Ovaprim®: 0.25 (T2,0.050 (T3 y 0.75 ml/kg de peso vivo (T4, aplicadoen una sola dosificación, por inyección en la basede la aleta pectoral. Además, un grupo fue inducidocon 8 mg EPC/kg de peso vivo (TI, en dos inyeccionesde 10 y7 90% de la dosis total, con intervalo de 6horas, por vía intramuscular. Se indujeron entre seisy nueve hembras por tratamiento con igual númerode machos. El desempeño reproductivo fue evaluadomediante el índice de ovulación (hembras ovuladas/hembras tratadas, tasa de fertilización medida a las4 horas pos-eclosión (HPF, tasa de eclosión medidaa las 10 HPF y la fecundidad tanto absoluta comorelativa. El Ovaprim® mostró ser efectivo para inducirla ovulación del blanquillo en las dosificacionesevaluadas (0.25 a 0.75 mL/kg, con respuestassimilares en el desempeño reproductivo a lasobtenidas en EPC. La ovulación con Ovaprim® seobtuvo entre las 12.8 y 14.0 horas con temperaturapromedio del agua de 27.3ºC. El índice de ovulaciónosciló entre 66.7% (T2 y 83.3% (T3; la tasa defertilización osciló entre 88.0% (T3 y 42.0% (T1; latasa de eclosión osciló entre 83.7% (T3 y 40.3%(T1;la fecundidad absoluta osciló entre 40370.6 (T1 y82992.5 ovocitos/hembra (T2; la fecundad relativa,expresada en gramos de ovocitos/kg de hembra,osciló entre 32.1 (T3 y 63.1(T2; el di

  5. Axon diameter mapping in crossing fibers with diffusion MRI

    DEFF Research Database (Denmark)

    Zhang, Hui; Dyrby, Tim B; Alexander, Daniel C

    2011-01-01

    tissue than measures derived from diffusion tensor imaging. Most existing techniques for axon diameter mapping assume a single axon orientation in the tissue model, which limits their application to only the most coherently oriented brain white matter, such as the corpus callosum, where the single......This paper proposes a technique for a previously unaddressed problem, namely, mapping axon diameter in crossing fiber regions, using diffusion MRI. Direct measurement of tissue microstructure of this kind using diffusion MRI offers a new class of biomarkers that give more specific information about...... orientation assumption is a reasonable one. However, fiber crossings and other complex configurations are widespread in the brain. In such areas, the existing techniques will fail to provide useful axon diameter indices for any of the individual fiber populations. We propose a novel crossing fiber tissue...

  6. Fiber Optic Detection of Action Potentials in Axons

    National Research Council Canada - National Science Library

    Smela, Elisabeth

    2006-01-01

    In prior exploratory research, we had designed a fiber optic sensor utilizing a long period Bragg grating for the purpose of detecting action potentials in axons optically, through a change in index...

  7. Spontaneous axonal regeneration in rodent spinal cord after ischemic injury

    DEFF Research Database (Denmark)

    von Euler, Mia; Janson, A M; Larsen, Jytte Overgaard

    2002-01-01

    cells, while other fibers were unmyelinated. Immunohistochemistry demonstrated that some of the regenerated fibers were tyrosine hydroxylase- or serotonin-immunoreactive, indicating a central origin. These findings suggest that there is a considerable amount of spontaneous regeneration after spinal cord......Here we present evidence for spontaneous and long-lasting regeneration of CNS axons after spinal cord lesions in adult rats. The length of 200 kD neurofilament (NF)-immunolabeled axons was estimated after photochemically induced ischemic spinal cord lesions using a stereological tool. The total...... length of all NF-immunolabeled axons within the lesion cavities was increased 6- to 10-fold at 5, 10, and 15 wk post-lesion compared with 1 wk post-surgery. In ultrastructural studies we found the putatively regenerating axons within the lesion to be associated either with oligodendrocytes or Schwann...

  8. The nigrostriatal pathway: axonal collateralization and compartmental specificity.

    Science.gov (United States)

    Prensa, L; Giménez-Amaya, J M; Parent, A; Bernácer, J; Cebrián, C

    2009-01-01

    This paper reviews two of the major features of the nigrostriatal pathway, its axonal collateralization, and compartmental specificity, as revealed by single-axon labeling experiments in rodents and immunocytological analysis of human postmortem tissue. The dorsal and ventral tiers of the substantia nigra pars compacta harbor various types of neurons the axons of which branch not only within the striatum but also in other major components of the basal ganglia. Furthermore, some nigrostriatal axons send collaterals both to thalamus and to brainstem pedunculopontine tegmental nucleus. In humans, the compartmental specificity of the nigrostriatal pathway is revealed by the fact that the matrix compartment is densely innervated by dopaminergic fibers, whereas the striosomes display different densities of dopaminergic terminals depending on their location within the striatum. The nigral neurons most severely affected in Parkinson's disease are the ventral tier cells that project to the matrix and form deep clusters in the substantia nigra pars reticulata.

  9. Syndecan Promotes Axon Regeneration by Stabilizing Growth Cone Migration

    Directory of Open Access Journals (Sweden)

    Tyson J. Edwards

    2014-07-01

    Full Text Available Growth cones facilitate the repair of nervous system damage by providing the driving force for axon regeneration. Using single-neuron laser axotomy and in vivo time-lapse imaging, we show that syndecan, a heparan sulfate (HS proteoglycan, is required for growth cone function during axon regeneration in C. elegans. In the absence of syndecan, regenerating growth cones form but are unstable and collapse, decreasing the effective growth rate and impeding regrowth to target cells. We provide evidence that syndecan has two distinct functions during axon regeneration: (1 a canonical function in axon guidance that requires expression outside the nervous system and depends on HS chains and (2 an intrinsic function in growth cone stabilization that is mediated by the syndecan core protein, independently of HS. Thus, syndecan is a regulator of a critical choke point in nervous system repair.

  10. Differential compartmentalization of mRNAs in squid giant axon.

    Science.gov (United States)

    Chun, J T; Gioio, A E; Crispino, M; Giuditta, A; Kaplan, B B

    1996-11-01

    Previously, we reported that the squid giant axon contains a heterogeneous population of mRNAs that includes beta-actin, beta-tubulin, kinesin, neurofilament proteins, and enolase. To define the absolute levels and relative distribution of these mRNAs, we have used competitive reverse transcription-PCR to quantify the levels of five mRNAs present in the giant axon and giant fiber lobe (GFL), the location of the parental cell soma. In the GFL, the number of transcripts for these mRNAs varied over a fourfold range, with beta-tubulin being the most abundant mRNA species (1.25 x 10(9) molecules per GFL). Based on transcript number, the rank order of mRNA levels in the GFL was beta-tubulin > beta-actin > kinesin > enolase > microtubule-associated protein (MAP) H1. In contrast, kinesin mRNA was most abundant in the axon (4.1 x 10(7) molecules per axon) with individual mRNA levels varying 15-fold. The rank order of mRNA levels in the axon was kinesin > beta-tubulin > MAP H1 > beta-actin > enolase. The relative abundance of the mRNA species in the axon did not correlate with the size of the transcript, nor was it directly related to their corresponding levels in the GFL. Taken together, these findings confirm that significant amounts of mRNA are present in the giant axon and suggest that specific mRNAs are differentially transported into the axonal domain.

  11. Fcγ receptor-mediated inflammation inhibits axon regeneration.

    Directory of Open Access Journals (Sweden)

    Gang Zhang

    Full Text Available Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy. We previously reported that disease-relevant anti-glycan autoantibodies inhibited axon regeneration, which echo the clinical association of these antibodies and poor recovery in Guillain-Barré Syndrome. However, the specific molecular and cellular elements involved in this antibody-mediated inhibition of axon regeneration are not previously defined. This study examined the role of Fcγ receptors and macrophages in the antibody-mediated inhibition of axon regeneration. A well characterized antibody passive transfer sciatic nerve crush and transplant models were used to study the anti-ganglioside antibody-mediated inhibition of axon regeneration in wild type and various mutant and transgenic mice with altered expression of specific Fcγ receptors and macrophage/microglia populations. Outcome measures included behavior, electrophysiology, morphometry, immunocytochemistry, quantitative real-time PCR, and western blotting. We demonstrate that the presence of autoantibodies, directed against neuronal/axonal cell surface gangliosides, in the injured mammalian peripheral nerves switch the proregenerative inflammatory environment to growth inhibitory milieu by engaging specific activating Fcγ receptors on recruited monocyte-derived macrophages to cause severe inhibition of axon regeneration. Our data demonstrate that the antibody orchestrated Fcγ receptor-mediated switch in inflammation is one mechanism underlying inhibition of axon regeneration. These findings have clinical implications for nerve repair and recovery in antibody-mediated immune neuropathies. Our results add to the complexity of axon regeneration in injured peripheral and central nervous systems as adverse effects of B cells and autoantibodies on neural injury and repair are increasingly recognized.

  12. Modality-Specific Axonal Regeneration: Towards selective regenerative neural interfaces

    Directory of Open Access Journals (Sweden)

    Parisa eLotfi

    2011-10-01

    Full Text Available Regenerative peripheral nerve interfaces have been proposed as viable alternatives for the natural control of robotic prosthetic devices. However, sensory and motor axons at the neural interface are of mixed submodality types, which difficult the specific recording from motor axons and the eliciting of precise sensory modalities through selective stimulation. Here we evaluated the possibility of using type-specific neurotrophins to preferentially entice the regeneration of defined axonal populations from transected peripheral nerves into separate compartments. Segregation of mixed sensory fibers from dorsal root ganglion neurons was evaluated in vitro by compartmentalized diffusion delivery of nerve growth factor (NGF and neurotrophin-3 (NT-3, to preferentially entice the growth of TrkA+ nociceptive and TrkC+ proprioceptive subsets of sensory neurons, respectively. The average axon length in the NGF channel increased 2.5 fold compared to that in saline or NT-3, whereas the number of branches increased 3 fold in the NT-3 channels. These results were confirmed using a 3-D Y-shaped in vitro assay showing that the arm containing NGF was able to entice a 5-fold increase in axonal length of unbranched fibers. To address if such segregation can be enticed in vivo, a Y-shaped tubing was used to allow regeneration of the transected adult rat sciatic nerve into separate compartments filled with either NFG or NT-3. A significant increase in the number of CGRP+ pain fibers were attracted towards the sural nerve, while N-52+ large diameter axons were observed in the tibial and NT-3 compartments. This study demonstrates the guided enrichment of sensory axons in specific regenerative chambers, and supports the notion that neurotrophic factors can be used to segregate sensory and perhaps motor axons in separate peripheral interfaces.

  13. Modality-specific axonal regeneration: toward selective regenerative neural interfaces.

    Science.gov (United States)

    Lotfi, Parisa; Garde, Kshitija; Chouhan, Amit K; Bengali, Ebrahim; Romero-Ortega, Mario I

    2011-01-01

    Regenerative peripheral nerve interfaces have been proposed as viable alternatives for the natural control of robotic prosthetic devices. However, sensory and motor axons at the neural interface are of mixed sub-modality types, which difficult the specific recording from motor axons and the eliciting of precise sensory modalities through selective stimulation. Here we evaluated the possibility of using type specific neurotrophins to preferentially entice the regeneration of defined axonal populations from transected peripheral nerves into separate compartments. Segregation of mixed sensory fibers from dorsal root ganglion neurons was evaluated in vitro by compartmentalized diffusion delivery of nerve growth factor (NGF) and neurotrophin-3 (NT-3), to preferentially entice the growth of TrkA+ nociceptive and TrkC+ proprioceptive subsets of sensory neurons, respectively. The average axon length in the NGF channel increased 2.5-fold compared to that in saline or NT-3, whereas the number of branches increased threefold in the NT-3 channels. These results were confirmed using a 3D "Y"-shaped in vitro assay showing that the arm containing NGF was able to entice a fivefold increase in axonal length of unbranched fibers. To address if such segregation can be enticed in vivo, a "Y"-shaped tubing was used to allow regeneration of the transected adult rat sciatic nerve into separate compartments filled with either NFG or NT-3. A significant increase in the number of CGRP+ pain fibers were attracted toward the sural nerve, while N-52+ large-diameter axons were observed in the tibial and NT-3 compartments. This study demonstrates the guided enrichment of sensory axons in specific regenerative chambers, and supports the notion that neurotrophic factors can be used to segregate sensory and perhaps motor axons in separate peripheral interfaces.

  14. MR imaging of a diffuse axonal injury

    International Nuclear Information System (INIS)

    Inoue, Yukiya; Okamoto, Hisayo; Mitsushima, Minoru; Hori, Tomokatsu; Sasaki, Mamoru; Teraoka, Akira.

    1989-01-01

    Six patients who had been diagnosed as having so-called a 'Diffuse Axonal Injury (DAI)' were examined by means of Magnetic Resonance Imaging (Yokogawa Resona 0.5T and Shimadzu SMT 50A). MRI revealed clear evidence of injured white matter in these patients, while X-ray CT scanning could not demonstrate such lesions definitely. The patients consisted of three adults and three adolescents. They had been injured by traffic accidents or falls. Every patient had lost consciousness immediately, and their coma had continued for at least two weeks after the trauma. X-ray CT scanning demonstrated no complicated lesion, such as intracranial hematoma or brain edema, resulting in increased intracranial pressure and cerebral herniation. In all of the patients, injuries of the deep white matter (corpus callosum, upper pons, or internal capsule, for example) were clearly found by T 2 -weighted imaging. Because these lesions had characteristic features in their localation, as has been described by Adams et al. these patients were diagnosed as having DAI. Also, it was interesting that the focal neurological deficits of these patients correlated well with the local injuries of the white matter. The three young patients recovered to various degrees, but the three adults passed into a vegetative state. The prognosis of the patients seemed to be determined by their age. Because the clinical diagnosis of DAI is controversial, the use of MRI will help in its clinical diagnosis and analysis. (author)

  15. Kinematics of turnaround and retrograde axonal transport

    International Nuclear Information System (INIS)

    Snyder, R.E.

    1986-01-01

    Rapid axonal transport of a pulse of 35 S-methionine-labelled material was studied in vitro in the sensory neurons of amphibian sciatic nerve using a position-sensitive detector. For 10 nerves studied at 23.0 +/- 0.2 degrees C it was found that a pulse moved in the anterograde direction characterized by front edge, peak, and trailing edge transport rates of (mm/d) 180.8 +/- 2.2 (+/- SEM), 176.6 +/- 2.3, and 153.7 +/- 3.0, respectively. Following its arrival at a distal ligature, a smaller pulse was observed to move in the retrograde direction characterized by front edge and peak transport rates of 158.0 +/- 7.3 and 110.3 +/- 3.5, respectively, indicating that retrograde transport proceeds at a rate of 0.88 +/- 0.04 that of anterograde. The retrograde pulse was observed to disperse at a rate greater than the anterograde. Reversal of radiolabel at the distal ligature began 1.49 +/- 0.15 h following arrival of the first radiolabel. Considerable variation was seen between preparations in the way radiolabel accumulated in the end (ligature) regions of the nerve. Although a retrograde pulse was seen in all preparations, in 7 of 10 preparations there was no evidence of this pulse accumulating within less than 2-3 mm of a proximal ligature; however, accumulation was observed within less than 5 mm in all preparations

  16. MR imaging of a diffuse axonal injury

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Yukiya; Okamoto, Hisayo; Mitsushima, Minoru; Hori, Tomokatsu (Tottori Univ., Yonago (Japan). School of Medicine); Sasaki, Mamoru; Teraoka, Akira

    1989-04-01

    Six patients who had been diagnosed as having so-called a 'Diffuse Axonal Injury (DAI)' were examined by means of Magnetic Resonance Imaging (Yokogawa Resona 0.5T and Shimadzu SMT 50A). MRI revealed clear evidence of injured white matter in these patients, while X-ray CT scanning could not demonstrate such lesions definitely. The patients consisted of three adults and three adolescents. They had been injured by traffic accidents or falls. Every patient had lost consciousness immediately, and their coma had continued for at least two weeks after the trauma. X-ray CT scanning demonstrated no complicated lesion, such as intracranial hematoma or brain edema, resulting in increased intracranial pressure and cerebral herniation. In all of the patients, injuries of the deep white matter (corpus callosum, upper pons, or internal capsule, for example) were clearly found by T{sub 2}-weighted imaging. Because these lesions had characteristic features in their localation, as has been described by Adams et al. these patients were diagnosed as having DAI. Also, it was interesting that the focal neurological deficits of these patients correlated well with the local injuries of the white matter. The three young patients recovered to various degrees, but the three adults passed into a vegetative state. The prognosis of the patients seemed to be determined by their age. Because the clinical diagnosis of DAI is controversial, the use of MRI will help in its clinical diagnosis and analysis. (author).

  17. Regeneración axonal posterior a lesiones traumáticas de médula espinal: papel crítico de galectina-1

    OpenAIRE

    Quintá, Héctor Ramiro; Pasquini, Juana Maria; Rabinovich, Gabriel Adrian; Pasquini, Laura Andrea

    2016-01-01

    Al producirse una lesión de médula espinal (LME), un sinnúmero de proteínas inhibidoras de la regeneración axonal ocupan el sitio de lesión en forma secuencial. La primer proteína en llegar al mismo se conoce como semaforina 3A (Sema3A), siendo además una de las más potentes por su acción de inhibir la regeneración axonal. A nivel mecanístico la unión de esta proteína al complejo-receptor neuronal neuropilin-1 (NRP-1)/PlexinA4 evita que se produzca regeneración axonal. En este trabajo de rev...

  18. Respuesta productiva de gallinas semipesadas inducidas al descanso ovárico en diferentes edades

    Directory of Open Access Journals (Sweden)

    Luis Galeano V.

    2012-12-01

    Full Text Available Objetivo. Evaluar el efecto de la inducción al descanso ovárico (DO a diferentes edades sobre la respuesta productiva en aves semipesadas productoras de huevo comercial. Materiales y método. Se usaron 840 aves de la línea Hy Line Brown con 64 semanas de edad, distribuidas en 10 tratamientos, consistentes en tres edades (65, 70 y 75 semanas con la aplicación de tres períodos de ayuno (5, 10 y 15 días y un control (sin DO. El análisis estadístico utilizó un modelo completamente aleatorizado, anidado, efecto fijo y balanceado. Se evaluó consumo de calcio durante el ayuno (g/ave/día, consumo de alimento (g/ave/día, porcentaje de producción, peso del huevo (g, conversión por masa de huevo y huevos por ave alojada (HAA. Resultados. La edad presentó efecto significativo (p<0.05 sobre las variables consumo de alimento, día del primer huevo postmuda, días sin producción, día postmuda de retorno al 50% de producción, peso del huevo, número de huevos, masa huevos, conversión y porcentaje de producción (p<0.01. Al comparar con el control, el tratamiento 75-5 presentó efecto significativo (p<0.05 para las variables: consumo de alimento, número de huevos promedio, masa huevos y conversión. Conclusiones. Las aves con mayor período de ayuno presentaron mayor período improductivo postmuda, grandes pérdidas de peso y alto consumo de alimento, lo que genera alta conversión e ineficiencia productiva. En comparación con reportes de literatura sobre DO en aves livianas, las aves semipesadas llegan al cese de producción en menos días y su período improductivo es menor.

  19. Axon-glia interaction and membrane traffic in myelin formation

    Directory of Open Access Journals (Sweden)

    Robin eWhite

    2014-01-01

    Full Text Available In vertebrate nervous systems myelination of neuronal axons has evolved to increase conduction velocity of electrical impulses with minimal space and energy requirements. Myelin is formed by specialised glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarisation followed by targeted myelin membrane expansion and compaction. Thereby, a myelin sheath of complex subdomain structure is established. Continuous communication between neurons and glial cells is essential for myelin maintenance and axonal integrity. A diverse group of diseases, from multiple sclerosis to schizophrenia, have been linked to malfunction of myelinating cells reflecting the physiological importance of the axon-glial unit. This review describes the mechanisms of axonal signal integration by oligodendrocytes emphasising the central role of the Src-family kinase Fyn during CNS myelination. Furthermore, we discuss myelin membrane trafficking with particular focus on endocytic recycling and the control of PLP (proteolipid protein transport by SNARE proteins. Finally, PLP mistrafficking is considered in the context of myelin diseases.

  20. Developmental time windows for axon growth influence neuronal network topology.

    Science.gov (United States)

    Lim, Sol; Kaiser, Marcus

    2015-04-01

    Early brain connectivity development consists of multiple stages: birth of neurons, their migration and the subsequent growth of axons and dendrites. Each stage occurs within a certain period of time depending on types of neurons and cortical layers. Forming synapses between neurons either by growing axons starting at similar times for all neurons (much-overlapped time windows) or at different time points (less-overlapped) may affect the topological and spatial properties of neuronal networks. Here, we explore the extreme cases of axon formation during early development, either starting at the same time for all neurons (parallel, i.e., maximally overlapped time windows) or occurring for each neuron separately one neuron after another (serial, i.e., no overlaps in time windows). For both cases, the number of potential and established synapses remained comparable. Topological and spatial properties, however, differed: Neurons that started axon growth early on in serial growth achieved higher out-degrees, higher local efficiency and longer axon lengths while neurons demonstrated more homogeneous connectivity patterns for parallel growth. Second, connection probability decreased more rapidly with distance between neurons for parallel growth than for serial growth. Third, bidirectional connections were more numerous for parallel growth. Finally, we tested our predictions with C. elegans data. Together, this indicates that time windows for axon growth influence the topological and spatial properties of neuronal networks opening up the possibility to a posteriori estimate developmental mechanisms based on network properties of a developed network.

  1. Parametric Probability Distribution Functions for Axon Diameters of Corpus Callosum

    Directory of Open Access Journals (Sweden)

    Farshid eSepehrband

    2016-05-01

    Full Text Available Axon diameter is an important neuroanatomical characteristic of the nervous system that alters in the course of neurological disorders such as multiple sclerosis. Axon diameters vary, even within a fiber bundle, and are not normally distributed. An accurate distribution function is therefore beneficial, either to describe axon diameters that are obtained from a direct measurement technique (e.g., microscopy, or to infer them indirectly (e.g., using diffusion-weighted MRI. The gamma distribution is a common choice for this purpose (particularly for the inferential approach because it resembles the distribution profile of measured axon diameters which has been consistently shown to be non-negative and right-skewed. In this study we compared a wide range of parametric probability distribution functions against empirical data obtained from electron microscopy images. We observed that the gamma distribution fails to accurately describe the main characteristics of the axon diameter distribution, such as location and scale of the mode and the profile of distribution tails. We also found that the generalized extreme value distribution consistently fitted the measured distribution better than other distribution functions. This suggests that there may be distinct subpopulations of axons in the corpus callosum, each with their own distribution profiles. In addition, we observed that several other distributions outperformed the gamma distribution, yet had the same number of unknown parameters; these were the inverse Gaussian, log normal, log logistic and Birnbaum-Saunders distributions.

  2. Sensory axon-derived neuregulin-1 is required for axoglial signaling and normal sensory function but not for long-term axon maintenance

    DEFF Research Database (Denmark)

    Fricker, F.R.; Zhu, N.; Tsantoulas, C.

    2009-01-01

    to represent large-diameter axons that have failed to myelinate. Conditional neuregulin-1 ablation resulted in a reduced sensitivity to noxious mechanical stimuli. These findings emphasize the importance of neuregulin-1 in mediating the signaling between axons and both myelinating and nonmyelinating Schwann...... cells required for normal sensory function. Sensory neuronal survival and axonal maintenance, however, are not dependent on axon-derived neuregulin-1 signaling in adulthood Udgivelsesdato: 2009/6/17...

  3. Acute pancreatitis induced by hypertriglyceridemia and treatment with plasmapheresis: case report = Pancreatitis aguda inducida por hipertrigliceridemia y tratamiento con plasmaféresis: reporte de un caso

    Directory of Open Access Journals (Sweden)

    Muñoz Ortiz, Édison

    2012-10-01

    Full Text Available Hypertriglyceridemia (HTG is a potential cause of acute pancreatitis (AP, especially when its values are greater than 1.000 mg/dL. Different therapeutic measures have been proposed for patients with AP secondary to HTG, including the one that seems to be more effective: plasmapheresis. We report the case of a patient with severe HTG (triglycerides 6.480 mg/dL that suffered from AP, and had favorable evolution with plasmapheresis.

  4. Hipoglucemia facticia inducida por insulina en un paciente diabético tipo 1 Facticious hypoglycaemia induced by insulin in a type 1 diabetic patient

    Directory of Open Access Journals (Sweden)

    Tania Espinosa Reyes

    2004-12-01

    Full Text Available La hipoglucemia facticia es un atentado deliberado para provocar niveles séricos bajos de glucosa con el uso de insulina o de agentes hipoglucemiantes orales. Paciente JCB, masculino, 12 años, blanco, diabético tipo 1 de 2 años de evolución. Motivo de consulta: episodios de hipoglucemia severa con convulsiones y coma. Se tomaron muestras para anticuerpos antiislotes pancreáticos (ICA y péptido C en condiciones basales y durante la hipoglucemia, así como determinaciones de hemoglobina glucosilada (HBA1 durante la evolución de la enfermedad, ultrasonografía, tomografía axial computadorizada (TAC y resonancia magnética nuclear (RMN de páncreas. Se obtuvieron insulinemias elevadas, valores extremadamente disminuidos de peptinemia C, incremento del índice de masa corporal y función renal y hepática dentro de parámetros normales. Los estudios imagenológicos fueron normales. Se concluye que a pesar de la relativa baja frecuencia de la hipoglucemia facticia en el diabético, es imprescindible tenerla en cuenta. La detección precoz facilita la atención psicológica temprana del paciente y previene la exposición a acciones que impliquen riesgo para la vida o daño permanente.Factitious hypoglycaemia is a deliberate attempt to provoke low serum levels of glucose by using insulin or lowering-glycaemia agents. A case is reported of a white, male, 12-year-old type 1 diabetic patient of 2 years of evolution. Chief complaint: episodes of severe hypoglycaemia with convulsions and coma. Samples for pancreatic anti-islet cell antibodies and peptide C were taken under basal conditions and during hypoglycaemia. Determinations of glucosylated haemoglobin (HBA1 during the evolution of the disease, ultrasonography, CAT and nuclear magnetic imaging of pancreas were performed. Elevated insulinemias, extremely reduced values of peptinemia C, increase of the body mass index, and renal and hepatic function within the normal parameters were obtained. The imaging studies were normal. It was concluded that in spite of the relative low frequency of factitious hypoglycemia in the diabetic, it is indispensable to take it into account. The premature detection makes easy the early psychological attention of the patient and prevents the exposure to actions implying risk for life or permanent damage.

  5. Actividad de caspasas inducida por astrovirus humanos en cultivos celulares y su relación con el procesamiento de la proteína estructural /

    OpenAIRE

    Baños Lara, María del Rocío

    2011-01-01

     tesis que para obtener el grado de Doctor en Ciencias Bioquímicas, presenta María del Rocío Baños Lara ; asesor Ernesto Méndez Salinas. 64 páginas : ilustraciones. Doctorado en Ciencias Bioquímicas UNAM, Instituto de Biotecnología, 2011

  6. Caracterización de las respuestas de defensa inducidas por hongos del género Trichoderma en Arabidopsis thaliana

    OpenAIRE

    Contreras Cornejo, Hexon Angel

    2012-01-01

    Los hongos filamentosos del género Trichoderma han sido reconocidos como agentes para el biocontrol de enfermedades vegetales. En este trabajo, investigamos los mecanismos implicados en las respuestas de defensa en Arabidopsis thaliana inoculadas con Trichoderma virens y Trichoderma atroviride. La interacción de Arabidopsis thaliana con Trichoderma indujo el crecimiento vegetal y activó respuestas de defensa. Estos resultados indican que ambos procesos no son inherentemente ...

  7. Disminución del daño oxidativo y efecto hipoglicemiante de la maca (Lepidium meyenii Walp) en ratas con diabetes inducida por streptozotocina

    OpenAIRE

    María Elena Rodrigo; Rubén Valdivieso; Silvia Suárez; Rosa Oriondo; Raquel Oré

    2011-01-01

    Introducción: La maca es consumida desde tiempos ancestrales como parte de la dieta. Se le ha atribuido propiedades medicinales y se encuentra incluida en la medicina tradicional peruana. Estudios recientes describen que la admistración de maca reduce la glicemia en animales normoglicémicos, pero los mecanismos involucrados no están muy claros. Objetivos: Determinar el efecto hipoglicemiante y antioxidante de la harina de maca (Lepidium meyenii Walp) del ecotipo amarillo, en ratas con diabete...

  8. Disminucion del daño oxidativo y efecto hipoglicemiante de la maca (Lepidium meyenii Walp) en ratas con diabetes inducida por streptozotocina

    OpenAIRE

    Rodrigo, María Elena; Valdivieso, Rubén; Suárez, Silvia; Oriondo, Rosa; Oré, Raquel

    2013-01-01

    Introducción: La maca es consumida desde tiempos ancestrales como parte de la dieta. Se le ha atribuido propiedades medicinales y se encuentra incluida en la medicina tradicional peruana. Estudios recientes describen que la admistración de maca reduce la glicemia en animales normoglicémicos, pero los mecanismos involucrados no están muy claros. Objetivos: Determinar el efecto hipoglicemiante y antioxidante de la harina de maca (Lepidium meyenii Walp) del ecotipo amarillo, en ratas con diabete...

  9. ESTUDIO SOBRE EL PAPEL PROTECTOR DE DT-DIAFORASA EN LA CITOTOXIDAD INDUCIDA POR LA OXIDACION Y TRANSPORTE DE LA NEUROTOXINA SALSOLINOL

    OpenAIRE

    DAGNINO SUBIABRE, ALEXIES ALBERTO

    2003-01-01

    Salsolinol (SAL) es un alcaloide que se forma espontánea y enzimáticamente a partir de dopamina (DA), en el citoplasma de las neuronas dopaminérgicas del cerebro humano. Su concentración está aumentada en el fluido cerebro espinal de pacientes con la enfermedad de Parkinson (EP) en la fase de diagnóstico. SAL induce además la muerte selectiva de las neuronas dopaminérgicas cuando se inyecta intracerebralmente en rata y activa la apoptosis en líneas celulares dopaminérgicas. En ...

  10. Entrada de calcio inducida por los oligómeros del péptido amiloide en la Enfermedad de Alzheimer

    OpenAIRE

    Caballero Ortega, Erica

    2013-01-01

    Los oligómeros del péptido amiloide (Aß1-42) se consideran como la neurotoxina presente en la enfermedad de Alzheimer. Nuestro grupo ha demostrado que los oligómeros, pero no las fibrillas, producen entrada de calcio en las neuronas y sobrecarga de calcio mitocondrial, lo cual lleva a la muerte celular. Sin embargo, la principal diana de los oligómeros es motivo de discusión. El objetivo es investigar las diferentes vías de entrada de calcio y el papel de la formación de conexiones sinápticas...

  11. Drug-induced acute esophageal lesions and use of ciprofloxacin Lesiones esofágicas agudas inducidas por drogas y uso de ciprofloxacino

    OpenAIRE

    V.M. Santos; M.V. Carneiro; L.R. Cruz; G.T.G. Paixão

    2012-01-01

    We report the case of a 95-year-old woman who had acute esophageal lesions while being treated with oral ciprofloxacin for an acute cystitis. On day 2 of treatment, she reported retroesternal pain with a globus sensation, and presented hematemesis and melena. There was no history of gastric or esophageal disturbances. An upper digestive endoscopy showed bleeding lesions on the middle third of the esophagus. Ciprofloxacin was discontinued and a proton pump inhibitor was administered. One week ...

  12. Regulación de la muerte celular inducida por activación en linfocitos T: papel de la Diacilglicerol Quinasa alfa

    OpenAIRE

    Alonso Gil, Roberto

    2005-01-01

    [ES]: La coordinación entre los procesos de muerte y proliferación celular juega un papel vital en el mantenimiento, homeostasis y el correcto funcionamiento del organismo [Golstein, 1998]. La muerte celular programada o apoptosis es un proceso de gran importancia fisiológica que se produce de forma natural en el desarrollo normal de los organismos pluricelulares, teniendo lugar en toda clase de eucariotas multicelulares: nemátodos, insectos, plantas, y vertebrados [Vaux et al., 1994; Ameise...

  13. Respuesta inmune sistémica y mucosal contra Neisseria meningitidis B inducida por estrategia de vacunación simultánea mucosal y parental

    Directory of Open Access Journals (Sweden)

    González E

    2009-08-01

    Full Text Available mmunization is one of the most successful and cost-effective health interventions ever. Immunization have been helping to reduce child mortality, improving maternal health and combating infectious diseases. In spite of its, undisputed past success and promising future, however, immunization remains an unfinished agenda because of them inadequate coverage. Several factors have been largely responsible of a difficulty to attain immunization coverage and have been recognized as a problems of current vaccines, such as: the number of dose, excessive use of parenteral route, a small number of adjuvants approve for use in human, higher reactogenicity and unavailability against intracellular pathogens, infected or altered cells and scanty feasibility to combined more than one antigen in the same formulation. For bacterial meningitis WHO estimates that 1.2 million cases occur annually and Neisseria meningitidis is the etiological agent in more than 40% of these cases although some meningococcal vaccines are available. To bear in mind these principals problems, a novel protocol for vaccination against N. meningitidis called Single Time Vaccination Strategy (SinTimVaS is proposed. Using female BALB/c mice, we induce systemic and mucosal immune responses against N. meningitidis with only one parenteral and one mucosal dose at the same time, employing the Finlay Adjuvants derivate from N. meningitidis, AFPL1 and AFCo1, respectively. In conclusion, SinTimVaS could increase the vaccination coverage and reduce the time-cost of vaccine campaigns, adding the possibility to increase the herd immunity by mucosal specific response induction.

  14. Thermoluminescence induced by X-rays in silica materials with metallic impurities; Termoluminiscencia inducida por los rayos X en materiales de silice con impurezas metalicas

    Energy Technology Data Exchange (ETDEWEB)

    Mendoza A, D.; Gonzalez M, P.; Espinosa P, M. [Instituto nacional de Investigaciones Nucleares, A.P. 18-1027, Mexico D.F. (Mexico); Salas, P.; Castano, V.M. [Instituto de Fisica, UNAM, Laboratorio Juriquilla, A.P. 1-1010, C.P. 76001, Queretaro (Mexico)

    1999-07-01

    Diverse materials of silica with Fe, Cu, Mg, and Mn impurities were synthesized by the sol-gel method, using tetraethyl orthosilicate as precursor. The materials obtained were subjected to thermal treatment at 500, 700 and 1000 Centigrade also they were irradiated with X-ray generated by a X-ray diffractometer which is installed in the ININ. The thermoluminescent signal was analysed and correlated with the type of impurities that are present in the material and with the grade of crystallinity produced by the thermal treatment in them. In according to the results obtained these materials show a thermoluminescent signal which is influenced by the crystallinity grade. It was analysed the behavior of the response for different doses, with the purpose of utilizing them to quantify very intense fields of radiation. (Author)

  15. Evolución cicatricial de úlceras cutáneas experimentales inducida por productos clínicos de limpieza de heridas

    OpenAIRE

    Chacón Ferrera, R.

    2013-01-01

    Programa de doctorado: Avances en Traumatología, Medicina del Deporte y Cuidados de Heridas [ES] Se plantea esta tesis con la finalidad de valorar la relación existente entre los diferentes productos clónicos utilizados en la limpieza de heridas (Agua destilada, Agua oxigenada, Suero fisiológico y Suero Glucosado), y su influencia sobre la evolución cicatricial. Para ello, se hace un recorrido conceptual de las heridas y sus diferentes métodos de resolución, haciendo hincapié en el proceso...

  16. CARACTERIZACIÓN EXPERIMENTAL DE LA CONCENTRACIÓN DE HOLLÍN EN LLAMAS DIESEL MEDIANTE INCANDESCENCIA INDUCIDA POR LÁSER

    OpenAIRE

    BUITRAGO GARCÍA, JORGE ENRIQUE

    2016-01-01

    [EN] Laser-induced incandescence (LII) is an optical diagnostic technique that can be used to measure the concentration and primary-particle size distributions of soot with high selectivity. This technique consists of rapid particle heating from the local ambient temperature to close to the soot sublimation temperature (~4000 K) by means of a highly energetic laser source, and the immediate recording of the strong thermal radiation as a result of a complex heat and mass transfer balance. The ...

  17. Homología cúbica : algoritmos para el cálculo de la aplicación inducida por una función continua

    OpenAIRE

    Quintero Barrios, Ezequiel Antonio

    2009-01-01

    La homología es una herramienta de topología algebraica cuyo significado geométrico está ligado a la noción de conectividad en formas multidimensionales. Los avances tecnológicos y el uso generalizado de los computadores han hecho posible que una gran número de profesionales, ya sean científicos, ingenieros, médicos o ejecutivos, tengan acceso a conjuntos enormes de datos cuyo análisis resulta crucial en el desarrollo de su profesión. El presente trabajo es la continuación de un proyecto prev...

  18. Modelling in vivo action potential propagation along a giant axon.

    Science.gov (United States)

    George, Stuart; Foster, Jamie M; Richardson, Giles

    2015-01-01

    A partial differential equation model for the three-dimensional current flow in an excitable, unmyelinated axon is considered. Where the axon radius is significantly below a critical value R(crit) (that depends upon intra- and extra-cellular conductivity and ion channel conductance) the resistance of the intracellular space is significantly higher than that of the extracellular space, such that the potential outside the axon is uniformly small whilst the intracellular potential is approximated by the transmembrane potential. In turn, since the current flow is predominantly axial, it can be shown that the transmembrane potential is approximated by a solution to the one-dimensional cable equation. It is noted that the radius of the squid giant axon, investigated by (Hodgkin and Huxley 1952e), lies close to R(crit). This motivates us to apply the three-dimensional model to the squid giant axon and compare the results thus found to those obtained using the cable equation. In the context of the in vitro experiments conducted in (Hodgkin and Huxley 1952e) we find only a small difference between the wave profiles determined using these two different approaches and little difference between the speeds of action potential propagation predicted. This suggests that the cable equation approximation is accurate in this scenario. However when applied to the it in vivo setting, in which the conductivity of the surrounding tissue is considerably lower than that of the axoplasm, there are marked differences in both wave profile and speed of action potential propagation calculated using the two approaches. In particular, the cable equation significantly over predicts the increase in the velocity of propagation as axon radius increases. The consequences of these results are discussed in terms of the evolutionary costs associated with increasing the speed of action potential propagation by increasing axon radius.

  19. Molecular Disorganization of Axons Adjacent to Human Cortical Microinfarcts

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    Hamza Coban

    2017-08-01

    Full Text Available Cortical microinfarcts (CMIs are microscopically identified wedge-shaped ischemic lesions that occur at or near the cortical surface and result from occlusion of penetrating arterioles. These microscopic lesions can be observed with high-resolution magnetic resonance imaging in aging brains and in patients with cerebrovascular disease. Recent studies have suggested that strategically located microinfarcts strongly correlate with cognitive deficits, which can contribute to Alzheimer’s disease as well as other forms of dementia. We have recently shown that the molecular organization of axons into functional microdomains is altered in areas adjacent to white matter lacunar and microinfarcts, creating a peri-infarct penumbral injury in surviving axons. Whether similar changes in nodal, adjacent paranodal, and proximal axon initial segment molecular organization occur in the cortex adjacent to human CMIs is not known. Paraffin-embedded sections of autopsy brain tissue from five patients with CMIs were immunofluorescently labeled for nodal and paranodal markers including beta-IV spectrin, ankyrin-G, and contactin-associated protein. High magnification images from the peri-infarct cortical tissue were generated using confocal microscopy. In surviving cortical tissue adjacent to microinfarcts, we observed a dramatic loss of axon initial segments, suggesting that neuronal firing capacity in adjacent cortical tissue is likely compromised. The number of identifiable nodal/paranodal complexes in surviving cortical tissue is reduced adjacent to microinfarcts, while the average paranodal length is increased indicating a breakdown of axoglial contact. This axonal microdomain disorganization occurs in the relative absence of changes in the structural integrity of myelinated axons as measured by myelin basic protein and neurofilament staining. These findings indicate that the molecular organization of surviving axons adjacent to human CMIs is abnormal

  20. Myelinated sensory and alpha motor axon regeneration in peripheral nerve neuromas

    Science.gov (United States)

    Macias, M. Y.; Lehman, C. T.; Sanger, J. R.; Riley, D. A.

    1998-01-01

    Histochemical staining for carbonic anhydrase and cholinesterase (CE) activities was used to analyze sensory and motor axon regeneration, respectively, during neuroma formation in transected and tube-encapsulated peripheral nerves. Median-ulnar and sciatic nerves in the rodent model permitted testing whether a 4 cm greater distance of the motor neuron soma from axotomy site or intrinsic differences between motor and sensory neurons influenced regeneration and neuroma formation 10, 30, and 90 days later. Ventral root radiculotomy confirmed that CE-stained axons were 97% alpha motor axons. Distance significantly delayed axon regeneration. When distance was negligible, sensory axons grew out sooner than motor axons, but motor axons regenerated to a greater quantity. These results indicate regeneration differences between axon subtypes and suggest more extensive branching of motor axons within the neuroma. Thus, both distance from injury site to soma and inherent motor and sensory differences should be considered in peripheral nerve repair strategies.

  1. Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties.

    Science.gov (United States)

    Casale, Amanda E; Foust, Amanda J; Bal, Thierry; McCormick, David A

    2015-11-25

    The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca(2+)-activated K(+) channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons contain three main

  2. Mechanistic logic underlying the axonal transport of cytosolic proteins

    Science.gov (United States)

    Scott, David A.; Das, Utpal; Tang, Yong; Roy, Subhojit

    2011-01-01

    Proteins vital to presynaptic function are synthesized in the neuronal perikarya and delivered into synapses via two modes of axonal transport. While membrane-anchoring proteins are conveyed in fast axonal transport via motor-driven vesicles, cytosolic proteins travel in slow axonal transport; via mechanisms that are poorly understood. We found that in cultured axons, populations of cytosolic proteins tagged to photoactivable-GFP (PA-GFP) move with a slow motor-dependent anterograde bias; distinct from vesicular-trafficking or diffusion of untagged PA-GFP. The overall bias is likely generated by an intricate particle-kinetics involving transient assembly and short-range vectorial spurts. In-vivo biochemical studies reveal that cytosolic proteins are organized into higher-order structures within axon-enriched fractions that are largely segregated from vesicles. Data-driven biophysical modeling best predicts a scenario where soluble molecules dynamically assemble into mobile supra-molecular structures. We propose a model where cytosolic proteins are transported by dynamically assembling into multi-protein complexes that are directly/indirectly conveyed by motors. PMID:21555071

  3. Functional complexity of the axonal growth cone: a proteomic analysis.

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    Adriana Estrada-Bernal

    Full Text Available The growth cone, the tip of the emerging neurite, plays a crucial role in establishing the wiring of the developing nervous system. We performed an extensive proteomic analysis of axonal growth cones isolated from the brains of fetal Sprague-Dawley rats. Approximately 2000 proteins were identified at ≥ 99% confidence level. Using informatics, including functional annotation cluster and KEGG pathway analysis, we found great diversity of proteins involved in axonal pathfinding, cytoskeletal remodeling, vesicular traffic and carbohydrate metabolism, as expected. We also found a large and complex array of proteins involved in translation, protein folding, posttranslational processing, and proteasome/ubiquitination-dependent degradation. Immunofluorescence studies performed on hippocampal neurons in culture confirmed the presence in the axonal growth cone of proteins representative of these processes. These analyses also provide evidence for rough endoplasmic reticulum and reveal a reticular structure equipped with Golgi-like functions in the axonal growth cone. Furthermore, Western blot revealed the growth cone enrichment, relative to fetal brain homogenate, of some of the proteins involved in protein synthesis, folding and catabolism. Our study provides a resource for further research and amplifies the relatively recently developed concept that the axonal growth cone is equipped with proteins capable of performing a highly diverse range of functions.

  4. Subtypes of GABAergic neurons project axons in the neocortex

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    Shigeyoshi Higo

    2009-11-01

    Full Text Available γ-aminobutyric acid (GABAergic neurons in the neocortex have been regarded as interneurons and speculated to modulate the activity of neurons locally. Recently, however, several experiments revealed that neuronal nitric oxide synthase (nNOS-positive GABAergic neurons project cortico-cortically with long axons. In this study, we illustrate Golgi-like images of the nNOS-positive GABAergic neurons using a nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d reaction and follow the emanating axon branches in cat brain sections. These axon branches projected cortico-cortically with other non-labeled arcuate fibers, contra-laterally via the corpus callosum and anterior commissure. The labeled fibers were not limited to the neocortex but found also in the fimbria of the hippocampus. In order to have additional information on these GABAergic neuron projections, we investigated green fluorescent protein (GFP-labeled GABAergic neurons in GAD67-Cre knock-in / GFP Cre-reporter mice. GFP-labeled axons emanate densely, especially in the fimbria, a small number in the anterior commissure, and very sparsely in the corpus callosum. These two different approaches confirm that not only nNOS-positive GABAergic neurons but also other subtypes of GABAergic neurons project long axons in the cerebral cortex and are in a position to be involved in information processing.

  5. Axonal transport and axon sprouting in the adult rat dentate gyrus: an autoradiographic study

    International Nuclear Information System (INIS)

    Goldowitz, D.; Cotman, C.W.

    1980-01-01

    In response to an entorhinal lesion, the commissural and associational afferents to the dentate gyrus have been shown to expand beyond their normal terminal zone into the area denervated by the entorhinal lesion. The present study has investigated the axonal transport of [ 3 H]-labeled proteins in the commissural and associational projections following an entorhinal lesion. Injections of [ 3 H]proline, [ 3 H]leucine or [ 3 H)fucose were given in the vicinity of the commissural and associational cells of origin before, immediately subsequent to, or at 5 to 15 days after the entorhinal lesion. The disposition of previously- or newly-synthesized proteins was examined in the commissural and associational terminal field at different times after an entorhinal lesion by light-microscopic autoradiography. (author)

  6. Fast and reliable identification of axons, axon initial segments and dendrites with local field potential recording

    DEFF Research Database (Denmark)

    Petersen, Anders V.; Johansen, Emil O.; Perrier, Jean-Francois

    2015-01-01

    The axon initial segment (AIS) is an essential neuronal compartment. It is usually where action potentials are initiated. Recent studies demonstrated that the AIS is a plastic structure that can be regulated by neuronal activity and by the activation of metabotropic receptors. Studying the AIS...... in live tissue can be difficult because its identification is not always reliable. Here we provide a new technique allowing a fast and reliable identification of the AIS in live brain slice preparations. By simultaneous recording of extracellular local field potentials and whole-cell patch-clamp recording...... of neurons, we can detect sinks caused by inward currents flowing across the membrane. We determine the location of the AIS by comparing the timing of these events with the action potential. We demonstrate that this method allows the unequivocal identification of the AIS of different types of neurons from...

  7. Fast and reliable identification of axons, axon initial segments and dendrites with local field potential recording

    Directory of Open Access Journals (Sweden)

    Anders Victor ePetersen

    2015-10-01

    Full Text Available The axon initial segment (AIS is an essential neuronal compartment. It is usually where action potentials are initiated. Recent studies demonstrated that the AIS is a plastic structure that can be regulated by neuronal activity and by the activation of metabotropic receptors. Studying the AIS in live tissue can be difficult because its identification is not always reliable. Here we provide a new technique allowing a fast and reliable identification of the AIS in live brain slice preparations. By simultaneous recoding of extracellular local field potentials and whole-cell patch-clamp recording of neurons, we can detect sinks caused by inward currents flowing across the membrane. We determine the location of the AIS by comparing the timing of these events with the action potential. We demonstrate that this method allows the unequivocal identification of the AIS of different types of neurons from the brain.

  8. Perilesional edema in radiation necrosis reflects axonal degeneration

    International Nuclear Information System (INIS)

    Perez-Torres, Carlos J; Yuan, Liya; Schmidt, Robert E; Rich, Keith M; Ackerman, Joseph JH; Garbow, Joel R

    2015-01-01

    Recently, we characterized a Gamma Knife® radiation necrosis mouse model with various magnetic resonance imaging (MRI) protocols to identify biomarkers useful in differentiation from tumors. Though the irradiation was focal to one hemisphere, a contralateral injury was observed that appeared to be localized in the white matter only. Interestingly, this injury was identifiable in T2-weighted images, apparent diffusion coefficient (ADC), and magnetization transfer ratio (MTR) maps, but not on post-contrast T1-weighted images. This observation of edema independent of vascular changes is akin to the perilesional edema seen in clinical radiation necrosis. The pathology underlying the observed white-matter MRI changes was explored by performing immunohistochemistry for healthy axons and myelin. The presence of both healthy axons and myelin was reduced in the contralateral white-matter lesion. Based on our immunohistochemical findings, the contralateral white-matter injury is most likely due to axonal degeneration

  9. The nano-architecture of the axonal cytoskeleton.

    Science.gov (United States)

    Leterrier, Christophe; Dubey, Pankaj; Roy, Subhojit

    2017-12-01

    The corporeal beauty of the neuronal cytoskeleton has captured the imagination of generations of scientists. One of the easiest cellular structures to visualize by light microscopy, its existence has been known for well over 100 years, yet we have only recently begun to fully appreciate its intricacy and diversity. Recent studies combining new probes with super-resolution microscopy and live imaging have revealed surprising details about the axonal cytoskeleton and, in particular, have discovered previously unknown actin-based structures. Along with traditional electron microscopy, these newer techniques offer a nanoscale view of the axonal cytoskeleton, which is important for our understanding of neuronal form and function, and lay the foundation for future studies. In this Review, we summarize existing concepts in the field and highlight contemporary discoveries that have fundamentally altered our perception of the axonal cytoskeleton.

  10. The axon-protective WLD(S) protein partially rescues mitochondrial respiration and glycolysis after axonal injury.

    Science.gov (United States)

    Godzik, Katharina; Coleman, Michael P

    2015-04-01

    The axon-protective Wallerian degeneration slow (WLD(S)) protein can ameliorate the decline in axonal ATP levels after neurite transection. Here, we tested the hypothesis that this effect is associated with maintenance of mitochondrial respiration and/or glycolysis. We used isolated neurites of superior cervical ganglion (SCG) cultures in the Seahorse XF-24 Metabolic Flux Analyser to determine mitochondrial respiration and glycolysis under different conditions. We observed that both mitochondrial respiration and glycolysis declined significantly during the latent phase of Wallerian degeneration. WLD(S) partially reduced the decline both in glycolysis and in mitochondrial respiration. In addition, we found that depleting NAD levels in uncut cultures led to changes in mitochondrial respiration and glycolysis similar to those rescued by WLD(S) after cut, suggesting that the maintenance of NAD levels in Wld(S) neurites after axonal injury at least partially underlies the maintenance of ATP levels. However, by using another axon-protective mutation (Sarm1(-/-)), we could demonstrate that rescue of basal ECAR (and hence probably glycolysis) rather than basal OCR (mitochondrial respiration) may be part of the protective phenotype to delay Wallerian degeneration. These findings open new routes to study glycolysis and the connection between NAD and ATP levels in axon degeneration, which may help to eventually develop therapeutic strategies to treat neurodegenerative diseases.

  11. Axoplasmic RNA species synthesized in the isolated squid giant axon.

    Science.gov (United States)

    Rapallino, M V; Cupello, A; Giuditta, A

    1988-07-01

    Isolated squid stellate nerves and giant fiber lobes were incubated for 8 hr in Millipore filtered sea water containing [3H]uridine. The electrophoretic patterns of radioactive RNA purified from the axoplasm of the giant axon and from the giant fiber lobe (cell bodies of the giant axon) demonstrated the presence of RNA species with mobilities corresponding to tRNA and rRNA. The presence of labeled rRNAs was confirmed by the behavior of the large rRNA component (31S) which, in the squid, readily dissociates into its two constituent moyeties (17S and 20S). Comparable results were obtained with the axonal sheath and the stellate nerve. In all the electrophoretic patterns, additional species of radioactive RNA migrated between the 4S and the 20S markers, i.e. with mobilities corresponding to presumptive mRNAs. Chromatographic analysis of the purified RNAs on oligo(dT)cellulose indicated the presence of labeled poly(A)+ RNA in all tissue samples. Radioactive poly(A)+ RNA represented approximately 1% of the total labeled RNA in the axoplasm, axonal sheath and stellate nerve, but more than 2% in the giant fiber lobe. The labeled poly(A)+ RNAs of the giant fibre lobe showed a prevalence of larger species in comparison to the axonal sheath and stellate nerve. In conclusion, the axoplasmic RNAs synthesized by the isolated squid giant axon appear to include all the major classes of axoplasmic RNAs, that is rRNA, tRNA and mRNA.

  12. Pannexin 1 Modulates Axonal Growth in Mouse Peripheral Nerves

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    Steven M. Horton

    2017-11-01

    Full Text Available The pannexin family of channels consists of three members—pannexin-1 (Panx1, pannexin-2 (Panx2, and pannexin-3 (Panx3 that enable the exchange of metabolites and signaling molecules between intracellular and extracellular compartments. Pannexin-mediated release of intracellular ATP into the extracellular space has been tied to a number of cellular activities, primarily through the activity of type P2 purinergic receptors. Previous work indicates that the opening of Panx1 channels and activation of purinergic receptors by extracellular ATP may cause inflammation and apoptosis. In the CNS (central nervous system and PNS (peripheral nervous system, coupled pannexin, and P2 functions have been linked to peripheral sensitization (pain pathways. Purinergic pathways are also essential for other critical processes in the PNS, including myelination and neurite outgrowth. However, whether such pathways are pannexin-dependent remains to be determined. In this study, we use a Panx1 knockout mouse model and pharmacological inhibitors of the Panx1 and the ATP-mediated signaling pathway to fill gaps in our understanding of Panx1 localization in peripheral nerves, roles for Panx1 in axonal outgrowth and myelination, and neurite extension. Our data show that Panx1 is localized to axonal, myelin, and vascular compartments of the peripheral nerves. Knockout of Panx1 gene significantly increased axonal caliber in vivo and axonal growth rate in cultured dorsal root ganglia (DRG neurons. Furthermore, genetic knockout of Panx1 or inhibition of components of purinergic signaling, by treatment with probenecid and apyrase, resulted in denser axonal outgrowth from cultured DRG explants compared to untreated wild-types. Our findings suggest that Panx1 regulates axonal growth in the peripheral nervous system.

  13. Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy.

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    Jia-Ying Sung

    Full Text Available This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr. Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (P<0.05, shortened strength-duration time constant (P<0.01, increased superexcitability (P<0.01, decreased subexcitability (P<0.05, decreased accommodation to depolarizing current (P<0.01, and a trend of decreased accommodation to hyperpolarizing current in threshold electrotonus. All the changes progressed into G1 (TNSr 1-8 and G2+3 (TNSr 9-24 groups. In contrast, motor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (P<0.01 in the G0 group. This study revealed that the development of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches.

  14. Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

    International Nuclear Information System (INIS)

    Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.; Svoboda, Kurt R.

    2015-01-01

    Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner.

  15. Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

    Energy Technology Data Exchange (ETDEWEB)

    Menelaou, Evdokia; Paul, Latoya T. [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Perera, Surangi N. [Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States); Svoboda, Kurt R., E-mail: svobodak@uwm.edu [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States)

    2015-04-01

    Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner.

  16. Períodos perturbados: disipación de energía y corrientes geomagnéticas inducidas

    Directory of Open Access Journals (Sweden)

    Patricia A. Larocca

    2010-06-01

    Full Text Available Se estudia, en un evento típico (12-13 de junio de 2005 las energías entrante y disipada en la magnetosfera ( y Ut respectivamente y el aumento de corrientes inducidas en un gasoducto ubicado en altas latitudes. Se analizan para el período citado los índices geomagnéticos AE y Dst, y la componente Bz del campo geomagnético interplanetario como indicadores del desarrollo del período perturbado. Se calculan los tiempos de decaimiento del anillo de corriente utilizando distintas aproximaciones de acuerdo con las fases de la tormenta. Durante este período se observaron variaciones geomagnéticas importantes que originaron corrientes geomagnéticas inducidas significativas sobre el gasoducto de la empresa Transcanada ubicado en la zona del valle del río Ottawa; pudiendo ser afectada la vida útil del mismo.In a typical event (12-13 June 2005, solar wind energy rate and total energy dissipation rate in the magnetosphere (e and Ut respectively and increased induced currents in a gas pipe located in the auroral zone are studied. For the period geomagnetic indices AE and Dst, and the Bz component of the interplanetary geomagnetic field are analyzed as indicators of the development of the troubled period. Ring current decay times are calculated using different approaches in accordance with the phases of the storm. During this period there were significant geomagnetic variations due to geomagnetic substorms and induced currents on the pipeline located in the Otawa River Valley, this fact could produce corrosion increases in its structure.

  17. IFNgamma enhances microglial reactions to hippocampal axonal degeneration

    DEFF Research Database (Denmark)

    Jensen, M B; Hegelund, I V; Lomholt, N D

    2000-01-01

    Glial reactivity is implicated in CNS repair and regenerative responses. Microglia, the cells responding earliest to axonal injury, produce tumor necrosis factor-alpha (TNFalpha), a cytokine with both cytopathic and neuroprotective effects. We have studied activation of hippocampal microglia...... periods. Message for the immune cytokine interferon-gamma (IFNgamma) was undetectable, and glial reactivity to axonal lesions occurred as normal in IFNgamma-deficient mice. Microglial responses to lesion-induced neuronal injury were markedly enhanced in myelin basic protein promoter-driven transgenic mice...

  18. Selective rab11 transport and the intrinsic regenerative ability of CNS axons.

    Science.gov (United States)

    Koseki, Hiroaki; Donegá, Matteo; Lam, Brian Yh; Petrova, Veselina; van Erp, Susan; Yeo, Giles Sh; Kwok, Jessica Cf; Ffrench-Constant, Charles; Eva, Richard; Fawcett, James W

    2017-08-08

    Neurons lose intrinsic axon regenerative ability with maturation, but the mechanism remains unclear. Using an in-vitro laser axotomy model, we show a progressive decline in the ability of cut CNS axons to form a new growth cone and then elongate. Failure of regeneration was associated with increased retraction after axotomy. Transportation into axons becomes selective with maturation; we hypothesized that selective exclusion of molecules needed for growth may contribute to regeneration decline. With neuronal maturity rab11 vesicles (which carry many molecules involved in axon growth) became selectively targeted to the somatodendritic compartment and excluded from axons by predominant retrograde transport However, on overexpression rab11 was mistrafficked into proximal axons, and these axons showed less retraction and enhanced regeneration after axotomy. These results suggest that the decline of intrinsic axon regenerative ability is associated with selective exclusion of key molecules, and that manipulation of transport can enhance regeneration.

  19. Axon diameter and intra-axonal volume fraction of the corticospinal tract in idiopathic normal pressure hydrocephalus measured by q-space imaging.

    Directory of Open Access Journals (Sweden)

    Kouhei Kamiya

    Full Text Available PURPOSE: Previous studies suggest that compression and stretching of the corticospinal tract (CST potentially cause treatable gait disturbance in patients with idiopathic normal pressure hydrocephalus (iNPH. Measurement of axon diameter with diffusion MRI has recently been used to investigate microstructural alterations in neurological diseases. In this study, we investigated alterations in the axon diameter and intra-axonal fraction of the CST in iNPH by q-space imaging (QSI analysis. METHODS: Nineteen patients with iNPH and 10 age-matched controls were recruited. QSI data were obtained with a 3-T system by using a single-shot echo planar imaging sequence with the diffusion gradient applied parallel to the antero-posterior axis. By using a two-component low-q fit model, the root mean square displacements of intra-axonal space ( =  axon diameter and intra-axonal volume fraction of the CST were calculated at the levels of the internal capsule and body of the lateral ventricle, respectively. RESULTS: Wilcoxon's rank-sum test revealed a significant increase in CST intra-axonal volume fraction at the paraventricular level in patients (p<0.001, whereas no significant difference was observed in the axon diameter. At the level of the internal capsule, neither axon diameter nor intra-axonal volume fraction differed significantly between the two groups. CONCLUSION: Our results suggest that in patients with iNPH, the CST does not undergo irreversible axonal damage but is rather compressed and/or stretched owing to pressure from the enlarged ventricle. These analyses of axon diameter and intra-axonal fraction yield insights into microstructural alterations of the CST in iNPH.

  20. Multiple sclerosis and anterograde axonal degeneration study by magnetic resonance

    International Nuclear Information System (INIS)

    Martinez Pardo, P.; Capdevila Cirera, A.; Sanz Marin, P.M.; Gili Planas, J.

    1993-01-01

    Multiple sclerosis (MS) is a disease of the central nervous system that affects specifically the myelin. Its diagnosis by imaging techniques is, since the development of magnetic resonance (MR), relatively simple, and its occasional association with anterograde axonal degeneration (WD) has been reported. In both disorders, there is a lengthening of the T1 and T2 relaxation times. In the present report, 76 patients with MS with less than 4 plaques in the typical periventricular position were studied retrospectively, resulting in a rate of association with anterograde axonal degeneration of 8%. We consider that in spite of their same behavior in MR,MS and WD, with moreover represent completely different pathologies, are perfectly differential by MR. The S-E images with longer repetition and echo times in the axial and coronal planes have proved to be those most sensitive for this differentiation. Given that MS is specific pathology of then myelin, the axonal damages in delayed until several plaques adjacent to an axon affect it. We consider that this, added to the restriction of our study group (less than 4 plaques), is the cause of the pow percentage of the MS-WD association in our study. (Author)

  1. Quantifying mechanical force in axonal growth and guidance

    Directory of Open Access Journals (Sweden)

    Ahmad Ibrahim Mahmoud Athamneh

    2015-09-01

    Full Text Available Mechanical force plays a fundamental role in neuronal development, physiology, and regeneration. In particular, research has shown that force is involved in growth cone-mediated axonal growth and guidance as well as stretch-induced elongation when an organism increases in size after forming initial synaptic connections. However, much of the details about the exact role of force in these fundamental processes remain unknown. In this review, we highlight (1 standing questions concerning the role of mechanical force in axonal growth and guidance and (2 different experimental techniques used to quantify forces in axons and growth cones. We believe that satisfying answers to these questions will require quantitative information about the relationship between elongation, forces, cytoskeletal dynamics, axonal transport, signaling, substrate adhesion, and stiffness contributing to directional growth advance. Furthermore, we address why a wide range of force values have been reported in the literature, and what these values mean in the context of neuronal mechanics. We hope that this review will provide a guide for those interested in studying the role of force in development and regeneration of neuronal networks.

  2. Model of fasciculation and sorting in mixed populations of axons

    Czech Academy of Sciences Publication Activity Database

    Chaudhuri, D.; Borowski, P.; Zápotocký, Martin

    2011-01-01

    Roč. 84, č. 2 (2011), e021908 ISSN 1539-3755 R&D Projects: GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : axon guidance * neurogenesis * mathematical model Subject RIV: FH - Neurology Impact factor: 2.255, year: 2011

  3. Axonal dynamics of excitatory and inhibitory neurons in somatosensory cortex.

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    Sally A Marik

    2010-06-01

    Full Text Available Cortical topography can be remapped as a consequence of sensory deprivation, suggesting that cortical circuits are continually modified by experience. To see the effect of altered sensory experience on specific components of cortical circuits, we imaged neurons, labeled with a genetically modified adeno-associated virus, in the intact mouse somatosensory cortex before and after whisker plucking. Following whisker plucking we observed massive and rapid reorganization of the axons of both excitatory and inhibitory neurons, accompanied by a transient increase in bouton density. For horizontally projecting axons of excitatory neurons there was a net increase in axonal projections from the non-deprived whisker barrel columns into the deprived barrel columns. The axon collaterals of inhibitory neurons located in the deprived whisker barrel columns retracted in the vicinity of their somata and sprouted long-range projections beyond their normal reach towards the non-deprived whisker barrel columns. These results suggest that alterations in the balance of excitation and inhibition in deprived and non-deprived barrel columns underlie the topographic remapping associated with sensory deprivation.

  4. Acute Motor Axonal Neuropathy in Association with Hepatitis E

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    Araz Al-Saffar

    2018-02-01

    Full Text Available Guillain–Barré syndrome (GBS is an acute peripheral neuropathy that develops as a result of post-infectious immune-mediated nerve injury. It can be classified into classic and variant GBS. Acute motor axonal neuropathy (AMAN is a subtype of GBS with the key clinical features of pure motor weakness, areflexia, absence of sensory symptoms, and lack of neurophysiologic evidence of demyelination. We reported a case of acute motor axonal neuropathy in association with hepatitis E infection. A young woman was referred to us after a period of nausea, fever, and diarrhea. She had unexplained muscle weakness at admission and has been diagnosed with acute hepatitis E infection. A rigorous clinical neurological assessment revealed bilateral symmetrical weakness, which affects the lower limbs more than the upper limbs, with no evidence of sensory involvement. Neurophysiological measurements indicated acute axonal injury without clues to demyelination. A diagnosis of acute motor axonal neuropathy subtype has been made, to which she only received supportive therapy. The symptoms resolved spontaneously and full recovery of motor function was attained after 35 days of weakness onset with complete normalization of neurophysiologic parameters.

  5. Investigation on the mechanism of peripheral axonal injury in glaucoma

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    Jun- Hong Zhao

    2013-05-01

    Full Text Available AIM: To compare the angles of longitudinal section of sclera around optic nerve heads and the never fiber layer changes in healthy adults and patients with glaucoma, and to investigate the mechanism of peripheral retinal axonal injury, with the combined knowledge of biomechanics. METHODS: The optical nerves and their peripheral tissue specimen in the 12 eyes from health adult donators and 12 eyes from glaucoma patient donators were dyed by Glees' method to compare the angles of longitudinal section of sclera around optic nerve heads(through optic nerve center, and to observe the anatomical features of the peripheral retinal axons. RESULTS: The mean angle of longitudinal section of sclera around optic nerve in healthy adults was 73.3°, while that in patients with absolute glaucoma was 75.6°. The difference showed no significance(t=1.44, P>0.05. There was a sharp bend in the course of peripheral optical fiber in healthy adults. However, the optic nerve fiber disappeared completely in patients with glaucoma end stage. CONCLUSION: The angle between the medial edge and leading edge of sclera(around optic nerve headsis an acute angle. The optical fiber in glaucoma end stage disappeared completely. The phenomenon may be related to high intraocular pressure, the sclera shape, the shear modulus of sclera and axons, and “axonal bending-injury” mechanism.

  6. IFNgamma enhances microglial reactions to hippocampal axonal degeneration

    DEFF Research Database (Denmark)

    Jensen, M B; Hegelund, I V; Lomholt, N D

    2000-01-01

    Glial reactivity is implicated in CNS repair and regenerative responses. Microglia, the cells responding earliest to axonal injury, produce tumor necrosis factor-alpha (TNFalpha), a cytokine with both cytopathic and neuroprotective effects. We have studied activation of hippocampal microglia to p...

  7. Differential Axonal Projection of Mitral and Tufted Cells in the Mouse Main Olfactory System

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    Shin Nagayama

    2010-09-01

    Full Text Available In the past decade, much has been elucidated regarding the functional organization of the axonal connection of olfactory sensory neurons to olfactory bulb (OB glomeruli. However, the manner in which projection neurons of the OB process odorant input and send this information to higher brain centers remains unclear. Here, we report long-range, large-scale tracing of the axonal projection patterns of OB neurons using two-photon microscopy. Tracer injection into a single glomerulus demonstrated widely distributed mitral/tufted cell axonal projections on the lateroventral surface of the mouse brain, including the anterior/posterior piriform cortex (PC and olfactory tubercle (OT. We noted two distinct groups of labeled axons: PC-orienting axons and OT-orienting axons. Each group occupied distinct parts of the lateral olfactory tract. PC-orienting axons projected axon collaterals to a wide area of the PC but only a few collaterals to the OT. OT-orienting axons densely projected axon collaterals primarily to the anterolateral OT (alOT. Different colored dye injections into the superficial and deep portions of the OB external plexiform layer revealed that the PC-orienting axon populations originated in presumed mitral cells and the OT-orienting axons in presumed tufted cells. These data suggest that although mitral and tufted cells receive similar odor signals from a shared glomerulus, they process the odor information in different ways and send their output to different higher brain centers via the PC and alOT.

  8. Efecto sedante del extracto alcóholico de hojas y flores de Melissa officinalis “Toronjil” MAS Matricaria chamomilla “Manzanilla” sobre la ansiedad inducida en ratones albinos

    OpenAIRE

    Buendía Ochoa, Jesús Pedro

    2015-01-01

    Introducción: Ansiedad enfermedad del milenio, el cual requiere tratamiento para evitar trastorno mayores. Objetivo: Determinar efecto sedante de Melissa officinalis “Toronjil” más Matricaria chamomilla “Manzanilla” sobre ansiedad inducida en ratones albinos. Diseño: Experimental. Lugar: Facultad de Medicina y Facultad de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos. Material Biológico: ratones, ratas albinos. Intervenciones: Treintaises ratones fueron inducidos a hiperacti...

  9. Neumonitis por hipersensibilidad en la ciudad de México

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    Carrillo-Rodríguez José G.

    2000-01-01

    Full Text Available OBJETIVO: Determinar la asociación entre la zona urbana de origen del paciente en la ciudad de México y la prevalencia de neumonitis por hipersensibilidad inducida por antígeno aviario. MATERIAL Y MÉTODOS: Se trata de un estudio de casos y controles realizado en el Instituto Nacional de Enfermedades Respiratorias, en la ciudad de México, en el año de 1999. Se estudiaron 109 casos con neumonitis por hipersensibilidad y 184 controles: de éstos, 39, con fibrosis pulmonar idiopática; 63, con tuberculosis pulmonar, y 82, con asma. La ciudad de México y las zonas conurbadas se dividieron en cinco zonas geográficas: centro, noreste, sureste, noroeste y el suroeste. Se calcularon las prevalencias de las diferentes enfermedades por zona urbana de los pacientes que participaron en el estudio; como medida de asociación, se estimó la razón de momios, con un intervalo de confianza al 95%. Asimismo, se realizó regresión logística múltiple ajustando por edad, sexo y estrato socioeconómico. RESULTADOS: Ochenta casos de neumonitis por hipersensibilidad se concentraron en el sur del noreste de las zonas conurbadas y la parte norte del sureste de la ciudad de México, 48 y 32, respectivamente (RM= 3.86, IC 95% 2.17-6.96. Treinta y seis controles de asma se localizaron en el suroeste de la ciudad de México, zona donde se ubica el Intituto Nacional de Enfermedades Respiratorias (p<0.05 y cuatro en la zona conurbada. Los controles de tuberculosis pulmonar y fibrosis pulmonar idiopática estuvieron dispersos en la ciudad de México y en las zonas conurbadas. CONCLUSIONES: La zona sur del noreste y el norte de la sureste están asociadas a la neumonitis por hipersensibilidad. Las causas de esta asociación no parece ser geográfica, pero existe el antecedente de que esa zona fue basurero de la ciudad, por lo que partículas orgánicas en el ambiente pudieran coadyuvar a la aparición de esta enfermedad.

  10. Genetic Deletion of the Transcriptional Repressor NFIL3 Enhances Axon Growth In Vitro but Not Axonal Repair In Vivo

    NARCIS (Netherlands)

    van der Kallen, Loek R; Eggers, Ruben; Ehlert, Erich M; Verhaagen, J.; Smit, August B; van Kesteren, Ronald E

    2015-01-01

    Axonal regeneration after injury requires the coordinated expression of genes in injured neurons. We previously showed that either reducing expression or blocking function of the transcriptional repressor NFIL3 activates transcription of regeneration-associated genes Arg1 and Gap43 and strongly

  11. Axonal regeneration and development of de novo axons from distal dendrites of adult feline commissural interneurons after a proximal axotomy

    DEFF Research Database (Denmark)

    Fenrich, Keith K; Skelton, Nicole; MacDermid, Victoria E

    2007-01-01

    Following proximal axotomy, several types of neurons sprout de novo axons from distal dendrites. These processes may represent a means of forming new circuits following spinal cord injury. However, it is not know whether mammalian spinal interneurons, axotomized as a result of a spinal cord injur...

  12. Oligodendrocyte Development in the Absence of Their Target Axons In Vivo.

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    Rafael Almeida

    Full Text Available Oligodendrocytes form myelin around axons of the central nervous system, enabling saltatory conduction. Recent work has established that axons can regulate certain aspects of oligodendrocyte development and myelination, yet remarkably oligodendrocytes in culture retain the ability to differentiate in the absence of axons and elaborate myelin sheaths around synthetic axon-like substrates. It remains unclear the extent to which the life-course of oligodendrocytes requires the presence of, or signals derived from axons in vivo. In particular, it is unclear whether the specific axons fated for myelination regulate the oligodendrocyte population in a living organism, and if so, which precise steps of oligodendrocyte-cell lineage progression are regulated by target axons. Here, we use live-imaging of zebrafish larvae carrying transgenic reporters that label oligodendrocyte-lineage cells to investigate which aspects of oligodendrocyte development, from specification to differentiation, are affected when we manipulate the target axonal environment. To drastically reduce the number of axons targeted for myelination, we use a previously identified kinesin-binding protein (kbp mutant, in which the first myelinated axons in the spinal cord, reticulospinal axons, do not fully grow in length, creating a region in the posterior spinal cord where most initial targets for myelination are absent. We find that a 73% reduction of reticulospinal axon surface in the posterior spinal cord of kbp mutants results in a 27% reduction in the number of oligodendrocytes. By time-lapse analysis of transgenic OPC reporters, we find that the reduction in oligodendrocyte number is explained by a reduction in OPC proliferation and survival. Interestingly, OPC specification and migration are unaltered in the near absence of normal axonal targets. Finally, we find that timely differentiation of OPCs into oligodendrocytes does not depend at all on the presence of target axons

  13. Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: lesion staging and dynamic changes of axons and microglial subsets.

    Science.gov (United States)

    Oyanagi, Kiyomitsu; Kinoshita, Michiaki; Suzuki-Kouyama, Emi; Inoue, Teruhiko; Nakahara, Asa; Tokiwai, Mika; Arai, Nobutaka; Satoh, Jun-Ichi; Aoki, Naoya; Jinnai, Kenji; Yazawa, Ikuru; Arai, Kimihito; Ishihara, Kenji; Kawamura, Mitsuru; Ishizawa, Keisuke; Hasegawa, Kazuko; Yagisita, Saburo; Amano, Naoji; Yoshida, Kunihiro; Terada, Seishi; Yoshida, Mari; Akiyama, Haruhiko; Mitsuyama, Yoshio; Ikeda, Shu-Ichi

    2017-11-01

    The brains of 10 Japanese patients with adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) encompassing hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD) and eight Japanese patients with Nasu-Hakola disease (N-HD) and five age-matched Japanese controls were examined neuropathologically with special reference to lesion staging and dynamic changes of microglial subsets. In both diseases, the pathognomonic neuropathological features included spherically swollen axons (spheroids and globules), axon loss and changes of microglia in the white matter. In ALSP, four lesion stages based on the degree of axon loss were discernible: Stage I, patchy axon loss in the cerebral white matter without atrophy; Stage II, large patchy areas of axon loss with slight atrophy of the cerebral white matter and slight dilatation of the lateral ventricles; Stage III, extensive axon loss in the cerebral white matter and dilatation of the lateral and third ventricles without remarkable axon loss in the brainstem and cerebellum; Stage IV, devastated cerebral white matter with marked dilatation of the ventricles and axon loss in the brainstem and/or cerebellum. Internal capsule and pontine base were relatively well preserved in the N-HD, even at Stage IV, and the swollen axons were larger with a higher density in the ALSP. Microglial cells immunopositive for CD68, CD163 or CD204 were far more obvious in ALSP, than in N-HD, and the shape and density of the cells changed in each stage. With progression of the stage, clinical symptoms became worse to apathetic state, and epilepsy was frequently observed in patients at Stages III and IV in both diseases. From these findings, it is concluded that (i) shape, density and subsets of microglia change dynamically along the passage of stages and (ii) increase of IBA-1-, CD68-, CD163- and CD204-immunopositive cells precedes loss of axons in ALSP. © 2016

  14. An αII Spectrin-Based Cytoskeleton Protects Large-Diameter Myelinated Axons from Degeneration.

    Science.gov (United States)

    Huang, Claire Yu-Mei; Zhang, Chuansheng; Zollinger, Daniel R; Leterrier, Christophe; Rasband, Matthew N

    2017-11-22

    Axons must withstand mechanical forces, including tension, torsion, and compression. Spectrins and actin form a periodic cytoskeleton proposed to protect axons against these forces. However, because spectrins also participate in assembly of axon initial segments (AISs) and nodes of Ranvier, it is difficult to uncouple their roles in maintaining axon integrity from their functions at AIS and nodes. To overcome this problem and to determine the importance of spectrin cytoskeletons for axon integrity, we generated mice with αII spectrin-deficient peripheral sensory neurons. The axons of these neurons are very long and exposed to the mechanical forces associated with limb movement; most lack an AIS, and some are unmyelinated and have no nodes. We analyzed αII spectrin-deficient mice of both sexes and found that, in myelinated axons, αII spectrin forms a periodic cytoskeleton with βIV and βII spectrin at nodes of Ranvier and paranodes, respectively, but that loss of αII spectrin disrupts this organization. Avil-cre;Sptan1 f/f mice have reduced numbers of nodes, disrupted paranodal junctions, and mislocalized Kv1 K + channels. We show that the density of nodal βIV spectrin is constant among axons, but the density of nodal αII spectrin increases with axon diameter. Remarkably, Avil-cre;Sptan1 f/f mice have intact nociception and small-diameter axons, but severe ataxia due to preferential degeneration of large-diameter myelinated axons. Our results suggest that nodal αII spectrin helps resist the mechanical forces experienced by large-diameter axons, and that αII spectrin-dependent cytoskeletons are also required for assembly of nodes of Ranvier. SIGNIFICANCE STATEMENT A periodic axonal cytoskeleton consisting of actin and spectrin has been proposed to help axons resist the mechanical forces to which they are exposed (e.g., compression, torsion, and stretch). However, until now, no vertebrate animal model has tested the requirement of the spectrin cytoskeleton in

  15. Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner.

    Science.gov (United States)

    Mitew, Stanislaw; Gobius, Ilan; Fenlon, Laura R; McDougall, Stuart J; Hawkes, David; Xing, Yao Lulu; Bujalka, Helena; Gundlach, Andrew L; Richards, Linda J; Kilpatrick, Trevor J; Merson, Tobias D; Emery, Ben

    2018-01-22

    Mounting evidence suggests that neuronal activity influences myelination, potentially allowing for experience-driven modulation of neural circuitry. The degree to which neuronal activity is capable of regulating myelination at the individual axon level is unclear. Here we demonstrate that stimulation of somatosensory axons in the mouse brain increases proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) within the underlying white matter. Stimulated axons display an increased probability of being myelinated compared to neighboring non-stimulated axons, in addition to being ensheathed with thicker myelin. Conversely, attenuating neuronal firing reduces axonal myelination in a selective activity-dependent manner. Our findings reveal that the process of selecting axons for myelination is strongly influenced by the relative activity of individual axons within a population. These observed cellular changes are consistent with the emerging concept that adaptive myelination is a key mechanism for the fine-tuning of neuronal circuitry in the mammalian CNS.

  16. Effect of vesicle traps on traffic jam formation in fast axonal transport.

    Science.gov (United States)

    Kuznetsov, A V

    2010-08-01

    The purpose of this paper is to develop a model for simulation of the formation of organelle traps in fast axonal transport. Such traps may form in the regions of microtubule polar mismatching. Depending on the orientation of microtubules pointing toward the trap region, these traps can accumulate either plus-end or minus-end oriented vesicles. The model predicts that the maximum concentrations of organelles occur at the boundaries of the trap regions; the overall concentration of organelles in the axon with traps is greatly increased compared to that in a healthy axon, which is expected to contribute to mechanical damages of the axon. The organelle traps induce hindrance to organelle transport down the axon; the total organelle flux down the axon with traps is found to be significantly reduced compared to that in a healthy axon. Copyright 2010 Elsevier Inc. All rights reserved.

  17. Efficient retrograde transport of pseudorabies virus within neurons requires local protein synthesis in axons.

    Science.gov (United States)

    Koyuncu, Orkide O; Perlman, David H; Enquist, Lynn W

    2013-01-16

    After replicating in epithelial cells, alphaherpesviruses such as pseudorabies virus (PRV) invade axons of peripheral nervous system neurons and undergo retrograde transport toward the distant cell bodies. Although several viral proteins engage molecular motors to facilitate transport, the initial steps and neuronal responses to infection are poorly understood. Using compartmented neuron cultures to physically separate axon infection from cell bodies, we found that PRV infection induces local protein synthesis in axons, including proteins involved in cytoskeletal remodeling, intracellular trafficking, signaling, and metabolism. This rapid translation of axonal mRNAs is required for efficient PRV retrograde transport and infection of cell bodies. Furthermore, induction of axonal damage, which also induces local protein synthesis, prior to infection reduces virion trafficking, suggesting that host damage signals and virus particles compete for retrograde transport. Thus, similar to axonal damage, virus infection induces local protein translation in axons, and viruses likely exploit this response for invasion. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Retinal ganglion cells: Energetics, compartmentation, axonal transport, cytoskeletons and vulnerability.

    Science.gov (United States)

    Yu, Dao-Yi; Cringle, Stephen J; Balaratnasingam, Chandrakumar; Morgan, William H; Yu, Paula K; Su, Er-Ning

    2013-09-01

    Retinal ganglion cells (RGCs) are specialized projection neurons that relay an immense amount of visual information from the retina to the brain. RGC signal inputs are collected by dendrites and output is distributed from the cell body via very thin (0.5-1 μm) and long (∼50 mm) axons. The RGC cell body is larger than other retinal neurons, but is still only a very small fraction (one ten thousandths) of the length and total surface area of the axon. The total distance traversed by RGCs extends from the retina, starting from synapses with bipolar and amacrine cells, to the brain, to synapses with neurons in the lateral geniculate nucleus. This review will focus on the energy demands of RGCs and the relevant tissues that surround them. RGC survival and function unexceptionally depends upon free energy, predominantly adenosine triphosphate (ATP). RGC energy metabolism is vastly different when compared to that of the photoreceptors. Each subcellular component of the RGC is remarkably different in terms of structure, function and extracellular environment. The energy demands and distribution of each component are also distinct as evidenced by the uneven distribution of mitochondria and ATP within the RGC - signifying the presence of intracellular energy gradients. In this review we will describe RGCs as having four subcellular components, (1) Dendrites, (2) Cell body, (3) Non-myelinated axon, including intraocular and optic nerve head portions, and (4) Myelinated axon, including the intra-orbital and intracranial portions. We will also describe how RGCs integrate information from each subcellular component in order achieve intracellular homeostatic stability as well as respond to perturbations in the extracellular environment. The possible cellular mechanisms such as axonal transport and axonal cytoskeleton proteins that are involved in maintaining RGC energy homeostasis during normal and disease conditions will also be discussed in depth. The emphasis of this

  19. A growing field: The regulation of axonal regeneration by Wnt signaling.

    Science.gov (United States)

    Garcia, Armando L; Udeh, Adanna; Kalahasty, Karthik; Hackam, Abigail S

    2018-01-01

    The canonical Wnt/β-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system (CNS). Recently, studies in mammalian and fish model systems have demonstrated that Wnt/β-catenin signaling also promotes axonal regeneration in the adult optic nerve and spinal cord after injury, raising the possibility that Wnt could be developed as a therapeutic strategy. In this review, we summarize experimental evidence that reveals novel roles for Wnt signaling in the injured CNS, and discuss possible mechanisms by which Wnt ligands could overcome molecular barriers inhibiting axonal growth to promote regeneration. A central challenge in the neuroscience field is developing therapeutic strategies that induce robust axonal regeneration. Although adult axons have the capacity to respond to axonal guidance molecules after injury, there are several major obstacles for axonal growth, including extensive neuronal death, glial scars at the injury site, and lack of axonal guidance signals. Research in rodents demonstrated that activation of Wnt/β-catenin signaling in retinal neurons and radial glia induced neuronal survival and axonal growth, but that activation within reactive glia at the injury site promoted proliferation and glial scar formation. Studies in zebrafish spinal cord injury models confirm an axonal regenerative role for Wnt/β-catenin signaling and identified the cell types responsible. Additionally, in vitro and in vivo studies demonstrated that Wnt induces axonal and neurite growth through transcription-dependent effects of its central mediator β-catenin, potentially by inducing regeneration-promoting genes. Canonical Wnt signaling may also function through transcription-independent interactions of β-catenin with cytoskeletal elements, which could stabilize growing axons and control growth cone

  20. Squid Giant Axon Contains Neurofilament Protein mRNA but does not Synthesize Neurofilament Proteins.

    Science.gov (United States)

    Gainer, Harold; House, Shirley; Kim, Dong Sun; Chin, Hemin; Pant, Harish C

    2017-04-01

    When isolated squid giant axons are incubated in radioactive amino acids, abundant newly synthesized proteins are found in the axoplasm. These proteins are translated in the adaxonal Schwann cells and subsequently transferred into the giant axon. The question as to whether any de novo protein synthesis occurs in the giant axon itself is difficult to resolve because the small contribution of the proteins possibly synthesized intra-axonally is not easily distinguished from the large amounts of the proteins being supplied from the Schwann cells. In this paper, we reexamine this issue by studying the synthesis of endogenous neurofilament (NF) proteins in the axon. Our laboratory previously showed that NF mRNA and protein are present in the squid giant axon, but not in the surrounding adaxonal glia. Therefore, if the isolated squid axon could be shown to contain newly synthesized NF protein de novo, it could not arise from the adaxonal glia. The results of experiments in this paper show that abundant 3H-labeled NF protein is synthesized in the squid giant fiber lobe containing the giant axon's neuronal cell bodies, but despite the presence of NF mRNA in the giant axon no labeled NF protein is detected in the giant axon. This lends support to the glia-axon protein transfer hypothesis which posits that the squid giant axon obtains newly synthesized protein by Schwann cell transfer and not through intra-axonal protein synthesis, and further suggests that the NF mRNA in the axon is in a translationally repressed state.

  1. Neocortical axon arbors trade-off material and conduction delay conservation.

    Directory of Open Access Journals (Sweden)

    Julian M L Budd

    2010-03-01

    Full Text Available The brain contains a complex network of axons rapidly communicating information between billions of synaptically connected neurons. The morphology of individual axons, therefore, defines the course of information flow within the brain. More than a century ago, Ramón y Cajal proposed that conservation laws to save material (wire length and limit conduction delay regulate the design of individual axon arbors in cerebral cortex. Yet the spatial and temporal communication costs of single neocortical axons remain undefined. Here, using reconstructions of in vivo labelled excitatory spiny cell and inhibitory basket cell intracortical axons combined with a variety of graph optimization algorithms, we empirically investigated Cajal's conservation laws in cerebral cortex for whole three-dimensional (3D axon arbors, to our knowledge the first study of its kind. We found intracortical axons were significantly longer than optimal. The temporal cost of cortical axons was also suboptimal though far superior to wire-minimized arbors. We discovered that cortical axon branching appears to promote a low temporal dispersion of axonal latencies and a tight relationship between cortical distance and axonal latency. In addition, inhibitory basket cell axonal latencies may occur within a much narrower temporal window than excitatory spiny cell axons, which may help boost signal detection. Thus, to optimize neuronal network communication we find that a modest excess of axonal wire is traded-off to enhance arbor temporal economy and precision. Our results offer insight into the principles of brain organization and communication in and development of grey matter, where temporal precision is a crucial prerequisite for coincidence detection, synchronization and rapid network oscillations.

  2. Coevolution of axon guidance molecule Slit and its receptor Robo.

    Directory of Open Access Journals (Sweden)

    Qi Yu

    Full Text Available Coevolution is important for the maintenance of the interaction between a ligand and its receptor during evolution. The interaction between axon guidance molecule Slit and its receptor Robo is critical for the axon repulsion in neural tissues, which is evolutionarily conserved from planarians to humans. However, the mechanism of coevolution between Slit and Robo remains unclear. In this study, we found that coordinated amino acid changes took place at interacting sites of Slit and Robo by comparing the amino acids at these sites among different organisms. In addition, the high level correlation between evolutionary rate of Slit and Robo was identified in vertebrates. Furthermore, the sites under positive selection of slit and robo were detected in the same lineage such as mosquito and teleost. Overall, our results provide evidence for the coevolution between Slit and Robo.

  3. Ensayo piloto de biorremediación de suelos contaminados por hidrocarburos. Fase ll

    Directory of Open Access Journals (Sweden)

    Gloria Lucía Camargo Millán

    2009-06-01

    Full Text Available  El estudio de la biodegradación de los hidrocarburos compuestos,altamente contaminantes y tóxicos, es de interéspara la descontaminación de ambientes afectados por derramesde petróleo. Aunque este proceso se presenta demanera natural, es demasiado lento, razón por la que sehace necesario el uso de técnicas de biorremediación parafacilitar la acción microbiana sobre los contaminantes. Anivel experimental este proceso se realiza por etapas o ensayos,ya sean de laboratorio, pilotos, de campo oimplementación. Previamente a este estudio se trabajó unaetapa a nivel de laboratorio, donde se observó la remociónde hidrocarburo en un suelo contaminado de manera inducida,aislándose bacterias capaces de su degradación, loque mostró que el proceso es factible. El presente estudiocorresponde a la etapa a nivel piloto, cuyo objetivo eracuantificar la tasa de remoción de hidrocarburo en muestrasde suelo contaminadas con crudo de castilla provenientede diez terrarios, a los cuales se les inoculó bacteriastotales y bacterias Pseudomonas aeruginosa.

  4. Activated retinal glia mediated axon regeneration in experimental glaucoma.

    Science.gov (United States)

    Lorber, Barbara; Guidi, Alessandra; Fawcett, James W; Martin, Keith R

    2012-01-01

    Glaucoma, a leading cause of blindness, is a neurodegenerative disease characterized by progressive loss of retinal ganglion cell axons in the optic nerve and their cell bodies in the retina. Reactive retinal glial changes have been observed in glaucoma but the role of such glial changes in the pathogenesis of the condition remains unclear. In the present study we found that retinal ganglion cells in an experimental animal model of glaucoma have an increased axon regenerative potential. Regeneration of adult rat retinal ganglion cell axons after optic nerve crush was significantly increased in vivo when combined with intraocular pressure-induced experimental glaucoma. This enhanced axon regeneration response was correlated with a significant increase in activation of glial fibrillary acidic protein+retinal glia. Using a dissociated retinal ganglion cell culture model we showed that reducing the number of activated retinal glia with a glial specific toxin, α-Aminoadipic acid, significantly reduced the growth potential of retinal ganglion cells from glaucomatous rat eyes, suggesting that activated retinal glia mediate, at least in part, the growth promoting effect. This was shown to be mediated by both membrane-bound and soluble glial-derived factors. Neurotrophin and ciliary neurotrophic/leukemia inhibitory factor blockers did not affect the regenerative potential, excluding these growth factors as principal mediators of the enhanced growth response occurring in glaucomatous retinal cultures. These observations are the first to reveal that retinal ganglion cells from glaucomatous rat eyes have an enhanced regenerative capacity. Furthermore, our results suggest that activated retinal glia mediate at least part of this response. Further work to understand and enhance the regeneration-promoting effect of activated retinal glia is required to determine if this approach could be useful as part of a therapeutic strategy to encourage optic nerve regeneration in glaucoma

  5. [Craniocerebral trauma: magnetic resonance imaging of diffuse axonal injury].

    Science.gov (United States)

    Mallouhi, A

    2014-09-01

    Acceleration-deceleration rotational brain trauma is a common cause of disability or death in young adults and often leads to a focal destruction of axons. The resulting pathology, axonal shear injury is referred to as diffuse axonal injury (DAI). The DAI-associated lesions occur bilaterally, are widely dispersed and have been observed in the surface and deep white matter. They are found near to and far from the impact site. When DAI is clinically suspected, magnetic resonance imaging (MRI) is the method of choice for further clarification, especially in patients where cranial computed tomography (CT) is inconspicuous. To investigate the presence of DAI after traumatic brain injury (TBI), a multimodal MRI approach is applied including the common structural and also functional imaging sequences. For structural MRI, fluid-attenuated inversion recovery (FLAIR) weighted and susceptibility contrast imaging (SWI) are the sequences mainly used. The SWI technique is extremely sensitive to blood breakdown products, which appear as small signal voids at three locations, at the gray-white interface, in the corpus callosum and in the brain stem. Functional MRI comprises a group of constantly developing techniques that have great potential in optimal evaluation of the white matter in patients after craniocerebral trauma. These imaging techniques allow the visualization of changes associated with shear injuries, such as functional impairment of axons and decreased blood flow and abnormal metabolic activity of the brain parts affected. The multimodal MRI approach in patients with DAI results in a more detailed and differentiated representation of the underlying pathophysiological changes of the injured nerve tracts and helps to improve the diagnostic and prognostic accuracy of MRI. When DAI is suspected multimodal MRI should be performed as soon as possible after craniocerebral injury.

  6. Spontaneous axonal regeneration in rodent spinal cord after ischemic injury

    DEFF Research Database (Denmark)

    von Euler, Mia; Janson, A M; Larsen, Jytte Overgaard

    2002-01-01

    cells, while other fibers were unmyelinated. Immunohistochemistry demonstrated that some of the regenerated fibers were tyrosine hydroxylase- or serotonin-immunoreactive, indicating a central origin. These findings suggest that there is a considerable amount of spontaneous regeneration after spinal cord...... lesions in rodents and that the fibers remain several months after injury. The findings of tyrosine hydroxylase- and serotonin-immunoreactivity in the axons suggest that descending central fibers contribute to this endogenous repair of ischemic spinal cord injury....

  7. Polyethylene glycol restores axonal conduction after corpus callosum transection.

    Science.gov (United States)

    Bamba, Ravinder; Riley, D Colton; Boyer, Richard B; Pollins, Alonda C; Shack, R Bruce; Thayer, Wesley P

    2017-05-01

    Polyethylene glycol (PEG) has been shown to restore axonal continuity after peripheral nerve transection in animal models. We hypothesized that PEG can also restore axonal continuity in the central nervous system. In this current experiment, coronal sectioning of the brains of Sprague-Dawley rats was performed after animal sacrifice. 3Brain high-resolution microelectrode arrays (MEA) were used to measure mean firing rate (MFR) and peak amplitude across the corpus callosum of the ex-vivo brain slices. The corpus callosum was subsequently transected and repeated measurements were performed. The cut ends of the corpus callosum were still apposite at this time. A PEG solution was applied to the injury site and repeated measurements were performed. MEA measurements showed that PEG was capable of restoring electrophysiology signaling after transection of central nerves. Before injury, the average MFRs at the ipsilateral, midline, and contralateral corpus callosum were 0.76, 0.66, and 0.65 spikes/second, respectively, and the average peak amplitudes were 69.79, 58.68, and 49.60 μV, respectively. After injury, the average MFRs were 0.71, 0.14, and 0.25 spikes/second, respectively and peak amplitudes were 52.11, 8.98, and 16.09 μV, respectively. After application of PEG, there were spikes in MFR and peak amplitude at the injury site and contralaterally. The average MFRs were 0.75, 0.55, and 0.47 spikes/second at the ipsilateral, midline, and contralateral corpus callosum, respectively and peak amplitudes were 59.44, 45.33, 40.02 μV, respectively. There were statistically differences in the average MFRs and peak amplitudes between the midline and non-midline corpus callosum groups ( P < 0.01, P < 0.05). These findings suggest that PEG restores axonal conduction between severed central nerves, potentially representing axonal fusion.

  8. Polyethylene glycol restores axonal conduction after corpus callosum transection

    Directory of Open Access Journals (Sweden)

    Ravinder Bamba

    2017-01-01

    Full Text Available Polyethylene glycol (PEG has been shown to restore axonal continuity after peripheral nerve transection in animal models. We hypothesized that PEG can also restore axonal continuity in the central nervous system. In this current experiment, coronal sectioning of the brains of Sprague-Dawley rats was performed after animal sacrifice. 3Brain high-resolution microelectrode arrays (MEA were used to measure mean firing rate (MFR and peak amplitude across the corpus callosum of the ex-vivo brain slices. The corpus callosum was subsequently transected and repeated measurements were performed. The cut ends of the corpus callosum were still apposite at this time. A PEG solution was applied to the injury site and repeated measurements were performed. MEA measurements showed that PEG was capable of restoring electrophysiology signaling after transection of central nerves. Before injury, the average MFRs at the ipsilateral, midline, and contralateral corpus callosum were 0.76, 0.66, and 0.65 spikes/second, respectively, and the average peak amplitudes were 69.79, 58.68, and 49.60 μV, respectively. After injury, the average MFRs were 0.71, 0.14, and 0.25 spikes/second, respectively and peak amplitudes were 52.11, 8.98, and 16.09 μV, respectively. After application of PEG, there were spikes in MFR and peak amplitude at the injury site and contralaterally. The average MFRs were 0.75, 0.55, and 0.47 spikes/second at the ipsilateral, midline, and contralateral corpus callosum, respectively and peak amplitudes were 59.44, 45.33, 40.02 μV, respectively. There were statistically differences in the average MFRs and peak amplitudes between the midline and non-midline corpus callosum groups (P < 0.01, P < 0.05. These findings suggest that PEG restores axonal conduction between severed central nerves, potentially representing axonal fusion.

  9. Two stable steady states in the Hodgkin-Huxley axons

    OpenAIRE

    Aihara, K.; Matsumoto, G.

    1983-01-01

    Two stable steady states were found in the numerical solution of the Hodgkin-Huxley equations for the intact squid axon bathed in potassium-rich sea water with an externally applied inward current. Under the conditions the two stable steady-states exist, the Hodgkin-Huxley equations have a complex bifurcation structure including, in addition to the two stable steady-states, a stable limit cycle, two unstable equilibrium points, and one asymptotically stable equilibrium point. It was also conc...

  10. Influence of the surgical manipulation of the colon in colonic induced carcinogenesis in rats Influencia de la manipulación quirúrgica del colon en la carcinogénesis cólica inducida en ratas

    Directory of Open Access Journals (Sweden)

    J. F. Noguera Aguilar

    2004-05-01

    1-2 dimetilhidrazina dihidrocloruro. Se identificaron los adenocarcinomas cólicos y se determinaron número de tumores, superficie tumoral y porcentaje de superficie tumoral. El análisis estadístico se realizó con modelos Anova de comparación de medias y con tablas de contingencia Chi cuadrado. Resultados: el número de tumores fue mayor en el grupo quirúrgico que en el control, apareciendo preferentemente alrededor del colon manipulado. La superficie y el porcentaje tumorales fueron mayores en el grupo quirúrgico que en el control, siendo mayores a su vez en el grupo con anastomosis frente al grupo con traumatismo cólico. Dentro de los grupos con anastomosis, presentó mayor superficie y porcentaje tumoral el grupo con adición de titanio frente al grupo con material reabsorbible. Conclusiones: la manipulación experimental del colon de la rata aumenta la carcinogénesis cólica farmacológicamente inducida. La creación de una anastomosis provoca un mayor incremento del proceso carcinogénico que la anastomosis simulada. Este proceso se ve además favorecido por la cantidad de material de sutura incluida en la anastomosis y por la naturaleza irreabsorbible de los materiales implantados en la línea anastomótica.

  11. Efectos de quercetina y naringenina sobre diversos modelos de úlcera gástrica experimental inducida en rata

    OpenAIRE

    Motilva Sánchez, Virginia

    1991-01-01

    La úlcera péptica es un conjunto de factores heterogéneos que se manifiestan como una disfunción de la capa mucosa gastrointestinal bañada por ácido y pepsina. En algunas úlceras, la agresión por pepsina-ácido es de importancia capital, en otras existe una carencia o defecto de las defensas de la mucosa. El tratamiento farmacológico de la úlcera péptica se ha dirigido fundamentalmente hacia estos dos factores y el número de fármacos disponibles ha crecido casi exponencialmente en los últim...

  12. Internalization and Axonal Transport of the HIV Glycoprotein gp120

    Science.gov (United States)

    Berth, Sarah; Caicedo, Hector Hugo; Sarma, Tulika; Morfini, Gerardo

    2015-01-01

    The HIV glycoprotein gp120, a neurotoxic HIV glycoprotein that is overproduced and shed by HIV-infected macrophages, is associated with neurological complications of HIV such as distal sensory polyneuropathy, but interactions of gp120 in the peripheral nervous system remain to be characterized. Here, we demonstrate internalization of extracellular gp120 in a manner partially independent of binding to its coreceptor CXCR4 by F11 neuroblastoma cells and cultured dorsal root ganglion neurons. Immunocytochemical and pharmacological experiments indicate that gp120 does not undergo trafficking through the endolysosomal pathway. Instead, gp120 is mainly internalized through lipid rafts in a cholesterol-dependent manner, with a minor fraction being internalized by fluid phase pinocytosis. Experiments using compartmentalized microfluidic chambers further indicate that, after internalization, endocytosed gp120 selectively undergoes retrograde but not anterograde axonal transport from axons to neuronal cell bodies. Collectively, these studies illuminate mechanisms of gp120 internalization and axonal transport in peripheral nervous system neurons, providing a novel framework for mechanisms for gp120 neurotoxicity. PMID:25636314

  13. Inner membrane fusion mediates spatial distribution of axonal mitochondria

    Science.gov (United States)

    Yu, Yiyi; Lee, Hao-Chih; Chen, Kuan-Chieh; Suhan, Joseph; Qiu, Minhua; Ba, Qinle; Yang, Ge

    2016-01-01

    In eukaryotic cells, mitochondria form a dynamic interconnected network to respond to changing needs at different subcellular locations. A fundamental yet unanswered question regarding this network is whether, and if so how, local fusion and fission of individual mitochondria affect their global distribution. To address this question, we developed high-resolution computational image analysis techniques to examine the relations between mitochondrial fusion/fission and spatial distribution within the axon of Drosophila larval neurons. We found that stationary and moving mitochondria underwent fusion and fission regularly but followed different spatial distribution patterns and exhibited different morphology. Disruption of inner membrane fusion by knockdown of dOpa1, Drosophila Optic Atrophy 1, not only increased the spatial density of stationary and moving mitochondria but also changed their spatial distributions and morphology differentially. Knockdown of dOpa1 also impaired axonal transport of mitochondria. But the changed spatial distributions of mitochondria resulted primarily from disruption of inner membrane fusion because knockdown of Milton, a mitochondrial kinesin-1 adapter, caused similar transport velocity impairment but different spatial distributions. Together, our data reveals that stationary mitochondria within the axon interconnect with moving mitochondria through fusion and fission and that local inner membrane fusion between individual mitochondria mediates their global distribution. PMID:26742817

  14. Dendritic and Axonal Wiring Optimization of Cortical GABAergic Interneurons.

    Science.gov (United States)

    Anton-Sanchez, Laura; Bielza, Concha; Benavides-Piccione, Ruth; DeFelipe, Javier; Larrañaga, Pedro

    2016-10-01

    The way in which a neuronal tree expands plays an important role in its functional and computational characteristics. We aimed to study the existence of an optimal neuronal design for different types of cortical GABAergic neurons. To do this, we hypothesized that both the axonal and dendritic trees of individual neurons optimize brain connectivity in terms of wiring length. We took the branching points of real three-dimensional neuronal reconstructions of the axonal and dendritic trees of different types of cortical interneurons and searched for the minimal wiring arborization structure that respects the branching points. We compared the minimal wiring arborization with real axonal and dendritic trees. We tested this optimization problem using a new approach based on graph theory and evolutionary computation techniques. We concluded that neuronal wiring is near-optimal in most of the tested neurons, although the wiring length of dendritic trees is generally nearer to the optimum. Therefore, wiring economy is related to the way in which neuronal arborizations grow irrespective of the marked differences in the morphology of the examined interneurons.

  15. Axonal Actin Transport Driven By Metastable Actin Filaments

    Science.gov (United States)

    Chakrabarty, Nilaj; Ganguly, Archan; Roy, Subhojit; Jung, Peter

    Actin is one of the key constituents of the neuronal cytoskeleton and is responsible for driving important cellular processes like axon elongation. Axonal actin is synthesized in the cell body and transported at rates of 0.25 - 3 mm/day, as shown by in-vivo pulse-chase radiolabelling studies. However, the underlying transport mechanisms are unknown. Recent experiments in cultured neurons have revealed a dynamic network of metastable actin filaments (actin trails). Actin trails seem to originate from focal actin hotspots which colocalize with stationary endosomes. Interestingly, the number of actin trails extending anterogradely is higher than the ones extending retrogradely. We hypothesize that the bulk axonal transport of actin originates from this directional asymmetry of the number of actin trails. To test this, we constructed a computational model of actin trail growth and simulated the pulse-chase experiment. In our model, local, metastable trails, which grow with their barbed ends anchored to the hotspots, drive the bulk anterograde transport. Our results indicate that the observed bias of the nucleation probabilities and the elongation rate of actin trails are sufficient to drive the bulk transport of actin at rates that agree with in-vivo pulse chase experiments.

  16. Prediction of Functional Outcome in Axonal Guillain-Barre Syndrome.

    Science.gov (United States)

    Sung, Eun Jung; Kim, Dae Yul; Chang, Min Cheol; Ko, Eun Jae

    2016-06-01

    To identify the factors that could predict the functional outcome in patients with the axonal type of Guillain-Barre syndrome (GBS). Two hundred and two GBS patients admitted to our university hospital between 2003 and 2014 were reviewed retrospectively. We defined a good outcome as being "able to walk independently at 1 month after onset" and a poor outcome as being "unable to walk independently at 1 month after onset". We evaluated the factors that differed between the good and poor outcome groups. Twenty-four patients were classified into the acute motor axonal neuropathy type. There was a statistically significant difference between the good and poor outcome groups in terms of the GBS disability score at admission, and GBS disability score and Medical Research Council sum score at 1 month after admission. In an electrophysiologic analysis, the good outcome group showed greater amplitude of median, ulnar, deep peroneal, and posterior tibial nerve compound muscle action potentials (CMAP) and greater amplitude of median, ulnar, and superficial peroneal sensory nerve action potentials (SNAP) than the poor outcome group. A lower GBS disability score at admission, high amplitude of median, ulnar, deep peroneal, and posterior tibial CMAPs, and high amplitude of median, ulnar, and superficial peroneal SNAPs were associated with being able to walk at 1 month in patients with axonal GBS.

  17. Daño al sistema nervioso inducido por nanopartículas : toxicidad celular inducida por nanopartículas de óxidos metálicos en células neuronales humanas

    OpenAIRE

    Laffon, Blanca; Iglesias, Vanessa; Costa, Carla; Costa, Solange; Teixeira, João Paulo; Mendez, Josefina

    2013-01-01

    Las nanopartículas (NP) de óxidos metálicos, como el dióxido de titanio (TiO2) y el óxido de zinc (ZnO), se utilizan en una gran variedad de aplicaciones industriales y médicas, incluyendo materiales de alta tecnología, plásticos, pinturas, implantes ortopédicos artificiales, derivados de papel, cosméticos y protectores solares. Los estudios sobre los efectos de estas NP en el sistema nervioso son muy escasos. El objetivo de este trabajo consiste en caracterizar tres NP de óxidos metálicos (u...

  18. Efectos protectores de la oleoiletanolamida en la neuroinflamación inducida por la administración de lipopolisacárido o por el consumo intensivo de alcohol

    OpenAIRE

    Antón Valadés, María

    2016-01-01

    La neuroinflamación es un fenómeno que contribuye a la progresión y agravamiento de enfermedades neurodegenerativas y neuropsiquiátricas, incluida la adicción a sustancias como el alcohol. Se han descrito acciones neuroprotectoras de mediadores lipídicos naturales derivados de la membrana celular, tales como la oleoiletanolamida, y su congénere la palmitoiletanolamida, ambos pertenecientes a la familia de las aciletanolamidas. Se desconoce con exactitud el potencial efecto terapéutico de esto...

  19. The proliferation induced by hyperthermia in NB69 cells is offset by a radar-like signal; La proliferacion inducida por hipertermia en celulas NB69 es contrarrestada por una senal de tipo radar

    Energy Technology Data Exchange (ETDEWEB)

    Trillo Ruiz, M. A.; Martinez Pascual, M. A.; Cid Torres, M. A.; Pague de la Vega, J. E.; Chacon Vargas, L.; Ubeda Maeso, A.

    2011-07-01

    The present study describes the proliferative response of the cell line NB69 human neuroblastoma, the simultaneous exposure to two physical agents: mild hyperthermia (+1 degree centigrade) and a pulsed signal RFsubthermal.

  20. Intra-axonal protein synthesis - a new target for neural repair?

    Directory of Open Access Journals (Sweden)

    Jeffery L Twiss

    2016-01-01

    Full Text Available Although initially argued to be a feature of immature neurons with incomplete polarization, there is clear evidence that neurons in the peripheral nervous system retain the capacity for intra-axonal protein synthesis well into adulthood. This localized protein synthesis has been shown to contribute to injury signaling and axon regeneration in peripheral nerves. Recent works point to potential for protein synthesis in axons of the vertebrate central nervous system. mRNAs and protein synthesis machinery have now been documented in lamprey, mouse, and rat spinal cord axons. Intra-axonal protein synthesis appears to be activated in adult vertebrate spinal cord axons when they are regeneration-competent. Rat spinal cord axons regenerating into a peripheral nerve graft contain mRNAs and markers of activated translational machinery. Indeed, levels of some growth-associated mRNAs in these spinal cord axons are comparable to the regenerating sciatic nerve. Markers of active translation tend to decrease when these axons stop growing, but can be reactivated by a second axotomy. These emerging observations raise the possibility that mRNA transport into and translation within axons could be targeted to facilitate regeneration in both the peripheral and central nervous systems.

  1. Sodium Channel β2 Subunits Prevent Action Potential Propagation Failures at Axonal Branch Points.

    Science.gov (United States)

    Cho, In Ha; Panzera, Lauren C; Chin, Morven; Hoppa, Michael B

    2017-09-27

    Neurotransmitter release depends on voltage-gated Na + channels (Na v s) to propagate an action potential (AP) successfully from the axon hillock to a synaptic terminal. Unmyelinated sections of axon are very diverse structures encompassing branch points and numerous presynaptic terminals with undefined molecular partners of Na + channels. Using optical recordings of Ca 2+ and membrane voltage, we demonstrate here that Na + channel β2 subunits (Na v β2s) are required to prevent AP propagation failures across the axonal arborization of cultured rat hippocampal neurons (mixed male and female). When Na v β2 expression was reduced, we identified two specific phenotypes: (1) membrane excitability and AP-evoked Ca 2+ entry were impaired at synapses and (2) AP propagation was severely compromised with >40% of axonal branches no longer responding to AP-stimulation. We went on to show that a great deal of electrical signaling heterogeneity exists in AP waveforms across the axonal arborization independent of axon morphology. Therefore, Na v β2 is a critical regulator of axonal excitability and synaptic function in unmyelinated axons. SIGNIFICANCE STATEMENT Voltage-gated Ca 2+ channels are fulcrums of neurotransmission that convert electrical inputs into chemical outputs in the form of vesicle fusion at synaptic terminals. However, the role of the electrical signal, the presynaptic action potential (AP), in modulating synaptic transmission is less clear. What is the fidelity of a propagating AP waveform in the axon and what molecules shape it throughout the axonal arborization? Our work identifies several new features of AP propagation in unmyelinated axons: (1) branches of a single axonal arborization have variable AP waveforms independent of morphology, (2) Na + channel β2 subunits modulate AP-evoked Ca 2+ -influx, and (3) β2 subunits maintain successful AP propagation across the axonal arbor. These findings are relevant to understanding the flow of excitation in the

  2. The disruption of mitochondrial axonal transport is an early event in neuroinflammation

    DEFF Research Database (Denmark)

    Errea, Oihana; Moreno, Beatriz; Gonzalez-Franquesa, Alba

    2015-01-01

    of neuroprotective therapies. Energy depletion due to mitochondrial dysfunction has been postulated as an important step in the damage of axons. This prompted us to study the effects of acute inflammation and oxidative stress on the morphology, transport, and function of mitochondria in axons. METHODS: Mouse......BACKGROUND: In brain inflammatory diseases, axonal damage is one of the most critical steps in the cascade that leads to permanent disability. Thus, identifying the initial events triggered by inflammation or oxidative stress that provoke axonal damage is critical for the development...... in axons, increasing the proportion of stationary mitochondria in axons after LPS challenge. Indeed, the two challenges used produced different effects: inflammation mostly reducing retrograde transport and oxidative stress slightly enhancing retrograde transportation. CONCLUSIONS: Neuroinflammation...

  3. Segregation of Axial Motor and Sensory Pathways via Heterotypic Trans-Axonal Signaling

    Science.gov (United States)

    Gallarda, Benjamin W.; Bonanomi, Dario; Müller, Daniel; Brown, Arthur; Alaynick, William A.; Andrews, Shane E.; Lemke, Greg; Pfaff, Samuel L.; Marquardt, Till

    2011-01-01

    Execution of motor behaviors relies on circuitries effectively integrating immediate sensory feedback to efferent pathways controlling muscle activity. It remains unclear how, during neuromuscular circuit assembly, sensory and motor projections become incorporated into tightly coordinated, yet functionally separate pathways. We report that, within axial nerves, establishment of discrete afferent and efferent pathways depends on coordinate signaling between coextending sensory and motor projections. These heterotypic axon-axon interactions require motor axonal EphA3/EphA4 receptor tyrosine kinases activated by cognate sensory axonal ephrin-A ligands. Genetic elimination of trans-axonal ephrin-A → EphA signaling in mice triggers drastic motor-sensory miswiring, culminating in functional efferents within proximal afferent pathways. Effective assembly of a key circuit underlying motor behaviors thus critically depends on trans-axonal signaling interactions resolving motor and sensory projections into discrete pathways. PMID:18403711

  4. Role of calpains in the injury-induced dysfunction and degeneration of the mammalian axon.

    Science.gov (United States)

    Ma, Marek

    2013-12-01

    Axonal injury and degeneration, whether primary or secondary, contribute to the morbidity and mortality seen in many acquired and inherited central nervous system (CNS) and peripheral nervous system (PNS) disorders, such as traumatic brain injury, spinal cord injury, cerebral ischemia, neurodegenerative diseases, and peripheral neuropathies. The calpain family of proteases has been mechanistically linked to the dysfunction and degeneration of axons. While the direct mechanisms by which transection, mechanical strain, ischemia, or complement activation trigger intra-axonal calpain activity are likely different, the downstream effects of unregulated calpain activity may be similar in seemingly disparate diseases. In this review, a brief examination of axonal structure is followed by a focused overview of the calpain family. Finally, the mechanisms by which calpains may disrupt the axonal cytoskeleton, transport, and specialized domains (axon initial segment, nodes, and terminals) are discussed. © 2013.

  5. A Combinatorial Approach to Induce Sensory Axon Regeneration into the Dorsal Root Avulsed Spinal Cord

    DEFF Research Database (Denmark)

    Hoeber, Jan; Konig, Niclas; Trolle, Carl

    2017-01-01

    restores sensory functions. In this study, we elucidate mechanisms underlying stem cell-mediated ingrowth of sensory axons after dorsal root avulsion (DRA). We show that human spinal cord neural stem/progenitor cells (hscNSPC), and also, mesoporous silica particles loaded with growth factor mimetics (Meso......MIM), supported sensory axon regeneration. However, when hscNSPC and MesoMIM were combined, sensory axon regeneration failed. Morphological and tracing analysis showed that sensory axons grow through the newly established glial scar along “bridges” formed by migrating stem cells. Coimplantation of Meso......MIM prevented stem cell migration, “bridges” were not formed, and sensory axons failed to enter the spinal cord. MesoMIM applied alone supported sensory axons ingrowth, but without affecting glial scar formation. In vitro, the presence of MesoMIM significantly impaired migration of hscNSPC without affecting...

  6. Inter-axonal interaction defines tiled presynaptic innervation in C. elegans

    OpenAIRE

    Mizumoto, Kota; Shen, Kang

    2013-01-01

    Cellular interactions between neighboring axons are essential for global topographic map formation. Here we show that axonal interactions also precisely instruct the location of synapses. Motoneurons form en passant synapses in Caenorhabditis elegans. While axons from the same neuron class significantly overlap, each neuron innervates a unique and tiled segment of the muscle field by restricting its synapses to a distinct subaxonal domain—a phenomenon we term “synaptic tiling”. Using DA8 and ...

  7. Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0524 TITLE:Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis PRINCIPAL INVESTIGATOR: Jeffrey D...29 Sep 2015 4. TITLE AND SUBTITLE Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis 5a. CONTRACT NUMBER W81XWH-14-1-0524...MCT1 in injured oligodendroglia of multiple sclerosis patients contributes to axon neurodegeneration and that increasing MCT1 will be protective in the

  8. Acutely damaged axons are remyelinated in multiple sclerosis and experimental models of demyelination.

    Science.gov (United States)

    Schultz, Verena; van der Meer, Franziska; Wrzos, Claudia; Scheidt, Uta; Bahn, Erik; Stadelmann, Christine; Brück, Wolfgang; Junker, Andreas

    2017-08-01

    Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de- and remyelination, we employed cuprizone- and focal lysolecithin-induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage. We observed damaged axons with signs of remyelination after cuprizone diet cessation and lysolecithin injection. Similar observations were made in early multiple sclerosis lesions. To assess the correlation of remyelination and axonal damage in multiple sclerosis lesions, we took advantage of a cohort of patients with early and late stage remyelinated lesions and assessed the number of APP- and SMI32- positive damaged axons and the density of SMI31-positive and silver impregnated preserved axons. Early de- and remyelinating lesions did not differ with respect to axonal density and axonal damage, but we observed a lower axonal density in late stage demyelinated multiple sclerosis lesions than in remyelinated multiple sclerosis lesions. Our findings suggest that remyelination may not only be protective over a long period of time, but may play an important role in the immediate axonal recuperation after a demyelinating insult. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

  9. Ribosomes and polyribosomes are present in the squid giant axon: an immunocytochemical study.

    Science.gov (United States)

    Sotelo, J R; Kun, A; Benech, J C; Giuditta, A; Morillas, J; Benech, C R

    1999-05-01

    Ribosomes and polyribosomes were detected by immuno-electron microscopy in the giant axon and small axons of the squid using a polyclonal antibody against rat brain ribosomes. The ribosomal fraction used as antigen was purified by ultracentrifugation on a sucrose density gradient and shown to contain ribosomal RNAs and native ribosomes. The polyclonal antibody raised in rabbits reacted with at least ten proteins on immunoblots of purified rat brain ribosomes as well as with a set of multiple ribosomal proteins prepared from the squid giant fiber lobe. Immunoreactions were performed on cryostat sections of the stellate nerve cut at a distance of more than 3 cm from the stellate ganglion, using pre-embedding techniques. Ribosomes and polyribosomes were identified within the giant axon and small axons using electron microscopic methods, following binding of peroxidase-conjugated anti-rabbit IgG secondary antibody. Polysomes were more frequently localized in peripheral axoplasm, including the cortical layer of the giant axon, and were generally associated with unidentified cytoskeletal filaments or with dense matrix material. The immunochemical demonstration of ribosomes and polyribosomes in the giant axon and small axons of the squid confirms similar observations in the squid and the goldfish obtained with the method of electron spectroscopic imaging, and strongly supports the view that a local system of protein synthesis is present in axons. The immunochemical method here described offers an alternative tool for the selective identification of ribosomes, and is likely to prove of value in the analyses of other axonal systems.

  10. Regulation of Axonal Midline Guidance by Prolyl 4-Hydroxylation in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Torpe, Nanna; Pocock, Roger David John

    2014-01-01

    , little is known of its importance in the control of axon guidance. In a screen of prolyl 4-hydroxylase (P4H) mutants, we found that genetic removal of a specific P4H subunit, DPY-18, causes dramatic defects in C. elegans neuroanatomy. In dpy-18 mutant animals, the axons of specific ventral nerve cord......Neuronal wiring during development requires that the growth cones of axons and dendrites are correctly guided to their appropriate targets. As in other animals, axon growth cones in Caenorhabditis elegans integrate information in their extracellular environment via interactions among transiently...

  11. Forced notch signaling inhibits commissural axon outgrowth in the developing chick central nerve system.

    Directory of Open Access Journals (Sweden)

    Ming Shi

    Full Text Available BACKGROUND: A collection of in vitro evidence has demonstrated that Notch signaling plays a key role in the growth of neurites in differentiated neurons. However, the effects of Notch signaling on axon outgrowth in an in vivo condition remain largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the neural tubes of HH10-11 chick embryos were in ovo electroporated with various Notch transgenes of activating or inhibiting Notch signaling, and then their effects on commissural axon outgrowth across the floor plate midline in the chick developing central nerve system were investigated. Our results showed that forced expression of Notch intracellular domain, constitutively active form of RBPJ, or full-length Hes1 in the rostral hindbrain, diencephalon and spinal cord at stage HH10-11 significantly inhibited commissural axon outgrowth. On the other hand, inhibition of Notch signaling by ectopically expressing a dominant-negative form of RBPJ promoted commissural axonal growth along the circumferential axis. Further results revealed that these Notch signaling-mediated axon outgrowth defects may be not due to the alteration of axon guidance since commissural axon marker TAG1 was present in the axons in floor plate midline, and also not result from the changes in cell fate determination of commissural neurons since the expression of postmitotic neuron marker Tuj1 and specific commissural markers TAG1 and Pax7 was unchanged. CONCLUSIONS/SIGNIFICANCE: We first used an in vivo system to provide evidence that forced Notch signaling negatively regulates commissural axon outgrowth.

  12. Alterations in the Local Axonal Environment Influence Target Reinnervation and Neuronal Survival after Postnatal Axotomy

    National Research Council Canada - National Science Library

    Dainer, Hugh M

    2000-01-01

    Following peripheral nerve injury in adult animals, Schwann cells (SC) proliferate and provide guidance in the local axonal environment by generating the infrastructure along which regenerating nerves grow...

  13. N-Propionylmannosamine stimulates axonal elongation in a murine model of sciatic nerve injury

    Directory of Open Access Journals (Sweden)

    Christian Witzel

    2015-01-01

    Full Text Available Increasing evidence indicates that sialic acid plays an important role during nerve regeneration. Sialic acids can be modified in vitro as well as in vivo using metabolic oligosaccharide engineering of the N-acyl side chain. N-Propionylmannosamine (ManNProp increases neurite outgrowth and accelerates the reestablishment of functional synapses in vitro. We investigated the influence of systemic ManNProp application using a specific in vivo mouse model. Using mice expressing axonal fluorescent proteins, we quantified the extension of regenerating axons, the number of regenerating axons, the number of arborising axons and the number of branches per axon 5 days after injury. Sciatic nerves from non-expressing mice were grafted into those expressing yellow fluorescent protein. We began a twice-daily intraperitoneal application of either peracetylated ManNProp (200 mg/kg or saline solution 5 days before injury, and continued it until nerve harvest (5 days after transection. ManNProp significantly increased the mean distance of axonal regeneration (2.49 mm vs. 1.53 mm; P < 0.005 and the number of arborizing axons (21% vs. 16% P = 0.008 5 days after sciatic nerve grafting. ManNProp did not affect the number of regenerating axons or the number of branches per arborizing axon. The biochemical glycoengineering of the N-acyl side chain of sialic acid might be a promising approach for improving peripheral nerve regeneration.

  14. The time course of ongoing activity during neuritis and following axonal transport disruption.

    Science.gov (United States)

    Satkeviciute, Ieva; Goodwin, George; Bove, Geoffrey M; Dilley, Andrew

    2018-02-21

    Local nerve inflammation (neuritis) leads to ongoing activity and axonal mechanical sensitivity (AMS) along intact nociceptor axons, and disrupts axonal transport. This phenomenon forms the most feasible cause of radiating pain, such as sciatica. We have previously shown that axonal transport disruption without inflammation or degeneration also leads to AMS, but does not cause ongoing activity at the time point when AMS occurs, despite causing cutaneous hypersensitivity. However, there have been no systematic studies of ongoing activity during neuritis or non-inflammatory axonal transport disruption. In this study, we present the time course of ongoing activity from primary sensory neurons following neuritis and vinblastine-induced axonal transport disruption. Whereas 24% of C/slow Aδ-fiber neurons had ongoing activity during neuritis, few (disruption of axonal transport without inflammation does not lead to ongoing activity in sensory neurons, including nociceptors, but does cause a rapid and transient development of AMS. Since it is proposed that AMS underlies mechanically-induced radiating pain, and a transient disruption of axonal transport (as previously reported) leads to transient AMS, it follows that processes that disrupt axonal transport, such as neuritis, must persist to maintain AMS and the associated symptoms.

  15. Segregation of ipsilateral retinal ganglion cell axons at the optic chiasm requires the Shh receptor Boc.

    Science.gov (United States)

    Fabre, Pierre J; Shimogori, Tomomi; Charron, Frédéric

    2010-01-06

    The pattern of contralaterally and ipsilaterally projecting retinal ganglion cell (RGC) axons at the optic chiasm is essential for the establishment of binocular vision. Contralateral axons cross the chiasm midline as they progress from the optic nerve to the optic tract. In contrast, ipsilateral axons deviate from the chiasm and continue in the ipsilateral optic tract, avoiding the chiasm midline. The molecular mechanism underlying this phenomenon is not completely understood. Here we show that the Sonic Hedgehog (Shh) receptor Boc is enriched in ipsilateral RGCs of the developing retina. Together with the presence of Shh at the midline, this complementary expression pattern led us to hypothesize that Shh might repel ipsilateral RGC axons at the chiasm. Consistent with this hypothesis, we found that only Boc-positive RGC axons retract in vitro in response to Shh and that this response is lost in Boc mutant RGCs. In vivo, we show that Boc is required for the normal segregation of ipsilateral axons at the optic chiasm and, conversely, that Boc expression in contralateral RGCs prevents their axons from crossing the optic chiasm. Together, these results suggest that Shh repels ipsilateral RGC axons at the optic chiasm via its receptor Boc. This work identifies a novel molecular pathway required for the segregation of axons at the optic chiasm.

  16. Regeneración axonal posterior a lesiones traumáticas de médula espinal: Papel crítico de galectina-1

    Directory of Open Access Journals (Sweden)

    Héctor R Quintá

    2014-08-01

    Full Text Available Al producirse una lesión de médula espinal (LME, un sinnúmero de proteínas inhibidoras de la regeneración axonal ocupan el sitio de lesión en forma secuencial. La primer proteína en llegar al mismo se conoce como semaforina 3A (Sema3A, siendo además una de las más potentes por su acción de inhibir la regeneración axonal. A nivel mecanístico la unión de esta proteína al complejo-receptor neuronal neuropilin-1 (NRP-1/PlexinA4 evita que se produzca regeneración axonal. En este trabajo de revisión se discutirá la acción de galectin-1 (Gal-1, una proteína endógena de unión a glicanos, que selectivamente se une al complejo-receptor NRP-1/PlexinA4 de las neuronas lesionadas a través de un mecanismo dependiente de interacciones lectina-glicano, interrumpiendo la señalización generada por Sema3A y permitiendo de esta manera la regeneración axonal y recuperación locomotora luego de producirse la LME. Mientras ambas formas de Gal-1 (monomérica y dimérica contribuyen a la inactivación de la microglia, solo la forma dimérica de Gal-1 es capaz de unirse al complejo-receptor NRP-1/PlexinA4 y promover regeneración axonal. Por lo tanto, Gal-1 dimérica produce recuperación de las lesiones espinales interfiriendo en la señalización de Sema3A a través de la unión al complejo-receptor NRP-1/PlexinA4, sugiriendo el uso de esta lectina en su forma dimérica para el tratamiento de pacientes con LME.

  17. Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients.

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    Jan Jessen Krut

    Full Text Available Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL in CSF with a novel, sensitive method.With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL (marker of neuronal injury, neopterin (intrathecal immunoactivation and CSF/Plasma albumin ratio (blood-brain barrier integrity were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200, HIV-associated dementia (HAD (n = 14 and on combinations antiretroviral treatment (cART (n = 85, and healthy controls (n = 204. 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation.While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups.Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further

  18. Mechanisms of hyperpolarization in regenerated mature motor axons in cat

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Krarup, Christian

    2004-01-01

    We found persistent abnormalities in the recovery of membrane excitability in long-term regenerated motor nerve fibres in the cat as indicated in the companion paper. These abnormalities could partly be explained by membrane hyperpolarization. To further investigate this possibility, we compared...... the changes in excitability in control nerves and long-term regenerated cat nerves (3-5 years after tibial nerve crush) during manoeuvres known to alter axonal membrane Na(+)-K(+) pump function: polarization, cooling to 20 degrees C, reperfusion after 10 min ischaemia, and up to 60 s of repetitive stimulation...

  19. GENERACION DE TOLERANCIA A DEFICIT HIDRICO MEDIANTE LA REGULACION INDUCIDA DE LA SINTESIS DE TOCOFEROLES ENTABACO (NICOTIANA TABACUM L.)

    OpenAIRE

    ESPINOZA CONTRERAS, ANALIA ANTONELLA

    2013-01-01

    Los tocoferoles o vitamina E, son compuestos orgánicos esenciales que ayudan a proteger las membranas contra el daño oxidativo provocado por diversas condiciones de estrés ambientales. Diversos estudios han demostrado que las deficiencias de tocoferol pueden causar alteraciones en; la germinación, el transporte de fotoasimilados, un retardo del crecimiento y las respuestas propias frente al estrés abiótico. Con esto se puede inferir que los tocoferoles pueden influir en los procesos fisiológi...

  20. Organophosphate-induced delayed neuropathy: case report Neuropatia tardia por organofosforado: relato de caso

    Directory of Open Access Journals (Sweden)

    Luiz Felipe R Vasconcellos

    2002-12-01

    Full Text Available Organophosphate induced delayed neuropathy (OPIDN is an uncommon clinical condition. It occurs in association with the ingestion of great amounts of organophosphate after the stimulation of cholinergic receptor. The clinical picture is characterized by a distal paresis in lower limbs associated with sensitive symptoms. Electrodiagnostic studies show a motor axonal neuropathy. Involvement of the central nervous system may occur. We describe a 39 years-old female patient who developed hyperesthesia associated with lower limbs paresis, fourteen days after she had ingested a Dichlorvos-based insecticide. Electrophysiological study was characterized by an axonal polyneuropathy pattern. Pyramidal tract dysfunction was observed later in upper limbs. Considering that both peripheral and central nervous systems are involved we believe that the more appropriated term would be organophosphate induced delayed neuropathy (OPIDN instead of organophosphate induced delayed polyneuropathy (OPIDP.A neuropatia tardia dos organofosforados (NTOF é condição clinica incomum. Geralmente ocorre após a intoxicação aguda por organofosforados, seguindo-se a fase de hiperestimulação colinérgica. O quadro clínico é caracterizado por déficit motor distal nos membros inferiores associado a sintomas sensitivos. O estudo eletroneuromiográfico tem demonstrado padrão axonal motor na maioria dos casos. Podem ocorrer sinais de comprometimento do sistema nervoso central. Descrevemos o caso de uma paciente de 39 anos que ingeriu inseticida a base de Dichlorvos e quatorze dias após apresentou quadro de hiperestesia associado a paresia distal nos membros inferiores. Realizou eletroneuromiografia que se caracterizou por padrão compatível com polineuropatia axonal. Sinais piramidais, de aparecimento mais tardio, foram observados nos membros superiores. Diante do comprometimento do sistema nervoso periférico e central, também consideramos o termo neuropatia tardia por

  1. Relationship of acute axonal damage, Wallerian degeneration, and clinical disability in multiple sclerosis.

    Science.gov (United States)

    Singh, Shailender; Dallenga, Tobias; Winkler, Anne; Roemer, Shanu; Maruschak, Brigitte; Siebert, Heike; Brück, Wolfgang; Stadelmann, Christine

    2017-03-17

    Axonal damage and loss substantially contribute to the incremental accumulation of clinical disability in progressive multiple sclerosis. Here, we assessed the amount of Wallerian degeneration in brain tissue of multiple sclerosis patients in relation to demyelinating lesion activity and asked whether a transient blockade of Wallerian degeneration decreases axonal loss and clinical disability in a mouse model of inflammatory demyelination. Wallerian degeneration and acute axonal damage were determined immunohistochemically in the periplaque white matter of multiple sclerosis patients with early actively demyelinating lesions, chronic active lesions, and inactive lesions. Furthermore, we studied the effects of Wallerian degeneration blockage on clinical severity, inflammatory pathology, acute axonal damage, and long-term axonal loss in experimental autoimmune encephalomyelitis using Wallerian degeneration slow (Wld S ) mutant mice. The highest numbers of axons undergoing Wallerian degeneration were found in the perilesional white matter of multiple sclerosis patients early in the disease course and with actively demyelinating lesions. Furthermore, Wallerian degeneration was more abundant in patients harboring chronic active as compared to chronic inactive lesions. No co-localization of neuropeptide Y-Y1 receptor, a bona fide immunohistochemical marker of Wallerian degeneration, with amyloid precursor protein, frequently used as an indicator of acute axonal transport disturbance, was observed in human and mouse tissue, indicating distinct axon-degenerative processes. Experimentally, a delay of Wallerian degeneration, as observed in Wld S mice, did not result in a reduction of clinical disability or acute axonal damage in experimental autoimmune encephalomyelitis, further supporting that acute axonal damage as reflected by axonal transport disturbances does not share common molecular mechanisms with Wallerian degeneration. Furthermore, delaying Wallerian degeneration

  2. Gogo receptor contributes to retinotopic map formation and prevents R1-6 photoreceptor axon bundling.

    Directory of Open Access Journals (Sweden)

    Irina Hein

    Full Text Available BACKGROUND: Topographic maps form the basis of neural processing in sensory systems of both vertebrate and invertebrate species. In the Drosophila visual system, neighboring R1-R6 photoreceptor axons innervate adjacent positions in the first optic ganglion, the lamina, and thereby represent visual space as a continuous map in the brain. The mechanisms responsible for the establishment of retinotopic maps remain incompletely understood. RESULTS: Here, we show that the receptor Golden goal (Gogo is required for R axon lamina targeting and cartridge elongation in a partially redundant fashion with local guidance cues provided by neighboring axons. Loss of function of Gogo in large clones of R axons results in aberrant R1-R6 fascicle spacing. Gogo affects target cartridge selection only indirectly as a consequence of the disordered lamina map. Interestingly, small clones of gogo deficient R axons perfectly integrate into a proper retinotopic map suggesting that surrounding R axons of the same or neighboring fascicles provide complementary spatial guidance. Using single photoreceptor type rescue, we show that Gogo expression exclusively in R8 cells is sufficient to mediate targeting of all photoreceptor types in the lamina. Upon lamina targeting and cartridge selection, R axons elongate within their individual cartridges. Interestingly, here Gogo prevents bundling of extending R1-6 axons. CONCLUSION: Taken together, we propose that Gogo contributes to retinotopic map formation in the Drosophila lamina by controlling the distribution of R1-R6 axon fascicles. In a later developmental step, the regular position of R1-R6 axons along the lamina plexus is crucial for target cartridge selection. During cartridge elongation, Gogo allows R1-R6 axons to extend centrally in the lamina cartridge.

  3. N-cadherin regulates primary motor axon growth and branching during zebrafish embryonic development.

    Science.gov (United States)

    Brusés, Juan L

    2011-06-15

    N-cadherin is a classical type I cadherin that contributes to the formation of neural circuits by regulating growth cone migration and the formation of synaptic contacts. This study analyzed the role of N-cadherin in primary motor axons growth during development of the zebrafish (Danio rerio) embryo. After exiting the spinal cord, primary motor axons migrate ventrally through a common pathway and form the first neuromuscular junction with the muscle pioneer cells located at the horizontal myoseptum, which serves as a choice point for cell-type-specific pathway selection. Analysis of N-cadherin mutants (cdh2(hi3644Tg) ) and embryos injected with N-cadherin antisense morpholinos showed primary motor axons extending aberrant axonal branches at the choice point in ∼40% of the somitic hemisegments and an ∼150% increase in the number of branches per axon length within the ventral myotome. Analysis of individual axons trajectories showed that the caudal (CaP) and rostral (RoP) motor neurons axons formed aberrant branches at the choice point that abnormally extended in the rostrocaudal axis and ventrally to the horizontal myoseptum. Expression of a dominant-interfering N-cadherin cytoplasmic domain in primary motor neurons caused some axons to stall abnormally at the horizontal myoseptum and to impair their migration into the ventral myotome. However, in N-cadherin-depleted embryos, the majority of primary motor axons innervated their appropriate myotomal territories, indicating that N-cadherin regulates motor axon growth and branching without severely affecting the mechanisms that control axonal target selection. Copyright © 2011 Wiley-Liss, Inc.

  4. Plexin A3 and turnout regulate motor axonal branch morphogenesis in zebrafish.

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    Rajiv Sainath

    Full Text Available During embryogenesis motor axons navigate to their target muscles, where individual motor axons develop complex branch morphologies. The mechanisms that control axonal branching morphogenesis have been studied intensively, yet it still remains unclear when branches begin to form or how branch locations are determined. Live cell imaging of individual zebrafish motor axons reveals that the first axonal branches are generated at the ventral extent of the myotome via bifurcation of the growth cone. Subsequent branches are generated by collateral branching restricted to their synaptic target field along the distal portion of the axon. This precisely timed and spatially restricted branching process is disrupted in turnout mutants we identified in a forward genetic screen. Molecular genetic mapping positioned the turnout mutation within a 300 kb region encompassing eight annotated genes, however sequence analysis of all eight open reading frames failed to unambiguously identify the turnout mutation. Chimeric analysis and single cell labeling reveal that turnout function is required cell non-autonomously for intraspinal motor axon guidance and peripheral branch formation. turnout mutant motor axons form the first branch on time via growth cone bifurcation, but unlike wild-type they form collateral branches precociously, when the growth cone is still navigating towards the ventral myotome. These precocious collateral branches emerge along the proximal region of the axon shaft typically devoid of branches, and they develop into stable, permanent branches. Furthermore, we find that null mutants of the guidance receptor plexin A3 display identical motor axon branching defects, and time lapse analysis reveals that precocious branch formation in turnout and plexin A3 mutants is due to increased stability of otherwise short-lived axonal protrusions. Thus, plexin A3 dependent intrinsic and turnout dependent extrinsic mechanisms suppress collateral branch

  5. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

    Science.gov (United States)

    Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Gingras, Marie-Claude; Muthuswamy, Lakshmi B; Johns, Amber L; Miller, David K; Wilson, Peter J; Patch, Ann-Marie; Wu, Jianmin; Chang, David K; Cowley, Mark J; Gardiner, Brooke B; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J; Gill, Anthony J; Pinho, Andreia V; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R Scott; Humphris, Jeremy L; Kaplan, Warren; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chou, Angela; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Daly, Roger J; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M; Fisher, William E; Brunicardi, F Charles; Hodges, Sally E; Reid, Jeffrey G; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R; Dinh, Huyen; Buhay, Christian J; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E; Yung, Christina K; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A; Petersen, Gloria M; Gallinger, Steven; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A; Mann, Karen M; Jenkins, Nancy A; Perez-Mancera, Pedro A; Adams, David J; Largaespada, David A; Wessels, Lodewyk F A; Rust, Alistair G; Stein, Lincoln D; Tuveson, David A; Copeland, Neal G; Musgrove, Elizabeth A; Scarpa, Aldo; Eshleman, James R; Hudson, Thomas J; Sutherland, Robert L; Wheeler, David A; Pearson, John V; McPherson, John D; Gibbs, Richard A; Grimmond, Sean M

    2012-11-15

    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

  6. Imaging findings in diffuse axonal injury after closed head trauma

    Energy Technology Data Exchange (ETDEWEB)

    Parizel, P.M.; Oezsarlak, Oe.; Goethem, J.W. van; Hauwe, L. van den; Schepper, A.M. de [Department of Radiology, Universitair Ziekenhuis Antwerpen (University of Antwerp), Edegem (Belgium); Dillen, C.; Cosyns, P. [Department of Psychiatry, Universitair Ziekenhuis Antwerpen (University of Antwerp), Edegem (Belgium); Verlooy, J. [Department of Neurosurgery, Universitair Ziekenhuis Antwerpen (University of Antwerp), Edegem (Belgium)

    1998-07-01

    Even in patients with closed head trauma, brain parenchyma can be severely injured due to disruption of axonal fibers by shearing forces during acceleration, deceleration, and rotation of the head. In this article we review the spectrum of imaging findings in patients with diffuse axonal injuries (DAI) after closed head trauma. Knowledge of the location and imaging characteristics of DAI is important to radiologists for detection and diagnosis. Common locations of DAI include: cerebral hemispheric gray-white matter interface and subcortical white matter, body and splenium of corpus callosum, basal ganglia, dorsolateral aspect of brainstem, and cerebellum. In the acute phase, CT may show punctate hemorrhages. The true extent of brain involvement is better appreciated with MR imaging, because both hemorrhagic and non-hemorrhagic lesions (gliotic scars) can be detected. The MR appearance of DAI lesions depends on several factors, including age of injury, presence of hemorrhage or blood-breakdown products (e. g., hemosiderin), and type of sequence used. Technical aspects in MR imaging of these patients are discussed. Non-hemorrhagic lesions can be detected with fluid attenuated inversion recovery (FLAIR), proton-density-, or T2-weighted images, whereas gradient echo sequences with long TE increase the visibility of old hemorrhagic lesions. (orig.) With 12 figs., 12 refs.

  7. Rapid signaling in distinct dopaminergic axons during locomotion and reward

    Science.gov (United States)

    Howe, MW; Dombeck, DA

    2016-01-01

    Summary Dopaminergic projections from the midbrain to striatum are critical for motor control, as their degeneration in Parkinson’s disease results in profound movement deficits. Paradoxically, most recording methods report rapid phasic dopamine signaling (~100ms bursts) to unpredicted rewards, with little evidence for movement-related signaling. The leading model posits that phasic signaling in striatum targeting dopamine neurons drive reward-based learning, while slow variations in firing (tens of seconds to minutes) in these same neurons bias animals towards or away from movement. However, despite widespread acceptance of this model, current methods have provided little evidence to support or refute it. Here, using new optical recording methods, we report the discovery of rapid phasic signaling in striatum-targeting dopaminergic axons that was associated with, and capable of triggering, locomotion in mice. Axons expressing these signals were largely distinct from those signaling during unexpected rewards. These results suggest that dopaminergic neuromodulation can differentially impact motor control and reward learning with sub-second precision and suggest that both precise signal timing and neuronal subtype are important parameters to consider in the treatment of dopamine-related disorders. PMID:27398617

  8. Influencia mutua de la deformación y composición química sobre la precipitación inducida en aceros microaleados

    Directory of Open Access Journals (Sweden)

    Quispe, A.

    2005-12-01

    Full Text Available By means of torsion tests and applying the "back extrapolation" method, the static recrystallization kinetics in microalloyed steels with vanadium (V, niobium (Nb and titanium (Ti has been determined and, recrystallization-precipitation-time-temperature (RPTT diagrams have been plotted also graphically, which show the Recrystallization- Precipitation interaction. These diagrams show that the effect of the deformation on the precipitation kinetics depends of the microalloy content. In this sense, a new expression is proposed to relate the influence of the deformation and the chemical composition on the minimum incubation of the precipitation kinetics.

    Mediante ensayos de torsión y usando el método back extrapolation se ha determinado la cinética de recristalización estática de aceros microaleados con vanadio (V, niobio (Nb y titanio (Ti y, a partir de las mismas, ha sido posible dibujar los diagramas recristalizaciónprecipitación- tiempo-temperatura (RPTT, que muestran gráficamente la interacción recristalización-precipitación. Estos diagramas muestran que el efecto de la deformación en la cinética de precipitación depende del contenido de microaleante. En este sentido, se propone una nueva expresión para relacionar la influencia de la deformación y del contenido de microaleante sobre el periodo mínimo de incubación de la precipitación inducida.

  9. The Kinesin Adaptor Calsyntenin-1 Organizes Microtubule Polarity and Regulates Dynamics during Sensory Axon Arbor Development

    Directory of Open Access Journals (Sweden)

    Mary C. Halloran

    2017-04-01

    Full Text Available Axon growth and branching, and development of neuronal polarity are critically dependent on proper organization and dynamics of the microtubule (MT cytoskeleton. MTs must organize with correct polarity for delivery of diverse cargos to appropriate subcellular locations, yet the molecular mechanisms regulating MT polarity remain poorly understood. Moreover, how an actively branching axon reorganizes MTs to direct their plus ends distally at branch points is unknown. We used high-speed, in vivo imaging of polymerizing MT plus ends to characterize MT dynamics in developing sensory axon arbors in zebrafish embryos. We find that axonal MTs are highly dynamic throughout development, and that the peripheral and central axons of sensory neurons show differences in MT behaviors. Furthermore, we show that Calsyntenin-1 (Clstn-1, a kinesin adaptor required for sensory axon branching, also regulates MT polarity in developing axon arbors. In wild type neurons the vast majority of MTs are directed in the correct plus-end-distal orientation from early stages of development. Loss of Clstn-1 causes an increase in MTs polymerizing in the retrograde direction. These misoriented MTs most often are found near growth cones and branch points, suggesting Clstn-1 is particularly important for organizing MT polarity at these locations. Together, our results suggest that Clstn-1, in addition to regulating kinesin-mediated cargo transport, also organizes the underlying MT highway during axon arbor development.

  10. The role of mitochondria in axonal degeneration and tissue repair in MS

    NARCIS (Netherlands)

    van Horssen, J.; Witte, M.E.; Ciccarelli, O.

    2012-01-01

    Axonal injury is a key feature of multiple sclerosis (MS) pathology and is currently seen as the main correlate for permanent clinical disability. Although little is known about the pathogenetic mechanisms that drive axonal damage and loss, there is accumulating evidence highlighting the central

  11. Structure and Function of an Actin-Based Filter in the Proximal Axon

    Directory of Open Access Journals (Sweden)

    Varuzhan Balasanyan

    2017-12-01

    Full Text Available Summary: The essential organization of microtubules within neurons has been described; however, less is known about how neuronal actin is arranged and the functional implications of its arrangement. Here, we describe, in live cells, an actin-based structure in the proximal axon that selectively prevents some proteins from entering the axon while allowing the passage of others. Concentrated patches of actin in proximal axons are present shortly after axonal specification in rat and zebrafish neurons imaged live, and they mark positions where anterogradely traveling vesicles carrying dendritic proteins halt and reverse. Patches colocalize with the ARP2/3 complex, and when ARP2/3-mediated nucleation is blocked, a dendritic protein mislocalizes to the axon. Patches are highly dynamic, with few persisting longer than 30 min. In neurons in culture and in vivo, actin appears to form a contiguous, semipermeable barrier, despite its apparently sparse distribution, preventing axonal localization of constitutively active myosin Va but not myosin VI. : Balasanyan et al. find dynamic patches of actin in proximal axons of live neurons, mature and newly differentiated, in culture and in vivo. Patches contribute to a filter that sequesters some proteins within the somatodendritic domain while allowing others to pass into the axon, leading to polarized localization of proteins.

  12. The progeroid gene BubR1 regulates axon myelination and motor function

    NARCIS (Netherlands)

    Choi, C.I.; Yoo, K.H.; Hussaini, S.M.; Jeon, B.T.; Welby, J.; Gan, H.; Scarisbrick, I.A.; Zhang, Z.; Baker, D.J.; Deursen, J.M.A. van; Rodriguez, M.; Jang, M.H.

    2016-01-01

    Myelination, the process by which oligodendrocytes form the myelin sheath around axons, is key to axonal signal transduction and related motor function in the central nervous system (CNS). Aging is characterized by degenerative changes in the myelin sheath, although the molecular underpinnings of

  13. Modeling of the axon membrane skeleton structure and implications for its mechanical properties.

    Directory of Open Access Journals (Sweden)

    Yihao Zhang

    2017-02-01

    Full Text Available Super-resolution microscopy recently revealed that, unlike the soma and dendrites, the axon membrane skeleton is structured as a series of actin rings connected by spectrin filaments that are held under tension. Currently, the structure-function relationship of the axonal structure is unclear. Here, we used atomic force microscopy (AFM to show that the stiffness of the axon plasma membrane is significantly higher than the stiffnesses of dendrites and somata. To examine whether the structure of the axon plasma membrane determines its overall stiffness, we introduced a coarse-grain molecular dynamics model of the axon membrane skeleton that reproduces the structure identified by super-resolution microscopy. Our proposed computational model accurately simulates the median value of the Young's modulus of the axon plasma membrane determined by atomic force microscopy. It also predicts that because the spectrin filaments are under entropic tension, the thermal random motion of the voltage-gated sodium channels (Nav, which are bound to ankyrin particles, a critical axonal protein, is reduced compared to the thermal motion when spectrin filaments are held at equilibrium. Lastly, our model predicts that because spectrin filaments are under tension, any axonal injuries that lacerate spectrin filaments will likely lead to a permanent disruption of the membrane skeleton due to the inability of spectrin filaments to spontaneously form their initial under-tension configuration.

  14. Axonal and presynaptic protein synthesis: new insights into the biology of the neuron

    NARCIS (Netherlands)

    Giuditta, A.; Kaplan, B.B.; van Minnen, J.; Alvarez, J.; Koenig, E.

    2002-01-01

    The presence of a local mRNA translation system in axons and terminals was proposed almost 40 years ago. Over the ensuing period, an impressive body of evidence has grown to support this proposal - yet the nerve cell body is still considered to be the only source of axonal and presynaptic proteins.

  15. Blast overpressure induced axonal injury changes in rat brainstem and spinal cord

    Directory of Open Access Journals (Sweden)

    Srinivasu Kallakuri

    2015-01-01

    Full Text Available Introduction: Blast induced neurotrauma has been the signature wound in returning soldiers from the ongoing wars in Iraq and Afghanistan. Of importance is understanding the pathomechansim(s of blast overpressure (OP induced axonal injury. Although several recent animal models of blast injury indicate the neuronal and axonal injury in various brain regions, animal studies related to axonal injury in the white matter (WM tracts of cervical spinal cord are limited. Objective: The purpose of this study was to assess the extent of axonal injury in WM tracts of cervical spinal cord in male Sprague Dawley rats subjected to a single insult of blast OP. Materials and Methods: Sagittal brainstem sections and horizontal cervical spinal cord sections from blast and sham animals were stained by neurofilament light (NF-L chain and beta amyloid precursor protein immunocytochemistry and observed for axonal injury changes. Results: Observations from this preliminary study demonstrate axonal injury changes in the form of prominent swellings, retraction bulbs, and putative signs of membrane disruptions in the brainstem and cervical spinal cord WM tracts of rats subjected to blast OP. Conclusions: Prominent axonal injury changes following the blast OP exposure in brainstem and cervical spinal WM tracts underscores the need for careful evaluation of blast induced injury changes and associated symptoms. NF-L immunocytochemistry can be considered as an additional tool to assess the blast OP induced axonal injury.

  16. A high mitochondrial transport rate characterizes CNS neurons with high axonal regeneration capacity.

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    Romain Cartoni

    Full Text Available Improving axonal transport in the injured and diseased central nervous system has been proposed as a promising strategy to improve neuronal repair. However, the contribution of each cargo to the repair mechanism is unknown. DRG neurons globally increase axonal transport during regeneration. Because the transport of specific cargos after axonal insult has not been examined systematically in a model of enhanced regenerative capacity, it is unknown whether the transport of all cargos would be modulated equally in injured central nervous system neurons. Here, using a microfluidic culture system we compared neurons co-deleted for PTEN and SOCS3, an established model of high axonal regeneration capacity, to control neurons. We measured the axonal transport of three cargos (mitochondria, synaptic vesicles and late endosomes in regenerating axons and found that the transport of mitochondria, but not the other cargos, was increased in PTEN/SOCS3 co-deleted axons relative to controls. The results reported here suggest a pivotal role for this organelle during axonal regeneration.

  17. Schwann Cell and Axon: An Interlaced Unit-From Action Potential to Phenotype Expression.

    Science.gov (United States)

    Court, Felipe A; Alvarez, Jaime

    2016-01-01

    Here we propose a model of a peripheral axon with a great deal of autonomy from its cell body-the autonomous axon-but with a substantial dependence on its ensheathing Schwann cell (SC), the axon-SC unit. We review evidence in several fields and show that (i) axons can extend sprouts and grow without the concurrence of the cell body, but regulated by SCs; (ii) axons synthesize their proteins assisted by SCs that supply them with ribosomes and, probably, with mRNAs by way of exosomes; (iii) the molecular organization of the axoplasm, i.e., its phenotype, is regulated by the SC, as illustrated by the axonal microtubular content, which is down-regulated by the SC; and (iv) the axon has a program for self-destruction that is boosted by the SC. The main novelty of this model axon-SC unit is that it breaks with the notion that all proteins of the nerve cell are specified by its own nucleus. The notion of a collaborative specification of the axoplasm by more than one nucleus, which we present here, opens a new dimension in the understanding of the nervous system in health and disease and is also a frame of reference to understand other tissues or cell associations.

  18. N-docosahexaenoylethanolamine regulates Hedgehog signaling and promotes growth of cortical axons

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    Giorgi Kharebava

    2015-12-01

    Full Text Available Axonogenesis, a process for the establishment of neuron connectivity, is central to brain function. The role of metabolites derived from docosahexaenoic acid (DHA, 22:6n-3 that is specifically enriched in the brain, has not been addressed in axon development. In this study, we tested if synaptamide (N-docosahexaenoylethanolamine, an endogenous metabolite of DHA, affects axon growth in cultured cortical neurons. We found that synaptamide increased the average axon length, inhibited GLI family zinc finger 1 (GLI1 transcription and sonic hedgehog (Shh target gene expression while inducing cAMP elevation. Similar effects were produced by cyclopamine, a regulator of the Shh pathway. Conversely, Shh antagonized elevation of cAMP and blocked synaptamide-mediated increase in axon length. Activation of Shh pathway by a smoothened (SMO agonist (SAG or overexpression of SMO did not inhibit axon growth mediated by synaptamide or cyclopamine. Instead, adenylate cyclase inhibitor SQ22536 abolished synaptamide-mediated axon growth indicating requirement of cAMP elevation for this process. Our findings establish that synaptamide promotes axon growth while Shh antagonizes synaptamide-mediated cAMP elevation and axon growth by a SMO-independent, non-canonical pathway.

  19. Organophosphate-Related Alterations in Myelin and Axonal Transport in the Living Mammalian Brain

    Science.gov (United States)

    2014-10-01

    510. Duncan JE, Goldstein LS. 2006. The Genetics of Axonal Transport and Axonal Transport Disorders PLoS Genet . 2(9): e124. 25 Duysen EG, Li...Gitajn L, Rea W, Yang Y, Stein EA.2007. Cocaine -induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI

  20. Misdirection and guidance of regenerating axons after experimental nerve injury and repair

    NARCIS (Netherlands)

    de Ruiter, Godard C W; Spinner, Robert J; Verhaagen, J.; Malessy, Martijn J A

    Misdirection of regenerating axons is one of the factors that can explain the limited results often found after nerve injury and repair. In the repair of mixed nerves innervating different distal targets (skin and muscle), misdirection may, for example, lead to motor axons projecting toward skin,

  1. Misdirection and guidance of regenerating axons after experimental nerve injury and repair A review

    NARCIS (Netherlands)

    Ruiter, G.C.W.; Spinner, R.J.; Verhaagen, J.; Malessay, M.J.A.

    2014-01-01

    Misdirection of regenerating axons is one of the factors that can explain the limited results often found after nerve injury and repair. In the repair of mixed nerves innervating different distal targets (skin and muscle), misdirection may, for example, lead to motor axons projecting toward skin,

  2. Misdirection and guidance of regenerating motor axons after experimental nerve injury and repair

    NARCIS (Netherlands)

    Ruiter, Godard de

    2013-01-01

    Misdirection of regenerating motor axons is one of the factors that can explain the disappointing recovery of function often observed after nerve injury and repair. In the first part of this thesis we quantified misdirection of motor axon regeneration after different types of nerve injury and repair

  3. Frizzled3 controls axonal polarity and intermediate target entry during striatal pathway development

    NARCIS (Netherlands)

    Morello, Francesca; Prasad, Asheeta A.; Rehberg, Kati; Baptista Vieira de Sá, Renata; Antón-Bolaños, Noelia; Leyva-Diaz, Eduardo; Adolfs, Youri; Tissir, Fadel; López-Bendito, Guillermina; Pasterkamp, R. Jeroen

    2015-01-01

    The striatum is a large brain nucleus with an important role in the control of movement and emotions.Mediumspiny neurons (MSNs) are striatal output neurons forming prominent descending axon tracts that target different brain nuclei. However, how MSN axon tracts in the forebrain develop remains

  4. Axon-somatic back-propagation in detailed models of spinal alpha motoneurons

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    Pietro eBalbi

    2015-02-01

    Full Text Available Antidromic action potentials following distal stimulation of motor axons occasionally fail to invade the soma of alpha motoneurons in spinal cord, due to their passing through regions of high non-uniformity.Morphologically detailed conductance-based models of cat spinal alpha motoneurons have been developed, with the aim to reproduce and clarify some aspects of the electrophysiological behavior of the antidromic axon-somatic spike propagation. Fourteen 3D morphologically detailed somata and dendrites of cat spinal alpha motoneurons have been imported from an open-access web-based database of neuronal morphologies, NeuroMorpho.org, and instantiated in neurocomputational models. An axon hillock, an axonal initial segment and a myelinated axon are added to each model.By sweeping the diameter of the axonal initial segment (AIS and the axon hillock, as well as the maximal conductances of sodium channels at the AIS and at the soma, the developed models are able to show the relationships between different geometric and electrophysiological configurations and the voltage attenuation of the antidromically travelling wave.In particular, a greater than usually admitted sodium conductance at AIS is necessary and sufficient to overcome the dramatic voltage attenuation occurring during antidromic spike propagation both at the myelinated axon-AIS and at the AIS-soma transitions.

  5. Axonal remodeling in the corticospinal tract after stroke: how does rehabilitative training modulate it?

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    Naohiko Okabe

    2017-01-01

    Full Text Available Stroke causes long-term disability, and rehabilitative training is commonly used to improve the consecutive functional recovery. Following brain damage, surviving neurons undergo morphological alterations to reconstruct the remaining neural network. In the motor system, such neural network remodeling is observed as a motor map reorganization. Because of its significant correlation with functional recovery, motor map reorganization has been regarded as a key phenomenon for functional recovery after stroke. Although the mechanism underlying motor map reorganization remains unclear, increasing evidence has shown a critical role for axonal remodeling in the corticospinal tract. In this study, we review previous studies investigating axonal remodeling in the corticospinal tract after stroke and discuss which mechanisms may underlie the stimulatory effect of rehabilitative training. Axonal remodeling in the corticospinal tract can be classified into three types based on the location and the original targets of corticospinal neurons, and it seems that all the surviving corticospinal neurons in both ipsilesional and contralesional hemisphere can participate in axonal remodeling and motor map reorganization. Through axonal remodeling, corticospinal neurons alter their output selectivity from a single to multiple areas to compensate for the lost function. The remodeling of the corticospinal axon is influenced by the extent of tissue destruction and promoted by various therapeutic interventions, including rehabilitative training. Although the precise molecular mechanism underlying rehabilitation-promoted axonal remodeling remains elusive, previous data suggest that rehabilitative training promotes axonal remodeling by upregulating growth-promoting and downregulating growth-inhibiting signals.

  6. Neurobiology of axonal transport defects in motor neuron diseases: Opportunities for translational research?

    Science.gov (United States)

    De Vos, Kurt J; Hafezparast, Majid

    2017-09-01

    Intracellular trafficking of cargoes is an essential process to maintain the structure and function of all mammalian cell types, but especially of neurons because of their extreme axon/dendrite polarisation. Axonal transport mediates the movement of cargoes such as proteins, mRNA, lipids, membrane-bound vesicles and organelles that are mostly synthesised in the cell body and in doing so is responsible for their correct spatiotemporal distribution in the axon, for example at specialised sites such as nodes of Ranvier and synaptic terminals. In addition, axonal transport maintains the essential long-distance communication between the cell body and synaptic terminals that allows neurons to react to their surroundings via trafficking of for example signalling endosomes. Axonal transport defects are a common observation in a variety of neurodegenerative diseases, and mutations in components of the axonal transport machinery have unequivocally shown that impaired axonal transport can cause neurodegeneration (reviewed in El-Kadi et al., 2007, De Vos et al., 2008; Millecamps and Julien, 2013). Here we review our current understanding of axonal transport defects and the role they play in motor neuron diseases (MNDs) with a specific focus on the most common form of MND, amyotrophic lateral sclerosis (ALS). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Sensory axon-derived neuregulin-1 is required for axoglial signaling and normal sensory function but not for long-term axon maintenance

    DEFF Research Database (Denmark)

    Fricker, F.R.; Zhu, N.; Tsantoulas, C.

    2009-01-01

    Neuregulin-1 has a key role in mediating signaling between axons and Schwann cells during development. A limitation to studying its role in adulthood is the embryonic lethality of global Nrg1 gene deletion. We used the Cre-loxP system to generate transgenic mice in which neuregulin-1 is condition......Neuregulin-1 has a key role in mediating signaling between axons and Schwann cells during development. A limitation to studying its role in adulthood is the embryonic lethality of global Nrg1 gene deletion. We used the Cre-loxP system to generate transgenic mice in which neuregulin-1...... is conditionally ablated in the majority of small-diameter and a proportion of large-diameter sensory neurons that have axons conducting in the C- and Adelta-fiber range, respectively. Sensory neuron-specific neuregulin-1 ablation resulted in abnormally large Remak bundles with axons clustered in "polyaxonal...... cells required for normal sensory function. Sensory neuronal survival and axonal maintenance, however, are not dependent on axon-derived neuregulin-1 signaling in adulthood Udgivelsesdato: 2009/6/17...

  8. Intra-axonal Synthesis of SNAP25 Is Required for the Formation of Presynaptic Terminals

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    Andreia F.R. Batista

    2017-09-01

    Full Text Available Localized protein synthesis is a mechanism for developing axons to react acutely and in a spatially restricted manner to extracellular signals. As such, it is important for many aspects of axonal development, but its role in the formation of presynapses remains poorly understood. We found that the induced assembly of presynaptic terminals required local protein synthesis. Newly synthesized proteins were detectable at nascent presynapses within 15 min of inducing synapse formation in isolated axons. The transcript for the t-SNARE protein SNAP25, which is required for the fusion of synaptic vesicles with the plasma membrane, was recruited to presynaptic sites and locally translated. Inhibition of intra-axonal SNAP25 synthesis affected the clustering of SNAP25 and other presynaptic proteins and interfered with the release of synaptic vesicles from presynaptic sites. This study reveals a critical role for the axonal synthesis of SNAP25 in the assembly of presynaptic terminals.

  9. JMJD-1.2/PHF8 controls axon guidance by regulating Hedgehog-like signaling

    DEFF Research Database (Denmark)

    Riveiro, Alba; Mariani, Luca; Malmberg, Kim Emily

    2017-01-01

    Components of the KDM7 family of histone demethylases are implicated in neuronal development and one member, PHF8, is often found to be mutated in cases of X-linked mental retardation. However, how PHF8 regulates neurodevelopmental processes and contributes to the disease is still largely unknown...... the axonal defects. Deficiency of either wrt-8 or grl-16, or reduced expression of homologs of genes promoting Hedgehog signaling, restores correct axon guidance in jmjd-1.2 mutants. Genetic and overexpression data indicate that Hedgehog-related genes act on axon guidance through actin remodelers. Thus, our...... study highlights a novel function of jmjd-1.2 in axon guidance that might be relevant for the onset of X-linked mental retardation and provides compelling evidence of a conserved function of the Hedgehog pathway in C. elegans axon migration....

  10. Lost in the jungle: new hurdles for optic nerve axon regeneration.

    Science.gov (United States)

    Pernet, Vincent; Schwab, Martin E

    2014-07-01

    The poor regenerative capacity of injured central nervous system (CNS) axons leads to permanent neurological deficits after brain, spinal cord, or optic nerve lesions. In the optic nerve, recent studies showed that stimulation of the cytokine or mammalian target of rapamycin (mTOR) signaling pathways potently enhances sprouting and regeneration of injured retinal ganglion cell axons in adult mice, but does not allow the majority of axons to reach their main cerebral targets. New analyses have revealed axon navigation defects in the optic nerve and at the optic chiasm under conditions of strong growth stimulation. We propose that a balanced growth stimulatory treatment will have to be combined with guidance factors and suppression of local growth inhibitory factors to obtain the full regeneration of long CNS axonal tracts. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay

    DEFF Research Database (Denmark)

    Colak, Dilek; Ji, Sheng-Jian; Porse, Bo T

    2013-01-01

    Growth cones enable axons to navigate toward their targets by responding to extracellular signaling molecules. Growth-cone responses are mediated in part by the local translation of axonal messenger RNAs (mRNAs). However, the mechanisms that regulate local translation are poorly understood. Here we...... show that Robo3.2, a receptor for the Slit family of guidance cues, is synthesized locally within axons of commissural neurons. Robo3.2 translation is induced by floor-plate-derived signals as axons cross the spinal cord midline. Robo3.2 is also a predicted target of the nonsense-mediated mRNA decay.......2 expression. These data show that local translation is regulated by mRNA stability and that NMD acts locally to influence axonal pathfinding....

  12. PACSIN1, a Tau-interacting protein, regulates axonal elongation and branching by facilitating microtubule instability.

    Science.gov (United States)

    Liu, Yingying; Lv, Kaosheng; Li, Zenglong; Yu, Albert C H; Chen, Jianguo; Teng, Junlin

    2012-11-16

    Tau is a major member of the neuronal microtubule-associated proteins. It promotes tubulin assembly and stabilizes axonal microtubules. Previous studies have demonstrated that Tau forms cross-bridges between microtubules, with some particles located on cross-bridges, suggesting that some proteins interact with Tau and might be involved in regulating Tau-related microtubule dynamics. This study reports that PACSIN1 interacts with Tau in axon. PACSIN1 blockade results in impaired axonal elongation and a higher number of primary axonal branches in mouse dorsal root ganglia neurons, which is induced by increasing the binding ability of Tau to microtubules. In PACSIN1-blocked dorsal root ganglia neurons, a greater amount of Tau is inclined to accumulate in the central domain of growth cones, and it promotes the stability of the microtubule network. Taken together, these results suggest that PACSIN1 is an important Tau binding partner in regulating microtubule dynamics and forming axonal plasticity.

  13. Axonal sprouting regulates myelin basic protein gene expression in denervated mouse hippocampus

    DEFF Research Database (Denmark)

    Jensen, M B; Poulsen, F R; Finsen, B

    2000-01-01

    to 35 days after transection of the entorhino-hippocampal perforant path axonal projection. In situ hybridization analysis showed that anterograde axonal and terminal degeneration lead to upregulated oligodendrocyte MBP mRNA expression starting between day 2 and day 4, in (1) the deep part of stratum...... axonal and terminal degeneration, myelin degenerative changes, microglial activation and axotomi-induced axonal sprouting. Oligodendrocyte MBP mRNA expression reached maximum in both these areas at day 7. MBP gene transcription remained constant in stratum radiatum, stratum pyramidale and stratum oriens...... of CA1, areas that were unaffected by perforant path transection. These results provide strong evidence that oligodendrocyte MBP gene expression can be regulated by axonal sprouting independently of microglial activation in the injured adult CNS....

  14. Activity-dependent myelination of parvalbumin interneurons mediated by axonal morphological plasticity.

    Science.gov (United States)

    Stedehouder, J; Brizee, D; Shpak, G; Kushner, S A

    2018-03-05

    Axonal myelination of neocortical pyramidal neurons is dynamically modulated by neuronal activity. Recent studies have shown that a substantial proportion of neocortical myelin content is contributed by fast-spiking, parvalbumin (PV)-positive interneurons. However, it remains unknown whether the myelination of PV + interneurons is also modulated by intrinsic activity. Here, we utilized cell-type specific Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in adult male and female mice to activate a sparse population of medial prefrontal cortex PV + interneurons. Using single-cell axonal reconstructions, we find that DREADD-stimulated PV + interneurons exhibit a nearly two-fold increase in total length of myelination, predominantly mediated by a parallel increase of axonal arborization and number of internodes. In contrast, the distribution of axonal inter-branch segment distance and myelin internode length were not significantly altered. Topographical analysis revealed that myelination of DREADD-stimulated cells extended to higher axonal branch orders, while retaining a similar inter-branch distance threshold for myelination. Together, our results demonstrate that chemogenetically-induced neuronal activity increases the myelination of neocortical PV + interneurons mediated at least in part by an elaboration of their axonal morphology. SIGNIFICANCE STATEMENT Myelination is the wrapping of an axon in order to optimize conduction velocity in an energy-efficient manner. Previous studies have shown that myelination of neocortical pyramidal neurons is experience and activity-dependent. We now show that activity-dependent myelin plasticity in the adult neocortex extends to parvalbumin-expressing fast-spiking interneurons. Specifically, chemogenetic stimulation of parvalbumin interneurons in the medial prefrontal cortex significantly enhanced axonal myelination, which was paralleled by an increase in axonal arborization. This suggests that activity

  15. Axon Counts Yield Multiple Options for Triceps Fascicular Nerve to Axillary Nerve Transfer.

    Science.gov (United States)

    Khair, M Michael; Schreiber, Joseph J; Rosenblatt, Lauren; Byun, David J; Lee, Steve K; Wolfe, Scott W

    2016-11-01

    To evaluate the relative axonal match between potential donor and recipient nerves, so that maximal reinnervation potential may be reached with the least chance of donor site morbidity. In 10 fresh-frozen cadaveric specimens, the main trunk and anterior, posterior, sensory and teres minor branches of the axillary nerve were identified, as were the radial nerve branches to the long, medial, and lateral heads of the triceps. The swing distances of the triceps fascicular nerve branches and the axillary nerve branches relative to the inferior border of the teres major muscle were recorded. Histomorphological analysis and axon counts were performed on sections of each branch. The median number of axons in the main axillary trunk was 7,887, with 4,052, 1,242, and 1,161 axons in the anterior, posterior, and teres minor branches, respectively. All specimens had a single long head triceps branch (median, 2,302 axons), a range of 1 to 3 branches to the medial head of the triceps (composite axon count, 2,198 axons), and 1 to 3 branches to the lateral head of the triceps (composite average, 1,462 axons). The medial and lateral head branches had sufficient swing distance to reach the anterior branch of the axillary nerve in all 10 specimens, with only 4 specimens having adequate long head branch swing distances. It is anatomically feasible to transfer multiple branches of the radial nerve supplying the medial, lateral, and sometimes, long head of the triceps to all branches of the axillary nerve in an attempt to reinnervate the deltoid and teres minor muscles. Understanding the axon counts of the different possible transfer combinations will improve operative flexibility and enable peripheral nerve surgeons to reinnervate for both abduction and external rotation with the highest donor/recipient axon count ratios. Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  16. Dorsal column sensory axons degenerate due to impaired microvascular perfusion after spinal cord injury in rats

    Science.gov (United States)

    Muradov, Johongir M.; Ewan, Eric E.; Hagg, Theo

    2013-01-01

    The mechanisms contributing to axon loss after spinal cord injury (SCI) are largely unknown but may involve microvascular loss as we have previously suggested. Here, we used a mild contusive injury (120 kdyn IH impactor) at T9 in rats focusing on ascending primary sensory dorsal column axons, anterogradely traced from the sciatic nerves. The injury caused a rapid and progressive loss of dorsal column microvasculature and oligodendrocytes at the injury site and penumbra and a ~70% loss of the sensory axons, by 24 hours. To model the microvascular loss, focal ischemia of the T9 dorsal columns was achieved via phototoxic activation of intravenously injected rose bengal. This caused an ~53% loss of sensory axons and an ~80% loss of dorsal column oligodendrocytes by 24 hours. Axon loss correlated with the extent and axial length of microvessel and oligodendrocyte loss along the dorsal column. To determine if oligodendrocyte loss contributes to axon loss, the glial toxin ethidium bromide (EB; 0.3 µg/µl) was microinjected into the T9 dorsal columns, and resulted in an ~88% loss of dorsal column oligodendrocytes and an ~56% loss of sensory axons after 72 hours. EB also caused an ~72% loss of microvessels. Lower concentrations of EB resulted in less axon, oligodendrocyte and microvessel loss, which were highly correlated (R2 = 0.81). These data suggest that focal spinal cord ischemia causes both oligodendrocyte and axon degeneration, which are perhaps linked. Importantly, they highlight the need of limiting the penumbral spread of ischemia and oligodendrocyte loss after SCI in order to protect axons. PMID:23978615

  17. Efecto citoprotector y antisecretor del aceite de Copaifera officinalis en lesiones gástricas inducidas en ratas

    Directory of Open Access Journals (Sweden)

    Jorge Arroyo

    2009-06-01

    Full Text Available Objetivos: Demostrar el efecto gastroprotector del aceite de Copaifera officinalis usando indometacina y ligadura de píloro en ratas. Diseño: Estudio preclínico. Lugar: Facultades de Medicina, de Farmacia y Bioquímica. Universidad Nacional Mayor de San Marcos, Lima, Perú. Material biológico: Ratas y aceite de copaiba. Intervenciones: Se colectó el aceite de copaiba en Ucayali, Pucallpa. La citoproteccción fue evaluada con indometacina, considerando un grupo control normal, indometacina, grupos de aceite de copaiba y omeprazol. Las lesiones de la mucosa gástrica fueron calificadas como las compatibles con necrosis local (tejido no viable, hiperemia, enrojecimiento presente y hemorragia, empleando la escala de puntaje observacional; y la úlcera, según la escala de Macallister modificado. El ensayo de antisecreción fue realizado por el modelo de ligadura del píloro, en el que 24 ratas albinas fueron divididas al azar en 3 grupos; un control, otro de aceite de copaiba 40mg/kg y un tercero de omeprazol 10 mg/kg. Después de 4 horas de ligazón, fueron sacrificados, extrayéndose los estómagos; con mucho cuidado se midió el volumen y se determinó el pH de la secreción gástrica, por potenciometría. Se realizó evaluación histopatológica según Devi. Principales medidas de resultados: Lesiones ulcerosas. Resultados: Los resultados indicaron 100% de efecto citoprotector con el aceite de copaiba y de 97,8% para el omeprazol (p<0,0001, ratificado con los hallazgos histopatológicos; la disminución del volumen de secreción fue 79,4% para omeprazol y 42,8% para el aceite de copaiba (p<0,001, con incremento del pH. Conclusiones: En condiciones experimentales, el aceite de copaiba fue efectivo como agente gastroprotector en ratas con inducción de úlcera gástrica.

  18. Sincronización de la ovulación y el ciclo inducido por el efecto "macho" mediante la administración de progesterona por vía intravaginal en cabras en período de anestro estacional

    OpenAIRE

    Mogedas Moreno, María

    2016-01-01

    Algunos de los métodos alternativos a los tratamientos hormonales clásicos utilizando progestágenos y eCG, para la inducción y sincronización del celo y la ovulación, unido a la inseminación artificial (IA) a tiempo fijo en ganado caprino, están basados como el IMA.PRO2® en el estímulo por la presencia de los machos (efecto macho) y la sincronización de la ovulación inducida mediante prostaglandina F2α o sus análogos. En estos métodos, la administración de una dosis baja de progesterona o pro...

  19. Construcción de un modelo animal de fibrosis pulmonar inducido por Bleomicina

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    Dacia Malambo García

    2016-01-01

    Full Text Available La fibrosis pulmonar es una enfermedad crónica, progresiva y letal, cuya etiología se desconoce. El modelo de fibrosis pulmonar inducida por Bleomicina en ratas es útil para ilustrar la patobiología in vivo de la enfermedad, así como para identificar nuevos blancos farmacológicos y estimar la eficiencia de nuevas moléculas o procedimientos Objetivo: El objetivo de este trabajo fue construir un modelo animal de fibrosis pulmonar secundaria a Bleomicina, en ratas Wistar, como herramienta que pueda servir de base para futuros diseños experimentales. Materiales y métodos: Se trabajó con dos grupos de ratas Wistar para la administración del medicamento por vía intratraqueal. El grupo experimental recibió una dosis única (2.0 U/Kg de Bleomicina, mientras que el grupo control recibió un volumen equivalente de solución salina. A los 14 o 28 días se realizó un lavado broncoalveolar con recuento total y diferencial celular y análisis histopatológico pulmonar. Resultados: La histología de una parte del grupo experimental tratado con Bleomicina y sacrificado a los 14 días reveló daño pulmonar caracterizado por inflamación aguda, hemorragia intraalveolar y proliferación fibroblástica intersticial incipiente; en el resto del grupo experimental la histología a 28 días reveló además alteración de la arquitectura pulmonar debida a fibrosis y aumento en el número de macrófagos intraalveolares e inflamación linfocitaria. Conclusiones: Se implementó satisfactoriamente un modelo de fibrosis pulmonar inducido farmacológicamente por Bleomicina en ratas Wistar.

  20. Reversible Axonal Dystrophy by Calcium Modulation in Frataxin-Deficient Sensory Neurons of YG8R Mice

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    Belén Mollá

    2017-08-01

    Full Text Available Friedreich’s ataxia (FRDA is a peripheral neuropathy involving a loss of proprioceptive sensory neurons. Studies of biopsies from patients suggest that axonal dysfunction precedes the death of proprioceptive neurons in a dying-back process. We observed that the deficiency of frataxin in sensory neurons of dorsal root ganglia (DRG of the YG8R mouse model causes the formation of axonal spheroids which retain dysfunctional mitochondria, shows alterations in the cytoskeleton and it produces impairment of axonal transport and autophagic flux. The homogenous distribution of axonal spheroids along the neurites supports the existence of continues focal damages. This lead us to propose for FRDA a model of distal axonopathy based on axonal focal damages. In addition, we observed the involvement of oxidative stress and dyshomeostasis of calcium in axonal spheroid formation generating axonal injury as a primary cause of pathophysiology. Axonal spheroids may be a consequence of calcium imbalance, thus we propose the quenching or removal extracellular Ca2+ to prevent spheroids formation. In our neuronal model, treatments with BAPTA and o-phenanthroline reverted the axonal dystrophy and the mitochondrial dysmorphic parameters. These results support the hypothesis that axonal pathology is reversible in FRDA by pharmacological manipulation of intracellular Ca2+ with Ca2+ chelators or metalloprotease inhibitors, preventing Ca2+-mediated axonal injury. Thus, the modulation of Ca2+ levels may be a relevant therapeutic target to develop early axonal protection and prevent dying-back neurodegeneration.

  1. A macroscopic model of traffic jams in axons.

    Science.gov (United States)

    Kuznetsov, A V; Avramenko, A A

    2009-04-01

    The purpose of this paper is to develop a minimal macroscopic model capable of explaining the formation of traffic jams in fast axonal transport. The model accounts for the decrease of the number density of positively (and negatively) oriented microtubules near the location of the traffic jam due to formation of microtubule swirls; the model also accounts for the reduction of the effective velocity of organelle transport in the traffic jam region due to organelles falling off microtubule tracks more often in the swirl region. The model is based on molecular-motor-assisted transport equations and the hydrodynamic model of traffic jams in highway traffic. Parametric analyses of the model's predictions for various values of viscosity of the traffic flow, variance of the velocity distribution, diffusivity of microtubule-bound and free organelles, rate constants for binding to and detachment from microtubules, relaxation time, and average motor velocities of the retrograde and anterograde transport, are carried out.

  2. Neurogenetics of slow axonal transport: from cells to animals.

    Science.gov (United States)

    Sadananda, Aparna; Ray, Krishanu

    2012-09-01

    Slow axonal transport is a multivariate phenomenon implicated in several neurodegenerative disorders. Recent reports have unraveled the molecular basis of the transport of certain slow component proteins, such as the neurofilament subunits, tubulin, and certain soluble enzymes such as Ca(2+)/calmodulin-dependent protein kinase IIa (CaM kinase IIa), etc., in tissue cultured neurons. In addition, genetic analyses also implicate microtubule-dependent motors and other housekeeping proteins in this process. However, the biological relevance of this phenomenon is not so well understood. Here, the authors have discussed the possibility of adopting neurogenetic analyses in multiple model organisms to correlate molecular level measurements of the slow transport phenomenon to animal behavior, thus facilitating the investigation of its biological efficacy.

  3. The axonal guidance receptor neogenin promotes acute inflammation.

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    Klemens König

    Full Text Available Neuronal guidance proteins (NGP were originally described in the context of axonal growth and migration. Yet recent work has demonstrated that NGPs also serve as guidance cues for immune competent cells. A crucial target receptor for NGPs during embryonic development is the neogenin receptor, however its role during acute inflammation is unknown. We report here that neogenin is abundantly expressed outside the nervous system and that animals with endogenous repression of neogenin (Neo1(-/- demonstrate attenuated changes of acute inflammation. Studies using functional inhibition of neogenin resulted in a significant attenuation of inflammatory peritonitis. In studies employing bone marrow chimeric animals we found the hematopoietic presence of Neo1(-/- to be responsible for the attenuated inflammatory response. Taken together our studies suggest that the guidance receptor neogenin holds crucial importance for the propagation of an acute inflammatory response and further define mechanisms shared between the nervous and the immune system.

  4. Video Object Tracking in Neural Axons with Fluorescence Microscopy Images

    Directory of Open Access Journals (Sweden)

    Liang Yuan

    2014-01-01

    tracking. In this paper, we describe two automated tracking methods for analyzing neurofilament movement based on two different techniques: constrained particle filtering and tracking-by-detection. First, we introduce the constrained particle filtering approach. In this approach, the orientation and position of a particle are constrained by the axon’s shape such that fewer particles are necessary for tracking neurofilament movement than object tracking techniques based on generic particle filtering. Secondly, a tracking-by-detection approach to neurofilament tracking is presented. For this approach, the axon is decomposed into blocks, and the blocks encompassing the moving neurofilaments are detected by graph labeling using Markov random field. Finally, we compare two tracking methods by performing tracking experiments on real time-lapse image sequences of neurofilament movement, and the experimental results show that both methods demonstrate good performance in comparison with the existing approaches, and the tracking accuracy of the tracing-by-detection approach is slightly better between the two.

  5. Ephexin1 Is Required for Eph-Mediated Limb Trajectory of Spinal Motor Axons.

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    Chang, Chih-Ju; Chang, Ming-Yuan; Chou, Szu-Yi; Huang, Chi-Chen; Chuang, Jian-Ying; Hsu, Tsung-I; Chang, Hsing-Fang; Wu, Yi-Hsin; Wu, Chung-Che; Morales, Daniel; Kania, Artur; Kao, Tzu-Jen

    2018-02-21

    The precise assembly of a functional nervous system relies on the guided migration of axonal growth cones, which is made possible by signals transmitted to the cytoskeleton by cell surface-expressed guidance receptors. We investigated the function of ephexin1, a Rho guanine nucleotide exchange factor, as an essential growth-cone guidance intermediary in the context of spinal lateral motor column (LMC) motor axon trajectory selection in the limb mesenchyme. Using in situ mRNA detection, we first show that ephexin1 is expressed in LMC neurons of chick and mouse embryos at the time of spinal motor axon extension into the limb. Ephexin1 loss of function and gain of function using in ovo electroporation in chick LMC neurons, of either sex, perturbed LMC axon trajectory selection, demonstrating an essential role of ephexin1 in motor axon guidance. In addition, ephexin1 loss in mice of either sex led to LMC axon trajectory selection errors. We also show that ephexin1 knockdown attenuates the growth preference of LMC neurites against ephrins in vitro and Eph receptor-mediated retargeting of LMC axons in vivo , suggesting that ephexin1 is required in Eph-mediated LMC motor axon guidance. Finally, both ephexin1 knockdown and ectopic expression of nonphosphorylatable ephexin1 mutant attenuated the retargeting of LMC axons caused by Src overexpression, implicating ephexin1 as an Src target in Eph signal relay in this context. In summary, our findings demonstrate that ephexin1 is essential for motor axon guidance and suggest an important role in relaying ephrin:Eph signals that mediate motor axon trajectory selection. SIGNIFICANCE STATEMENT The proper development of functioning neural circuits requires precise nerve connections among neurons or between neurons and their muscle targets. The Eph tyrosine kinase receptors expressed in neurons are important in many contexts during neural-circuit formation, such as axon outgrowth, axon guidance, and synaptic formation, and have been

  6. Neuron Morphology Influences Axon Initial Segment Plasticity123

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    2016-01-01

    In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation. PMID:27022619

  7. Dynein is the motor for retrograde axonal transport of organelles

    International Nuclear Information System (INIS)

    Schnapp, B.J.; Reese, T.S.

    1989-01-01

    Vesicular organelles in axons of nerve cells are transported along microtubules either toward their plus ends (fast anterograde transport) or toward their minus ends (retrograde transport). Two microtubule-based motors were previously identified by examining plastic beads induced to move along microtubules by cytosol fractions from the squid giant axon: (i) an anterograde motor, kinesin, and (ii) a retrograde motor, which is characterized here. The retrograde motor, a cytosolic protein previously termed HMW1, was purified from optic lobes and extruded axoplasm by nucleotide-dependent microtubule affinity and release; microtubule gliding was used as the assay of motor activity. The following properties of the retrograde motor suggest that it is cytoplasmic dynein: (i) sedimentation at 20-22 S with a heavy chain of Mr greater than 200,000 that coelectrophoreses with the alpha and beta subunits of axonemal dynein, (ii) cleavage by UV irradiation in the presence of ATP and vanadate, and (iii) a molecular structure resembling two-headed dynein from axonemes. Furthermore, bead movement toward the minus end of microtubules was blocked when axoplasmic supernatants were treated with UV/vanadate. Treatment of axoplasmic supernatant with UV/vanadate also blocks the retrograde movement of purified organelles in vitro without changing the number of anterograde moving organelles, indicating that dynein interacts specifically with a subgroup of organelles programmed to move toward the cell body. However, purified optic lobe dynein, like purified kinesin, does not by itself promote the movement of purified organelles along microtubules, suggesting that additional axoplasmic factors are necessary for retrograde as well as anterograde transport

  8. Multichannel activity propagation across an engineered axon network

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    Chen, H. Isaac; Wolf, John A.; Smith, Douglas H.

    2017-04-01

    Objective. Although substantial progress has been made in mapping the connections of the brain, less is known about how this organization translates into brain function. In particular, the massive interconnectivity of the brain has made it difficult to specifically examine data transmission between two nodes of the connectome, a central component of the ‘neural code.’ Here, we investigated the propagation of multiple streams of asynchronous neuronal activity across an isolated in vitro ‘connectome unit.’ Approach. We used the novel technique of axon stretch growth to create a model of a long-range cortico-cortical network, a modular system consisting of paired nodes of cortical neurons connected by axon tracts. Using optical stimulation and multi-electrode array recording techniques, we explored how input patterns are represented by cortical networks, how these representations shift as they are transmitted between cortical nodes and perturbed by external conditions, and how well the downstream node distinguishes different patterns. Main results. Stimulus representations included direct, synaptic, and multiplexed responses that grew in complexity as the distance between the stimulation source and recorded neuron increased. These representations collapsed into patterns with lower information content at higher stimulation frequencies. With internodal activity propagation, a hierarchy of network pathways, including latent circuits, was revealed using glutamatergic blockade. As stimulus channels were added, divergent, non-linear effects were observed in local versus distant network layers. Pairwise difference analysis of neuronal responses suggested that neuronal ensembles generally outperformed individual cells in discriminating input patterns. Significance. Our data illuminate the complexity of spiking activity propagation in cortical networks in vitro, which is characterized by the transformation of an input into myriad outputs over several network layers

  9. Compensatory axon sprouting for very slow axonal die‐back in a transgenic model of spinal muscular atrophy type III

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    Udina, Esther; Putman, Charles T.; Harris, Luke R.; Tyreman, Neil; Cook, Victoria E.

    2017-01-01

    Key points Smn +/− transgenic mouse is a model of the mildest form of spinal muscular atrophy.Although there is a loss of spinal motoneurons in 11‐month‐old animals, muscular force is maintained.This maintained muscular force is mediated by reinnervation of the denervated fibres by surviving motoneurons.The spinal motoneurons in these animals do not show an increased susceptibility to death after nerve injury and they retain their regenerative capacity.We conclude that the hypothesized immaturity of the neuromuscular system in this model cannot explain the loss of motoneurons by systematic die‐back. Abstract Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans and is the leading genetic cause of infantile death. Patients lack the SMN1 gene with the severity of the disease depending on the number of copies of the highly homologous SMN2 gene. Although motoneuron death in the Smn +/− transgenic mouse model of the mildest form of SMA, SMA type III, has been reported, we have used retrograde tracing of sciatic and femoral motoneurons in the hindlimb with recording of muscle and motor unit isometric forces to count the number of motoneurons with intact neuromuscular connections. Thereby, we investigated whether incomplete maturation of the neuromuscular system induced by survival motoneuron protein (SMN) defects is responsible for die‐back of axons relative to survival of motoneurons. First, a reduction of ∼30% of backlabelled motoneurons began relatively late, at 11 months of age, with a significant loss of 19% at 7 months. Motor axon die‐back was affirmed by motor unit number estimation. Loss of functional motor units was fully compensated by axonal sprouting to retain normal contractile force in four hindlimb muscles (three fast‐twitch and one slow‐twitch) innervated by branches of the sciatic nerve. Second, our evaluation of whether axotomy of motoneurons in the adult Smn +/− transgenic mouse increases their

  10. Compensatory axon sprouting for very slow axonal die-back in a transgenic model of spinal muscular atrophy type III.

    Science.gov (United States)

    Udina, Esther; Putman, Charles T; Harris, Luke R; Tyreman, Neil; Cook, Victoria E; Gordon, Tessa

    2017-03-01

    Smn +/- transgenic mouse is a model of the mildest form of spinal muscular atrophy. Although there is a loss of spinal motoneurons in 11-month-old animals, muscular force is maintained. This maintained muscular force is mediated by reinnervation of the denervated fibres by surviving motoneurons. The spinal motoneurons in these animals do not show an increased susceptibility to death after nerve injury and they retain their regenerative capacity. We conclude that the hypothesized immaturity of the neuromuscular system in this model cannot explain the loss of motoneurons by systematic die-back. Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans and is the leading genetic cause of infantile death. Patients lack the SMN1 gene with the severity of the disease depending on the number of copies of the highly homologous SMN2 gene. Although motoneuron death in the Smn +/- transgenic mouse model of the mildest form of SMA, SMA type III, has been reported, we have used retrograde tracing of sciatic and femoral motoneurons in the hindlimb with recording of muscle and motor unit isometric forces to count the number of motoneurons with intact neuromuscular connections. Thereby, we investigated whether incomplete maturation of the neuromuscular system induced by survival motoneuron protein (SMN) defects is responsible for die-back of axons relative to survival of motoneurons. First, a reduction of ∼30% of backlabelled motoneurons began relatively late, at 11 months of age, with a significant loss of 19% at 7 months. Motor axon die-back was affirmed by motor unit number estimation. Loss of functional motor units was fully compensated by axonal sprouting to retain normal contractile force in four hindlimb muscles (three fast-twitch and one slow-twitch) innervated by branches of the sciatic nerve. Second, our evaluation of whether axotomy of motoneurons in the adult Smn +/- transgenic mouse increases their susceptibility to cell death demonstrated

  11. Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy.

    Science.gov (United States)

    Sasaki, Yo; Araki, Toshiyuki; Milbrandt, Jeffrey

    2006-08-16

    Axonal degeneration occurs in many neurodegenerative diseases and after traumatic injury and is a self-destructive program independent from programmed cell death. Previous studies demonstrated that overexpression of nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) or exogenous application of nicotinamide adenine dinucleotide (NAD) can protect axons of cultured dorsal root ganglion (DRG) neurons from degeneration caused by mechanical or neurotoxic injury. In mammalian cells, NAD can be synthesized from multiple precursors, including tryptophan, nicotinic acid, nicotinamide, and nicotinamide riboside (NmR), via multiple enzymatic steps. To determine whether other components of these NAD biosynthetic pathways are capable of delaying axonal degeneration, we overexpressed each of the enzymes involved in each pathway and/or exogenously administered their respective substrates in DRG cultures and assessed their capacity to protect axons after axotomy. Among the enzymes tested, Nmnat1 had the strongest protective effects, whereas nicotinamide phosphoribosyl transferase and nicotinic acid phosphoribosyl transferase showed moderate protective activity in the presence of their substrates. Strong axonal protection was also provided by Nmnat3, which is predominantly located in mitochondria, and an Nmnat1 mutant localized to the cytoplasm, indicating that the subcellular location of NAD production is not crucial for protective activity. In addition, we showed that exogenous application of the NAD precursors that are the substrates of these enzymes, including nicotinic acid mononucleotide, nicotinamide mononucleotide, and NmR, can also delay axonal degeneration. These results indicate that stimulation of NAD biosynthetic pathways via a variety of interventions may be useful in preventing or delaying axonal degeneration.

  12. Glia initiate brain assembly through non-canonical Chimaerin/Furin axon guidance in C. elegans

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    Rapti, Georgia; Li, Chang; Shan, Alan; Lu, Yun; Shaham, Shai

    2017-01-01

    Brain assembly is hypothesized to begin when pioneer axons extend over non-neuronal cells, forming tracts guiding follower axons. Yet pioneer-neuron identities, their guidance substrates, and their interactions, are not well understood. Here, using time-lapse embryonic imaging, genetics, protein-interaction, and functional studies, we uncover the early events of C. elegans brain assembly. We demonstrate that C. elegans glia are key for assembly initiation, guiding pioneer and follower axons using distinct signals. Pioneer sublateral neurons, with unique growth properties, anatomy, and innervation, cooperate with glia to mediate follower-axon guidance. We further identify a CHIN-1/Chimaerin-KPC-1/Furin double mutant that severely disrupts assembly. CHIN-1/Chimaerin and KPC-1/Furin function non-canonically in glia and pioneer neurons for guidance-cue trafficking. We exploit this bottleneck to define roles for glial Netrin and Semaphorin in pioneer- and follower-axon guidance, respectively, and for glial and pioneer-neuron Flamingo/CELSR in follower-axon navigation. Altogether, our studies reveal previously-unknown glial roles in pioneer-axon guidance, suggesting conserved brain-assembly principles. PMID:28846083

  13. Expression of plasminogen activator inhibitor-1 by olfactory ensheathing glia promotes axonal regeneration.

    Science.gov (United States)

    Simón, Diana; Martín-Bermejo, Maria Jesús; Gallego-Hernández, Maria Teresa; Pastrana, Erika; García-Escudero, Vega; García-Gómez, Ana; Lim, Filip; Díaz-Nido, Javier; Avila, Jesús; Moreno-Flores, Maria Teresa

    2011-10-01

    Olfactory ensheathing glia (OEG) cells are known to facilitate repair following axotomy of adult neurons, although the molecular mechanisms involved are not fully understood. We previously identified plasminogen activator inhibitor-1 (PAI-1), proteinase-activated receptor-1 (PAR-1), and thrombomodulin (TM) as candidates to regulate rat OEG-dependent axonal regeneration. In this study, we have validated the involvement of these proteins in promoting axonal regeneration by immortalized human OEGs. We studied the effect of silencing these proteins in OEGs on their capacity to promote the regeneration of severed adult retinal ganglion cells (RGCs) axons. Our results support the role of glial PAI-1 as a downstream effector of PAR-1 in promoting axon regeneration. In contrast, we found that TM inhibits OEG induced-axonal regeneration. We also assessed the signaling pathways downstream of PAR-1 that might modulate PAI-1 expression, observing that specifically inhibiting Gα(i), Rho kinase, or PLC and PKC downregulated the expression of PAI-1 in OEGs, with a concomitant reduction in OEG-dependent axon regeneration in adult RGCs. Our findings support an important role for the thrombin system in regulating adult axonal regeneration by OEGs. Copyright © 2011 Wiley-Liss, Inc.

  14. The Influence of Glutamate on Axonal Compound Action Potential In Vitro.

    Science.gov (United States)

    Abouelela, Ahmed; Wieraszko, Andrzej

    2016-01-01

    Background  Our previous experiments demonstrated modulation of the amplitude of the axonal compound action potential (CAP) by electrical stimulation. To verify assumption that glutamate released from axons could be involved in this phenomenon, the modification of the axonal CAP induced by glutamate was investigated. Objectives  The major objective of this research is to verify the hypothesis that axonal activity would trigger the release of glutamate, which in turn would interact with specific axonal receptors modifying the amplitude of the action potential. Methods  Segments of the sciatic nerve were exposed to exogenous glutamate in vitro, and CAP was recorded before and after glutamate application. In some experiments, the release of radioactive glutamate analog from the sciatic nerve exposed to exogenous glutamate was also evaluated. Results  The glutamate-induced increase in CAP was blocked by different glutamate receptor antagonists. The effect of glutamate was not observed in Ca-free medium, and was blocked by antagonists of calcium channels. Exogenous glutamate, applied to the segments of sciatic nerve, induced the release of radioactive glutamate analog, demonstrating glutamate-induced glutamate release. Immunohistochemical examination revealed that axolemma contains components necessary for glutamatergic neurotransmission. Conclusion  The proteins of the axonal membrane can under the influence of electrical stimulation or exogenous glutamate change membrane permeability and ionic conductance, leading to a change in the amplitude of CAP. We suggest that increased axonal activity leads to the release of glutamate that results in changes in the amplitude of CAPs.

  15. Optogenetically enhanced axon regeneration: motor versus sensory neuron-specific stimulation.

    Science.gov (United States)

    Ward, Patricia J; Clanton, Scott L; English, Arthur W

    2018-02-01

    Brief neuronal activation in injured peripheral nerves is both necessary and sufficient to enhance motor axon regeneration, and this effect is specific to the activated motoneurons. It is less clear whether sensory neurons respond in a similar manner to neuronal activation following peripheral axotomy. Further, it is unknown to what extent enhancement of axon regeneration with increased neuronal activity relies on a reflexive interaction within the spinal circuitry. We used mouse genetics and optical tools to evaluate the precision and selectivity of system-specific neuronal activation to enhance axon regeneration in a mixed nerve. We evaluated sensory and motor axon regeneration in two different mouse models expressing the light-sensitive cation channel, channelrhodopsin (ChR2). We selectively activated either sensory or motor axons using light stimulation combined with transection and repair of the sciatic nerve. Regardless of genotype, the number of ChR2-positive neurons whose axons had regenerated successfully was greater following system-specific optical treatment, with no effect on the number of ChR2-negative neurons (whether motor or sensory neurons). We conclude that acute system-specific neuronal activation is sufficient to enhance both motor and sensory axon regeneration. This regeneration-enhancing effect is likely cell autonomous. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  16. Modeling the mechanics of axonal fiber tracts using the embedded finite element method.

    Science.gov (United States)

    Garimella, Harsha T; Kraft, Reuben H

    2017-05-01

    A subject-specific human head finite element model with embedded axonal fiber tractography obtained from diffusion tensor imaging was developed. The axonal fiber tractography finite element model was coupled with the volumetric elements in the head model using the embedded element method. This technique enables the calculation of axonal strains and real-time tracking of the mechanical response of the axonal fiber tracts. The coupled model was then verified using pressure and relative displacement-based (between skull and brain) experimental studies and was employed to analyze a head impact, demonstrating the applicability of this method in studying axonal injury. Following this, a comparison study of different injury criteria was performed. This model was used to determine the influence of impact direction on the extent of the axonal injury. The results suggested that the lateral impact loading is more dangerous compared to loading in the sagittal plane, a finding in agreement with previous studies. Through this analysis, we demonstrated the viability of the embedded element method as an alternative numerical approach for studying axonal injury in patient-specific human head models. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Impaired JIP3-dependent axonal lysosome transport promotes amyloid plaque pathology.

    Science.gov (United States)

    Gowrishankar, Swetha; Wu, Yumei; Ferguson, Shawn M

    2017-10-02

    Lysosomes robustly accumulate within axonal swellings at Alzheimer's disease (AD) amyloid plaques. However, the underlying mechanisms and disease relevance of such lysosome accumulations are not well understood. Motivated by these problems, we identified JNK-interacting protein 3 (JIP3) as an important regulator of axonal lysosome transport and maturation. JIP3 knockout mouse neuron primary cultures accumulate lysosomes within focal axonal swellings that resemble the dystrophic axons at amyloid plaques. These swellings contain high levels of amyloid precursor protein processing enzymes (BACE1 and presenilin 2) and are accompanied by elevated Aβ peptide levels. The in vivo importance of the JIP3-dependent regulation of axonal lysosomes was revealed by the worsening of the amyloid plaque pathology arising from JIP3 haploinsufficiency in a mouse model of AD. These results establish the critical role of JIP3-dependent axonal lysosome transport in regulating amyloidogenic amyloid precursor protein processing and support a model wherein Aβ production is amplified by plaque-induced axonal lysosome transport defects. © 2017 Gowrishankar et al.

  18. Characterizing Semaphorin-Mediated Effects on Sensory and Motor Axon Pathfinding and Connectivity During Embryonic Development.

    Science.gov (United States)

    Huettl, Rosa Eva; Huber, Andrea B

    2017-01-01

    How are precise connectivity to peripheral targets and corresponding sensory-motor networks established during developmental innervation of the vertebrate extremities? The formation of functional sensory-motor circuits requires highly appropriate temporal and spatial regulation of axon growth which is achieved through the combination of different molecular mechanisms such as communication between heterotypic fiber systems, axon-environment, or axon-glia interactions that ensure proper fasciculation and accurate pathfinding to distal targets. Family members of the class 3 semaphorins and their cognate receptors, the neuropilins, were shown to govern various events during wiring of central and peripheral circuits, with mice lacking Sema3-Npn signaling showing deficits in timing of growth, selective fasciculation, guidance fidelity, and coupling of sensory axon growth to motor axons at developmental time points. Given the accuracy with which these processes have to interact in a stepwise manner, deficiency of the smallest cog in the wheel may impact severely on the faithful establishment and functionality of peripheral circuitries, ultimately leading to behavioral impairments or even cause the death of the animal. Reliable quantitative analyses of sensory-motor fasciculation, extension, and guidance of axons to their cognate target muscles and the skin during development, but also assessment of physiological and behavioral consequences at adult age, are therefore a necessity to extend our understanding of the molecular mechanisms of peripheral circuit formation. In this chapter we provide a detailed methodology to characterize class 3 semaphorin-mediated effects on peripheral sensory and motor axon pathfinding and connectivity during embryonic development.

  19. Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development.

    Science.gov (United States)

    Thomas-Jinu, Swapna; Gordon, Patricia M; Fielding, Triona; Taylor, Richard; Smith, Bradley N; Snowden, Victoria; Blanc, Eric; Vance, Caroline; Topp, Simon; Wong, Chun-Hao; Bielen, Holger; Williams, Kelly L; McCann, Emily P; Nicholson, Garth A; Pan-Vazquez, Alejandro; Fox, Archa H; Bond, Charles S; Talbot, William S; Blair, Ian P; Shaw, Christopher E; Houart, Corinne

    2017-04-19

    Recent progress revealed the complexity of RNA processing and its association to human disorders. Here, we unveil a new facet of this complexity. Complete loss of function of the ubiquitous splicing factor SFPQ affects zebrafish motoneuron differentiation cell autonomously. In addition to its nuclear localization, the protein unexpectedly localizes to motor axons. The cytosolic version of SFPQ abolishes motor axonal defects, rescuing key transcripts, and restores motility in the paralyzed sfpq null mutants, indicating a non-nuclear processing role in motor axons. Novel variants affecting the conserved coiled-coil domain, so far exclusively found in fALS exomes, specifically affect the ability of SFPQ to localize in axons. They broadly rescue morphology and motility in the zebrafish mutant, but alter motor axon morphology, demonstrating functional requirement for axonal SFPQ. Altogether, we uncover the axonal function of the splicing factor SFPQ in motor development and highlight the importance of the coiled-coil domain in this process. VIDEO ABSTRACT. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. The Drosophila HEM-2/NAP1 homolog KETTE controls axonal pathfinding and cytoskeletal organization.

    Science.gov (United States)

    Hummel, T; Leifker, K; Klämbt, C

    2000-04-01

    In Drosophila, the correct formation of the segmental commissures depends on neuron-glial interactions at the midline. The VUM midline neurons extend axons along which glial cells migrate in between anterior and posterior commissures. Here, we show that the gene kette is required for the normal projection of the VUM axons and subsequently disrupts glial migration. Axonal projection defects are also found for many other moto- and interneurons. In addition, kette affects the cell morphology of mesodermal and epidermal derivatives, which show an abnormal actin cytoskeleton. The KETTE protein is homologous to the transmembrane protein HEM-2/NAP1 evolutionary conserved from worms to vertebrates. In vitro analysis has shown a specific interaction of the vertebrate HEM-2/NAP1 with the SH2-SH3 adapter protein NCK and the small GTPase RAC1, which both have been implicated in regulating cytoskeleton organization and axonal growth. Hypomorphic kette mutations lead to axonal defects similar to mutations in the Drosophila NCK homolog dreadlocks. Furthermore, we show that kette and dock mutants genetically interact. NCK is thought to interact with the small G proteins RAC1 and CDC42, which play a role in axonal growth. In line with these observations, a kette phenocopy can be obtained following directed expression of mutant DCDC42 or DRAC1 in the CNS midline. In addition, the kette mutant phenotype can be partially rescued by expression of an activated DRAC1 transgene. Our data suggest an important role of the HEM-2 protein in cytoskeletal organization during axonal pathfinding.

  1. GDF10 Is a Signal for Axonal Sprouting and Functional Recovery after Stroke

    Science.gov (United States)

    Li, S; Nie, EH; Yin, Y; Benowitz, LI; Tung, S; Vinters, HV; Bahjat, FR; Stenzel-Poore, MP; Kawaguchi, R; Coppola, G; Carmichael, ST

    2016-01-01

    Stroke produces a limited process of neural repair. Axonal sprouting in cortex adjacent to the infarct is part of this recovery process, but the signal that initiates axonal sprouting is not known. Growth and Differentiation Factor 10 (GDF10) is induced in peri-infarct neurons in mouse, non-human primate and human. GDF10 promotes axonal outgrowth in vitro in mouse, rat and human neurons through TGFβRI/II signaling. Using pharmacogenetic gain and loss of function studies, GDF10 produces axonal sprouting and enhanced functional recovery after stroke; knocking down GDF10 blocks axonal sprouting and reduces recovery. RNA-seq from peri-infarct cortical neurons indicates that GDF10 downregulates PTEN and upregulates PI3 kinase signaling and induces specific axonal guidance molecules. Unsupervised genome-wide association analysis of the GDF10 transcriptome shows that it is not related to neurodevelopment but may partially overlap with other CNS injury patterns. GDF10 is a stroke-induced signal for axonal sprouting and functional recovery. PMID:26502261

  2. The Microtubule Regulatory Protein Stathmin Is Required to Maintain the Integrity of Axonal Microtubules in Drosophila.

    Directory of Open Access Journals (Sweden)

    Jason E Duncan

    Full Text Available Axonal transport, a form of long-distance, bi-directional intracellular transport that occurs between the cell body and synaptic terminal, is critical in maintaining the function and viability of neurons. We have identified a requirement for the stathmin (stai gene in the maintenance of axonal microtubules and regulation of axonal transport in Drosophila. The stai gene encodes a cytosolic phosphoprotein that regulates microtubule dynamics by partitioning tubulin dimers between pools of soluble tubulin and polymerized microtubules, and by directly binding to microtubules and promoting depolymerization. Analysis of stai function in Drosophila, which has a single stai gene, circumvents potential complications with studies performed in vertebrate systems in which mutant phenotypes may be compensated by genetic redundancy of other members of the stai gene family. This has allowed us to identify an essential function for stai in the maintenance of the integrity of axonal microtubules. In addition to the severe disruption in the abundance and architecture of microtubules in the axons of stai mutant Drosophila, we also observe additional neurological phenotypes associated with loss of stai function including a posterior paralysis and tail-flip phenotype in third instar larvae, aberrant accumulation of transported membranous organelles in stai deficient axons, a progressive bang-sensitive response to mechanical stimulation reminiscent of the class of Drosophila mutants used to model human epileptic seizures, and a reduced adult lifespan. Reductions in the levels of Kinesin-1, the primary anterograde motor in axonal transport, enhance these phenotypes. Collectively, our results indicate that stai has an important role in neuronal function, likely through the maintenance of microtubule integrity in the axons of nerves of the peripheral nervous system necessary to support and sustain long-distance axonal transport.

  3. The Microtubule Regulatory Protein Stathmin Is Required to Maintain the Integrity of Axonal Microtubules in Drosophila

    Science.gov (United States)

    Duncan, Jason E.; Lytle, Nikki K.; Zuniga, Alfredo; Goldstein, Lawrence S. B.

    2013-01-01

    Axonal transport, a form of long-distance, bi-directional intracellular transport that occurs between the cell body and synaptic terminal, is critical in maintaining the function and viability of neurons. We have identified a requirement for the stathmin (stai) gene in the maintenance of axonal microtubules and regulation of axonal transport in Drosophila . The stai gene encodes a cytosolic phosphoprotein that regulates microtubule dynamics by partitioning tubulin dimers between pools of soluble tubulin and polymerized microtubules, and by directly binding to microtubules and promoting depolymerization. Analysis of stai function in Drosophila , which has a single stai gene, circumvents potential complications with studies performed in vertebrate systems in which mutant phenotypes may be compensated by genetic redundancy of other members of the stai gene family. This has allowed us to identify an essential function for stai in the maintenance of the integrity of axonal microtubules. In addition to the severe disruption in the abundance and architecture of microtubules in the axons of stai mutant Drosophila , we also observe additional neurological phenotypes associated with loss of stai function including a posterior paralysis and tail-flip phenotype in third instar larvae, aberrant accumulation of transported membranous organelles in stai deficient axons, a progressive bang-sensitive response to mechanical stimulation reminiscent of the class of Drosophila mutants used to model human epileptic seizures, and a reduced adult lifespan. Reductions in the levels of Kinesin-1, the primary anterograde motor in axonal transport, enhance these phenotypes. Collectively, our results indicate that stai has an important role in neuronal function, likely through the maintenance of microtubule integrity in the axons of nerves of the peripheral nervous system necessary to support and sustain long-distance axonal transport. PMID:23840848

  4. Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade

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    Alexandre Dumoulin

    2018-04-01

    Full Text Available Axonal branching is a key process in the establishment of circuit connectivity within the nervous system. Molecular-genetic studies have shown that a specific form of axonal branching—the bifurcation of sensory neurons at the transition zone between the peripheral and the central nervous system—is regulated by a cyclic guanosine monophosphate (cGMP-dependent signaling cascade which is composed of C-type natriuretic peptide (CNP, the receptor guanylyl cyclase Npr2, and cGMP-dependent protein kinase Iα (cGKIα. In the absence of any one of these components, neurons in dorsal root ganglia (DRG and cranial sensory ganglia no longer bifurcate, and instead turn in either an ascending or a descending direction. In contrast, collateral axonal branch formation which represents a second type of axonal branch formation is not affected by inactivation of CNP, Npr2, or cGKI. Whereas axon bifurcation was lost in mouse mutants deficient for components of CNP-induced cGMP formation; the absence of the cGMP-degrading enzyme phosphodiesterase 2A had no effect on axon bifurcation. Adult mice that lack sensory axon bifurcation due to the conditional inactivation of Npr2-mediated cGMP signaling in DRG neurons demonstrated an altered shape of sensory axon terminal fields in the spinal cord, indicating that elaborate compensatory mechanisms reorganize neuronal circuits in the absence of bifurcation. On a functional level, these mice showed impaired heat sensation and nociception induced by chemical irritants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are normal. These data point to a critical role of axon bifurcation for the processing of acute pain perception.

  5. Extracellular matrix molecules play diverse roles in the growth and guidance of central nervous system axons

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    M.A. Pires-Neto

    1999-05-01

    Full Text Available Axon growth and guidance represent complex biological processes in which probably intervene diverse sets of molecular cues that allow for the appropriate wiring of the central nervous system (CNS. The extracellular matrix (ECM represents a major contributor of molecular signals either diffusible or membrane-bound that may regulate different stages of neural development. Some of the brain ECM molecules form tridimensional structures (tunnels and boundaries that appear during time- and space-regulated events, possibly playing relevant roles in the control of axon elongation and pathfinding. This short review focuses mainly on the recognized roles played by proteoglycans, laminin, fibronectin and tenascin in axonal development during ontogenesis.

  6. Axonal and presynaptic protein synthesis: new insights into the biology of the neuron.

    Science.gov (United States)

    Giuditta, Antonio; Kaplan, Barry B; van Minnen, Jan; Alvarez, Jaime; Koenig, Edward

    2002-08-01

    The presence of a local mRNA translation system in axons and terminals was proposed almost 40 years ago. Over the ensuing period, an impressive body of evidence has grown to support this proposal -- yet the nerve cell body is still considered to be the only source of axonal and presynaptic proteins. To dispel this lingering neglect, we now present the wealth of recent observations bearing on this central idea, and consider their impact on our understanding of the biology of the neuron. We demonstrate that extrasomatic translation sites, which are now well recognized in dendrites, are also present in axonal and presynaptic compartments.

  7. Current Opportunities for Clinical Monitoring of Axonal Pathology in Traumatic Brain Injury

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    Parmenion P. Tsitsopoulos

    2017-11-01

    Full Text Available Traumatic brain injury (TBI is a multidimensional and highly complex disease commonly resulting in widespread injury to axons, due to rapid inertial acceleration/deceleration forces transmitted to the brain during impact. Axonal injury leads to brain network dysfunction, significantly contributing to cognitive and functional impairments frequently observed in TBI survivors. Diffuse axonal injury (DAI is a clinical entity suggested by impaired level of consciousness and coma on clinical examination and characterized by widespread injury to the hemispheric white matter tracts, the corpus callosum and the brain stem. The clinical course of DAI is commonly unpredictable and it remains a challenging entity with limited therapeutic options, to date. Although axonal integrity may be disrupted at impact, the majority of axonal pathology evolves over time, resulting from delayed activation of complex intracellular biochemical cascades. Activation of these secondary biochemical pathways may lead to axonal transection, named secondary axotomy, and be responsible for the clinical decline of DAI patients. Advances in the neurocritical care of TBI patients have been achieved by refinements in multimodality monitoring for prevention and early detection of secondary injury factors, which can be applied also to DAI. There is an emerging role for biomarkers in blood, cerebrospinal fluid, and interstitial fluid using microdialysis in the evaluation of axonal injury in TBI. These biomarker studies have assessed various axonal and neuroglial markers as well as inflammatory mediators, such as cytokines and chemokines. Moreover, modern neuroimaging can detect subtle or overt DAI/white matter changes in diffuse TBI patients across all injury severities using magnetic resonance spectroscopy, diffusion tensor imaging, and positron emission tomography. Importantly, serial neuroimaging studies provide evidence for evolving axonal injury. Since axonal injury may be a key

  8. Axonal degeneration stimulates the formation of NG2+ cells and oligodendrocytes in the mouse

    DEFF Research Database (Denmark)

    Nielsen, Helle Hvilsted; Ladeby, Rune; Drøjdahl, Nina

    2006-01-01

    the response of the NG2+ cells to the different components of demyelinating pathology, we investigated the response of adult NG2+ cells to axonal degeneration in the absence of primary myelin or oligodendrocyte pathology. Axonal degeneration was induced in the hippocampal dentate gyrus of adult mice...... by transection of the entorhino-dentate perforant path projection. The acutely induced degeneration of axons and terminals resulted in a prompt response of NG2+ cells, consisting of morphological transformation, cellular proliferation, and upregulation of NG2 expression days 2-3 after surgery. This was followed...

  9. An Atypical SCF-like Ubiquitin Ligase Complex Promotes Wallerian Degeneration through Regulation of Axonal Nmnat2

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    Yuya Yamagishi

    2016-10-01

    Full Text Available Axon degeneration is a tightly regulated, self-destructive program that is a critical feature of many neurodegenerative diseases, but the molecular mechanisms regulating this program remain poorly understood. Here, we identify S-phase kinase-associated protein 1A (Skp1a, a core component of a Skp/Cullin/F-box (SCF-type E3 ubiquitin ligase complex, as a critical regulator of axon degeneration after injury in mammalian neurons. Depletion of Skp1a prolongs survival of injured axons in vitro and in the optic nerve in vivo. We demonstrate that Skp1a regulates the protein level of the nicotinamide adenine dinucleotide (NAD+ synthesizing enzyme nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2 in axons. Loss of axonal Nmnat2 contributes to a local ATP deficit that triggers axon degeneration. Knockdown of Skp1a elevates basal levels of axonal Nmnat2, thereby delaying axon degeneration through prolonged maintenance of axonal ATP. Consistent with Skp1a functioning through regulation of Nmnat2, Skp1a knockdown fails to protect axons from Nmnat2 knockdown. These results illuminate the molecular mechanism underlying Skp1a-dependent axonal destruction.

  10. Guidance of Drosophila Mushroom Body Axons Depends upon DRL-Wnt Receptor Cleavage in the Brain Dorsomedial Lineage Precursors

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    Elodie Reynaud

    2015-05-01

    Full Text Available In vivo axon pathfinding mechanisms in the neuron-dense brain remain relatively poorly characterized. We study the Drosophila mushroom body (MB axons, whose α and β branches connect to different brain areas. We show that the Ryk family WNT5 receptor, DRL (derailed, which is expressed in the dorsomedial lineages, brain structure precursors adjacent to the MBs, is required for MB α branch axon guidance. DRL acts to capture and present WNT5 to MB axons rather than transduce a WNT5 signal. DRL’s ectodomain must be cleaved and shed to guide α axons. DRL-2, another Ryk, is expressed within MB axons and functions as a repulsive WNT5 signaling receptor. Finally, our biochemical data support the existence of a ternary complex composed of the cleaved DRL ectodomain, WNT5, and DRL-2. Thus, the interaction of MB-extrinsic and -intrinsic Ryks via their common ligand acts to guide MB α axons.

  11. Sorting of cargos between axons and dendrites: modelling of differences in cargo transport in these two types of neurites.

    Science.gov (United States)

    Kuznetsov, A V

    2014-05-01

    Explaining how intracellular cargos are sorted between axons and dendrites is important for a mechanistic understanding of what happens in many neurodegenerative disorders. A simple model of cargo sorting relies on differences in microtubule (MT) orientation between axons and dendrites: in mammalian neurons all MTs in axons have their plus ends directed outward while in proximal regions of dendrites the MT polarity is mixed. It can therefore be assumed that cargos that need to be driven into axons associate with kinesin motors while cargos that need to be driven into dendrites associate with dynein motors. This paper develops equations of cargo transport in axons and dendrites based on the above assumptions. Propagation of a pulse of radiolabelled cargos entering an axon and dendrite is simulated. The model equations are solved utilising the Laplace transform method. Differences in cargo transport between axons and dendrites are discussed.

  12. Myosin-V Induces Cargo Immobilization and Clustering at the Axon Initial Segment

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    Anne F. J. Janssen

    2017-08-01

    Full Text Available The selective transport of different cargoes into axons and dendrites underlies the polarized organization of the neuron. Although it has become clear that the combined activity of different motors determines the destination and selectivity of transport, little is known about the mechanistic details of motor cooperation. For example, the exact role of myosin-V in opposing microtubule-based axon entries has remained unclear. Here we use two orthogonal chemically-induced heterodimerization systems to independently recruit different motors to cargoes. We find that recruiting myosin-V to kinesin-propelled cargoes at approximately equal numbers is sufficient to stall motility. Kinesin-driven cargoes entering the axon were arrested in the axon initial segment (AIS upon myosin-V recruitment and accumulated in distinct actin-rich hotspots. Importantly, unlike proposed previously, myosin-V did not return these cargoes to the cell body, suggesting that additional mechanism are required to establish cargo retrieval from the AIS.

  13. Islet Coordinately Regulates Motor Axon Guidance and Dendrite Targeting through the Frazzled/DCC Receptor

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    Celine Santiago

    2017-02-01

    Full Text Available Motor neuron axon targeting in the periphery is correlated with the positions of motor neuron inputs in the CNS, but how these processes are coordinated to form a myotopic map remains poorly understood. We show that the LIM homeodomain factor Islet (Isl controls targeting of both axons and dendrites in Drosophila motor neurons through regulation of the Frazzled (Fra/DCC receptor. Isl is required for fra expression in ventrally projecting motor neurons, and isl and fra mutants have similar axon guidance defects. Single-cell labeling indicates that isl and fra are also required for dendrite targeting in a subset of motor neurons. Finally, overexpression of Fra rescues axon and dendrite targeting defects in isl mutants. These results indicate that Fra acts downstream of Isl in both the periphery and the CNS, demonstrating how a single regulatory relationship is used in multiple cellular compartments to coordinate neural circuit wiring.

  14. Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury*

    Science.gov (United States)

    van Niekerk, Erna A.; Tuszynski, Mark H.; Lu, Paul; Dulin, Jennifer N.

    2016-01-01

    Following axotomy, a complex temporal and spatial coordination of molecular events enables regeneration of the peripheral nerve. In contrast, multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration in the central nervous system. In this review, we examine the current understanding of differences in protein expression and post-translational modifications, activation of signaling networks, and environmental cues that may underlie the divergent regenerative capacity of central and peripheral axons. We also highlight key experimental strategies to enhance axonal regeneration via modulation of intraneuronal signaling networks and the extracellular milieu. Finally, we explore potential applications of proteomics to fill gaps in the current understanding of molecular mechanisms underlying regeneration, and to provide insight into the development of more effective approaches to promote axonal regeneration following injury to the nervous system. PMID:26695766

  15. Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury.

    Science.gov (United States)

    van Niekerk, Erna A; Tuszynski, Mark H; Lu, Paul; Dulin, Jennifer N

    2016-02-01

    Following axotomy, a complex temporal and spatial coordination of molecular events enables regeneration of the peripheral nerve. In contrast, multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration in the central nervous system. In this review, we examine the current understanding of differences in protein expression and post-translational modifications, activation of signaling networks, and environmental cues that may underlie the divergent regenerative capacity of central and peripheral axons. We also highlight key experimental strategies to enhance axonal regeneration via modulation of intraneuronal signaling networks and the extracellular milieu. Finally, we explore potential applications of proteomics to fill gaps in the current understanding of molecular mechanisms underlying regeneration, and to provide insight into the development of more effective approaches to promote axonal regeneration following injury to the nervous system. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Vertebrate Fidgetin Restrains Axonal Growth by Severing Labile Domains of Microtubules

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    Lanfranco Leo

    2015-09-01

    Full Text Available Individual microtubules (MTs in the axon consist of a stable domain that is highly acetylated and a labile domain that is not. Traditional MT-severing proteins preferentially cut the MT in the stable domain. In Drosophila, fidgetin behaves in this fashion, with targeted knockdown resulting in neurons with a higher fraction of acetylated (stable MT mass in their axons. Conversely, in a fidgetin knockout mouse, the fraction of MT mass that is acetylated is lower than in the control animal. When fidgetin is depleted from cultured rodent neurons, there is a 62% increase in axonal MT mass, all of which is labile. Concomitantly, there are more minor processes and a longer axon. Together with experimental data showing that vertebrate fidgetin targets unacetylated tubulin, these results indicate that vertebrate fidgetin (unlike its fly ortholog regulates neuronal development by tamping back the expansion of the labile domains of MTs.

  17. Progress of Research on Diffuse Axonal Injury after Traumatic Brain Injury

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    Junwei Ma

    2016-01-01

    Full Text Available The current work reviews the concept, pathological mechanism, and process of diagnosing of DAI. The pathological mechanism underlying DAI is complicated, including axonal breakage caused by axonal retraction balls, discontinued protein transport along the axonal axis, calcium influx, and calpain-mediated hydrolysis of structural protein, degradation of axonal cytoskeleton network, the changes of transport proteins such as amyloid precursor protein, and changes of glia cells. Based on the above pathological mechanism, the diagnosis of DAI is usually made using methods such as CT, traditional and new MRI, biochemical markers, and neuropsychological assessment. This review provides a basis in literature for further investigation and discusses the pathological mechanism. It may also facilitate improvement of the accuracy of diagnosis for DAI, which may come to play a critical role in breaking through the bottleneck of the clinical treatment of DAI and improving the survival and quality of life of patients through clear understanding of pathological mechanisms and accurate diagnosis.

  18. Lithium Enhances Axonal Regeneration in Peripheral Nerve by Inhibiting Glycogen Synthase Kinase 3β Activation

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    Huanxing Su

    2014-01-01

    Full Text Available Brachial plexus injury often involves traumatic root avulsion resulting in permanent paralysis of the innervated muscles. The lack of sufficient regeneration from spinal motoneurons to the peripheral nerve (PN is considered to be one of the major causes of the unsatisfactory outcome of various surgical interventions for repair of the devastating injury. The present study was undertaken to investigate potential inhibitory signals which influence axonal regeneration after root avulsion injury. The results of the study showed that root avulsion triggered GSK-3β activation in the injured motoneurons and remaining axons in the ventral funiculus. Systemic application of a clinical dose of lithium suppressed activated GSK-3β in the lesioned spinal cord to the normal level and induced extensive axonal regeneration into replanted ventral roots. Our study suggests that GSK-3β activity is involved in negative regulation for axonal elongation and regeneration and lithium, the specific GSK-3β inhibitor, enhances motoneuron regeneration from CNS to PNS.

  19. Phosphatidylserine improves axonal transport by inhibition of HDAC and has potential in treatment of neurodegenerative diseases

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    Shiran Naftelberg

    2017-01-01

    Full Text Available Familial dysautonomia (FD is a rare children neurodegenerative disease caused due to a point mutation in the IKBKAP gene that results in decreased IKK complex-associated protein (IKAP protein production. The disease affects mostly the dorsal root ganglion (DRG and the sympathetic ganglion. Recently, we found that the molecular mechanisms underlying neurodegeneration in FD patients are defects in axonal transport of nerve growth factors and microtubule stability in the DRG. Neurons are highly polarized cells with very long axons. In order to survive and maintain proper function, neurons depend on transport of proteins and other cellular components from the neuronal body along the axons. We further demonstrated that IKAP is necessary for axon maintenance and showed that phosphatidylserine acts as an HDAC6 inhibitor to rescue neuronal function in FD cells. In this review, we will highlight our latest research findings.

  20. Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling

    DEFF Research Database (Denmark)

    Cheng, Jin; Sahani, Sadhna; Hausrat, Torben Johann

    2016-01-01

    Precise connection of thalamic barreloids with their corresponding cortical barrels is critical for processing of vibrissal sensory information. Here, we show that PRG-2, a phospholipid-interacting molecule, is important for thalamocortical axon guidance. Developing thalamocortical fibers both in...

  1. Celulitis por citomegalovirus

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    A. Ruiz Lascano

    2002-12-01

    Full Text Available Las lesiones cutáneas por citomegalovirus (CMV son infrecuentes y a menudo una manifestación tardía de una enfermedad sistémica, que generalmente anuncia un curso fatal. Comunicamos un caso de celulitis por CMV: una mujer de 70 años con trasplante renal efectuado 1 mes antes de la consulta, terapia inmunosupresora con ciclosporina A y metilprednisona. La paciente ingresó por fiebre, dolor e impotencia funcional en pierna derecha. Comprobamos la existencia de una placa de 8 por 4 cm eritematoedematosa. La tratamos con antibióticos sin mejoría, por lo que realizamos un estudio histopatológico de piel que mostró cambios citopáticos compatibles con infección por CMV. Los cultivos bacteriológicos y micológicos fueron negativos. La inmunohistoquímica específica para CMV y el estudio de reacción en cadena de la polimerasa (PCR de la biopsia de piel fueron positivas, al igual que la antigenemia. El tratamiento con ganciclovir produjo la mejoría del cuadro clínico. En la literatura revisada no hemos encontrado la celulitis como manifestación de enfermedad cutánea por CMV.

  2. Embolia pulmonar por polimetilmetacrilato

    OpenAIRE

    Héctor Gómez Santa María; Mauro García Aurelio; Yanina Castillo Costa; Víctor Mauro; Carlos Barrero

    2009-01-01

    Los primeros registros de embolia pulmonar por polimetilmetacrilato se publicaron recientemente (2003) y desde entonces se describieron no más de 15 casos. Se presenta el caso de un paciente joven a quien dos meses antes de la consulta se le había efectuado una vertebroplastia percutánea con polimetilmetacrilato. Por síntomas pleuríticos se le realizó una radiografía de tórax, que evidenció múltiples imágenes radioopacas en ambos campos pulmonares. La embolia pulmonar por polimetilmetacrilato...

  3. Tormenta simpática paroxística siguiendo a injuria Axonal difusa Paroxysmal sympathetic storm after diffuse axonal head injury

    OpenAIRE

    Pablo Young; Barbara C. Finn; Debora Pellegrini; Elias D. Soloaga; Julio E. Bruetman

    2006-01-01

    El término tormenta simpática paroxística se utiliza como sinónimo de alteraciones episódicas de la temperatura corporal, la presión arterial, la frecuencia respiratoria y cardíaca, el tamaño pupilar y el nivel de conciencia, que coinciden con hiperhidrosis, salivación excesiva y postura extensora. Esto siempre en el contexto de una injuria axonal difusa grave que sigue a un traumatismo encéfalo-craneano (TEC) grave. Presentamos dos pacientes jóvenes con injuria axonal difusa secundaria a TEC...

  4. Chondroitin sulfate proteoglycans negatively regulate the positioning of mitochondria and endoplasmic reticulum to distal axons.

    Science.gov (United States)

    Sainath, Rajiv; Armijo-Weingart, Lorena; Ketscheck, Andrea; Xu, Zhuxuan; Li, Shuxin; Gallo, Gianluca

    2017-12-01

    Chondroitin sulfate proteoglycans (CSPGs) are components of the extracellular matrix that inhibit the extension and regeneration of axons. However, the underlying mechanism of action remains poorly understood. Mitochondria and endoplasmic reticulum (ER) are functionally inter-linked organelles important to axon development and maintenance. We report that CSPGs impair the targeting of mitochondria and ER to the growth cones of chicken embryonic sensory axons. The effect of CSPGs on the targeting of mitochondria is blocked by inhibition of the LAR receptor for CSPGs. The regulation of the targeting of mitochondria and ER to the growth cone by CSPGs is due to attenuation of PI3K signaling, which is known to be downstream of LAR receptor activation. Dynactin is a required component of the dynein motor complex that drives the normally occurring retrograde evacuation of mitochondria from growth cones. CSPGs elevate the levels of p150 Glu dynactin found in distal axons, and inhibition of the interaction of dynactin with dynein increased axon lengths on CSPGs. CSPGs decreased the membrane potential of mitochondria, and pharmacological inhibition of mitochondria respiration at the growth cone independent of manipulation of mitochondria positioning impaired axon extension. Combined inhibition of dynactin and potentiation of mitochondria respiration further increased axon lengths on CSPGs relative to inhibition of dynactin alone. These data reveal that the regulation of the localization of mitochondria and ER to growth cones is a previously unappreciated aspect of the effects of CSPGs on embryonic axons. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1351-1370, 2017. © 2017 Wiley Periodicals, Inc.

  5. Selective axonal growth of embryonic hippocampal neurons according to topographic features of various sizes and shapes

    Directory of Open Access Journals (Sweden)

    Christine E Schmidt

    2010-12-01

    Full Text Available David Y Fozdar1*, Jae Y Lee2*, Christine E Schmidt2–6, Shaochen Chen1,3–5,7,1Departments of Mechanical Engineering, 2Chemical Engineering, 3Biomedical Engineering; 4Center for Nano Molecular Science and Technology; 5Texas Materials Institute; 6Institute of Neuroscience; 7Microelectronics Research Center, The University of Texas at Austin, Austin, TX, USA *Contributed equally to this workPurpose: Understanding how surface features influence the establishment and outgrowth of the axon of developing neurons at the single cell level may aid in designing implantable scaffolds for the regeneration of damaged nerves. Past studies have shown that micropatterned ridge-groove structures not only instigate axon polarization, alignment, and extension, but are also preferred over smooth surfaces and even neurotrophic ligands.Methods: Here, we performed axonal-outgrowth competition assays using a proprietary four-quadrant topography grid to determine the capacity of various micropatterned topographies to act as stimuli sequestering axon extension. Each topography in the grid consisted of an array of microscale (approximately 2 µm or submicroscale (approximately 300 nm holes or lines with variable dimensions. Individual rat embryonic hippocampal cells were positioned either between two juxtaposing topographies or at the borders of individual topographies juxtaposing unpatterned smooth surface, cultured for 24 hours, and analyzed with respect to axonal selection using conventional imaging techniques.Results: Topography was found to influence axon formation and extension relative to smooth surface, and the distance of neurons relative to topography was found to impact whether the topography could serve as an effective cue. Neurons were also found to prefer submicroscale over microscale features and holes over lines for a given feature size.Conclusion: The results suggest that implementing physical cues of various shapes and sizes on nerve guidance conduits

  6. Developmental plasticity of ascending spinal axons studies using the North American opossum, Didelphis virginiana.

    Science.gov (United States)

    Terman, J R; Wang, X M; Martin, G F

    1999-01-11

    The objectives of the present study were to determine if axons of all ascending tracts grow through the lesion after transection of the thoracic spinal cord during development in the North American opossum, and if so, whether they reach regions of the brain they normally innervate. Opossum pups were subjected to transection of the mid-thoracic cord at PD5, PD8, PD12, PD20, or PD26 and injections of Fast Blue (FB) into the lower thoracic or upper lumbar cord 30-40 days or 6 months later. In the PD5 transected cases, labeled axons were present in all of the supraspinal areas labeled by comparable injections in unlesioned, age-matched controls. In the experimental cases, however, labeled axons appeared to be fewer in number and in some areas more restricted in location than in the controls. When lesions were made at PD8, labeled axons were present in the brain of animals allowed to survive 30-40 days prior to FB injections but they were not observed in those allowed to survive 6 months. When lesions were made at PD12 or later, labeled axons were never found rostral to the lesion. It appears, therefore, that axons of all ascending spinal pathways grow though the lesion after transection of the thoracic cord in developing opossums and that they innervate appropriate areas of the brain. Interestingly, the critical period for such growth is shorter than that for most descending axons, suggesting that factors which influence loss of developmental plasticity are not the same for all axons.

  7. Activation of ganglion cells and axon bundles using epiretinal electrical stimulation.

    Science.gov (United States)

    Grosberg, Lauren E; Ganesan, Karthik; Goetz, Georges A; Madugula, Sasidhar S; Bhaskhar, Nandita; Fan, Victoria; Li, Peter; Hottowy, Pawel; Dabrowski, Wladyslaw; Sher, Alexander; Litke, Alan M; Mitra, Subhasish; Chichilnisky, E J

    2017-09-01

    Epiretinal prostheses for treating blindness activate axon bundles, causing large, arc-shaped visual percepts that limit the quality of artificial vision. Improving the function of epiretinal prostheses therefore requires understanding and avoiding axon bundle activation. This study introduces a method to detect axon bundle activation on the basis of its electrical signature and uses the method to test whether epiretinal stimulation can directly elicit spikes in individual retinal ganglion cells without activating nearby axon bundles. Combined electrical stimulation and recording from isolated primate retina were performed using a custom multielectrode system (512 electrodes, 10-μm diameter, 60-μm pitch). Axon bundle signals were identified by their bidirectional propagation, speed, and increasing amplitude as a function of stimulation current. The threshold for bundle activation varied across electrodes and retinas, and was in the same range as the threshold for activating retinal ganglion cells near their somas. In the peripheral retina, 45% of electrodes that activated individual ganglion cells (17% of all electrodes) did so without activating bundles. This permitted selective activation of 21% of recorded ganglion cells (7% of expected ganglion cells) over the array. In one recording in the central retina, 75% of electrodes that activated individual ganglion cells (16% of all electrodes) did so without activating bundles. The ability to selectively activate a subset of retinal ganglion cells without axon bundles suggests a possible novel architecture for future epiretinal prostheses. NEW & NOTEWORTHY Large-scale multielectrode recording and stimulation were used to test how selectively retinal ganglion cells can be electrically activated without activating axon bundles. A novel method was developed to identify axon activation on the basis of its unique electrical signature and was used to find that a subset of ganglion cells can be activated at single

  8. Numerical analysis of the method of internal dialysis of giant axons

    OpenAIRE

    Horn, L.W.

    1983-01-01

    This paper presents a numerical analysis of the method of internal dialysis used for studies of membrane transport in giant axons. Account is taken of the complete geometry, end effects, and finite dialyzate flow rates. Both influx and efflux experimental conditions are considered. Results place quantitative limits on system performance that are sufficiently general for use in experimental design. The completeness of solute equilibration and the uniformity of solute concentration at the axon ...

  9. The Impact of Motor Axon Misdirection and Attrition on Behavioral Deficit Following Experimental Nerve Injuries

    Science.gov (United States)

    Alant, Jacob Daniel de Villiers; Senjaya, Ferry; Ivanovic, Aleksandra; Forden, Joanne; Shakhbazau, Antos; Midha, Rajiv

    2013-01-01

    Peripheral nerve transection and neuroma-in-continuity injuries are associated with permanent functional deficits, often despite successful end-organ reinnervation. Axonal misdirection with non-specific reinnervation, frustrated regeneration and axonal attrition are believed to be among the anatomical substrates that underlie the poor functional recovery associated with these devastating injuries. Yet, functional deficits associated with axonal misdirection in experimental neuroma-in-continuity injuries have not yet been studied. We hypothesized that experimental neuroma-in-continuity injuries would result in motor axon misdirection and attrition with proportional persistent functional deficits. The femoral nerve misdirection model was exploited to assess major motor pathway misdirection and axonal attrition over a spectrum of experimental nerve injuries, with neuroma-in-continuity injuries simulated by the combination of compression and traction forces in 42 male rats. Sciatic nerve injuries were employed in an additional 42 rats, to evaluate the contribution of axonal misdirection to locomotor deficits by a ladder rung task up to 12 weeks. Retrograde motor neuron labeling techniques were utilized to determine the degree of axonal misdirection and attrition. Characteristic histological neuroma-in-continuity features were demonstrated in the neuroma-in-continuity groups and poor functional recovery was seen despite successful nerve regeneration and muscle reinnervation. Good positive and negative correlations were observed respectively between axonal misdirection (pinjuries of mixed motor nerves that contribute to the long-term functional deficits. Although widely accepted in theory, to our knowledge, this is the first experimental evidence to convincingly demonstrate these correlations with data inclusive of the neuroma-in-continuity spectrum. This work emphasizes the need to focus on strategies that promote both robust and accurate nerve regeneration to optimize

  10. Dysfunction of axonal membrane conductances in adolescents and young adults with spinal muscular atrophy

    OpenAIRE

    Farrar, Michelle A.; Vucic, Steve; Lin, Cindy S.-Y.; Park, Susanna B.; Johnston, Heather M.; du Sart, Desir?e; Bostock, Hugh; Kiernan, Matthew C.

    2011-01-01

    Spinal muscular atrophy is distinct among neurodegenerative conditions of the motor neuron, with onset in developing and maturing patients. Furthermore, the rate of degeneration appears to slow over time, at least in the milder forms. To investigate disease pathophysiology and potential adaptations, the present study utilized axonal excitability studies to provide insights into axonal biophysical properties and explored correlation with clinical severity. Multiple excitability indices (stimul...

  11. Independent signaling by Drosophila insulin receptor for axon guidance and growth

    Directory of Open Access Journals (Sweden)

    Caroline Rita Li

    2014-01-01

    Full Text Available The Drosophila insulin receptor (DInR regulates a diverse array of biological processes including growth, axon guidance, and sugar homeostasis. Growth regulation by DInR is mediated by Chico, the Drosophila homolog of vertebrate insulin-receptor-substrate proteins IRS1-4. In contrast, DInR regulation of photoreceptor axon guidance in the developing visual system is mediated by the SH2-SH3 domain adaptor protein Dreadlocks (Dock. In vitro studies by others identified five NPXY motifs, one in the juxtamembrane region and four in the signaling C-terminal tail (C-tail, important for interaction with Chico. Here we used yeast two-hybrid assays to identify regions in the DInR C-tail that interact with Dock. These Dock-binding sites were in separate portions of the C-tail from the previously identified Chico-binding sites. To test whether these sites are required for growth or axon guidance in whole animals, a panel of DInR proteins, in which the putative Chico and Dock interaction sites had been mutated individually or in combination, were tested for their ability to rescue viability, growth, and axon guidance defects of dinr mutant flies. Sites required for viability were identified. Unexpectedly, mutation of both putative Dock binding sites, either individually or in combination, did not lead to defects in photoreceptor axon guidance. Thus, either sites also required for viability are necessary for DInR function in axon guidance and/or there is redundancy built into the DInR/Dock interaction such that Dock is able to interact with multiple regions of DInR. We also found that simultaneous mutation of all 5 NPXY motifs implicated in Chico interaction drastically decreased growth in both male and female adult flies. Mutation of these 5 NPXY motifs did not affect photoreceptor axon guidance, showing that different sites within DInR control growth and axon guidance.

  12. Hydrogels as scaffolds and delivery systems to enhance axonal regeneration after injuries

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    Oscar A. Carballo-Molina

    2015-02-01

    Full Text Available Damage caused to neural tissue by disease or injury frequently produces a discontinuity in the nervous system. Such damage generates diverse alterations that are commonly permanent, due to the limited regeneration capacity of the adult nervous system, particularly the Central Nervous System (CNS. The cellular reaction to noxious stimulus leads to several events such as the formation of glial and fibrous scars, which inhibit axonal regeneration in both the CNS and the Peripheral Nervous System (PNS. Although in the PNS there is some degree of nerve regeneration, it is common that the growing axons reinnervate incorrect areas, causing mismatches. Providing a permissive substrate for axonal regeneration in combination with delivery systems for the release of molecules, which enhances axonal growth, could increase regeneration and the recovery of functions in the CNS or the PNS. Currently, there are no effective vehicles to supply growth factors or cells to the damaged/diseased nervous system. Hydrogels are polymers that are biodegradable, biocompatible and have the capacity to deliver a large range of molecules in situ. The inclusion of cultured neural cells into hydrogels forming three-dimensional structures allows the formation of synapses and neuronal survival. There is also evidence showing that hydrogels constitute an amenable substrate for axonal growth of endogenous or grafted cells, overcoming the presence of axonal regeneration inhibitory molecules, in both the central and peripheral nervous systems. Recent experiments suggest that hydrogels can carry and deliver several proteins relevant for improving neuronal survival and axonal growth. Although the use of hydrogels is appealing, its effectiveness is still a matter of discussion, and more results are needed to achieve consistent recovery using different parameters. This review also discusses areas of opportunity where hydrogels can be applied, in order to promote axonal regeneration of

  13. Myelin-associated proteins labelled by slow axonal transport

    International Nuclear Information System (INIS)

    Giorgi, P.P.; DuBois, H.

    1981-01-01

    This paper deals with the problem of protein metabolism and provides evidence that the neuronal contribution to myelin metabolism may be restricted to lipids only. On the other hand this line of research led to the partial characterization of a group of neuronal proteins probably involved in axo-glial interactions subserving the onset of myelination and the structural maintenance of the mature myelin sheath. Intraocular injection of radioactive amino acids allows the study of the anterograde transport of labelled proteins along retinofugal fibres which are well myelinated. Myelin extracted from the optic nerve and tract under these conditions also contains labelled proteins. Three hypotheses are available to explain this phenomenon. To offer an explanation for this phenomenon the work was planned as follows. a) Characterization of the spatio-temporal pattern of labelling of myelin, in order to define the experimental conditions (survival time and region of the optic pathway to be studied) necessary to obtain maximal labelling. b) Characterization (by gel electrophoresis) of the myelin-associated proteins which become labelled by axonal transport, in order to work on a consistent pattern of labelling. c) Investigation of the possible mechanism responsible for the labelling of myelin-associated proteins. (Auth.)

  14. EFFECT OF DETERGENT ON ELECTRICAL PROPERTIES OF SQUID AXON MEMBRANE.

    Science.gov (United States)

    KISHIMOTO, U; ADELMAN, W J

    1964-05-01

    The effects of detergents on squid giant axon action and resting potentials as well as membrane conductances in the voltage clamp have been studied. Anionic detergents (sodium lauryl sulfate, 0.1 to 1.0 mM; dimethyl benzene sulfonate, 1 to 20 mM, pH 7.6) cause a temporary increase and a later decrease of action potential height and the value of the resting potential. Cationic detergent (cetyl trimethyl ammonium chloride, 6 x 10(-5)M or more, pH 7.6) generally brings about immediate and irreversible decreases in the action and resting potentials. Non-ionic detergent (tween 80, 0.1 M, pH 7.6) causes a slight reversible reduction of action potential height without affecting the value of the resting potential. Both anionic and cationic detergents generally decrease the sodium and potassium conductances irreversibly. The effect of non-ionic detergent is to decrease the sodium conductance reversibly, leaving the potassium conductance almost unchanged.

  15. Axon ensheathment and metabolic supply by glial cells in Drosophila.

    Science.gov (United States)

    Schirmeier, Stefanie; Matzat, Till; Klämbt, Christian

    2016-06-15

    Neuronal function requires constant working conditions and a well-balanced supply of ions and metabolites. The metabolic homeostasis in the nervous system crucially depends on the presence of glial cells, which nurture and isolate neuronal cells. Here we review recent findings on how these tasks are performed by glial cells in the genetically amenable model organism Drosophila melanogaster. Despite the small size of its nervous system, which would allow diffusion of metabolites, a surprising division of labor between glial cells and neurons is evident. Glial cells are glycolytically active and transfer lactate and alanine to neurons. Neurons in turn do not require glycolysis but can use the glially provided compounds for their energy homeostasis. Besides feeding neurons, glial cells also insulate neuronal axons in a way similar to Remak fibers in the mammalian nervous system. The molecular mechanisms orchestrating this insulation require neuregulin signaling and resemble the mechanisms controlling glial differentiation in mammals surprisingly well. We hypothesize that metabolic cross talk and insulation of neurons by glial cells emerged early during evolution as two closely interlinked features in the nervous system. This article is part of a Special Issue entitled SI: Myelin Evolution. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Mechanisms of neurodegeneration and axonal dysfunction in multiple sclerosis.

    Science.gov (United States)

    Friese, Manuel A; Schattling, Benjamin; Fugger, Lars

    2014-04-01

    Multiple sclerosis (MS) is the most frequent chronic inflammatory disease of the CNS, and imposes major burdens on young lives. Great progress has been made in understanding and moderating the acute inflammatory components of MS, but the pathophysiological mechanisms of the concomitant neurodegeneration--which causes irreversible disability--are still not understood. Chronic inflammatory processes that continuously disturb neuroaxonal homeostasis drive neurodegeneration, so the clinical outcome probably depends on the balance of stressor load (inflammation) and any remaining capacity for neuronal self-protection. Hence, suitable drugs that promote the latter state are sorely needed. With the aim of identifying potential novel therapeutic targets in MS, we review research on the pathological mechanisms of neuroaxonal dysfunction and injury, such as altered ion channel activity, and the endogenous neuroprotective pathways that counteract oxidative stress and mitochondrial dysfunction. We focus on mechanisms inherent to neurons and their axons, which are separable from those acting on inflammatory responses and might, therefore, represent bona fide neuroprotective drug targets with the capability to halt MS progression.

  17. Diffuse Axonal Injury: Epidemiology, Outcome and Associated Risk Factors

    Directory of Open Access Journals (Sweden)

    Rita de Cassia Almeida Vieira

    2016-10-01

    Full Text Available Abstract Diffuse axonal injury (DAI, a type of traumatic injury, is known for its severe consequences. However, there are few studies describing the outcomes of DAI and the risk factors associated with it. This study aimed to describe the outcome for patients with a primary diagnosis of DAI six months after trauma and to identify sociodemographic and clinical factors associated with mortality and dependence at this time point. Seventy-eight patients with DAI were recruited from July 2013 to February 2014 in a prospective cohort study. Patient outcome was analyzed using the Extended Glasgow Outcome Scale (GOS-E within six months of the traumatic injury. The mean Injury Severity Score was 35.0 (SD = 11.9, and the mean New Injury Severity Score (NISS was 46.2 (SD = 15.9. Mild DAI was observed in 44.9% of the patients and severe DAI in 35.9%. Six months after trauma, 30.8% of the patients had died, and 45.1% had shown full recovery according to the GOS-E. In the logistic regression model, the severity variables—DAI with hypoxia, as measured by peripheral oxygen saturation, and hypotension with NISS value—had a statistically significant association with patient mortality; on the other hand, severity of DAI and length of hospital stay were the only significant predictors for dependence. Therefore, severity of DAI emerged as a risk factor for both mortality and dependence.

  18. Detection of functional homotopy in traumatic axonal injury

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jian; Gao, Lei; Xie, Kai; Zhan, Jie; Luo, Xiaoping; Wang, Huifang; Zhang, Huifang; Zhao, Jing; Zhou, Fuqing; Zeng, Xianjun; He, Laichang; He, Yulin; Gong, Honghan [Nanchang University, Department of Radiology, The First Affiliated Hospital, Nanchang City, Jiangxi (China)

    2017-01-15

    This study aimed to explore the interhemispheric intrinsic connectivity in traumatic axonal injury (TAI) patients. Twenty-one patients with TAI (14 males, seven females; mean age, 38.71 ± 15.25 years) and 22 well-matched healthy controls (16 males, six females; mean age, 38.50 ± 13.82 years) were recruited, and from them we obtained resting-state fMRI data. Interhemispheric coordination was examined using voxel-mirrored homotopic connectivity (VMHC) and seed-based functional connectivity analysis was performed. We observed significantly decreased VMHC in a number of regions in TAI patients, including the prefrontal, temporal, occipital, parietal, and posterior cingulate cortices, thalami and cerebellar posterior lobes. Subsequent seed-based functional connectivity analysis revealed widely disrupted functional connectivity between the regions of local homotopic connectivity deficits and other areas of the brain, particularly the areas subserving the default, salience, integrative, and executive systems. The lower VMHC of the inferior frontal gyrus and basal ganglia, thalamus, and caudate were significant correlated with the Beck Depression Inventory score, Clinical Dementia Rating score, and Mini-Mental State Examination score, respectively. TAI is associated with regionally decreased interhemispheric interactions and extensively disrupted seed-based functional connectivity, generating further evidence of diffuse disconnection being associated with clinical symptoms in TAI patients. (orig.)

  19. MRI findings in acute diffuse axonal injured patients

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Hidetaka [Nippon Medical School, Tokyo (Japan)

    2001-07-01

    Diffuse axonal injury (DAI) in the acute stage was clinically evaluated using magnetic resonance imaging (MRI), which is considered superior to computed tomography (CT) in detecting parenchymal brain lesions. MRI was disadvantageous, however, to patients suffering from acute severe head injury because of the long time required to construct imaging and unstable patient vital signs. We conducted MRI safely under a high magnetic field (1.5 tesla) in acute DAI by close observation and with nonmagnetic respirator and electrocardiographic monitoring. MRI was conducted in 95 patients diagnosed with DAI classified into mild (14), moderate (17) and severe (64) DAI by criteria established by Gennarelli (1986). In patients with mild or moderate DAI, CT revealed no lesion in the parenchymal area although MRI detected lesions in every case, mainly in cortical white matter or basal ganglia. In patients with severe DAI, CT revealed parenchymal lesions in 14 although MRI detected further lesions in cortical white matter, basal ganglia, corpus callosum and brainstem in every case. These results correspond well to the experimental model Gennarelli's. This study concluded that MRI was useful in assessing acute DAI patients. (author)

  20. BDNF promotes target innervation of Xenopus mandibular trigeminal axons in vivo.

    Science.gov (United States)

    Huang, Jeffrey K; Dorey, Karel; Ishibashi, Shoko; Amaya, Enrique

    2007-05-31

    Trigeminal nerves consist of ophthalmic, maxillary, and mandibular branches that project to distinct regions of the facial epidermis. In Xenopus embryos, the mandibular branch of the trigeminal nerve extends toward and innervates the cement gland in the anterior facial epithelium. The cement gland has previously been proposed to provide a short-range chemoattractive signal to promote target innervation by mandibular trigeminal axons. Brain derived neurotrophic factor, BDNF is known to stimulate axon outgrowth and branching. The goal of this study is to determine whether BDNF functions as the proposed target recognition signal in the Xenopus cement gland. We found that the cement gland is enriched in BDNF mRNA transcripts compared to the other neurotrophins NT3 and NT4 during mandibular trigeminal nerve innervation. BDNF knockdown in Xenopus embryos or specifically in cement glands resulted in the failure of mandibular trigeminal axons to arborise or grow into the cement gland. BDNF expressed ectodermal grafts, when positioned in place of the cement gland, promoted local trigeminal axon arborisation in vivo. BDNF is necessary locally to promote end stage target innervation of trigeminal axons in vivo, suggesting that BDNF functions as a short-range signal that stimulates mandibular trigeminal axon arborisation and growth into the cement gland.

  1. Axonal wiring in neural development: Target-independent mechanisms help to establish precision and complexity.

    Science.gov (United States)

    Petrovic, Milan; Schmucker, Dietmar

    2015-09-01

    The connectivity patterns of many neural circuits are highly ordered and often impressively complex. The intricate order and complexity of neuronal wiring remain not only a challenge for questions related to circuit functions but also for our understanding of how they develop with such an apparent precision. The chemotropic guidance of the growing axon by target-derived cues represents a central paradigm for how neurons get connected with the correct target cells. However, many studies reveal a remarkable variety of important target-independent wiring mechanisms. These mechanisms include axonal sorting, axonal tiling, growth cone polarization, as well as cell-intrinsic mechanisms underlying growth cone sprouting, and neurite branching. Our review focuses on target independent wiring mechanisms and in particular on recent progress emerging from studies on three different sensory systems: olfactory, visual, and somatosensory. We discuss molecular mechanisms that operate during axon-axon interactions or constitute axon-intrinsic functions and outline how they complement the well-known target-dependent wiring mechanisms. © 2015 WILEY Periodicals, Inc.

  2. Effects of medium flow on axon growth with or without nerve growth factor.

    Science.gov (United States)

    Kumamoto, Junichi; Kitahata, Hiroyuki; Goto, Makiko; Nagayama, Masaharu; Denda, Mitsuhiro

    2015-09-11

    Axon growth is a crucial process in regeneration of damaged nerves. On the other hand, elongation of nerve fibers in the epidermis has been observed in skin of atopic dermatitis patients. Thus, regulation of nerve fiber extension might be an effective strategy to accelerate nerve regeneration and/or to reduce itching in pruritus dermatosis. We previously demonstrated that neurons and epidermal keratinocytes similarly contain multiple receptors that are activated by various environmental factors, and in particular, keratinocytes are influenced by shear stress. Thus, in the present study, we evaluated the effects of micro-flow of the medium on axon growth in the presence or absence of nerve growth factor (NGF), using cultured dorsal-root-ganglion (DRG) cells. The apparatus, AXIS™, consists of two chambers connected by a set of microgrooves, through which signaling molecules and axons, but not living cells, can pass. When DRG cells were present in chamber 1, NGF was present in chamber 2, and micro-flow was directed from chamber 1 to chamber 2, axon growth was significantly increased compared with other conditions. Acceleration of axon growth in the direction of the micro-flow was also observed in the absence of NGF. These results suggest that local micro-flow might significantly influence axon growth. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. PTEN deletion from adult-generated dentate granule cells disrupts granule cell mossy fiber axon structure.

    Science.gov (United States)

    LaSarge, Candi L; Santos, Victor R; Danzer, Steve C

    2015-03-01

    Dysregulation of the mTOR-signaling pathway is implicated in the development of temporal lobe epilepsy. In mice, deletion of PTEN from hippocampal dentate granule cells leads to mTOR hyperactivation and promotes the rapid onset of spontaneous seizures. The mechanism by which these abnormal cells initiate epileptogenesis, however, is unclear. PTEN-knockout granule cells develop abnormally, exhibiting morphological features indicative of increased excitatory input. If these cells are directly responsible for seizure genesis, it follows that they should also possess increased output. To test this prediction, dentate granule cell axon morphology was quantified in control and PTEN-knockout mice. Unexpectedly, PTEN deletion increased giant mossy fiber bouton spacing along the axon length, suggesting reduced innervation of CA3. Increased width of the mossy fiber axon pathway in stratum lucidum, however, which likely reflects an unusual increase in mossy fiber axon collateralization in this region, offsets the reduction in boutons per axon length. These morphological changes predict a net increase in granule cell innervation of CA3. Increased diameter of axons from PTEN-knockout cells would further enhance granule cell communication with CA3. Altogether, these findings suggest that amplified information flow through the hippocampal circuit contributes to seizure occurrence in the PTEN-knockout mouse model of temporal lobe epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Kinesin mRNA is present in the squid giant axon.

    Science.gov (United States)

    Gioio, A E; Chun, J T; Crispino, M; Capano, C P; Giuditta, A; Kaplan, B B

    1994-07-01

    Recently, we reported the construction of a cDNA library encoding a heterogeneous population of polyadenylated mRNAs present in the squid giant axon. The nucleic acid sequencing of several randomly selected clones led to the identification of cDNAs encoding beta-actin and beta-tubulin, two relatively abundant axonal mRNA species. To continue characterization of this unique mRNA population, the axonal cDNA library was screened with a cDNA probe encoding the carboxy terminus of the squid kinesin heavy chain. The sequencing of several positive clones unambiguously identified axonal kinesin cDNA clones. The axonal localization of kinesin mRNA was subsequently verified by in situ hybridization histochemistry. In addition, the presence of kinesin RNA sequences in the axoplasmic polyribosome fraction was demonstrated using PCR methodology. In contrast to these findings, mRNA encoding the squid sodium channel was not detected in axoplasmic RNA, although these sequences were relatively abundant in the giant fiber lobe. Taken together, these findings demonstrate that kinesin mRNA is a component of a select group of mRNAs present in the squid giant axon, and suggest that kinesin may be synthesized locally in this model invertebrate motor neuron.

  5. Local gene expression in axons and nerve endings: the glia-neuron unit.

    Science.gov (United States)

    Giuditta, Antonio; Chun, Jong Tai; Eyman, Maria; Cefaliello, Carolina; Bruno, Anna Paola; Crispino, Marianna

    2008-04-01

    Neurons have complex and often extensively elongated processes. This unique cell morphology raises the problem of how remote neuronal territories are replenished with proteins. For a long time, axonal and presynaptic proteins were thought to be exclusively synthesized in the cell body, which delivered them to peripheral sites by axoplasmic transport. Despite this early belief, protein has been shown to be synthesized in axons and nerve terminals, substantially alleviating the trophic burden of the perikaryon. This observation raised the question of the cellular origin of the peripheral RNAs involved in protein synthesis. The synthesis of these RNAs was initially attributed to the neuron soma almost by default. However, experimental data and theoretical considerations support the alternative view that axonal and presynaptic RNAs are also transcribed in the flanking glial cells and transferred to the axon domain of mature neurons. Altogether, these data suggest that axons and nerve terminals are served by a distinct gene expression system largely independent of the neuron cell body. Such a local system would allow the neuron periphery to respond promptly to environmental stimuli. This view has the theoretical merit of extending to axons and nerve terminals the marginalized concept of a glial supply of RNA (and protein) to the neuron cell body. Most long-term plastic changes requiring de novo gene expression occur in these domains, notably in presynaptic endings, despite their intrinsic lack of transcriptional capacity. This review enlightens novel perspectives on the biology and pathobiology of the neuron by critically reviewing these issues.

  6. A Simple Method for 3D Analysis of Immunolabeled Axonal Tracts in a Transparent Nervous System

    Directory of Open Access Journals (Sweden)

    Morgane Belle

    2014-11-01

    Full Text Available Clearing techniques have been developed to transparentize mouse brains, thereby preserving 3D structure, but their complexity has limited their use. Here, we show that immunolabeling of axonal tracts followed by optical clearing with solvents (3DISCO and light-sheet microscopy reveals brain connectivity in mouse embryos and postnatal brains. We show that the Robo3 receptor is selectively expressed by medial habenula axons forming the fasciculus retroflexus (FR and analyzed the development of this commissural tract in mutants of the Slit/Robo and DCC/Netrin pathways. Netrin-1 and DCC are required to attract FR axons to the midline, but the two mutants exhibit specific and heterogeneous axon guidance defects. Moreover, floor-plate-specific deletion of Slit ligands with a conditional Slit2 allele perturbs not only midline crossing by FR axons but also their anteroposterior distribution. In conclusion, this method represents a unique and powerful imaging tool to study axonal connectivity in mutant mice.

  7. Propagation of action potentials along complex axonal trees. Model and implementation.

    Science.gov (United States)

    Manor, Y; Gonczarowski, J; Segev, I

    1991-12-01

    Axonal trees are typically morphologically and physiologically complicated structures. Because of this complexity, axonal trees show a large repertoire of behavior: from transmission lines with delay, to frequency filtering devices in both temporal and spatial domains. Detailed theoretical exploration of the electrical behavior of realistically complex axonal trees is notably lacking, mainly because of the absence of a simple modeling tool. AXONTREE is an attempt to provide such a simulator. It is written in C for the SUN workstation and implements both a detailed compartmental modeling of Hodgkin and Huxley-like kinetics, and a more abstract, event-driven, modeling approach. The computing module of AXONTREE is introduced together with its input/output features. These features allow graphical construction of arbitrary trees directly on the computer screen, and superimposition of the results on the simulated structure. Several numerical improvements that increase the computational efficiency by a factor of 5-10 are presented; most notable is a novel method of dynamic lumping of the modeled tree into simpler representations ("equivalent cables"). AXONTREE's performance is examined using a reconstructed terminal of an axon from a Y cell in cat visual cortex. It is demonstrated that realistically complicated axonal trees can be handled efficiently. The application of AXONTREE for the study of propagation delays along axonal trees is presented in the companion paper (Manor et al., 1991).

  8. mRNP assembly, axonal transport, and local translation in neurodegenerative diseases.

    Science.gov (United States)

    Khalil, Bilal; Morderer, Dmytro; Price, Phillip L; Liu, Feilin; Rossoll, Wilfried

    2018-02-17

    The development, maturation, and maintenance of the mammalian nervous system rely on complex spatiotemporal patterns of gene expression. In neurons, this is achieved by the expression of differentially localized isoforms and specific sets of mRNA-binding proteins (mRBPs) that regulate RNA processing, mRNA trafficking, and local protein synthesis at remote sites within dendrites and axons. There is growing evidence that axons contain a specialized transcriptome and are endowed with the machinery that allows them to rapidly alter their local proteome via local translation and protein degradation. This enables axons to quickly respond to changes in their environment during development, and to facilitate axon regeneration and maintenance in adult organisms. Aside from providing autonomy to neuronal processes, local translation allows axons to send retrograde injury signals to the cell soma. In this review, we discuss evidence that disturbances in mRNP transport, granule assembly, axonal localization, and local translation contribute to pathology in various neurodegenerative diseases, including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). Copyright © 2018. Published by Elsevier B.V.

  9. Vesicular Axonal Transport is Modified In Vivo by Tau Deletion or Overexpression in Drosophila

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    Yasmina Talmat-Amar

    2018-03-01

    Full Text Available Structural microtubule associated protein Tau is found in high amount in axons and is involved in several neurodegenerative diseases. Although many studies have highlighted the toxicity of an excess of Tau in neurons, the in vivo understanding of the endogenous role of Tau in axon morphology and physiology is poor. Indeed, knock-out mice display no strong cytoskeleton or axonal transport phenotype, probably because of some important functional redundancy with other microtubule-associated proteins (MAPs. Here, we took advantage of the model organism Drosophila, which genome contains only one homologue of the Tau/MAP2/MAP4 family to decipher (endogenous Tau functions. We found that Tau depletion leads to a decrease in microtubule number and microtubule density within axons, while Tau excess leads to the opposite phenotypes. Analysis of vesicular transport in tau mutants showed altered mobility of vesicles, but no change in the total amount of putatively mobile vesicles, whereas both aspects were affected when Tau was overexpressed. In conclusion, we show that loss of Tau in tau mutants not only leads to a decrease in axonal microtubule density, but also impairs axonal vesicular transport, albeit to a lesser extent compared to the effects of an excess of Tau.

  10. Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism

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    Suda Shiro

    2011-08-01

    Full Text Available Abstract Background Axon-guidance proteins play a crucial role in brain development. As the dysfunction of axon-guidance signaling is thought to underlie the microstructural abnormalities of the brain in people with autism, we examined the postmortem brains of people with autism to identify any changes in the expression of axon-guidance proteins. Results The mRNA and protein expression of axon-guidance proteins, including ephrin (EFNA4, eEFNB3, plexin (PLXNA4, roundabout 2 (ROBO2 and ROBO3, were examined in the anterior cingulate cortex and primary motor cortex of autistic brains (n = 8 and n = 7, respectively and control brains (n = 13 and n = 8, respectively using real-time reverse-transcriptase PCR (RT-PCR and western blotting. Real-time RT-PCR revealed that the relative expression levels of EFNB3, PLXNA4A and ROBO2 were significantly lower in the autistic group than in the control group. The protein levels of these three genes were further analyzed by western blotting, which showed that the immunoreactive values for PLXNA4 and ROBO2, but not for EFNB3, were significantly reduced in the ACC of the autistic brains compared with control brains. Conclusions In this study, we found decreased expression of axon-guidance proteins such as PLXNA4 and ROBO2 in the brains of people with autism, and suggest that dysfunctional axon-guidance protein expression may play an important role in the pathophysiology of autism.

  11. Fractional cable equation for general geometry: A model of axons with swellings and anomalous diffusion

    Science.gov (United States)

    López-Sánchez, Erick J.; Romero, Juan M.; Yépez-Martínez, Huitzilin

    2017-09-01

    Different experimental studies have reported anomalous diffusion in brain tissues and notably this anomalous diffusion is expressed through fractional derivatives. Axons are important to understand neurodegenerative diseases such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease. Indeed, abnormal accumulation of proteins and organelles in axons is a hallmark of these diseases. The diffusion in the axons can become anomalous as a result of this abnormality. In this case the voltage propagation in axons is affected. Another hallmark of different neurodegenerative diseases is given by discrete swellings along the axon. In order to model the voltage propagation in axons with anomalous diffusion and swellings, in this paper we propose a fractional cable equation for a general geometry. This generalized equation depends on fractional parameters and geometric quantities such as the curvature and torsion of the cable. For a cable with a constant radius we show that the voltage decreases when the fractional effect increases. In cables with swellings we find that when the fractional effect or the swelling radius increases, the voltage decreases. Similar behavior is obtained when the number of swellings and the fractional effect increase. Moreover, we find that when the radius swelling (or the number of swellings) and the fractional effect increase at the same time, the voltage dramatically decreases.

  12. Quantitative muscle ultrasound is useful for evaluating secondary axonal degeneration in chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Hokkoku, Keiichi; Matsukura, Kiyoshi; Uchida, Yudai; Kuwabara, Midori; Furukawa, Yuichi; Tsukamoto, Hiroshi; Hatanaka, Yuki; Sonoo, Masahiro

    2017-10-01

    In chronic inflammatory demyelinating polyneuropathy (CIDP), exclusion of secondary axonal degeneration is challenging with conventional methods such as nerve conduction study (NCS), needle electromyography, and nerve biopsy. Increased echo intensity (EI) and decreased muscle thickness (MT) identified on muscle ultrasound (MUS) examination represent muscle denervation due to axonal degeneration in neurogenic disorders, suggesting MUS as a new tool to detect secondary axonal degeneration in patients with CIDP. EI and MT of abductor pollicis brevis, abductor digiti minimi, and first dorsal interosseous muscles were measured in 16 CIDP patients. Raw values were converted into z -scores using data from 60 normal controls (NCs). Six of 45 muscles showed abnormally high EI and low MT, suggesting denervation following secondary axonal degeneration. These six muscles belonged to two patients with long disease history, unresponsiveness to treatment, and long interval from onset to initial therapy. There were no significant differences in EI and MT ( p  = .23 and .67, respectively) between the CIDP and NC groups, although NCS results revealed obvious demyelinating abnormalities in all CIDP patients, suggesting the fact that muscle structures will be preserved, and EI and MT will not change unless secondary axonal degeneration occurs in CIDP. MUS is a promising tool for evaluating secondary axonal degeneration in patients with CIDP.

  13. Methodological advances in imaging intravital axonal transport [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    James N. Sleigh

    2017-03-01

    Full Text Available Axonal transport is the active process whereby neurons transport cargoes such as organelles and proteins anterogradely from the cell body to the axon terminal and retrogradely in the opposite direction. Bi-directional transport in axons is absolutely essential for the functioning and survival of neurons and appears to be negatively impacted by both aging and diseases of the nervous system, such as Alzheimer’s disease and amyotrophic lateral sclerosis. The movement of individual cargoes along axons has been studied in vitro in live neurons and tissue explants for a number of years; however, it is currently unclear as to whether these systems faithfully and consistently replicate the in vivo situation. A number of intravital techniques originally developed for studying diverse biological events have recently been adapted to monitor axonal transport in real-time in a range of live organisms and are providing novel insight into this dynamic process. Here, we highlight these methodological advances in intravital imaging of axonal transport, outlining key strengths and limitations while discussing findings, possible improvements, and outstanding questions.

  14. Plum, an immunoglobulin superfamily protein, regulates axon pruning by facilitating TGF-β signaling.

    Science.gov (United States)

    Yu, Xiaomeng M; Gutman, Itai; Mosca, Timothy J; Iram, Tal; Ozkan, Engin; Garcia, K Christopher; Luo, Liqun; Schuldiner, Oren

    2013-05-08

    Axon pruning during development is essential for proper wiring of the mature nervous system, but its regulation remains poorly understood. We have identified an immunoglobulin superfamily (IgSF) transmembrane protein, Plum, that is cell autonomously required for axon pruning of mushroom body (MB) γ neurons and for ectopic synapse refinement at the developing neuromuscular junction in Drosophila. Plum promotes MB γ neuron axon pruning by regulating the expression of Ecdysone Receptor-B1, a key initiator of axon pruning. Genetic analyses indicate that Plum acts to facilitate signaling of Myoglianin, a glial-derived TGF-β, on MB γ neurons upstream of the type-I TGF-β receptor Baboon. Myoglianin, Baboon, and Ecdysone Receptor-B1 are also required for neuromuscular junction ectopic synapse refinement. Our study highlights both IgSF proteins and TGF-β facilitation as key promoters of developmental axon elimination and demonstrates a mechanistic conservation between MB axon pruning during metamorphosis and the refinement of ectopic larval neuromuscular connections. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Producción de IFN−γ en cultivos de linfocitos humanos por efecto de los extractos metanólicos de cuatro ecotipos de Lepidium peruvianum, Chacón (Brassicaceae

    Directory of Open Access Journals (Sweden)

    Libertad Alzamora

    2013-05-01

    Full Text Available Se estudió la actividad inmunoduladora sobre cultivos de linfocitos T humanos de sangre periférica. Se evaluó la producción de IFN−γ inducida por los extractos metanólicos (EM de los ecotipos blanco, negro, rojo y morado de Lepidium peruvianum (conocida también como Lepidium meyenii Walp. maca. Luego de cultivar los linfocitos con los respectivos EM de maca durante 14 horas sólo el EM del ecotipo morado indujo la producción significativa de IFN−γ cuantificada mediante Elispot. El extracto metanólico del ecotipo morado de maca posee propiedades inmunoestimuladoras importantes, desencadenando la activación de linfocitos T humanos.

  16. Embolia pulmonar por polimetilmetacrilato

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    Héctor Gómez Santa María

    2009-01-01

    Full Text Available Los primeros registros de embolia pulmonar por polimetilmetacrilato se publicaron recientemente (2003 y desde entonces se describieron no más de 15 casos. Se presenta el caso de un paciente joven a quien dos meses antes de la consulta se le había efectuado una vertebroplastia percutánea con polimetilmetacrilato. Por síntomas pleuríticos se le realizó una radiografía de tórax, que evidenció múltiples imágenes radioopacas en ambos campos pulmonares. La embolia pulmonar por polimetilmetacrilato es una complicación muy poco frecuente de ese procedimiento y un diagnóstico diferencial para tener en cuenta en pacientes con el antecedente y que consulten por dolor precordial o disnea.REV ARGENT CARDIOL 2009;77:129-130.

  17. Infección inducida en el roedor selvático Dasyprocta leporina (Rodentia: Dasyproctidae), con huevos larvados de Lagochilascaris minor (Nematoda: Ascarididae)

    OpenAIRE

    Gregorio,S.; Volcán,G.; Clemencia,E.; Medrano,P.

    1990-01-01

    Ejemplares de Dasyprocta leporina Linnaeus, 1758 fueron criados alejados de su ambiente natural. A los 3 ó 4 meses de edad, se los inoculó por vía oral con huevos de Lagochilascaris minor Leiper, 1909 obtenidos de una paciente nativa. Los huevos se los incubó por más de 80 dias, para que de ellos fuese posible obtener por compresión mecánica, larvas que se mantuviesen vivas en medio acuoso por 48 horas o más. Sacrificados los animales a los 14 ó 46 dias posteriores a la infección, se hallaron...

  18. Dendritic Branch Intersections Are Structurally Regulated Targets for Efficient Axonal Wiring and Synaptic Clustering

    Science.gov (United States)

    Pinchas, Monika; Baranes, Danny

    2013-01-01

    Synaptic clustering on dendritic branches enhances plasticity, input integration and neuronal firing. However, the mechanisms guiding axons to cluster synapses at appropriate sites along dendritic branches are poorly understood. We searched for such a mechanism by investigating the structural overlap between dendritic branches and axons in a simplified model of neuronal networks - the hippocampal cell culture. Using newly developed software, we converted images of meshes of overlapping axonal and dendrites into topological maps of intersections, enabling quantitative study of overlapping neuritic geometry at the resolution of single dendritic branch-to-branch and axon-to-branch crossings. Among dendro-dendritic crossing configurations, it was revealed that the orientations through which dendritic branches cross is a regulated attribute. While crossing angle distribution among branches thinner than 1 µm appeared to be random, dendritic branches 1 µm or wider showed a preference for crossing each other at angle ranges of either 50°–70° or 80°–90°. It was then found that the dendro-dendritic crossings themselves, as well as their selective angles, both affected the path of axonal growth. Axons displayed 4 fold stronger tendency to traverse within 2 µm of dendro-dendritic intersections than at farther distances, probably to minimize wiring length. Moreover, almost 70% of the 50°–70° dendro-denritic crossings were traversed by axons from the obtuse angle’s zone, whereas only 15% traversed through the acute angle’s zone. By contrast, axons showed no orientation restriction when traversing 80°–90° crossings. When such traverse behavior was repeated by many axons, they converged in the vicinity of dendro-dendritic intersections, thereby clustering their synaptic connections. Thus, the vicinity of dendritic branch-to-branch crossings appears to be a regulated structure used by axons as a target for efficient wiring and as a preferred site for synaptic

  19. Transient developmental Purkinje cell axonal torpedoes in healthy and ataxic mouse cerebellum

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    Lovisa Ljungberg

    2016-11-01

    Full Text Available Information is carried out of the cerebellar cortical microcircuit via action potentials propagated along Purkinje cell axons. In several human neurodegenerative diseases, focal axonal swellings on Purkinje cells – known as torpedoes – have been associated with Purkinje cell loss. Interestingly, torpedoes are also reported to appear transiently during development in rat cerebellum. The function of Purkinje cell axonal torpedoes in health as well as in disease is poorly understood. We investigated the properties of developmental torpedoes in the postnatal mouse cerebellum of wildtype and transgenic mice. We found that Purkinje cell axonal torpedoes transiently appeared on axons of Purkinje neurons, with the largest number of torpedoes observed at postnatal day 11 (P11. This was after peak developmental apoptosis had occurred, when Purkinje cell counts in a lobule were static, suggesting that most developmental torpedoes appear on axons of neurons that persist into adulthood. We found that developmental torpedoes were not associated with a presynaptic GABAergic marker, indicating that they are not synapses. They were seldom found at axonal collateral branch points, and lacked microglia enrichment, suggesting that they are unlikely to be involved in axonal refinement. Interestingly, we found several differences between developmental torpedoes and disease-related torpedoes: developmental torpedoes occured largely on myelinated axons, and were not associated with changes in basket cell innervation on their parent soma. Disease-related torpedoes are typically reported to contain neurofilament; while the majority of developmental torpedoes did as well, a fraction of smaller developmental torpedoes did not. These differences indicate that developmental torpedoes may not be functionally identical to disease-related torpedoes. To study this further, we used a mouse model of spinocerebellar ataxia type 6 (SCA6, and found elevated disease

  20. Sustained maximal voluntary contraction produces independent changes in human motor axons and the muscle they innervate.

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    David A Milder

    Full Text Available The repetitive discharges required to produce a sustained muscle contraction results in activity-dependent hyperpolarization of the motor axons and a reduction in the force-generating capacity of the muscle. We investigated the relationship between these changes in the adductor pollicis muscle and the motor axons of its ulnar nerve supply, and the reproducibility of these changes. Ten subjects performed a 1-min maximal voluntary contraction. Activity-dependent changes in axonal excitability were measured using threshold tracking with electrical stimulation at the wrist; changes in the muscle were assessed as evoked and voluntary electromyography (EMG and isometric force. Separate components of axonal excitability and muscle properties were tested at 5 min intervals after the sustained contraction in 5 separate sessions. The current threshold required to produce the target muscle action potential increased immediately after the contraction by 14.8% (p<0.05, reflecting decreased axonal excitability secondary to hyperpolarization. This was not correlated with the decline in amplitude of muscle force or evoked EMG. A late reversal in threshold current after the initial recovery from hyperpolarization peaked at -5.9% at ∼35 min (p<0.05. This pattern was mirrored by other indices of axonal excitability revealing a previously unreported depolarization of motor axons in the late recovery period. Measures of axonal excitability were relatively stable at rest but less so after sustained activity. The coefficient of variation (CoV for threshold current increase was higher after activity (CoV 0.54, p<0.05 whereas changes in voluntary (CoV 0.12 and evoked twitch (CoV 0.15 force were relatively stable. These results demonstrate that activity-dependent changes in motor axon excitability are unlikely to contribute to concomitant changes in the muscle after sustained activity in healthy people. The variability in axonal excitability after sustained activity

  1. Neural ECM molecules in axonal and synaptic homeostatic plasticity.

    Science.gov (United States)

    Frischknecht, Renato; Chang, Kae-Jiun; Rasband, Matthew N; Seidenbecher, Constanze I

    2014-01-01

    Neural circuits can express different forms of plasticity. So far, Hebbian synaptic plasticity was considered the most important plastic phenomenon, but over the last decade, homeostatic mechanisms gained more interest because they can explain how a neuronal network maintains stable baseline function despite multiple plastic challenges, like developmental plasticity, learning, or lesion. Such destabilizing influences can be counterbalanced by the mechanisms of homeostatic plasticity, which restore the stability of neuronal circuits. Synaptic scaling is a mechanism in which neurons can detect changes in their own firing rates through a set of molecular sensors that then regulate receptor trafficking to scale the accumulation of glutamate receptors at synaptic sites. Additional homeostatic mechanisms allow local changes in synaptic activation to generate local synaptic adaptations and network-wide changes in activity, which lead to adjustments in the balance between excitation and inhibition. The molecular pathways underlying these forms of homeostatic plasticity are currently under intense investigation, and it becomes clear that the extracellular matrix (ECM) of the brain, which surrounds individual neurons and integrates them into the tissue, is an important element in these processes. As a highly dynamic structure, which can be remodeled and degraded in an activity-dependent manner and in concerted action of neurons and glial cells, it can on one hand promote structural and functional plasticity and on the other hand stabilize neural microcircuits. This chapter highlights the composition of brain ECM with particular emphasis on perisynaptic and axonal matrix formations and its involvement in plastic and adaptive processes of the central nervous system.

  2. Channelrhodopsin-2 localised to the axon initial segment.

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    Matthew S Grubb

    2010-10-01

    Full Text Available The light-gated cation channel Channelrhodopsin-2 (ChR2 is a powerful and versatile tool for controlling neuronal activity. Currently available versions of ChR2 either distribute uniformly throughout the plasma membrane or are localised specifically to somatodendritic or synaptic domains. Localising ChR2 instead to the axon initial segment (AIS could prove an extremely useful addition to the optogenetic repertoire, targeting the channel directly to the site of action potential initiation, and limiting depolarisation and associated calcium entry elsewhere in the neuron. Here, we describe a ChR2 construct that we localised specifically to the AIS by adding the ankyrinG-binding loop of voltage-gated sodium channels (Na(vII-III to its intracellular terminus. Expression of ChR2-YFP-Na(vII-III did not significantly affect the passive or active electrical properties of cultured rat hippocampal neurons. However, the tiny ChR2 currents and small membrane depolarisations resulting from AIS targeting meant that optogenetic control of action potential firing with ChR2-YFP-Na(vII-III was unsuccessful in baseline conditions. We did succeed in stimulating action potentials with light in some ChR2-YFP-Na(vII-III-expressing neurons, but only when blocking KCNQ voltage-gated potassium channels. We discuss possible alternative approaches to obtaining precise control of neuronal spiking with AIS-targeted optogenetic constructs and propose potential uses for our ChR2-YFP-Na(vII-III probe where subthreshold modulation of action potential initiation is desirable.

  3. Necl-4/SynCAM-4 is expressed in myelinating oligodendrocytes but not required for axonal myelination.

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    Ying Zhu

    Full Text Available The timing and progression of axonal myelination are precisely controlled by intercellular interactions between neurons and glia in development. Previous in vitro studies demonstrated that Nectin like 4 (Necl-4, also known as cell adhesion molecule Cadm-4 or SynCAM-4 plays an essential role in axonal myelination by Schwann cells in the peripheral nervous system (PNS. However, the role of Necl-4 protein in axonal myelination in the developing central nervous system (CNS has remained unknown. In this study, we discovered upregulation of Necl-4 expression in mature oligodendrocytes at perinatal stages when axons undergo active myelination. We generated Necl4 gene knockout mice, but found that disruption of Necl-4 gene did not affect oligodendrocyte differentiation and myelin formation in the CNS. Surprisingly, disruption of Necl-4 had no significant effect on axonal myelination in the PNS either. Therefore, our results demonstrated that Necl-4 is dispensable for axonal myelination in the developing nervous system.

  4. Matrix metalloproteinase 2 and membrane type 1 matrix metalloproteinase co-regulate axonal outgrowth of mouse retinal ganglion cells

    DEFF Research Database (Denmark)

    Gaublomme, Djoere; Buyens, Tom; De Groef, Lies

    2014-01-01

    , we were able to show that broad-spectrum MMP inhibition reduces axon outgrowth of mouse retinal ganglion cells (RGCs), implicating MMPs as beneficial factors in axonal regeneration. Additional studies, using more specific MMP inhibitors and MMP-deficient mice, disclosed that both MMP-2 and MT1-MMP......, but not MMP-9, are involved in this process. Furthermore, administration of a novel antibody to MT1-MMP that selectively blocks pro-MMP-2 activation revealed a functional co-involvement of these proteinases in determining RGC axon outgrowth. Subsequent immunostainings showed expression of both MMP-2 and MT1......-MMP in RGC axons and glial cells. Finally, results from combined inhibition of MMP-2 and β1-integrin were suggestive for a functional interaction between these molecules. Overall, our data indicate MMP-2 and MT1-MMP as promising axonal outgrowth-promoting molecules. Axonal regeneration in the central...

  5. Neurotoxicity and aggressiveness triggered by low-level lead in children: a review Neurotoxicidad y agresividad desencadenadas por bajos niveles de plomo en niños: una revisión

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    Kelly Polido Kaneshiro Olympio

    2009-09-01

    Full Text Available Lead-induced neurotoxicity acquired by low-level long-term exposure has special relevance for children. A plethora of recent reports has demonstrated a direct link between low-level lead exposure and deficits in the neurobehavioral-cognitive performance manifested from childhood through adolescence. In many studies, aggressiveness and delinquency have also been suggested as symptoms of lead poisoning. Several environmental, occupational and domestic sources of contaminant lead and consequent health risks are largely identified and understood, but the occurrences of lead poisoning remain numerous. There is an urgent need for public health policies to prevent lead poisoning so as to reduce individual and societal damages and losses. In this paper we describe unsuspected sources of contaminant lead, discuss the economic losses and urban violence possibly associated with lead contamination and review the molecular basis of lead-induced neurotoxicity, emphasizing its effects on the social behavior, delinquency and IQ of children and adolescents.La neurotoxicidad adquirida inducida por la exposición prolongada a bajos niveles de plomo tiene una importancia especial en los niños. Una plétora de publicaciones recientes ha demostrado el vínculo directo existente entre la exposición a bajos niveles de plomo y el déficit en el desempeño neuroconductual-cognitivo manifestado desde la infancia hasta el final de la adolescencia. En numerosos estudios, la agresividad y la delincuencia juvenil también se han considerado síntomas de la intoxicación por plomo. Se han identificado y explicado ampliamente varias fuentes ambientales, laborales y domésticas de contaminación por plomo y los riesgos resultantes para la salud, pero aún son numerosos los casos de intoxicación por plomo. Se necesitan urgentes políticas de salud pública para prevenir la intoxicación por plomo de manera de reducir los daños y las pérdidas, tanto individuales como para la

  6. Primary neuron culture for nerve growth and axon guidance studies in zebrafish (Danio rerio.

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    Zheyan Chen

    Full Text Available Zebrafish (Danio rerio is a widely used model organism in genetics and developmental biology research. Genetic screens have proven useful for studying embryonic development of the nervous system in vivo, but in vitro studies utilizing zebrafish have been limited. Here, we introduce a robust zebrafish primary neuron culture system for functional nerve growth and guidance assays. Distinct classes of central nervous system neurons from the spinal cord, hindbrain, forebrain, and retina from wild type zebrafish, and fluorescent motor neurons from transgenic reporter zebrafish lines, were dissociated and plated onto various biological and synthetic substrates to optimize conditions for axon outgrowth. Time-lapse microscopy revealed dynamically moving growth cones at the tips of extending axons. The mean rate of axon extension in vitro was 21.4±1.2 µm hr(-1 s.e.m. for spinal cord neurons, which corresponds to the typical ∼0.5 mm day(-1 growth rate of nerves in vivo. Fluorescence labeling and confocal microscopy demonstrated that bundled microtubules project along axons to the growth cone central domain, with filamentous actin enriched in the growth cone peripheral domain. Importantly, the growth cone surface membrane expresses receptors for chemotropic factors, as detected by immunofluorescence microscopy. Live-cell functional assays of axon extension and directional guidance demonstrated mammalian brain-derived neurotrophic factor (BDNF-dependent stimulation of outgrowth and growth cone chemoattraction, whereas mammalian myelin-associated glycoprotein inhibited outgrowth. High-resolution live-cell Ca(2+-imaging revealed local elevation of cytoplasmic Ca(2+ concentration in the growth cone induced by BDNF application. Moreover, BDNF-induced axon outgrowth, but not basal outgrowth, was blocked by treatments to suppress cytoplasmic Ca(2+ signals. Thus, this primary neuron culture model system may be useful for studies of neuronal development

  7. Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase

    International Nuclear Information System (INIS)

    Yang Dongren; Howard, Angela; Bruun, Donald; Ajua-Alemanj, Mispa; Pickart, Cecile; Lein, Pamela J.

    2008-01-01

    A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE -/- ) versus wild type (AChE +/+ ) mice indicated that while these OPs inhibited axonal growth in AChE +/+ DRG neurons, they had no effect on axonal growth in AChE -/- DRG neurons. However, transfection of AChE -/- DRG neurons with cDNA encoding full-length AChE restored the wild type response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs

  8. Axon and dendrite geography predict the specificity of synaptic connections in a functioning spinal cord network

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    Borisyuk Roman

    2007-09-01

    Full Text Available Abstract Background How specific are the synaptic connections formed as neuronal networks develop and can simple rules account for the formation of functioning circuits? These questions are assessed in the spinal circuits controlling swimming in hatchling frog tadpoles. This is possible because detailed information is now available on the identity and synaptic connections of the main types of neuron. Results The probabilities of synapses between 7 types of identified spinal neuron were measured directly by making electrical recordings from 500 pairs of neurons. For the same neuron types, the dorso-ventral distributions of axons and dendrites were measured and then used to calculate the probabilities that axons would encounter particular dendrites and so potentially form synaptic connections. Surprisingly, synapses were found between all types of neuron but contact probabilities could be predicted simply by the anatomical overlap of their axons and dendrites. These results suggested that synapse formation may not require axons to recognise specific, correct dendrites. To test the plausibility of simpler hypotheses, we first made computational models that were able to generate longitudinal axon growth paths and reproduce the axon distribution patterns and synaptic contact probabilities found in the spinal cord. To test if probabilistic rules could produce functioning spinal networks, we then made realistic computational models of spinal cord neurons, giving them established cell-specific properties and connecting them into networks using the contact probabilities we had determined. A majority of these networks produced robust swimming activity. Conclusion Simple factors such as morphogen gradients controlling dorso-ventral soma, dendrite and axon positions may sufficiently constrain the synaptic connections made between different types of neuron as the spinal cord first develops and allow functional networks to form. Our analysis implies that

  9. Rescuing axons from degeneration does not affect retinal ganglion cell death

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    S. de Lima

    2016-01-01

    Full Text Available After a traumatic injury to the central nervous system, the distal stumps of axons undergo Wallerian degeneration (WD, an event that comprises cytoskeleton and myelin breakdown, astrocytic gliosis, and overexpression of proteins that inhibit axonal regrowth. By contrast, injured neuronal cell bodies show features characteristic of attempts to initiate the regenerative process of elongating their axons. The main molecular event that leads to WD is an increase in the intracellular calcium concentration, which activates calpains, calcium-dependent proteases that degrade cytoskeleton proteins. The aim of our study was to investigate whether preventing axonal degeneration would impact the survival of retinal ganglion cells (RGCs after crushing the optic nerve. We observed that male Wistar rats (weighing 200-400 g; n=18 treated with an exogenous calpain inhibitor (20 mM administered via direct application of the inhibitor embedded within the copolymer resin Evlax immediately following optic nerve crush showed a delay in the onset of WD. This delayed onset was characterized by a decrease in the number of degenerated fibers (P<0.05 and an increase in the number of preserved fibers (P<0.05 4 days after injury. Additionally, most preserved fibers showed a normal G-ratio. These results indicated that calpain inhibition prevented the degeneration of optic nerve fibers, rescuing axons from the process of axonal degeneration. However, analysis of retinal ganglion cell survival demonstrated no difference between the calpain inhibitor- and vehicle-treated groups, suggesting that although the calpain inhibitor prevented axonal degeneration, it had no effect on RGC survival after optic nerve damage.

  10. ON Cone Bipolar Cell Axonal Synapses in the OFF Inner Plexiform Layer of the Rabbit Retina

    Science.gov (United States)

    Lauritzen, J. Scott; Anderson, James R.; Jones, Bryan W.; Watt, Carl B.; Mohammed, Shoeb; Hoang, John V.; Marc, Robert E.

    2012-01-01

    Analysis of the rabbit retinal connectome RC1 reveals that the division between the ON and OFF inner plexiform layer (IPL) is not structurally absolute. ON cone bipolar cells make non-canonical axonal synapses onto specific targets and receive amacrine cell synapses in the nominal OFF layer, creating novel motifs, including inhibitory crossover networks. Automated transmission electron microscope (ATEM) imaging, molecular tagging, tracing, and rendering of ≈ 400 bipolar cells reveals axonal ribbons in 36% of ON cone bipolar cells, throughout the OFF IPL. The targets include GABA-positive amacrine cells (γACs), glycine-positive amacrine cells (GACs) and ganglion cells. Most ON cone bipolar cell axonal contacts target GACs driven by OFF cone bipolar cells, forming new architectures for generating ON-OFF amacrine cells. Many of these ON-OFF GACs target ON cone bipolar cell axons, ON γACs and/or ON-OFF ganglion cells, representing widespread mechanisms for OFF to ON crossover inhibition. Other targets include OFF γACs presynaptic to OFF bipolar cells, forming γAC-mediated crossover motifs. ON cone bipolar cell axonal ribbons drive bistratified ON-OFF ganglion cells in the OFF layer and provide ON drive to polarity-appropriate targets such as bistratified diving ganglion cells (bsdGCs). The targeting precision of ON cone bipolar cell axonal synapses shows that this drive incidence is necessarily a joint distribution of cone bipolar cell axonal frequency and target cell trajectories through a given volume of the OFF layer. Such joint distribution sampling is likely common when targets are sparser than sources and when sources are coupled, as are ON cone bipolar cells. PMID:23042441

  11. A multi-component model of the developing retinocollicular pathway incorporating axonal and synaptic growth.

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    Keith B Godfrey

    2009-12-01

    Full Text Available During development, neurons extend axons to different brain areas and produce stereotypical patterns of connections. The mechanisms underlying this process have been intensively studied in the visual system, where retinal neurons form retinotopic maps in the thalamus and superior colliculus. The mechanisms active in map formation include molecular guidance cues, trophic factor release, spontaneous neural activity, spike-timing dependent plasticity (STDP, synapse creation and retraction, and axon growth, branching and retraction. To investigate how these mechanisms interact, a multi-component model of the developing retinocollicular pathway was produced based on phenomenological approximations of each of these mechanisms. Core assumptions of the model were that the probabilities of axonal branching and synaptic growth are highest where the combined influences of chemoaffinity and trophic factor cues are highest, and that activity-dependent release of trophic factors acts to stabilize synapses. Based on these behaviors, model axons produced morphologically realistic growth patterns and projected to retinotopically correct locations in the colliculus. Findings of the model include that STDP, gradient detection by axonal growth cones and lateral connectivity among collicular neurons were not necessary for refinement, and that the instructive cues for axonal growth appear to be mediated first by molecular guidance and then by neural activity. Although complex, the model appears to be insensitive to variations in how the component developmental mechanisms are implemented. Activity, molecular guidance and the growth and retraction of axons and synapses are common features of neural development, and the findings of this study may have relevance beyond organization in the retinocollicular pathway.

  12. Inducción de la enzima triptófano 2,3 dioxigenasa por glucocorticoides y su papel en la tolerancia materna al feto

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    Angela Cadavid

    2004-02-01

    Full Text Available

    El mecanismo por el cual la madre no rechaza al feto, sigue siendo una incógnita en la inmunología de la reproducción. Una de las hipótesis planteadas es la inmunosupresión mediada por el catabolismo del triptófano, el cual es un amino ácido sencial para la proliferación de los linfocitos T. Una de las nzimas que cataboliza el triptófano es la triptófano 2,3 ioxigenasa (TDO.
    La TDO es inducida por los glucocorticoides en el hígado, pero aún no se conoce si estos inducen la producción de la TDO n la interfase materno fetal al interactuar con los receptores resentes en células estromales y NK; En un modelo murino, e observó que la TDO se expresa en la interfase materno etal con un pico que coincide con el de mayor actividad de egradación del triptófano, sugiriendo entonces que esta nzima puede estar involucrada en la tolerancia materna al feto.

     

     

  13. Development of the Early Axon Scaffold in the Rostral Brain of the Small Spotted Cat Shark (Scyliorhinus canicula) Embryo

    OpenAIRE

    Ware, Michelle; Waring, Colin P.; Schubert, Frank R.

    2014-01-01

    International audience; The cat shark is increasingly used as a model for Chondrichthyes, an evolutionarily important sister group of the bony vertebrates that include teleosts and tetrapods. In the bony vertebrates, the first axon tracts form a highly conserved early axon scaffold. The corresponding structure has not been well characterised in cat shark and will prove a useful model for comparative studies. Using pan-neural markers, the early axon scaffold of the cat shark, Scyliorhinus cani...

  14. Dynamics of degeneration and regeneration in developing zebrafish peripheral axons reveals a requirement for extrinsic cell types

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    Villegas Rosario

    2012-06-01

    Full Text Available Abstract Background Understanding the cellular mechanisms regulating axon degeneration and regeneration is crucial for developing treatments for nerve injury and neurodegenerative disease. In neurons, axon degeneration is distinct from cell body death and often precedes or is associated with the onset of disease symptoms. In the peripheral nervous system of both vertebrates and invertebrates, after degeneration of detached fragments, axons can often regenerate to restore function. Many studies of axonal degeneration and regeneration have used in vitro approaches, but the influence of extrinsic cell types on these processes can only be fully addressed in live animals. Because of its simplicity and superficial location, the larval zebrafish posterior lateral line (pLL nerve is an ideal model system for live studies of axon degeneration and regeneration. Results We used laser axotomy and time-lapse imaging of pLL axons to characterize the roles of leukocytes, Schwann cells and target sensory hair cells in axon degeneration and regeneration in vivo. Immune cells were essential for efficient removal of axonal debris after axotomy. Schwann cells were required for proper fasciculation and pathfinding of regenerating axons to their target cells. Intact target hair cells were not themselves required for regeneration, but chemical ablation of neuromasts caused axons to transiently deviate from their normal paths. Conclusions Macrophages, Schwann cells, and target sensory organs are required for distinct aspects of pLL axon degeneration or regeneration in the zebrafish larva. Our work introduces a powerful vertebrate model for analyzing axonal degeneration and regeneration in the living animal and elucidating the role of extrinsic cell types in these processes.

  15. Implicación de NF-κB y p53 en la expresión de receptores de muerte-TRAIL y apoptosis por procianidinas en células metastásicas humanas SW620

    Directory of Open Access Journals (Sweden)

    María Elena Maldonado

    2010-12-01

    Resultados. La muerte celular activada por procianidinas fue prevenida por inhibidores específicos de NF-κB y de p53: amino-4-(4-fenoxi-feniletilamino-quinazolina y pifitrina α, respectivamente. La quinazolina y la pifitrina α inhibieron la activación dependiente de procianidinas de TRAIL-DR4/DR5. Sin embargo, el aumento en la expresión de TRAIL-DR4 disminuyó significativamente sólo cuando la quinazolina y la pifitrina α se usaron simultáneamente; este efecto no se observó con cada uno por separado. No se observaron para TRAIL-DR5 estos efectos, lo cual sugiere que la expresión de cada receptor de muerte TRAIL puede estar regulada en forma diferente. Conclusiones. Estos datos sugieren que NF-κB y p53 se requieren parcialmente en la apoptosis de células SW620 inducida por procianidinas mediante el aumento en TRAIL-DR4/-DR5. La proporción de DR4/DR5 podría ser un factor determinante en la activación de la apoptosis por vía de TRAIL-DR4/-DR5.

  16. Bergmann glia and the recognition molecule CHL1 organize GABAergic axons and direct innervation of Purkinje cell dendrites.

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    Fabrice Ango

    2008-04-01

    Full Text Available The geometric and subcellular organization of axon arbors distributes and regulates electrical signaling in neurons and networks, but the underlying mechanisms have remained elusive. In rodent cerebellar cortex, stellate interneurons elaborate characteristic axon arbors that selectively innervate Purkinje cell dendrites and likely regulate dendritic integration. We used GFP BAC transgenic reporter mice to examine the cellular processes and molecular mechanisms underlying the development of stellate cell axons and their innervation pattern. We show that stellate axons are organized and guided towards Purkinje cell dendrites by an intermediate scaffold of Bergmann glial (BG fibers. The L1 family immunoglobulin protein Close Homologue of L1 (CHL1 is localized to apical BG fibers and stellate cells during the development of stellate axon arbors. In the absence of CHL1, stellate axons deviate from BG fibers and show aberrant branching and orientation. Furthermore, synapse formation between aberrant stellate axons and Purkinje dendrites is reduced and cannot be maintained, leading to progressive atrophy of axon terminals. These results establish BG fibers as a guiding scaffold and CHL1 a molecular signal in the organization of stellate axon arbors and in directing their dendritic innervation.

  17. Regulated viral BDNF delivery in combination with Schwann cells promotes axonal regeneration through capillary alginate hydrogels after spinal cord injury.

    Science.gov (United States)

    Liu, Shengwen; Sandner, Beatrice; Schackel, Thomas; Nicholson, LaShae; Chtarto, Abdelwahed; Tenenbaum, Liliane; Puttagunta, Radhika; Müller, Rainer; Weidner, Norbert; Blesch, Armin

    2017-09-15

    Grafting of cell-seeded alginate capillary hydrogels into a spinal cord lesion site provides an axonal bridge while physically directing regenerating axonal growth in a linear pattern. However, without an additional growth stimulus, bridging axons fail to extend into the distal host spinal cord. Here we examined whether a combinatory strategy would support regeneration of descending axons across a cervical (C5) lateral hemisection lesion in the rat spinal cord. Following spinal cord transections, Schwann cell (SC)-seeded alginate hydrogels were grafted to the lesion site and AAV5 expressing brain-derived neurotrophic factor (BDNF) under control of a tetracycline-regulated promoter was injected caudally. In addition, we examined whether SC injection into the caudal spinal parenchyma would further enhance regeneration of descending axons to re-enter the host spinal cord. Our data show that both serotonergic and descending axons traced by biotinylated dextran amine (BDA) extend throughout the scaffolds. The number of regenerating axons is significantly increased when caudal BDNF expression is activated and transient BDNF delivery is able to sustain axons after gene expression is switched off. Descending axons are confined to the caudal graft/host interface even with continuous BDNF expression for 8weeks. Only with a caudal injection of SCs, a pathway facilitating axonal regeneration through the host/graft interface is generated allowing axons to successfully re-enter the caudal spinal cord. Recovery from spinal cord injury is poor due to the limited regeneration observed in the adult mammalian central nervous system. Biomaterials, cell transplantation and growth factors that can guide axons across a lesion site, provide a cellular substrate, stimulate axon growth and have shown some promise in increasing the growth distance of regenerating axons. In the present study, we combined an alginate biomaterial with linear channels with transplantation of Schwann cells within

  18. Molecular mechanisms of retinal ganglion cell degeneration in glaucoma and future prospects for cell body and axonal protection

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    Yasunari eMunemasa

    2013-01-01

    Full Text Available Glaucoma, which affects more than 70 million people worldwide, is a heterogeneous group of disorders with a resultant common denominator; optic neuropathy, eventually leading to irreversible blindness. The clinical manifestations of primary open-angle glaucoma (POAG, the most common subtype of glaucoma, include excavation of the optic disc and progressive loss of visual field. Axonal degeneration of retinal ganglion cells (RGCs and apoptotic death of their cell bodies are observed in glaucoma, in which the reduction of intraocular pressure is known to slow progression of the disease. A pattern of localized retinal nerve fiber layer defects in glaucoma patients indicates that axonal degeneration may precede RGC body death in this condition. The mechanisms of degeneration of neuronal cell bodies and their axons may differ. In this review, we addressed the molecular mechanisms of cell body death and axonal degeneration in glaucoma and proposed axonal protection in addition to cell body protection. The concept of axonal protection may become a new therapeutic strategy to prevent further axonal degeneration or revive dying axons in patients with preperimetric glaucoma. Further study will be needed to clarify whether the combination therapy of axonal protection and cell body protection will have greater protective effects in early or progressive glaucomatous optic neuropathy.

  19. Patterns of axonal branching of neurons of the substantia nigra pars reticulata and pars lateralis in the rat.

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    Cebrián, Carolina; Parent, André; Prensa, Lucía

    2005-11-21

    Axons from neurons of the rat substantia nigra pars reticulata (SNr) and pars lateralis (SNl) were traced after injecting their cell body with biotinylated dextran amine. Thirty-two single axons were reconstructed from serial sagittal sections with a camera lucida, whereas four other SNr axons were reconstructed in the coronal plane to determine whether they innervate the contralateral hemisphere. Four distinct types of SNr projection neurons were identified based on their main axonal targets: type I neurons that project to the thalamus; type II neurons that target the thalamus, the superior colliculus (SC), and the pedunculopontine tegmental nucleus (PPTg); type III neurons that project to the periaqueductal gray matter and the thalamus; and type IV neurons that target the deep mesencephalic nucleus (DpMe) and the SC. The axons of the SNl showed the same branching patterns as SNr axons of types I, II, and IV. The coronal reconstructions demonstrated that SNr neurons innervate the thalamus, the SC, and the DpMe bilaterally. At the thalamic level, SNr and SNl axons targeted preferentially the ventral medial, ventral lateral, paracentral, parafascicular, and mediodorsal nuclei. Axons reaching the SC arborized selectively within the deep layers of this structure. Our results reveal that the SNr and SNl harbor several subtypes of projection neurons endowed with a highly patterned set of axon collaterals. This organization allows single neurons of these output structures of the basal ganglia to exert a multifaceted influence on a wide variety of diencephalic and midbrain structures. (c) 2005 Wiley-Liss, Inc.

  20. Intraneural Injection of ATP Stimulates Regeneration of Primary Sensory Axons in the Spinal Cord.

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    Wu, Dongsheng; Lee, Sena; Luo, Juan; Xia, Haijian; Gushchina, Svetlana; Richardson, Peter M; Yeh, John; Krügel, Ute; Franke, Heike; Zhang, Yi; Bo, Xuenong

    2018-02-07

    Injury to the peripheral axons of sensory neurons strongly enhances the regeneration of their central axons in the spinal cord. It remains unclear on what molecules that initiate such conditioning effect. Because ATP is released extracellularly by nerve and other tissue injury, we hypothesize that injection of ATP into a peripheral nerve might mimic the stimulatory effect of nerve injury on the regenerative state of the primary sensory neurons. We found that a single injection of 6 μl of 150 μm ATP into female rat sciatic nerve quadrupled the number of axons growing into a lesion epicenter in spinal cord after a concomitant dorsal column transection. A second boost ATP injection 1 week after the first one markedly reinforced the stimulatory effect of a single injection. Single ATP injection increased expression of phospho-STAT3 and GAP43, two markers of regenerative activity, in sensory neurons. Double ATP injections sustained the activation of phospho-STAT3 and GAP43, which may account for the marked axonal growth across the lesion epicenter. Similar studies performed on P2X7 or P2Y2 receptor knock-out mice indicate P2Y2 receptors are involved in the activation of STAT3 after ATP injection or conditioning lesion, whereas P2X7 receptors are not. Injection of ATP at 150 μm caused little Wallerian degeneration and behavioral tests showed no significant long-term adverse effects on sciatic nerve functions. The results in this study reveal possible mechanisms underlying the stimulation of regenerative programs and suggest a practical strategy for stimulating axonal regeneration following spinal cord injury. SIGNIFICANCE STATEMENT Injury of peripheral axons of sensory neurons has been known to strongly enhance the regeneration of their central axons in the spinal cord. In this study, we found that injection of ATP into a peripheral nerve can mimic the effect of peripheral nerve injury and significantly increase the number of sensory axons growing across lesion

  1. Glial progenitor cell migration promotes CNS axon growth on functionalized electroconducting microfibers.

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    Collazos-Castro, Jorge E; García-Rama, Concepción; Alves-Sampaio, Alexandra

    2016-04-15

    Electroactive systems that promote directional axonal growth and migration of glial progenitor cells (GPC) are needed for the treatment of neurological injuries. We report the functionalization of electroconducting microfibers with multiple biomolecules that synergistically stimulate the proliferation and migration of GPC, which in turn induce axonal elongation from embryonic cerebral cortex neurons. PEDOT doped with poly[(4-styrenesulfonic acid)-co-(maleic acid)] was synthesized on carbon microfibers and used for covalent attachment of molecules to the electroactive surface. The molecular complexes that promoted GPC proliferation and migration, followed by axonal extension, were composed of polylysine, heparin, basic fibroblast growth factor (bFGF), and matricellular proteins; the combination of bFGF with vitronectin or fibronectin being indispensable for sustained glial and axonal growth. The rate of glial-induced axonal elongation was about threefold that of axons growing directly on microfibers functionalized with polylysine alone. Electrical stimuli applied through the microfibers released bFGF and fibronectin from the polymer surface, consequently reducing GPC proliferation and promoting their differentiation into astrocytes, without causing cell detachment or toxicity. These results suggest that functionalized electroactive microfibers may provide a multifunctional tool for controlling neuron-glia interactions and enhancing neural repair. We report a multiple surface functionalization strategy for electroconducting microfibers (MFs), in order to promote proliferation and guided migration of glial precursor cells (GPC) and consequently create a permissive substrate for elongation of central nervous system (CNS) axons. GPC divided and migrated extensively on the functionalized MFs, leading to fast elongation of embryonic cerebral cortex axons. The application of electric pulses thorough the MFs controlled glial cell division and differentiation. The

  2. Slow Muscle Precursors Lay Down a Collagen XV Matrix Fingerprint to Guide Motor Axon Navigation.

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    Guillon, Emilie; Bretaud, Sandrine; Ruggiero, Florence

    2016-03-02

    The extracellular matrix (ECM) provides local positional information to guide motoneur