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Sample records for axonal inducida por

  1. Osteomalacia inducida por tumor: hemangiopericitoma rinosinusal

    Directory of Open Access Journals (Sweden)

    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

    OpenAIRE

    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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    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.

  5. 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.

  6. Osteonecrosis de hueso maxilar inducida por bisfosfonatos

    OpenAIRE

    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...

  7. Osteoporosis secundaria y Osteoporosis inducida por glucocorticoides (OIG

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Osteomalacia inducida por tumor: hemangiopericitoma rinosinusal Tumor-induced osteomalacia: rhinosinusal hemangiopericytoma

    Directory of Open Access Journals (Sweden)

    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.Tumor-induced osteomalacia is a rare disease of bone metabolism. The characteristic of this disease is an increase in phosphate excretion followed by hypophosphatemia, due to phosphaturic agents produced by different types of tumors. Tumor resection results in complete resolution of clinical, biochemical and radiological abnormalities. We present the case of a 61 year old man with signs, symptoms and laboratory findings consistent with oncogenic osteomalacia due to a rhino-sinusal mesenchymal tumor. The histological diagnosis showed a vascular neoplasm: hemangiopericytoma.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. Paciente con trombocitopenia trombótica inducida por heparina en hemodiálisis: abordaje de la anticoagulación del circuito

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    Mirian García Martínez

    Full Text Available Resumen El tratamiento renal sustitutivo de hemodiálisis es una técnica de depuración sanguínea extraterrenal, que requiere proteger al circuito extracorpóreo del paciente. Actualmente la heparina es el anticoagulante endovenoso de elección para evitar este tipo de complicaciones intradiálisis, siendo necesaria la individualización de las dosis por paciente. La trombocitopenia trombótica inducida por heparina es uno de los posibles efectos secundarios producidos por la administración de heparina. La bivalirudina es un inhibidor directo y específico de la trombina, útil en diferentes procedimientos, siendo utilizado en pacientes con problemas con la heparina y con fracaso renal crónico terminal que requieren terapias de diálisis continuas. Caso clínico: Paciente de 46 años, con múltiples antecedentes personales. Al inicio de su proceso debutó con una Gangrena de Fournier secundaria a isquemia de extremidades inferiores, por lo que precisó tratamiento anticoagulante. Hasta la fecha no presentó alergias medicamentosas conocidas. Posteriormente se objetivó plaquetopenia progresiva con diagnóstico de trombocitopenia inducida por heparina tipo II por lo que se restringió la heparina de bajo peso molecular y la heparina sódica, indicándose anticoagulación con Sintrom y Bivalirudina en casos de procedimientos con alto riesgo de sangrado. Conclusiones: Los pacientes de hemodiálisis en nuestro hospital, tienen como pauta habitual de anticoagulación la heparina. En este caso el diagnostico precoz de la trombocitopenia trombótica inducida por la heparina, fue crucial para evitar daños mayores, siendo el equipo de enfermería la piedra angular en el tratamiento en la sala de hemodiálisis.

  18. 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...

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

    OpenAIRE

    López-Jaramillo, Patricio; Sotomayor-Rubio, Katherine; Sotomayor-Rubio, Arístides; López-López, Cristina

    2014-01-01

    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 d...

  20. 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.

  1. Efecto de Gentianella alborosea en esteatosis hepática no alcohólica inducida por dieta hiperlipídica en ratas holtzman hembras

    OpenAIRE

    L Ugaz-Soto; JH Zafra-Tanaka; María E. Tapia Vicente

    2013-01-01

    Objetivo: Determinar el efecto del extracto de Gentianella alborosea como tratamiento contra esteatosis hepática no alcohólica (EHNA)  inducida por dieta hiperlipídica en ratas Holtzman hembras. Métodos: Diseño: Estudio experimental incompleto. Lugar: Universidad Nacional Mayor de San Marcos, Lima, Perú. Participantes: Ratas Holtzman hembras. Intervenciones: Se utilizó 32 ratas repartidas en 4 grupos (n=8) distribuidos aleatoriamente: grupo control negativo, control positivo con dieta hiperli...

  2. 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

  3. 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 ...

  4. Mecanismos de Defensa del Hospedero en Estomatitis Sub-Protesica Inducida por Candida

    OpenAIRE

    Cardozo de Pardi, Elba Inés

    2002-01-01

    La Estomatitis Sub-Protésica (E.S.P.) es una entidad que se localiza principalmente en la mucosa del paladar que se encuentra por debajo de la superficie de ajuste de las prótesis removibles parciales y totales. Esta patología es más común en mujeres que en hombres y se observa más frecuentemente en sujetos con edades comprendidas entre 25 y 90 años. Diversos estudios han revelado que la E.S.P. está asociada con la detección de especies de Candida y de otros microorganismos, mientras que otro...

  5. 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...

  6. Degeneracion axónica inducida por tratamiento local con diisopropilfluorofosfato

    OpenAIRE

    Mauricio, María Cruz; Carrera, Victoria; Vilanova Gisbert, Eugenio; Juan Herrero, Joaquín de

    1989-01-01

    Existen especies animales, incluida la humana y las aves, susceptibles de manifestar una polineuropatía retardada tras una intoxicación accidental o la dosificación sistémica experimental con algunos compuestos organfosforados. En este estudio se planteó observar la existencia o no de lesiones nerviosas producidas tras la administración de diisopropilfluorofosfato por via local, siguiendo un modelo de dosificación "in situ". Aquí se describen las observaciones clínicas y lesiones morfológicas...

  7. 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.

  8. 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

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

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    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.

  10. 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

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

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    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.

  12. 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.

  13. 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.

  14. Protección inducida por nanococleatos derivados de proteoliposomas de Leptospira interrogans serovar Canicola

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    Beatriz Tamargo

    2012-04-01

    Full Text Available Desde los años 20 del pasado siglo, hasta el presente, en el mundo se han desarrollado y empleado vacunas de células enteras contra la leptospirosis que confieren una corta inmunidad; la mayoría no adyuvadas y dirigidas, fundamentalmente, contra los diferentes serogrupos de la especie Leptospira interrogans, contenidos en las preparaciones. Numerosos han sido los intentos realizados para lograr una formulación vacunal más pura, efectiva, de amplio espectro y duración de la protección que las bacterinas de células enteras inactivadas. Sin embargo, hasta el momento no se ha registrado ninguna vacuna con tales características. En el presente trabajo se obtuvieron antígenos de membrana externa a partir de una cepa cubana autóctona (Cepa 87, L. interrogans serovar Canicola, mediante una modificación de la tecnología para la producción de vesículas de membrana, patentada por investigadores del Instituto Finlay. Estos antígenos con estructura nanoproteoliposómica fueron formulados/adyuvados mediante diferentes estrategias, logrando cinco preparaciones con estructura coclear, que constituyen nanopartículas de aproximadamente 100 a 150 nm de largo y entre 15 a 30 nm de diámetro. Los inmunógenos se inocularon en el biomodelo Mesocrisetus aureatus, con dos dosis e intervalo de seis semanas. El reto fue realizado con 100.000 DL 50 . Los resultados demuestran que las nuevas formulaciones vacunales confieren protección frente al reto homólogo y fueron capaces de eliminar el estado de portador, lo que unido a la robustez del método de preparación, el mayor nivel de pureza, en comparación con las bacterinas, y la no necesidad del hidróxido de aluminio, las convierten en una alternativa de interés para continuar su desarrollo.

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

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    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

  16. 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’.

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

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    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.

  18. Hiperalgesia Inducida por Opioides

    OpenAIRE

    Jiménez Salazar, Andrés

    2013-01-01

    Los opioides producen analgesia a través de un efecto inhibitorio sobre el sistema nociceptivo principalmente. Hasta la fecha, los opioides siguen siendo los analgésicos más potentes para el manejo de dolor moderado a severo. La Asociación Internacional del Estudio del Dolor (IASP, en inglés) define hiperalgesia como "un aumento de la respuesta a un estímulo que normalmente es doloroso". En contraste, está bien establecido que la terapia crónica con opioides se asocia con el desarrollo de ...

  19. Efecto de Gentianella alborosea en esteatosis hepática no alcohólica inducida por dieta hiperlipídica en ratas holtzman hembras

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    L Ugaz-Soto

    2013-01-01

    Full Text Available Objetivo: Determinar el efecto del extracto de Gentianella alborosea como tratamiento contra esteatosis hepática no alcohólica (EHNA  inducida por dieta hiperlipídica en ratas Holtzman hembras. Métodos: Diseño: Estudio experimental incompleto. Lugar: Universidad Nacional Mayor de San Marcos, Lima, Perú. Participantes: Ratas Holtzman hembras. Intervenciones: Se utilizó 32 ratas repartidas en 4 grupos (n=8 distribuidos aleatoriamente: grupo control negativo, control positivo con dieta hiperlipídica, dosis 1 (35 mg/kg y dosis 2 (70 mg/kg. Se indujo EHNA con dieta hiperlipídica (Carbohidratos: 26%, Lípidos: 59% y Proteínas: 15% Calorías durante un período de 21 días, ad libitum. Luego, se administró el extracto acuoso de Gentianella alborosea por 4 días. Finalmente, se extrajeron los hígados para evaluar las alteraciones histopatológicas del parénquima hepático. Principales medidas de resultados: Se realizó el conteo microscópico de hepatocitos afectados con macrovacuolas, y los resultados fueron comparados mediante las pruebas de ANOVA (p<0,05 y HSD de Tukey (p<0,05. Resultados: Se encontró diferencias significativas (p<0.05 en el porcentaje de hepatocitos afectados entre los grupos dosis 1 (3.25 ± 2.27 y el control positivo (7.50 ± 3.76. Además, no se encontró diferencia significativa entre los grupos dosis 1 y dosis 2. Conclusiones: No se pudo determinar el efecto de Gentianella alborosea sobre la esteatosis hepática no alcohólica inducida por dieta hiperlipídica en ratas Holtzman hembra, por lo que se recomiendan estudios posteriores.

  20. EFECTO DE GENTIANELLA ALBOROSEA EN ESTEATOSIS HEPÁTICA NO ALCOHÓLICA INDUCIDA POR DIETA HIPERLIPÍDICA EN RATAS HOLTZMAN HEMBRAS

    Directory of Open Access Journals (Sweden)

    L. Ugaz-Soto

    2012-01-01

    Full Text Available Objetivo: Determinar el efecto del extracto de Gentianella alborosea como tratamiento contra esteatosis hepática no alcohólica (EHNA inducida por dieta hiperlipídica en ratas Holtzman hembras. Métodos: Diseño: Estudio experimental incompleto. Lugar: Universidad Nacional Mayor de San Marcos, Lima, Perú. Participantes: Ratas Holtzman hembras. Intervenciones: Se utilizó 32 ratas repartidas en 4 grupos (n=8 distribuidos aleatoriamente: grupo control negativo, control positivo con dieta hiperlipídica, dosis 1 (35 mg/kg y dosis 2 (70 mg/kg. Se indujo EHNA con dieta hiperlipídica (Carbohidratos: 26%, Lípidos: 59% y Proteínas: 15% Calorías durante un período de 21 días, ad libitum. Luego, se administró el extracto acuoso de Gentianella alborosea por 4 días. Finalmente, se extrajeron los hígados para evaluar las alteraciones histopatológicas del parénquima hepático. Principales medidas de resultados: Se realizó el conteo microscópico de hepatocitos afectados con macrovacuolas, y los resultados fueron comparados mediante las pruebas de ANOVA (p<0,05 y HSD de Tukey (p<0,05. Resultados: Se encontró diferencias significativas (p<0.05 en el porcentaje de hepatocitos afectados entre los grupos dosis 1 (3.25 ± 2.27 y el control positivo (7.50 ± 3.76. Además, no se encontró diferencia significativa entre los grupos dosis 1 y dosis 2. Conclusiones: No se pudo determinar el efecto de Gentianella alborosea sobre la esteatosis hepática no alcohólica inducida por dieta hiperlipídica en ratas Holtzman hembra, por lo que se recomiendan estudios posteriores.

  1. Pregancy-induced hypertension and birthweight Hipertensión inducida por el embarazo y peso de los productos al nacer

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    Nicolás Padilla Raygoza

    2013-03-01

    Full Text Available Objective. The objective of this work was to measure the existing association between preg­nancy-induced hypertension and birthweight at the Celaya General Hospital. Study design. Cross-sectional, observational, analytic study. Subjects: Registries of women admitted to the Celaya General Hospital for delivery during 2008. Variables: Pregnancy-induced hypertension (blood pressure of 140/90 mmHg or higher after 20 weeks of gestation, sub-classified as gestational hypertension (blood pressure of 140/90 mmHg or higher without proteinuria and toxemia (blood pressure of 140/90 mmHg or higher with proteinuria; birthweight ( 3 500 g. Statistical analysis: it was calculated the Analysis of Variance (ANOVA test was performed between the status of arterial hypertension and birthweight, and was adjusted using gestational age. Results. From the sample of 5 478 registries, 14.73% (n = 807 of women had pregnancy-induced hypertension; from them, 10.92% (n = 598 had gestational hypertension and 3.82% (n = 209 preclampsia/eclampsia. Newborns from hypertensive mothers had an average birthweight of 3 049.27 ± 600.22 g, while the birth­weight of newborns from normotensive mothers was 3 104.94 ± 502.57 g, considering: ANOVA F = 1.49, p = 0.00001: adjusted by gestational age, F = 1.51, p = 0.0168. Conclu­sion. Newborns of normotensive and gestational hypertensive mothers showed differences in birthweight; gestational age acted as a confounder.Objetivo. Medir la asociación que existe entre la hipertensión inducida por el embarazo y el peso al nacer de los neonatos, en el Hospital General de Celaya. Tipo de estudio. Observacio­nal, transversal y analítico. Sujetos: 1 Registros de mujeres embarazadas (n = 5 478, admi­tidas para su resolución obstétrica, en el Hospital General de Celaya durante el año 2008, y 2 registros del peso al nacer de los neonatos de estas mujeres. Variables: 1 Hipertensión inducida por el embarazo (presión arterial de 140/90 mmHg o

  2. 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.

  3. 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.

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

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    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.

  5. 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.

  6. 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

  7. Los niveles de anticuerpos anti factor plaquetario 4-heparina y el índice 4T para trombocitopenia inducida por heparina

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    Marta E. Martinuzzo

    2012-02-01

    Full Text Available La trombocitopenia inducida por heparina (HIT es un efecto adverso del tratamiento con heparina, mediada por anticuerpos anti complejo factor plaquetario 4 (PF4-heparina (HPIA. La HIT es frecuentemente moderada pero pueden desarrollarse complicaciones trombóticas. El diagnóstico precoz es importante. La detección de HPIA por ELISA tiene alta sensibilidad pero baja especificidad (títulos bajos sin significación clínica. El índice de las 4T (índice 4T puede detectar pacientes con alto riesgo de HIT. El propósito del estudio fue correlacionar los niveles de HPIA y el índice 4T de un grupo de pacientes derivados a nuestro centro. Evaluamos 84 pacientes, 34 de ellos desarrollaron trombosis. Cada médico completó un cuestionario clínico que fue remitido con la muestra a nuestro centro. Los cuestionarios fueron analizados por un investigador externo y el índice 4T se calculó previamente al ensayo. Los HPIA se determinaron por un ELISA (Asserachrom HPIA que detecta los 3 isotipos, IgG, IgM e IgA, único reactivo disponible en Argentina. Los resultados se expresaron como porcentaje de absorbancia (%ABS. La correlación del índice 4T con los HPIA fue 0.472 (rho spearman, p < 0.001. Los pacientes con índice 4T ≥ 6 presentaban %ABS mayores que los ≤ 5 (67 vs. 39, p < 0.001. Aquéllos con trombosis presentaron títulos mayores que los que no la desarrollaron (%ABS 59 vs. 39, p = 0.017. En conclusión: Los títulos altos de HPIA medidos por ELISA, que detecta los 3 isotipos, correlacionaron claramente con el índice 4T ≥ 6 y fueron más frecuentes en los pacientes con trombosis, coincidiendo con lo ya descripto para ensayos de ELISA específicos para isotipo IgG.

  8. 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.

  9. “Corrosión Inducida por Bacterias Sulfato Reductoras Termófilas de 60°C en la Unión Soldada del Acero API 5L- X60.”

    OpenAIRE

    Romero Romero, Justo Román

    2012-01-01

    En esta investigación se estudio el efecto de la corrosión inducida por Bacterias Sulfato Reductoras (BSR) termófilas a 60oC en el metal base (MB) y la unión soldada (US) del acero API X-60. Las bacterias sulfato reductoras fueron aisladas en el medio sólido postgate con la técnica de estriado, y fueron resembradas hasta obtener la misma morfología. El medio postgate fue seleccionado entre otros medios de cultivo, por el óptimo crecimiento que presento la BSR. Se preparar...

  10. Efectos del extracto de semillas de uva sobre la cistopatia diabética inducida por estreptozotocina en ratas

    OpenAIRE

    María Lourdes Arruzazabala; Yazmín Ravelo; Daisy Carbajal; Vivian Molina; Rosa Mas

    2010-01-01

    La diabetes por estreptozotocina (STZ) en ratas se produce como consecuencia de la necrosis subtotal de los islotes pancreáticos y provoca hiperglicemia, hipoinsulinemia, disminución de la ganancia en peso y aumento del peso de la vejiga, así como hipercontractilidad al carbacol por sobreexpresión de los ARNm-receptores muscarínicos M2 y M3 del detrusor y el urotelio. El extracto de semillas de uva (ESU), rico en flavonoides, ha mostrado efectos antioxidantes y neuroprotectores en modelos exp...

  11. Determinación de la profundidad y duración de la neutropenia inducida por ciclofosfamida en ratones hembras MPF de la cepa Udea: ICR(cd-1

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    Omar Vesga

    2004-02-01

    Full Text Available

    El modelo murino de infección del muslo emplea animales neutropénicos para poder determinar la eficacia intrínseca de los antibióticos in vivo. Sin embargo, no se ha definido el número de neutrófilos y la duración de la neutropenia inducida por ciclofosfamida (CFM intraperitoneal (IP, información fundamental
    para valorar la reproducibilidad y confiabilidad del modelo.

     

     

  12. Agroquímicos en Argentina: Genotoxicidad y citotoxicidad inducida por principios activos y sus formulaciones comerciales

    OpenAIRE

    Larramendy, Marcelo L; Molinari, Gabriela; González, Norma V; Pilili, Juan P; Candioti, Josefina Vera; Reigosa, Miguel A; Soloneski, Sonia

    2010-01-01

    Uno de los objetivos principales de nuestro laboratorio es evaluar comparativamente los efectos geno-citotóxicos ejercidos in vitro e in vivo sobre células de vertebrados por principios activos de agroquímicos y sus formulaciones comerciales de uso masivo en Argentina. Entre los mismos caben mencionarse, los herbicidas 2,4-D y 2,4-D DMA®, dicamba y Banvel®, el fungicida zineb y Azzurro®, los insecticidas carbofurán y Furadan®, pirimicarb y Aficida®, como también el endectocida ivermectina e I...

  13. 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.

     

     

  14. 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

  15. 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

  16. Análisis proteómico de la resistencia inducida por micorrización al patógeno foliar Sclerotinia sclerotiorum en frijol (Phaseolus vulgaris l.)

    OpenAIRE

    Quintero Zamora, Edalhí

    2014-01-01

    En los últimos años se han reportado diversos estudios sobre la resistencia inducida por micorrización al ataque de patógenos, en éstos se han determinado los cambios de expresión de genes y proteínas que ocurren en las raíces de plantas colonizadas por hongos micorrízicos arbusculares. Recientemente, se han iniciado estudios para entender cómo afecta esta interacción a la parte aérea de la planta. En nuestro grupo de investigación se llevó a cabo el estudio del efecto de la micorrizaci...

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. Respuesta inmune y expresión de genes en el camarón blanco (Litopenaeus vannamei) inducida por inmunoestimulantes microbianos

    OpenAIRE

    Moreno Herrera, Jesús Tomás

    2014-01-01

    En este trabajo se evaluó el efecto inmunoestimulante de bacterias ácido lácticas y levaduras muertas por calor en Litopenaeus vannamei, cultivado en el laboratorio. La mezcla inmunoestimulante (MI) en polvo se adicionó en el alimento. Se realizó un bioensayo de 26 días en tinas de plástico con 80 L de agua de mar filtrada, aireación constante y 10 organismos por tina. La alimentación se realizó dos veces al día, la limpieza diariamente y la determinación de parámetros fisicoquímicos cada 3 d...

  4. 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

  5. Efecto del estrés durante diferentes etapas del ciclo vital sobre el desarrollo de obesidad inducida por la dieta

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    Paternain, L. (Laura); Martinez, J.A. (José Alfredo); Campión-Zabalza, J. (Javier)

    2016-01-01

    La creciente prevalencia de la obesidad no puede ser atribuible únicamente a factores genéticos o a una mala nutrición como pueden ser las dietas altas en grasa, sino también al estilo de vida y a factores ambientales adversos. Dentro del estilo de vida, la sociedad actual se caracteriza por tener un ritmo acelerado, lo que produce una elevación de la tasa de estrés en la población. Este aumento paralelo tanto de las tasas de obesidad como del estrés, hace necesario el estudio de la interacci...

  6. Modulación del tono vascular por la sobre-expresión de receptores a canabinoides CB1 y CB2 en arterioesclerosis inducida en ratas

    OpenAIRE

    Espinoza P., María Rosa

    2013-01-01

    La arteriosclerosis, es un proceso degenerativo responsable de la mayor parte de las enfermedades cardiovasculares, es una enfermedad compleja que se produce a partir de múltiples factores de riesgo. Se ha observado que los compuestos derivados de la planta cannabis sativa provocan efectos vasorelajantes por medio de receptores específicos CB1 y CB2. ACPA y JWH 133 son potentes agonistas a estos receptores, se desconoce el papel que desempeñan en la arteriosclerosis provocando una relajación ...

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. Tratamiento de agua potable por filtración inducida en una laguna costera en el sur de Brasil Bank filtration drinking water treatment in a costal lagoon in south Brazil

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    Luis Guillermo Romero Esquivel

    2012-12-01

    Full Text Available La filtración inducida (FI consiste en obtener agua potable de pozos situados en acuíferos de aluvión u otro tipo de depósitos no consolidados conectados hidráulicamente con una fuente de agua superficial. La posibilidad de aplicar esta técnica en las riberas de la laguna Lagoa do Peri, Brasil, se evaluó a nivel piloto. Por medio de observación y de análisis granulométricos se determinó que el fondo de la laguna y el acuífero aledaño presentan una textura arenosa. Además, ensayos de permeámetro de carga constante, de tubo de carga variable y de bombeo, mostraron que la conductividad hidráulica en las mismas zonas se encuentra cercana a 10-4 m/s, misma magnitud encontrada en otras latitudes donde la FI se aplica con éxito. El agua captada en un pozo a 20 m de la Lagoa do Peri presentó valores de turbidez y color aparente acordes con los patrones de calidad locales. Se observó un aumento en la dureza y la alcalinidad, atribuido a la erosión de los materiales del subsuelo, sin llegar a superar lo estipulado en la legislación. Finalmente, el agua producida por la FI mostró ser de mejor calidad en términos de turbidez y color aparente que el agua de la laguna tratada por filtración directa en una estación de tratamiento (ETA ubicada en el lugar. El agua producida por la FI presentó condiciones anóxicas que harían necesario el postratamiento por aireación y filtración, proceso en el cual se podría aprovechar la infraestructura de la ETA existente.Bank filtration (BF consists in obtaining drinking water from wells in alluvial aquifers or other unconsolidated deposits hydraulically connected with a surface water source. The possibility of applying this technique was evaluated in a pilot scale on the banks of the Lagoa do Peri lagoon, Brazil. Observation and grain size analysis showed that the bottom of the lagoon and the adjacent aquifer have sandy texture. In addition, tests of constant head permeameter, standpipe falling

  12. 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.

  13. Determinación del índice de resistencia a la insulina mediante homa y su relación con el riesgo de hipertensión inducida por el embarazo Insulin resistance index assessment by homa and its relation with the risk of pregnancy induced hypertension

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    Jesús Sierra-Laguado

    Full Text Available Objetivo: investigar si el grado de resistencia a la insulina determinado por el índice HOMA, predice de manera temprana el desarrollo de hipertensión inducida por el embarazo en gestantes colombianas. Diseño-métodos: se realizó un estudio de casos y controles anidado en una cohorte prospectiva de 438 mujeres primigestantes, normotensas y con edad gestacional menor de 30 semanas. Se determinó el índice HOMA a partir de la medición de glucemia e insulina plasmática en ayunas, por métodos de glucosa oxidasa y quimioluminiscencia, respectivamente. Resultados: veintitrés mujeres desarrollaron hipertensión inducida por el embarazo (5,25%. Se seleccionaron de forma aleatoria dos embarazadas normotensas como controles por cada caso, pareadas por edad materna y gestacional al momento de su inclusión. Las mujeres que posteriormente desarrollaron hipertensión inducida por el embarazo presentaron mayores niveles de HOMA (1,48 ± 0,98 vs. 0,96 ± 0,70, pObjective: to assess whether insulin resistance determined by homeostatic model assessment (HOMA is an early predictor of the development of pregnancy induced hypertension in Colombian pregnant women. Methods: we conducted a nested case control study in a prospective cohort of four hundred and thirty eigth normotensive primigravidae women, with gestational age < 30 weeks. The HOMA was calculated using fasting plasma concentrations of glucose and insulin, determined by glucose-oxidase and chemoluminiscence methods, respectively. Results: twenty-three pregnant women developed pregnancy induced hypertension (5.25%. Two normotensive pregnant women were selected as controls for each case, matched by gestational and maternal age at enrollment. The women who subsequently developed pregnancy induced hypertension had higher levels of HOMA (1.48 ± 0.98 vs 0.96 ± 0.70, p<0.001, which was associated with an increased risk of developing pregnancy induced hypertension (OR: 3.8, IC95%: 1.1-12.8 p=0

  14. 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.

  15. 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

  16. 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.

  17. Estudio del D-004 sobre la defensa antioxidante endógena en ratas con hiperplasia prostática inducida por inyección de testosterona Study of D-004 on the endogenous antioxidant defence in rats presenting with prostate hyperplasia induced by testosterone injection

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    Yohani Pérez Guerra

    2010-06-01

    Full Text Available La hiperplasia prostática benigna, enfermedad común en hombres mayores de 50 años de edad, se caracteriza por el crecimiento incontrolado de la glándula prostática y la presencia de síntomas del tracto bajo urinario. El estrés oxidativo ha sido recientemente asociado con la causa de esta enfermedad. El D-004, extracto lipídico del fruto de la Roystonea regia, ha mostrado reducir la hiperplasia prostática inducida por testosterona en roedores y producir efectos antioxidantes in vitro e in vivo, pero sus efectos sobre las enzimas del sistema antioxidante endógeno no han sido estudiados. Este trabajo investigó los efectos del tratamiento oral con D-004, durante 14 días, sobre las enzimas superóxido dismutasa y catalasa en ratas con hiperplasia prostática inducida por testosterona. Los animales se distribuyeron en 4 grupos: un control negativo y tres inyectados con testosterona: uno tratado con el vehículo (control positivo y dos con D-004 (400 y 800 mg/kg, respectivamente. Se determinó la capacidad antioxidante total del plasma y las actividades de las enzimas superóxido dismutasa y catalasa en eritocitos lisados y plasma, respectivamente. El tratamiento oral con D-004 (400 y 800 mg/kg previno de modo marcado y significativo el agrandamiento de la próstata inducido con testosterona en ratas, y aumentó significativamente la capacidad antioxidante del plasma y la actividad de la catalasa, sin modificar la actividad de la superóxido dismutasa. Estos resultados sugieren que la actividad antioxidante del D-004 está relacionada, al menos parcialmente, con la estimulación de algunas enzimas del sistema antioxidante endógeno.Benign prostatic hyperplasia, a common disease in men aged over 50 is characterized by uncontrolled growth of prostatic gland and the presence of low urinary tract symptoms. The oxidative stress has been recently associated with the disease cause. The D-004, a lipid extract from Roystonea regia, reduces the

  18. 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

  19. Análisis Ultraestructural del Efecto Neuroprotector de la Melatonina sobre las lesiones del Cortex Cerebeloso del Embrión de Pollo inducidas por Glutamato Monosódico.

    OpenAIRE

    García de la Oliva, Alejandro

    2017-01-01

    En el presente estudio analizamos el efecto neuroprotector que la administración exógena de la melatonina ejerce sobre las lesiones neurodegenerativas de la corteza cerebelosa del embrión de pollo causadas por excitotoxicidad glutamatérgica. Para ello hemos diseñado un modelo experimental que nos permite: por un lado, evaluar y seguir la evolución de las lesiones que sobre el desarrollo de la corteza cerebelosa produce la administración de gl...

  20. 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

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

    OpenAIRE

    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...

  2. 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.

  3. 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.

  4. 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...

  5. 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.

  6. 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.

  7. 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.

  8. Meteorites as space probes for cosmic rays; Les meteorites en tant que sondes spatiales pour les rayons cosmiques; Meteority v kachestve prob mezhplanetnogo prostranstva dlya izucheniya kosmicheskikh luchej; Los meteoritos como sondas espaciales para evaluar la actividad inducida por los rayos cosmicos

    Energy Technology Data Exchange (ETDEWEB)

    Schaeffer, O A; Stoenner, R W; Davis, R Jr [Chemistry Department, Brookhaven National Laboratory, Upton, L. I., NY (United States)

    1962-01-15

    'activite imputable a l'argon-37 (periode: 35 jours) et a l'argon-39 (periode: 325 ans). Ils comparent ces activites relatives aux taux de production de ces isotopes que l'on obtient en bombardant un echantillon de la meteorite avec des protons ayant une energie de 3 GeV. Les auteurs concluent que, dans les limites d'erreur, le flux de rayons cosmiques est le meme dans la ceinture asteroide que dans le voisinage de l'orbite terrestre. (author) [Spanish] Para determinar la constancia espacial de la radiacion cosmica de elevada energia en el interior del sistema solar, los autores midieron la radiactividad, inducida por los rayos cosmicos, de un elemento de periodo corto y de un elemento de periodo largo en un meteorito caido recientemente. El experimento se basa en el hecho de que los meteoritos siguen orbitas muy excetricas y, por ello, pueden ser utilizados como sondas espaciales en la region situada entre la orbita terrestre y el cinturon de asteroides. La actividad de periodo corto se produce mientras el meteorito se encuentra en las proximidades de la orbita terrestre, en tanto que la actividad de periodo largo es inducida en toda la orbita descrita por el meteorito. Los autores efectuaron las mediciones en el condrito Hamlet que cayo en Indiana el 13 de octubre de 1.959. Evaluaron las actividades astribuibles al argon-37 (periodo: 35 dias) y al argon-39 (periodo: 325 anos). Compararon los valores relativos de estas actividades con los indices de produccion de esos isotopos que se alcanzan bombardeando una muestra del meteorito con protones de 3 GeV. Se llega a la conclusion de que la intensidad de la radiacion cosmica es igual, dentro de los limites de error, en el cinturon de asteroides que en las proximidades de la orbita terrestre. (author) [Russian] Byl proizveden opyt ispytaniya prostranstvennogo postoyanstva kosmicheskogo izlucheniya vysokikh ehnergij v solnechnoj sisteme putem zamera iskusstvennoj korotkozhivushchej i dol- gozhivushchej radioaktivnosti kosmicheskikh

  9. 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

  10. Multiple sclerosis and anterograde axonal degeneration study by magnetic resonance. Asociacion de esclerosis multiple y degeneracion Walleriana estudio por resonancia magnetica

    Energy Technology Data Exchange (ETDEWEB)

    Martinez Pardo, P; Capdevila Cirera, A; Sanz Marin, P M; Gili Planas, J [Centro de Resonancia Magnetica de Barcelona (Spain)

    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).

  11. MODELO EXPERIMENTAL DE GLOMERULONEFRITIS MEMBRANOSA INDUCIDA CON ALBUMINA BOVINA

    Directory of Open Access Journals (Sweden)

    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

  12. Copolymerization of Ethylene Induced by Cobalt-60 Gamma Radiation; Copolymerisation de l'ethylene induite par des rayons gamma du cobalt-60; Sopolimerizatsiya ehtilena pod dejstviem gamma-izlucheniya ot istochnika ks'yali-60; Copolimerizacion del etileno inducida por las radiaciones gamma del cobalto-60

    Energy Technology Data Exchange (ETDEWEB)

    Steinberg, M.; Colombo, P. [Brookhaven National Laboratory, Long Island, NY (United States)

    1963-11-15

    }C et a des pressions initiales allant jusqu'a 680 atm. On a procede aux experiences, en milieu statique, dans des systemes a deux phases, a l'exception du systeme ethylene-oxyde de carbone. La separation des copolymeres a ete obtenue par des methodes d'extraction par solvant et de precipitation fractionnee. L'identification a ete faite au moyen de la spectroscopic aux infrarouges. La composition a ete determinee par analyse elementaire. Les auteurs donnent une evaluation partielle de certains produits de la reaction, y compris les points de fusion cristalline, les densites, les caracteristiques de solubilite et les poids moleculaires. La copolymerisation de l'ethylene a ete etablie avec chacun des monomeres suivants : styrene, methacrylate de methyle, acetate de vinyle, acrylonitrile, acetate d'allyle, isobutylene, chlorotiifluoroethylene, transbutene-2, acrylate de methyle, isoprene, propylene, chlorure de vinyle, butene-1, cis-butene-2, oxyde de carbone, pyrrolidone de vinyle, methyle- vinyle-cetone et divinyle-benzene. Les auteurs ont trouve que les donnees experimentales obtenues dans l'etude du systeme ethylene-oxyde de carbone suivaient une forme lineaire de l'equation de composition du copolymere. Pour le rapport {alpha} des constantes de vitesse specifiques de l'oxyde de carbone et de l'ethylene, ils ont determine la valeur 22,0, ce qui montre que l'oxyde de carbone en tant que monomere est active a tel point qu'il se fixe a l'extremite d'une chaftie de radicaux libres d'ethylene 22 fois plus vite que ne le fait un monomere d'ethylene. (author) [Spanish] Los autores estudiaron la copolimerizacion del etileno, inducida por las radiaciones gamma, con una serie de diversos monometos, a 20{sup o}C y presiones iniciales de hasta 680 atm. Los experimentos se llevaron a cabo estaticamente en sistemas bifasicos, salvo en el caso del etileno-oxido de carbono. La separacion de los copolimeros se llevo a cabo por extraccion mediante disolventes y por precipitacion

  13. 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

    Directory of Open Access Journals (Sweden)

    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

  14. 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

    Directory of Open Access Journals (Sweden)

    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

  15. 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

    Directory of Open Access Journals (Sweden)

    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

  16. 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 ...

  17. Las defensas inducidas en trigos comerciales

    OpenAIRE

    Càrdenas, David; Giménez, Daniel O.; Castro, Ana María

    2015-01-01

    Las plantas presentan múltiples tipos de estrategias de defensas ante sus patógenos y plagas y frente a estreses ambientales. En muchos casos las defensas constitutivas acarrean costos metabólicos altos que provocan mermas del rendimiento cuando no ocurren en el ciclo de cultivo ataquesde plagas o patógenos. Las defensas inducibles en cambio sólo se activan ante elicitores específicos producidos por la interacción con los agresores bióticos, si bien conllevan gastos energéticos sólo ocurre an...

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Axonal GABAA receptors.

    Science.gov (United States)

    Trigo, Federico F; Marty, Alain; Stell, Brandon M

    2008-09-01

    Type A GABA receptors (GABA(A)Rs) are well established as the main inhibitory receptors in the mature mammalian forebrain. In recent years, evidence has accumulated showing that GABA(A)Rs are prevalent not only in the somatodendritic compartment of CNS neurons, but also in their axonal compartment. Evidence for axonal GABA(A)Rs includes new immunohistochemical and immunogold data: direct recording from single axonal terminals; and effects of local applications of GABA(A)R modulators on action potential generation, on axonal calcium signalling, and on neurotransmitter release. Strikingly, whereas presynaptic GABA(A)Rs have long been considered inhibitory, the new studies in the mammalian brain mostly indicate an excitatory action. Depending on the neuron that is under study, axonal GABA(A)Rs can be activated by ambient GABA, by GABA spillover, or by an autocrine action, to increase either action potential firing and/or transmitter release. In certain neurons, the excitatory effects of axonal GABA(A)Rs persist into adulthood. Altogether, axonal GABA(A)Rs appear as potent neuronal modulators of the mammalian CNS.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. Axons take a dive

    Science.gov (United States)

    Tong, Cheuk Ka; Cebrián-Silla, Arantxa; Paredes, Mercedes F; Huang, Eric J; García-Verdugo, Jose Manuel; Alvarez-Buylla, Arturo

    2015-01-01

    In the walls of the lateral ventricles of the adult mammalian brain, neural stem cells (NSCs) and ependymal (E1) cells share the apical surface of the ventricular–subventricular zone (V–SVZ). In a recent article, we show that supraependymal serotonergic (5HT) axons originating from the raphe nuclei in mice form an extensive plexus on the walls of the lateral ventricles where they contact E1 cells and NSCs. Here we further characterize the contacts between 5HT supraependymal axons and E1 cells in mice, and show that suprependymal axons tightly associated to E1 cells are also present in the walls of the human lateral ventricles. These observations raise interesting questions about the function of supraependymal axons in the regulation of E1 cells. PMID:26413556

  3. Electrophysiology of Axonal Constrictions

    Science.gov (United States)

    Johnson, Christopher; Jung, Peter; Brown, Anthony

    2013-03-01

    Axons of myelinated neurons are constricted at the nodes of Ranvier, where they are directly exposed to the extracellular space and where the vast majority of the ion channels are located. These constrictions are generated by local regulation of the kinetics of neurofilaments the most important cytoskeletal elements of the axon. In this paper we discuss how this shape affects the electrophysiological function of the neuron. Specifically, although the nodes are short (about 1 μm) in comparison to the distance between nodes (hundreds of μm) they have a substantial influence on the conduction velocity of neurons. We show through computational modeling that nodal constrictions (all other features such as numbers of ion channels left constant) reduce the required fiber diameter for a given target conduction velocity by up to 50% in comparison to an unconstricted axon. We further show that the predicted optimal fiber morphologies closely match reported fiber morphologies. Supported by The National Science Foundation (IOS 1146789)

  4. 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

  5. Síndrome de Munchausen por mandato

    OpenAIRE

    Esteban, Miguel A.; Pérez, Miriam R.; Bracco, Anahí

    2006-01-01

    El Síndrome de Munchausen por mandato, "un trastorno ficticio, por el cual la enfermedad del niño es inducida, promovida o provocada por la persona más próxima a él, generalmente su madre", es todavía mal conocido y su génesis imperfectamente comprendida. Esta comunicación está destinada a esclarecer al pediatra esta patología, con elevada morbilidad y secuelas, como así también de altísima mo...

  6. Glia to axon RNA transfer.

    Science.gov (United States)

    Sotelo, José Roberto; Canclini, Lucía; Kun, Alejandra; Sotelo-Silveira, José Roberto; Calliari, Aldo; Cal, Karina; Bresque, Mariana; Dipaolo, Andrés; Farias, Joaquina; Mercer, John A

    2014-03-01

    The existence of RNA in axons has been a matter of dispute for decades. Evidence for RNA and ribosomes has now accumulated to a point at which it is difficult to question, much of the disputes turned to the origin of these axonal RNAs. In this review, we focus on studies addressing the origin of axonal RNAs and ribosomes. The neuronal soma as the source of most axonal RNAs has been demonstrated and is indisputable. However, the surrounding glial cells may be a supplemental source of axonal RNAs, a matter scarcely investigated in the literature. Here, we review the few papers that have demonstrated that glial-to-axon RNA transfer is not only feasible, but likely. We describe this process in both invertebrate axons and vertebrate axons. Schwann cell to axon ribosomes transfer was conclusively demonstrated (Court et al. [2008]: J. Neurosci 28:11024-11029; Court et al. [2011]: Glia 59:1529-1539). However, mRNA transfer still remains to be demonstrated in a conclusive way. The intercellular transport of mRNA has interesting implications, particularly with respect to the integration of glial and axonal function. This evolving field is likely to impact our understanding of the cell biology of the axon in both normal and pathological conditions. Most importantly, if the synthesis of proteins in the axon can be controlled by interacting glia, the possibilities for clinical interventions in injury and neurodegeneration are greatly increased. Copyright © 2013 Wiley Periodicals, Inc.

  7. Efecto hipolipidémico del extracto acuoso de las hojas de Artocarpus altilis "árbol del pan" en Rattus norvegicus con hiperlipidemia inducida

    Directory of Open Access Journals (Sweden)

    Julio Campos Florián

    2013-01-01

    Full Text Available La presente investigación tuvo como objetivo demostrar la actividad hipolipidémica del extracto acuoso de las hojas del árbol del pan, Artocarpus altilis, en un modelo de hiperlipidemia aguda inducida con tritón X-305, utilizando como especímenes Rattus norvegicus machos, peso promedio 204,5 g, a los que se les administró por vía oral 0,05 g/100 g y 0,2 g/100 g del extracto acuoso de A. altilis; se incluyó un grupo control negativo que recibió solución salina fisiológica y un grupo control positivo hiperlipidémico. Luego de 24 horas de administrar los tratamientos, se realizaron las mediciones en suero de las concentraciones de colesterol y triglicéridos. Encontramos reducciones significativas (p < 0,01 tanto de las cifras de colesterol, como de triglicéridos en relación a las concentraciones obtenidas en el grupo control positivo. También encontramos diferencia significativa (p < 0,01 entre las concentraciones de triglicéridos de los animales tratados con las dos dosis del extracto acuoso de A. altilis. Concluimos que el extracto acuoso de las hojas de A. altilis presenta efecto hipolipidémico a las dosis ensayadas para el modelo de hiperlipidemia inducida con tritón X-305.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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)

  13. 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)

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. MECANISMOS CELULARES IMPLICADOS EN EL DESARROLLO DE HIPERTROFIA DEL MUSCULO ESQUELETICO INDUCIDA POR TESTOSTERONA

    OpenAIRE

    BASUALTO ALARCON, CARLA EDITH

    2012-01-01

    El músculo esquelético es un tejido blanco para la acción de los esteroides anabólicos, siendo la testosterona la principal hormona fisiológica. Esta hormona actúa diferencialmente durante el desarrollo de un individuo cumpliendo roles diversos en el período embrionario, en la pubertad y en la vida adulta. Se ha demostrado que la testosterona es capaz de inducir un incremento en la masa muscular de individuos adultos tratados con dosis supra-fisiológicas, sin embargo los mecanismos c...

  20. Efecto hipolipidémico del extracto acuoso de las hojas de Artocarpus altilis "árbol del pan" en Rattus norvegicus con hiperlipidemia inducida

    OpenAIRE

    Julio Campos Florián

    2013-01-01

    La presente investigación tuvo como objetivo demostrar la actividad hipolipidémica del extracto acuoso de las hojas del árbol del pan, Artocarpus altilis, en un modelo de hiperlipidemia aguda inducida con tritón X-305, utilizando como especímenes Rattus norvegicus machos, peso promedio 204,5 g, a los que se les administró por vía oral 0,05 g/100 g y 0,2 g/100 g del extracto acuoso de A. altilis; se incluyó un grupo control negativo que recibió solución salina fisiológica y un grupo control po...

  1. 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.

  2. The genetics of axonal transport and axonal transport disorders.

    Directory of Open Access Journals (Sweden)

    Jason E Duncan

    2006-09-01

    Full Text Available Neurons are specialized cells with a complex architecture that includes elaborate dendritic branches and a long, narrow axon that extends from the cell body to the synaptic terminal. The organized transport of essential biological materials throughout the neuron is required to support its growth, function, and viability. In this review, we focus on insights that have emerged from the genetic analysis of long-distance axonal transport between the cell body and the synaptic terminal. We also discuss recent genetic evidence that supports the hypothesis that disruptions in axonal transport may cause or dramatically contribute to neurodegenerative diseases.

  3. Cross-Sections for Low-Energy Neutron-Induced Fission; Sections Efficaces de Fission pour des Neutrons de Faible Energie; 0421 0415 0427 0415 041d 0418 042f 0414 0415 041b 0415 041d 0418 042f , 0412 042b 0417 0412 0410 041d 041d 041e 0413 041e 041d 0415 0419 0422 0420 041e 041d 0410 041c 0418 041d 0418 0417 K 041e 0419 042d 041d 0415 0420 0413 0418 0418 ; Secciones Eficaces en la Fision Inducida por Neutrones de Baja Energia

    Energy Technology Data Exchange (ETDEWEB)

    Rae, E. R. [Atomic Energy Research Establishment, Harwell, Didcot, Berks. (United Kingdom)

    1965-07-15

    charge des noyaux cibles fournit egalement de nombreux renseignements sur la structure des noyaux lourds. Dans le cas d'un noyau cible susceptible de fission thermique, lorsque l'energie des neutrons augmente, la section efficace presente d'abord des variations inversement proportionnelles a la vitesse, puis une region ou des pics de resonance aigus apparaissent, et en dernier lieu une region de continu caracterisee par des variations relativement regulieres. Tous ces phenomenes peuvent recevoir une explication theorique, mais il semble tres difficile d'expliquer quantitativement certaines caracteristiques des donnees. Lors de mesures recentes de sections efficaces destinees a repondre aux besoins de la technologie des reacteurs, les chercheurs se sont surtout efforces d'ameliorer la resolution en energie ainsi que la precision des donnees relatives aux combustibles; ils ont ete ainsi amenes a etudier plus en detail la region de resonance qui a un grand interet pour les calculs de l'effet Doppler dans les reacteurs. Des mesures plus precises a des niveaux d'energie assez eleves ont fait apparaitre dans certains cas l'existence de sections efficaces de fission assez importantes en dessous du seuil d'energie de fission. Ces mesures ont ensuite appele l'attention des chercheurs sur l'interpretation des sections efficaces en fonction de modeles nucleaires qui reposent sur des donnees quantitatives sures. Le memoire expose les principales caracteristiques des sections efficaces de fission par neutrons et en donne une interpretation. Il met l'accent sur les ameliorations qui ont recemment ete apportees a la qualite des mesures et aux essais d'interpretation quantitative de certains aspects des donnees recueillies. (author) [Spanish] Las secciones eficaces de fision, inducida por neutrones, de los nucleos pesados son de fundamental importancia para la tecnologia de la produccion de energia nuclear. Asimismo, la manera en que estas secciones eficaces varian segun la energia

  4. 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.

  5. Axon density and axon orientation dispersion in children born preterm

    NARCIS (Netherlands)

    Kelly, Claire E.; Thompson, Deanne K.; Chen, Jian; Leemans, Alexander; Adamson, Christopher L.; Inder, Terrie E.; Cheong, Jeanie L Y; Doyle, Lex W.; Anderson, Peter J.

    2016-01-01

    Background Very preterm birth (VPT, <32 weeks' gestation) is associated with altered white matter fractional anisotropy (FA), the biological basis of which is uncertain but may relate to changes in axon density and/or dispersion, which can be measured using Neurite Orientation Dispersion and Density

  6. Optofluidic control of axonal guidance

    Science.gov (United States)

    Gu, Ling; Ordonez, Simon; Black, Bryan; Mohanty, Samarendra K.

    2013-03-01

    Significant efforts are being made for control on axonal guidance due to its importance in nerve regeneration and in the formation of functional neuronal circuitry in-vitro. These include several physical (topographic modification, optical force, and electric field), chemical (surface functionalization cues) and hybrid (electro-chemical, photochemical etc) methods. Here, we report comparison of the effect of linear flow versus microfluidic flow produced by an opticallydriven micromotor in guiding retinal ganglion axons. A circularly polarized laser tweezers was used to hold, position and spin birefringent calcite particle near growth cone, which in turn resulted in microfluidic flow. The flow rate and resulting shear-force on axons could be controlled by a varying the power of the laser tweezers beam. The calcite particles were placed separately in one chamber and single particle was transported through microfluidic channel to another chamber containing the retina explant. In presence of flow, the turning of axons was found to strongly correlate with the direction of flow. Turning angle as high as 90° was achieved. Optofluidic-manipulation can be applied to other types of mammalian neurons and also can be extended to stimulate mechano-sensing neurons.

  7. The axonal cytoskeleton : from organization to function

    NARCIS (Netherlands)

    Kevenaar, Josta T; Hoogenraad, Casper C

    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

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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

  11. Trolox reduces the effect of ethanol on acetylcholine-induced contractions and oxidative stress in the isolated rabbit duodenum El Trolox reduce el efecto del etanol sobre las contracciones inducidas a la acetilcolina y el estrés oxidativo en duodeno aislado de conejo

    Directory of Open Access Journals (Sweden)

    Diego S. Fagundes

    2011-08-01

    Full Text Available Trolox is a hydrophilic analogue of vitamin E and a free radical scavenger. Ethanol diminishes the amplitude of spontaneous contractions and acetylcholine (ACh-induced contractions in rabbit duodenum. The aim of this work was to study the effect of Trolox on the alterations induced by ethanol on contractility and lipid peroxidation in the duodenum. The duodenal contractility studies in vitro were carried out in an organ bath and the levels of malondialdehyde and 4-hydroxyalkenals (MDA+4-HAD were measured by spectrophotometry. Trolox increased the reduction induced by ethanol on the amplitude of spontaneous contractions in longitudinal muscle but not in circular muscle. Trolox 4 mM decreased the effects of ethanol on ACh-induced contractions and on MDA+4-HDA concentrations. We conclude that Trolox might prevent oxidative stress induced by ethanol in the duodenum.El Trolox es un análogo hidrofílico de la vitamina E y un agente que secuestra radicales libres. El etanol disminuye la amplitud de las contracciones espontáneas y las contracciones inducidas a la acetilcolina en el duodeno de conejo. El objetivo de este trabajo era estudiar el efecto del Trolox en las alteraciones inducidas por el etanol sobre la contractilidad y la peroxidación lipídica en el duodeno. Los estudios de contractilidad duodenal in vitro se realizaron en un baño de órganos y los niveles de MDA+4-HDA se midieron por espectofotometría. El Trolox aumentó la reducción inducida por el etanol sobre la amplitud de las contracciones espontáneas en el músculo longitudinal pero no en el músculo circular de duodeno. El Trolox 4 mM redujo los efectos del etanol sobre las contracciones inducidas a la acetilcolina y sobre las concentraciones de MDA+4-HDA. Se concluye que el Trolox podría prevenir el estrés oxidativo inducido por el etanol en el duodeno.

  12. 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.

  13. Elucidation of axonal transport by radioautography

    International Nuclear Information System (INIS)

    Droz, Bernard.

    1979-01-01

    Radioautography permits to distinguish various pathways within the axons: the axoplasm which includes soluble enzymes and constituents of the cytoskeleton moving with slow axoplasmic flow; the mitochondria which are conveyed as organelles; the smooth endoplasmic reticulum which ensures the fast axonal transport of membrane constituents delivered to axolemma, synaptic vesicles, presynaptic membranes or mitochondria. Furthermore radioautography makes it possible to visualize intercellular exchanges of molecules between axon and glia

  14. 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......, action potential propagation and structural integrity of the distal segment are maintained. The aim of this study was to investigate in vivo the changes in membrane function of motor axons during the 'latent' phase of Wallerian degeneration. Multiple indices of axonal excitability of the tibial nerve...

  15. Axonal regeneration in zebrafish spinal cord

    Science.gov (United States)

    Hui, Subhra Prakash

    2018-01-01

    Abstract In the present review we discuss two interrelated events—axonal damage and repair—known to occur after spinal cord injury (SCI) in the zebrafish. Adult zebrafish are capable of regenerating axonal tracts and can restore full functionality after SCI. Unlike fish, axon regeneration in the adult mammalian central nervous system is extremely limited. As a consequence of an injury there is very little repair of disengaged axons and therefore functional deficit persists after SCI in adult mammals. In contrast, peripheral nervous system axons readily regenerate following injury and hence allow functional recovery both in mammals and fish. A better mechanistic understanding of these three scenarios could provide a more comprehensive insight into the success or failure of axonal regeneration after SCI. This review summarizes the present understanding of the cellular and molecular basis of axonal regeneration, in both the peripheral nervous system and the central nervous system, and large scale gene expression analysis is used to focus on different events during regeneration. The discovery and identification of genes involved in zebrafish spinal cord regeneration and subsequent functional experimentation will provide more insight into the endogenous mechanism of myelination and remyelination. Furthermore, precise knowledge of the mechanism underlying the extraordinary axonal regeneration process in zebrafish will also allow us to unravel the potential therapeutic strategies to be implemented for enhancing regrowth and remyelination of axons in mammals. PMID:29721326

  16. 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.

  17. Differential effects of myostatin deficiency on motor and sensory axons.

    Science.gov (United States)

    Jones, Maria R; Villalón, Eric; Northcutt, Adam J; Calcutt, Nigel A; Garcia, Michael L

    2017-12-01

    Deletion of myostatin in mice (MSTN -/- ) alters structural properties of peripheral axons. However, properties like axon diameter and myelin thickness were analyzed in mixed nerves, so it is unclear whether loss of myostatin affects motor, sensory, or both types of axons. Using the MSTN -/- mouse model, we analyzed the effects of increasing the number of muscle fibers on axon diameter, myelin thickness, and internode length in motor and sensory axons. Axon diameter and myelin thickness were increased in motor axons of MSTN -/- mice without affecting internode length or axon number. The number of sensory axons was increased without affecting their structural properties. These results suggest that motor and sensory axons establish structural properties by independent mechanisms. Moreover, in motor axons, instructive cues from the neuromuscular junction may play a role in co-regulating axon diameter and myelin thickness, whereas internode length is established independently. Muscle Nerve 56: E100-E107, 2017. © 2017 Wiley Periodicals, Inc.

  18. 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.

  19. Axon-Axon Interactions Regulate Topographic Optic Tract Sorting via CYFIP2-Dependent WAVE Complex Function.

    Science.gov (United States)

    Cioni, Jean-Michel; Wong, Hovy Ho-Wai; Bressan, Dario; Kodama, Lay; Harris, William A; Holt, Christine E

    2018-03-07

    The axons of retinal ganglion cells (RGCs) are topographically sorted before they arrive at the optic tectum. This pre-target sorting, typical of axon tracts throughout the brain, is poorly understood. Here, we show that cytoplasmic FMR1-interacting proteins (CYFIPs) fulfill non-redundant functions in RGCs, with CYFIP1 mediating axon growth and CYFIP2 specifically involved in axon sorting. We find that CYFIP2 mediates homotypic and heterotypic contact-triggered fasciculation and repulsion responses between dorsal and ventral axons. CYFIP2 associates with transporting ribonucleoprotein particles in axons and regulates translation. Axon-axon contact stimulates CYFIP2 to move into growth cones where it joins the actin nucleating WAVE regulatory complex (WRC) in the periphery and regulates actin remodeling and filopodial dynamics. CYFIP2's function in axon sorting is mediated by its binding to the WRC but not its translational regulation. Together, these findings uncover CYFIP2 as a key regulatory link between axon-axon interactions, filopodial dynamics, and optic tract sorting. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  20. 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.

  1. 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.

  2. Efectos del fMLP y de los antioxidantes sobre funciones inducidas por lipopolisacáridos bacterianos

    OpenAIRE

    Vulcano, Marisa

    1997-01-01

    En el presente tabajo de Tesis se evaluaron las consecuencias de las interacciones de los lipopolisacáridos (LPS) y de los péptidos formilados de las bacterias Gram negativas sobre la activación de distintas funciones celulares involucradas en el desencadenamiento de la respuesta inflamatoria a la infección. En particular, se analizaron los efectos de estos dos componentes bacterianos sobre la activación del estallido respiratorio y la producción de TNF-α en células fagocíticas humanas. Los r...

  3. CARACTERIZACION DE GENES DESHIDRINA EN EUCALYPTUS GLOBULUS CUYA EXPRESION ES INDUCIDA POR LA ACLIMATACION A BAJA TEMPERATURA

    OpenAIRE

    FERNANDEZ REYES, MARTA ALEJANDRA

    2011-01-01

    Eucalyptus globulus es una especie importante para la producción de pulpa de madera en Chile, sin embargo presenta una gran sensibilidad a temperaturas de congelamiento. Durante los últimos años, muchos estudios han enfocado sus esfuerzos en dilucidar los mecanismos que regulan la respuesta de las plantas a baja temperatura, mediante el análisis de la expresión génica. En el presente trabajo se estudia la expresión de genes deshidrina durante el proceso de aclimatación a baja temperatura y...

  4. CARACTERIZACION DE GENES DESHIDRINA EN EUCALYPTUS GLOBULUS CUYA EXPRESION ES INDUCIDA POR LA ACLIMATACION A BAJA TEMPERATURA

    OpenAIRE

    FERNANDEZ REYES ; MARTA ALEJANDRA; FERNANDEZ REYES ; MARTA ALEJANDRA

    2011-01-01

    Eucalyptus globulus es una especie importante para la producción de pulpa de madera en Chile, sin embargo presenta una gran sensibilidad a temperaturas de congelamiento. Durante los últimos años, muchos estudios han enfocado sus esfuerzos en dilucidar los mecanismos que regulan la respuesta de las plantas a baja temperatura, mediante el análisis de la expresión génica. En el presente trabajo se estudia la expresión de genes deshidrina durante el proceso de aclimatación a baja temperatura y la...

  5. 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.

  6. 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.

  7. Axonal inclusions in the crab Hemigrapsus nudus.

    Science.gov (United States)

    Smith, R S

    1978-10-01

    Light microscopic examination of living giant axons from the walking legs of Hemigrapsus nudus revealed intra-axonal inclusions which were usually several tens of micrometers long and about 5 micron wide. The inclusions were filled with small light-scattering particles. The inclusions were shown, by thin section electron microscopy, to be composed largely 68% by volume) of mitochondria. Each inclusion was surrounded by membrane bounded spaces which are presumed to represent a part of the smooth endoplasmic reticulum. Similar inclusions were not found in the leg axons of a variety of other decapod crustaceans.

  8. 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.

  9. 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

  10. Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins.

    Science.gov (United States)

    Yalçın, Belgin; Zhao, Lu; Stofanko, Martin; O'Sullivan, Niamh C; Kang, Zi Han; Roost, Annika; Thomas, Matthew R; Zaessinger, Sophie; Blard, Olivier; Patto, Alex L; Sohail, Anood; Baena, Valentina; Terasaki, Mark; O'Kane, Cahir J

    2017-07-25

    Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function.

  11. Con-nectin axons and dendrites.

    Science.gov (United States)

    Beaudoin, Gerard M J

    2006-07-03

    Unlike adherens junctions, synapses are asymmetric connections, usually between axons and dendrites, that rely on various cell adhesion molecules for structural stability and function. Two cell types of adhesion molecules found at adherens junctions, cadherins and nectins, are thought to mediate homophilic interaction between neighboring cells. In this issue, Togashi et al. (see p. 141) demonstrate that the differential localization of two heterophilic interacting nectins mediates the selective attraction of axons and dendrites in cooperation with cadherins.

  12. 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: Neuroscience s (including psychophysiology Impact factor: 4.431, year: 2016

  13. 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

  14. 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

  15. Epigenetic regulation of axon and dendrite growth

    Directory of Open Access Journals (Sweden)

    Ephraim F Trakhtenberg

    2012-03-01

    Full Text Available Neuroregenerative therapies for central nervous system (CNS injury, neurodegenerative disease, or stroke require axons of damaged neurons to grow and reinnervate their targets. However, mature mammalian CNS neurons do not regenerate their axons, limiting recovery in these diseases (Yiu and He, 2006. CNS’ regenerative failure may be attributable to the development of an inhibitory CNS environment by glial-associated inhibitory molecules (Yiu and He, 2006, and by various cell-autonomous factors (Sun and He, 2010. Intrinsic axon growth ability also declines developmentally (Li et al., 1995; Goldberg et al., 2002; Bouslama-Oueghlani et al., 2003; Blackmore and Letourneau, 2006 and is dependent on transcription (Moore et al., 2009. Although neurons’ intrinsic capacity for axon growth may depend in part on the panoply of expressed transcription factors (Moore and Goldberg, 2011, epigenetic factors such as the accessibility of DNA and organization of chromatin are required for downstream genes to be transcribed. Thus a potential approach to overcoming regenerative failure focuses on the epigenetic mechanisms regulating regenerative gene expression in the CNS. Here we review molecular mechanisms regulating the epigenetic state of DNA through chromatin modifications, their implications for regulating axon and dendrite growth, and important new directions for this field of study.

  16. 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.

  17. Estrés oxidativo y otras respuestas fisiológicas inducidas por el alpeorujo transformado por hongos saprobios en plantas de tomate (Solanum lycopersicum L.)

    OpenAIRE

    García Sánchez, Mercedes

    2013-01-01

    El cultivo del olivar y la obtención industrial de aceite de oliva tienen una extraordinaria importancia económica y social en España y, particularmente, en Andalucía. Actualmente, el sistema de extracción de aceite de oliva es la centrifugación de dos fases tras el que se obtiene una fase oleosa o aceite y un residuo semisólido denominado alpeorujo. Se ha observado, que el alpeorujo presenta un elevado contenido en materia orgánica, nutrientes minerales y un pH ligeramente ácido lo que plant...

  18. 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

  19. Creatine pretreatment protects cortical axons from energy depletion in vitro

    Science.gov (United States)

    Shen, Hua; Goldberg, Mark P.

    2012-01-01

    Creatine is a natural nitrogenous guanidino compound involved in bioenergy metabolism. Although creatine has been shown to protect neurons of the central nervous system (CNS) from experimental hypoxia/ischemia, it remains unclear if creatine may also protect CNS axons, and if the potential axonal protection depends on glial cells. To evaluate the direct impact of creatine on CNS axons, cortical axons were cultured in a separate compartment from their somas and proximal neurites using a modified two-compartment culture device. Axons in the axon compartment were subjected to acute energy depletion, an in vitro model of white matter ischemia, by exposure to 6 mM sodium azide for 30 min in the absence of glucose and pyruvate. Energy depletion reduced axonal ATP by 65%, depolarized axonal resting potential, and damaged 75% of axons. Application of creatine (10 mM) to both compartments of the culture at 24 h prior to energy depletion significantly reduced axonal damage by 50%. In line with the role of creatine in the bioenergy metabolism, this application also alleviated the axonal ATP loss and depolarization. Inhibition of axonal depolarization by blocking sodium influx with tetrodotoxin also effectively reduced the axonal damage caused by energy depletion. Further study revealed that the creatine effect was independent of glial cells, as axonal protection was sustained even when creatine was applied only to the axon compartment (free from somas and glial cells) for as little as 2 h. In contrast, application of creatine after energy depletion did not protect axons. The data provide the first evidence that creatine pretreatment may directly protect CNS axons from energy deficiency. PMID:22521466

  20. [Severe, subacute axonal polyneuropathy due to hypophosphatemia].

    NARCIS (Netherlands)

    Eijk, J.J.J. van; Abdo, W.F.; Deurwaarder, E. den; Zwarts, M.J.; Warrenburg, B.P.C. van de

    2010-01-01

    A 46-year-old man receiving tube feeding because of anorexia and weight loss developed progressive neurological symptoms initially resembling Guillain-Barre syndrome. Eventually axonal neuropathy due to severe hypophosphatemia was diagnosed. Hypophosphatemia can be caused by the so-called refeeding

  1. 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

  2. Drug therapy for chronic idiopathic axonal polyneuropathy

    NARCIS (Netherlands)

    Warendorf, Janna; Vrancken, Alexander F.J.E.; van Schaik, Ivo N.; Hughes, Richard A.C.; Notermans, Nicolette C.

    2017-01-01

    Background: Chronic idiopathic axonal polyneuropathy (CIAP) is an insidiously progressive sensory or sensorimotor polyneuropathy that affects elderly people. Although severe disability or handicap does not occur, CIAP reduces quality of life. CIAP is diagnosed in 10% to 25% of people referred for

  3. Drug therapy for chronic idiopathic axonal polyneuropathy

    NARCIS (Netherlands)

    Warendorf, Janna; Vrancken, Alexander F. J. E.; van Schaik, Ivo N.; Hughes, Richard A. C.; Notermans, Nicolette C.

    2017-01-01

    Chronic idiopathic axonal polyneuropathy (CIAP) is an insidiously progressive sensory or sensorimotor polyneuropathy that affects elderly people. Although severe disability or handicap does not occur, CIAP reduces quality of life. CIAP is diagnosed in 10% to 25% of people referred for evaluation of

  4. 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.

  5. Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion

    Directory of Open Access Journals (Sweden)

    Ren Song

    2016-02-01

    Full Text Available Infection by alphaherpesviruses, including herpes simplex virus (HSV and pseudorabies virus (PRV, typically begins at epithelial surfaces and continues into the peripheral nervous system (PNS. Inflammatory responses are induced at the infected peripheral site prior to invasion of the PNS. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which includes the interferons (IFNs. The fundamental question is how do PNS cell bodies respond to these distant, potentially damaging events experienced by axons. Using compartmented cultures that physically separate neuron axons from cell bodies, we found that pretreating isolated axons with beta interferon (IFN-β or gamma interferon (IFN-γ significantly diminished the number of herpes simplex virus 1 (HSV-1 and PRV particles moving in axons toward the cell bodies in a receptor-dependent manner. Exposing axons to IFN-β induced STAT1 phosphorylation (p-STAT1 only in axons, while exposure of axons to IFN-γ induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated antiviral effects induced by IFN-γ, but not those induced by IFN-β. Proteomic analysis of IFN-β- or IFN-γ-treated axons identified several differentially regulated proteins. Therefore, unlike treatment with IFN-γ, IFN-β induces a noncanonical, local antiviral response in axons. The activation of a local IFN response in axons represents a new paradigm for cytokine control of neuroinvasion.

  6. 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.

  7. Axonal excitability properties in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Vucic, Steve; Kiernan, Matthew C

    2006-07-01

    To investigate axolemmal ion channel function in patients diagnosed with sporadic amyotrophic lateral sclerosis (ALS). A recently described threshold tracking protocol was implemented to measure multiple indices of axonal excitability in 26 ALS patients by stimulating the median motor nerve at the wrist. The excitability indices studied included: stimulus-response curve (SR); strength-duration time constant (tauSD); current/threshold relationship; threshold electrotonus to a 100 ms polarizing current; and recovery curves to a supramaximal stimulus. Compound muscle action potential (CMAP) amplitudes were significantly reduced in ALS patients (ALS, 2.84+/-1.17 mV; controls, 8.27+/-1.09 mV, P<0.0005) and the SR curves for both 0.2 and 1 ms pulse widths were shifted in a hyperpolarized direction. Threshold electrotonus revealed a greater threshold change to both depolarizing and hyperpolarizing conditioning stimuli, similar to the 'fanned out' appearance that occurs with membrane hyperpolarization. The tauSD was significantly increased in ALS patients (ALS, 0.50+/-0.03 ms; controls, 0.42+/-0.02 ms, P<0.05). The recovery cycle of excitability following a conditioning supramaximal stimulus revealed increased superexcitability in ALS patients (ALS, 29.63+/-1.25%; controls, 25.11+/-1.01%, P<0.01). Threshold tracking studies revealed changes indicative of widespread dysfunction in axonal ion channel conduction, including increased persistent Na+ channel conduction, and abnormalities of fast paranodal K+ and internodal slow K+ channel function, in ALS patients. An increase in persistent Na+ conductances coupled with reduction in K+ currents would predispose axons of ALS patients to generation of fasciculations and cramps. Axonal excitability studies may provide insight into mechanisms responsible for motor neuron loss in ALS.

  8. 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".

  9. Retinoic acid signaling in axonal regeneration

    Directory of Open Access Journals (Sweden)

    Radhika ePuttagunta

    2012-01-01

    Full Text Available Following an acute central nervous system injury, axonal regeneration and functional recovery are extremely limited. This is due to an extrinsic inhibitory growth environment and the lack of intrinsic growth competence. Retinoic acid (RA signaling, essential in developmental dorsoventral patterning and specification of spinal motor neurons, has been shown through its receptor, the transcription factor RA receptor β2 (RARß2, to induce axonal regeneration following spinal cord injury (SCI. Recently, it has been shown that in dorsal root ganglia neurons, cAMP levels were greatly increased by lentiviral RARβ2 expression and contributed to neurite outgrowth. Moreover, RARβ agonists, in cerebellar granule neurons and in the brain in vivo, induced phosphoinositide 3-kinase dependent phosphorylation of AKT that was involved in RARβ-dependent neurite outgrowth. More recently, RA-RARß pathways were shown to directly transcriptionally repress a member of the inhibitory Nogo receptor complex, Lingo-1, under an axonal growth inhibitory environment in vitro as well as following spinal injury in vivo. This perspective focuses on these newly discovered molecular mechanisms and future directions in the field.

  10. Dependence of regenerated sensory axons on continuous neurotrophin-3 delivery.

    Science.gov (United States)

    Hou, Shaoping; Nicholson, LaShae; van Niekerk, Erna; Motsch, Melanie; Blesch, Armin

    2012-09-19

    Previous studies have shown that injured dorsal column sensory axons extend across a spinal cord lesion site if axons are guided by a gradient of neurotrophin-3 (NT-3) rostral to the lesion. Here we examined whether continuous NT-3 delivery is necessary to sustain regenerated axons in the injured spinal cord. Using tetracycline-regulated (tet-off) lentiviral gene delivery, NT-3 expression was tightly controlled by doxycycline administration. To examine axon growth responses to regulated NT-3 expression, adult rats underwent a C3 dorsal funiculus lesion. The lesion site was filled with bone marrow stromal cells, tet-off-NT-3 virus was injected rostral to the lesion site, and the intrinsic growth capacity of sensory neurons was activated by a conditioning lesion. When NT-3 gene expression was turned on, cholera toxin β-subunit-labeled sensory axons regenerated into and beyond the lesion/graft site. Surprisingly, the number of regenerated axons significantly declined when NT-3 expression was turned off, whereas continued NT-3 expression sustained regenerated axons. Quantification of axon numbers beyond the lesion demonstrated a significant decline of axon growth in animals with transient NT-3 expression, only some axons that had regenerated over longer distance were sustained. Regenerated axons were located in white matter and did not form axodendritic synapses but expressed presynaptic markers when closely associated with NG2-labeled cells. A decline in axon density was also observed within cellular grafts after NT-3 expression was turned off possibly via reduction in L1 and laminin expression in Schwann cells. Thus, multiple mechanisms underlie the inability of transient NT-3 expression to fully sustain regenerated sensory axons.

  11. Formation of longitudinal axon pathways in Caenorhabditis elegans.

    Science.gov (United States)

    Hutter, Harald

    2017-11-18

    The small number of neurons and the simple architecture of the Caenorhabditis elegans (C. elegans) nervous system enables researchers to study axonal pathfinding at the level of individually identified axons. Axons in C. elegans extend predominantly along one of the two major body axes, the anterior-posterior axis and the dorso-ventral axis. This review will focus on axon navigation along the anterior-posterior axis, leading to the establishment of the longitudinal axon tracts, with a focus on the largest longitudinal axon tract, the ventral nerve cord (VNC). In the VNC, axons grow out in a stereotypic order, with early outgrowing axons (pioneers) playing an important role in guiding later outgrowing (follower) axons. Genetic screens have identified a number of genes specifically affecting the formation of longitudinal axon tracts. These genes include secreted proteins, putative receptors and adhesion molecules, as well as intracellular proteins regulating the cell's response to guidance cues. In contrast to dorso-ventral navigation, no major general guidance cues required for the establishment of longitudinal pathways have been identified so far. The limited penetrance of defects found in many mutants affecting longitudinal navigation suggests that guidance cues act redundantly in this process. The majority of the axon guidance genes identified in C. elegans are evolutionary conserved, i.e. have homologs in other animals, including vertebrates. For a number of these genes, a role in axon guidance has not been described outside C. elegans. Taken together, studies in C. elegans contribute to a fundamental understanding of the molecular basis of axonal navigation that can be extended to other animals, including vertebrates and probably humans as well. Copyright © 2017. Published by Elsevier Ltd.

  12. 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.

  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. 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 injury......, develop de novo axons. Our goal was to determine whether spinal commissural interneurons (CINs), axotomized by 3-4-mm midsagittal transection at C3, form de novo axons from distal dendrites. All experiments were performed on adult cats. CINs in C3 were stained with extracellular injections of Neurobiotin...... at 4-5 weeks post injury. The somata of axotomized CINs were identified by the presence of immunoreactivity for the axonal growth-associated protein-43 (GAP-43). Nearly half of the CINs had de novo axons that emerged from distal dendrites. These axons lacked immunoreactivity for the dendritic protein...

  15. Cannabinoid receptor CB2 modulates axon guidance

    DEFF Research Database (Denmark)

    Duff, Gabriel; Argaw, Anteneh; Cecyre, Bruno

    2013-01-01

    on axon guidance. These effects are specific to CB2R since no changes were observed in mice where the gene coding for this receptor was altered (cnr2 (-/-)). The CB2R induced morphological changes observed at the growth cone are PKA dependent and require the presence of the netrin-1 receptor, Deleted...... CB2R's implication in retinothalamic development. Overall, this study demonstrates that the contribution of endocannabinoids to brain development is not solely mediated by CB1R, but also involves CB2R....

  16. Neuropatia experimental por DDT: análise de nervo por microdissecção de fibras

    Directory of Open Access Journals (Sweden)

    Edison Matos Nóvak

    1984-09-01

    Full Text Available Estudou-se o nervo gênito-femural do rato albino submetido a intoxicação crônica por DDT, administrado por 180 dias na dose de 5 mg/kg de peso via oral. Os resultados mostraram proporção anormal de fibras tipo C, sendo sugerido ocorrer degeneração tipo axonal determinada pelo DDT.

  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. Axon guidance molecules in vascular patterning.

    Science.gov (United States)

    Adams, Ralf H; Eichmann, Anne

    2010-05-01

    Endothelial cells (ECs) form extensive, highly branched and hierarchically organized tubular networks in vertebrates to ensure the proper distribution of molecular and cellular cargo in the vertebrate body. The growth of this vascular system during development, tissue repair or in disease conditions involves the sprouting, migration and proliferation of endothelial cells in a process termed angiogenesis. Surprisingly, specialized ECs, so-called tip cells, which lead and guide endothelial sprouts, share many feature with another guidance structure, the axonal growth cone. Tip cells are motile, invasive and extend numerous filopodial protrusions sensing growth factors, extracellular matrix and other attractive or repulsive cues in their tissue environment. Axonal growth cones and endothelial tip cells also respond to signals belonging to the same molecular families, such as Slits and Roundabouts, Netrins and UNC5 receptors, Semaphorins, Plexins and Neuropilins, and Eph receptors and ephrin ligands. Here we summarize fundamental principles of angiogenic growth, the selection and function of tip cells and the underlying regulation by guidance cues, the Notch pathway and vascular endothelial growth factor signaling.

  19. Parallel simulation of axon growth in the nervous system

    NARCIS (Netherlands)

    J. Wensch; B.P. Sommeijer (Ben)

    2002-01-01

    textabstractIn this paper we discuss a model from neurobiology, which describes theoutgrowth of axons from neurons in the nervous system. The model combines ordinary differential equations, defining the movement of the axons, with parabolic partial differential equations. The parabolic equations

  20. A dam for retrograde axonal degeneration in multiple sclerosis?

    NARCIS (Netherlands)

    Balk, L.J.; Twisk, J.W.R.; Steenwijk, M.D.; Daams, M.; Tewarie, P.; Killestein, J.; Uitdehaag, B.M.J.; Polman, C.H.; Petzold, A.F.S.

    2014-01-01

    Objective: Trans-synaptic axonal degeneration is a mechanism by which neurodegeneration can spread from a sick to a healthy neuron in the central nervous system. This study investigated to what extent trans-synaptic axonal degeneration takes place within the visual pathway in multiple sclerosis

  1. 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

  2. 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.

  3. 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.

  4. Internodal function in normal and regenerated mammalian axons

    DEFF Research Database (Denmark)

    Moldovan, M; Krarup, C

    2007-01-01

    AIM: Following Wallerian degeneration, peripheral myelinated axons have the ability to regenerate and, given a proper pathway, establish functional connections with targets. In spite of this capacity, the clinical outcome of nerve regeneration remains unsatisfactory. Early studies have found...... that regenerated internodes remain persistently short though this abnormality did not seem to influence recovery in conduction. It remains unclear to which extent abnormalities in axonal function itself may contribute to the poor outcome of nerve regeneration. METHODS: We review experimental evidence indicating...... that internodes play an active role in axonal function. RESULTS: By investigating internodal contribution to axonal excitability we have found evidence that axonal function may be permanently compromised in regenerated nerves. Furthermore, we illustrate that internodal function is also abnormal in regenerated...

  5. 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

  6. Axon diameter mapping in crossing fibers with diffusion MRI

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...... 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...... model to enable axon diameter mapping in voxels with crossing fibers. We show in simulation that the technique can provide robust axon diameter estimates in a two-fiber crossing with the crossing angle as small as 45 degrees. Using ex vivo imaging data, we further demonstrate the feasibility...

  7. 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.

  8. Axonal loss in the multiple sclerosis spinal cord revisited.

    Science.gov (United States)

    Petrova, Natalia; Carassiti, Daniele; Altmann, Daniel R; Baker, David; Schmierer, Klaus

    2018-05-01

    Preventing chronic disease deterioration is an unmet need in people with multiple sclerosis, where axonal loss is considered a key substrate of disability. Clinically, chronic multiple sclerosis often presents as progressive myelopathy. Spinal cord cross-sectional area (CSA) assessed using MRI predicts increasing disability and has, by inference, been proposed as an indirect index of axonal degeneration. However, the association between CSA and axonal loss, and their correlation with demyelination, have never been systematically investigated using human post mortem tissue. We extensively sampled spinal cords of seven women and six men with multiple sclerosis (mean disease duration= 29 years) and five healthy controls to quantify axonal density and its association with demyelination and CSA. 396 tissue blocks were embedded in paraffin and immuno-stained for myelin basic protein and phosphorylated neurofilaments. Measurements included total CSA, areas of (i) lateral cortico-spinal tracts, (ii) gray matter, (iii) white matter, (iv) demyelination, and the number of axons within the lateral cortico-spinal tracts. Linear mixed models were used to analyze relationships. In multiple sclerosis CSA reduction at cervical, thoracic and lumbar levels ranged between 19 and 24% with white (19-24%) and gray (17-21%) matter atrophy contributing equally across levels. Axonal density in multiple sclerosis was lower by 57-62% across all levels and affected all fibers regardless of diameter. Demyelination affected 24-48% of the gray matter, most extensively at the thoracic level, and 11-13% of the white matter, with no significant differences across levels. Disease duration was associated with reduced axonal density, however not with any area index. Significant association was detected between focal demyelination and decreased axonal density. In conclusion, over nearly 30 years multiple sclerosis reduces axonal density by 60% throughout the spinal cord. Spinal cord cross sectional area

  9. 4S RNA is transported axonally in normal and regenerating axons of the sciatic nerves of rats

    Energy Technology Data Exchange (ETDEWEB)

    Lindquist, T D; Ingoglia, N A; Gould, R M [Departments of Physiology and Neuroscience, New Jersey Medical School, Newark, NJ, USA

    1982-12-28

    Experiments were designed to determine if following injection of (/sup 3/H)uridine into the lumbar spinal cord of the rat, (/sup 3/H)RNA could be demonstrated within axons of the sciatic nerve, and if 4S RNA is the predominant predominant RNA species present in these axons.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. 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

  13. Compuestos fenólicos de la fracción metanólica de Bidens pilosa, sobre la neoplasia gástrica, inducida en ratas

    Directory of Open Access Journals (Sweden)

    Jorge Arroyo

    2007-06-01

    Full Text Available Objetivo: Determinar la influencia del extracto etanólico y la fracción metanólica conteniendo compuestos fenólicos y flavonoides de la planta entera de Bidens pilosa L sobre la neoplasia gástrica inducida en ratas con N-nitroso-N-metilurea (NMU. Diseño: Experimental. Lugar: Instituto de Investigaciones Clínicas-Bioterio Facultad de Medicina UNMSM. Material biológico: Ratas albinas cepa Holtzmann machos. Intervenciones: Según Ferraz de Souza y col., 2002, se dispuso de un grupo control normal, un grupo con NMU y grupos de NMU más tratamientos de extracto etanólico y fracción metanólica, a dosis de 300 mg/kg. Para la significancia estadística se consideró la p<0,05. Principales medidas de resultados: Progresión de la neoplasia gástrica inducida en ratas. Resultados: Indican displasia y estadios iniciales de carcinoma en los estómagos de las ratas, lo que fue menos evidente en los animales con tratamiento, siendo mejor el grupo que recibió fracción metanólica. El marcador de estrés oxidativo disminuyó en los grupos que recibieron tratamiento con la planta, resultando mejor la fracción metabólica. Se observó menor cantidad de micronúcleos (genotoxicidad en los animales que recibieron tratamiento. Conclusiones: El extracto etanólico y la fracción metanólica de Bidens pilosa L en las condiciones experimentales han detenido la progresión de la neoplasia gástrica inducida en ratas.

  14. 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.

  15. 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.

  16. Nutrición parenteral total en una paciente gestante con pancreatitis aguda e hipertrigliceridemia por déficit de lipoproteín lipasa

    OpenAIRE

    Contreras-Bolívar, Victoria; González-Molero, Inmaculada; Valdivieso, Pedro; Olveira, Gabriel

    2015-01-01

    Presentamos un caso de pancreatitis aguda severa inducida por hipertrigliceridemia secundaria a déficit de lipoproteín lipasa (LPL) en una paciente gestante con diabetes gestacional, manejada inicialmente con dieta, siendo necesario posteriormente llevar a cabo medidas de soporte nutricional artificial: nutrición parenteral total. El déficit de LPL causa hipertrigliceridemia severa y, frecuentemente, pancreatitis aguda de repetición, situación de difícil manejo y de importante gravedad durant...

  17. 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.

  18. 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

  19. 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

  20. 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

  1. Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb.

    Directory of Open Access Journals (Sweden)

    Rosa-Eva Huettl

    2011-02-01

    Full Text Available The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these processes are not well understood. Using cell-type specific ablation of the axon guidance receptor Neuropilin-1 (Npn-1 in spinal motoneurons or in sensory neurons in the dorsal root ganglia (DRG, we have explored the contribution of this signaling pathway to correct innervation of the limb. We show that Npn-1 controls the fasciculation of both projections and mediates inter-axonal communication. Removal of Npn-1 from sensory neurons results in defasciculation of sensory axons and, surprisingly, also of motor axons. In addition, the tight coupling between these two heterotypic axonal populations is lifted with sensory fibers now leading the spinal nerve projection. These findings are corroborated by partial genetic elimination of sensory neurons, which causes defasciculation of motor projections to the limb. Deletion of Npn-1 from motoneurons leads to severe defasciculation of motor axons in the distal limb and dorsal-ventral pathfinding errors, while outgrowth and fasciculation of sensory trajectories into the limb remain unaffected. Genetic elimination of motoneurons, however, revealed that sensory axons need only minimal scaffolding by motor axons to establish their projections in the distal limb. Thus, motor and sensory axons are mutually dependent on each other for the generation of their trajectories and interact in part through Npn-1-mediated fasciculation before and within the plexus region of the limbs.

  2. 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.

  3. 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 ...

  4. 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...

  5. Participación del óxido nítrico en las alteraciones comportamentales y neuroendócrinas inducidas por estrés prenatal

    OpenAIRE

    Maur, Damián Gustavo

    2015-01-01

    Durante el desarrollo prenatal los organismos son vulnerables a factores que pueden afectar su homeostasis. Ha sido demostrado que el estrés durante la preñez tiene efectos en la descendencia que pueden perdurar hasta la adultez, afectando numerosos procesos fisiológicos. Sin embargo, los mecanismos subyacentes aún no han sido completamente dilucidados. El objetivo de esta tesis fue estudiar la participación del óxido nítrico (NO) en las alteraciones comportamentales y neuroendócrinas inducid...

  6. Efecto preventivo de un extracto de cacao enriquecido en polifenoles sobre ratas con alteraciones endocrino metabólicas inducidas por sacarosa

    OpenAIRE

    Villagarcía, Hernán Gonzalo; González Arbeláez, Luisa Fernanda; Castro, María Cecilia; Ríos, José Luis; Massa, María Laura; Schinella, Guillermo Raúl; Francini, Flavio

    2016-01-01

    Existe una creciente evidencia de que el consumo de ciertos alimentos, suplementos alimenticios o bebidas tradicionales puede reducir el daño oxidativo en diferentes sistemas biológicos. Alimentos derivados del cacao, tales como polvos de cacao, chocolate y otros productos relacionado con el cacao son alimentos ricos en polifenoles derivados de las semillas fermentadas, tostados y procesados industrialmente de Theobroma cacao L. (Sterculiaceae). Estos productos, consumidos en todo el mundo...

  7. First Patagonian Course on 'Diagnosis and Therapy of Injuries Induced by Ionizing Radiation'; Primer curso patagonico 'Diagnostico y Tratamiento de Lesiones Inducidas por Radiaciones Ionizantes'

    Energy Technology Data Exchange (ETDEWEB)

    Bellotti, Mariela I., E-mail: bellotti@cab.cnea.gov.ar [Comision Nacional de Energia Atomica (CAB/CNEA), San Carlos de Bariloche (Argentina). Centro Atomico Bariloche. Lab. de Cavitacion y Biotecnologia; Andres, Pablo A., E-mail: andresp@cab.cnea.gov.ar [Comision Nacional de Energia Atomica (CAB/CNEA), San Carlos de Bariloche (Argentina). Centro Atomico Bariloche. Division Proteccion Radiologica; Cascón, Adriana S., E-mail: adrianacascon@yahoo.com [Instituto de Medicina, Radiomedicina y Seguridad (IMERASE SA), Buenos Aires, (Argentina)

    2013-07-01

    In Patagonia there are academic centers, health and industrial facilities that use ionizing radiations in its usual practices. However, they do not have protocols that respond to local needs. For this reason was held from October 5 to November 10, 2012 in Bariloche Atomic Center, a training course for health personnel. The range of topics covered ranged from the definition of dosimetry quantities, types of radiation and biological dosimetry, biological effects, radiation acute syndrome, radiation-induced cutaneous syndrome, internal contamination, screening in radiological emergencies, etc.The course provided a theoretical and practical guide about how to recognize and treat people exposed to radiations, guidelines for acting in radiological emergencies and a perception of the psychosocial impact of the radiation accidents.The result was a pocket book for health personnel that will be used in case of having a patient with radiation induced injury.

  8. Psicosis inducida ("foliex a deux" e intoxicación crónica por plomo.: Reporte de un caso y discusión.

    Directory of Open Access Journals (Sweden)

    Jaime Arias

    1996-04-01

    Full Text Available We report a case of two brothers suffering the same paranoia psychosis. The older one presented an altered consciousness and needed hospitalization. During hospitalization, he was considered as having lead chronic intoxication. The lead serum level was 65 ug/dl (N:<30 ug/dl and the lead hair was 25 pg/gr-tiss (N:<10 pg/gr-tiss. He also presented clinically with encephalopathy, disorder of the autonomic dysfunction. He leaded his body for eleven years because of delutional ideas, and induced these ideas and behavior to his brother (folie a deux. The coincidence between these disorders in extremely rare so we believe this case report is of clinical interesting. (Rev Med Hered 1996; 7: 101-104.

  9. Papel de hemo oxigensa-1 en la artritis inducida por transferencia de suero K/BxN. Caracterización del modelo experimental

    OpenAIRE

    Brines Juan, Rita

    2017-01-01

    La Artritis Reumatoide (AR) es una enfermedad sistémica, crónica y de carácter autoinmune que produce daño articular en los pacientes. Cursa con la degradación del hueso subcondral y del cartílago articular causando un gran dolor; además de ser una enfermedad incapacitante, puede provocar síntomas extraarticulares que afecten a otros órganos. El estudio de la patogenia y del tratamiento de la AR se desarrolla en gran medida sobre modelos animales de artritis experimental. En la actualidad...

  10. 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.

  11. 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)

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

    OpenAIRE

    López-Jaramillo, Patricio; Sotomayor Rubio, Katherine; Sotomayor-Rubio, Arístides; López López, Cristina

    2014-01-01

    Pregnancy induced hypertension, called preeclampsia (PE) when accompanied by proteinuria, is an alteration that occurs in the second trimester of pregnancy and is characterized by presence of hypertension and proteinuria. Adaptative physiologic changes occur during normal pregnancy including insulin-resistance (IR), hyperlipidemia, hypercoagulability, inflammation, and hyperdynamic circulatory status. Expression of these changes is exaggerated in women developing PE. These alterations are als...

  13. RESISTIVIDAD INDUCIDA POR SCATTERING ELECTRON-SUPERFICIE RUGOSA Y SCATTERING ELECTRON BORDE DE GRANO EN PELICULAS DELGADAS DE ORO DEPOSITADAS SOBRE MICA

    OpenAIRE

    HENRIQUEZ CORREA; RICARDO ANDRES; HENRIQUEZ CORREA; RICARDO ANDRES

    2010-01-01

    En este trabajo se presenta un método experimental que permite separar el efecto de las colisiones electrón-borde de grano y electrón-superficie sobre la resistividad eléctrica en películas delgadas de oro evaporadas sobre mica. Cuando el efecto de las colisiones electrón-borde de grano es dominante, la resistividad no depende del espesor de la muestra, el camino libre medio a 4 K es el diámetro medio de grano, la dependencia de la resistividad con temperatura puede ser descrit...

  14. Neurotrophin Signaling via Long-Distance Axonal Transport

    Science.gov (United States)

    Chowdary, Praveen D.; Che, Dung L.; Cui, Bianxiao

    2012-05-01

    Neurotrophins are a family of target-derived growth factors that support survival, development, and maintenance of innervating neurons. Owing to the unique architecture of neurons, neurotrophins that act locally on the axonal terminals must convey their signals across the entire axon for subsequent regulation of gene transcription in the cell nucleus. This long-distance retrograde signaling, a motor-driven process that can take hours or days, has been a subject of intense interest. In the last decade, live-cell imaging with high sensitivity has significantly increased our capability to track the transport of neurotrophins, their receptors, and subsequent signals in real time. This review summarizes recent research progress in understanding neurotrophin-receptor interactions at the axonal terminal and their transport dynamics along the axon. We emphasize high-resolution studies at the single-molecule level and also discuss recent technical advances in the field.

  15. 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...

  16. 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...

  17. Functional characterization and axonal transport of quantum dot labeled BDNF

    OpenAIRE

    Xie, Wenjun; Zhang, Kai; Cui, Bianxiao

    2012-01-01

    Brain derived neurotrophic factor (BDNF) plays a key role in the growth, development and maintenance of the central and peripheral nervous systems. Exogenous BDNF activates its membrane receptors at the axon terminal, and subsequently sends regulation signals to the cell body. To understand how BDNF signal propagates in neurons, it is important to follow the trafficking of BDNF after it is internalized at the axon terminal. Here we labeled BDNF with bright, photostable quantum dot (QD-BDNF) a...

  18. 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.

  19. Self-amplifying autocrine actions of BDNF in axon development

    OpenAIRE

    Cheng, Pei-Lin; Song, Ai-Hong; Wong, Yu-Hui; Wang, Sheng; Zhang, Xiang; Poo, Mu-Ming

    2011-01-01

    A critical step in neuronal development is the formation of axon/dendrite polarity, a process involving symmetry breaking in the newborn neuron. Local self-amplifying processes could enhance and stabilize the initial asymmetry in the distribution of axon/dendrite determinants, but the identity of these processes remains elusive. We here report that BDNF, a secreted neurotrophin essential for the survival and differentiation of many neuronal populations, serves as a self-amplifying autocrine f...

  20. 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.

  1. Dendrosomatic Sonic Hedgehog Signaling in Hippocampal Neurons Regulates Axon Elongation

    Science.gov (United States)

    Petralia, Ronald S.; Ott, Carolyn; Wang, Ya-Xian; Lippincott-Schwartz, Jennifer; Mattson, Mark P.

    2015-01-01

    The presence of Sonic Hedgehog (Shh) and its signaling components in the neurons of the hippocampus raises a question about what role the Shh signaling pathway may play in these neurons. We show here that activation of the Shh signaling pathway stimulates axon elongation in rat hippocampal neurons. This Shh-induced effect depends on the pathway transducer Smoothened (Smo) and the transcription factor Gli1. The axon itself does not respond directly to Shh; instead, the Shh signal transduction originates from the somatodendritic region of the neurons and occurs in neurons with and without detectable primary cilia. Upon Shh stimulation, Smo localization to dendrites increases significantly. Shh pathway activation results in increased levels of profilin1 (Pfn1), an actin-binding protein. Mutations in Pfn1's actin-binding sites or reduction of Pfn1 eliminate the Shh-induced axon elongation. These findings indicate that Shh can regulate axon growth, which may be critical for development of hippocampal neurons. SIGNIFICANCE STATEMENT Although numerous signaling mechanisms have been identified that act directly on axons to regulate their outgrowth, it is not known whether signals transduced in dendrites may also affect axon outgrowth. We describe here a transcellular signaling pathway in embryonic hippocampal neurons in which activation of Sonic Hedgehog (Shh) receptors in dendrites stimulates axon growth. The pathway involves the dendritic-membrane-associated Shh signal transducer Smoothened (Smo) and the transcription factor Gli, which induces the expression of the gene encoding the actin-binding protein profilin 1. Our findings suggest scenarios in which stimulation of Shh in dendrites results in accelerated outgrowth of the axon, which therefore reaches its presumptive postsynaptic target cell more quickly. By this mechanism, Shh may play critical roles in the development of hippocampal neuronal circuits. PMID:26658865

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. Pérdida auditiva por contaminación acústica laboral en Santiago de Chile

    OpenAIRE

    Salazar Bugueño, Ana María

    2013-01-01

    [spa] La Organización Mundial de la Salud (OMS) ha estimado que, aproximadamente, 278 millones de personas presentan déficit auditivo en el mundo; que el 50% de las pérdidas auditivas podrían evitarse mediante prevención, un diagnóstico precoz y una gestión eficaz y que, más de 4.000.000 de años de vida saludable se perdieron debido a las pérdidas auditivas inducidas por ruido. Lo anterior hace necesario establecer un modelo para predecir la pérdida auditiva por contaminación acústica laboral...

  7. Axonal Conduction Delays, Brain State, and Corticogeniculate Communication.

    Science.gov (United States)

    Stoelzel, Carl R; Bereshpolova, Yulia; Alonso, Jose-Manuel; Swadlow, Harvey A

    2017-06-28

    Thalamocortical conduction times are short, but layer 6 corticothalamic axons display an enormous range of conduction times, some exceeding 40-50 ms. Here, we investigate (1) how axonal conduction times of corticogeniculate (CG) neurons are related to the visual information conveyed to the thalamus, and (2) how alert versus nonalert awake brain states affect visual processing across the spectrum of CG conduction times. In awake female Dutch-Belted rabbits, we found 58% of CG neurons to be visually responsive, and 42% to be unresponsive. All responsive CG neurons had simple, orientation-selective receptive fields, and generated sustained responses to stationary stimuli. CG axonal conduction times were strongly related to modulated firing rates (F1 values) generated by drifting grating stimuli, and their associated interspike interval distributions, suggesting a continuum of visual responsiveness spanning the spectrum of axonal conduction times. CG conduction times were also significantly related to visual response latency, contrast sensitivity (C-50 values), directional selectivity, and optimal stimulus velocity. Increasing alertness did not cause visually unresponsive CG neurons to become responsive and did not change the response linearity (F1/F0 ratios) of visually responsive CG neurons. However, for visually responsive CG neurons, increased alertness nearly doubled the modulated response amplitude to optimal visual stimulation (F1 values), significantly shortened response latency, and dramatically increased response reliability. These effects of alertness were uniform across the broad spectrum of CG axonal conduction times. SIGNIFICANCE STATEMENT Corticothalamic neurons of layer 6 send a dense feedback projection to thalamic nuclei that provide input to sensory neocortex. While sensory information reaches the cortex after brief thalamocortical axonal delays, corticothalamic axons can exhibit conduction delays of <2 ms to 40-50 ms. Here, in the corticogeniculate

  8. Wnt5a regulates midbrain dopaminergic axon growth and guidance.

    Directory of Open Access Journals (Sweden)

    Brette D Blakely

    2011-03-01

    Full Text Available During development, precise temporal and spatial gradients are responsible for guiding axons to their appropriate targets. Within the developing ventral midbrain (VM the cues that guide dopaminergic (DA axons to their forebrain targets remain to be fully elucidated. Wnts are morphogens that have been identified as axon guidance molecules. Several Wnts are expressed in the VM where they regulate the birth of DA neurons. Here, we describe that a precise temporo-spatial expression of Wnt5a accompanies the development of nigrostriatal projections by VM DA neurons. In mice at E11.5, Wnt5a is expressed in the VM where it was found to promote DA neurite and axonal growth in VM primary cultures. By E14.5, when DA axons are approaching their striatal target, Wnt5a causes DA neurite retraction in primary cultures. Co-culture of VM explants with Wnt5a-overexpressing cell aggregates revealed that Wnt5a is capable of repelling DA neurites. Antagonism experiments revealed that the effects of Wnt5a are mediated by the Frizzled receptors and by the small GTPase, Rac1 (a component of the non-canonical Wnt planar cell polarity pathway. Moreover, the effects were specific as they could be blocked by Wnt5a antibody, sFRPs and RYK-Fc. The importance of Wnt5a in DA axon morphogenesis was further verified in Wnt5a-/- mice, where fasciculation of the medial forebrain bundle (MFB as well as the density of DA neurites in the MFB and striatal terminals were disrupted. Thus, our results identify a novel role of Wnt5a in DA axon growth and guidance.

  9. 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.

  10. 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

  11. 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

  12. Protein Prenylation Constitutes an Endogenous Brake on Axonal Growth

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    Hai Li

    2016-07-01

    Full Text Available Suboptimal axonal regeneration contributes to the consequences of nervous system trauma and neurodegenerative disease, but the intrinsic mechanisms that regulate axon growth remain unclear. We screened 50,400 small molecules for their ability to promote axon outgrowth on inhibitory substrata. The most potent hits were the statins, which stimulated growth of all mouse- and human-patient-derived neurons tested, both in vitro and in vivo, as did combined inhibition of the protein prenylation enzymes farnesyltransferase (PFT and geranylgeranyl transferase I (PGGT-1. Compensatory sprouting of motor axons may delay clinical onset of amyotrophic lateral sclerosis (ALS. Accordingly, elevated levels of PGGT1B, which would be predicted to reduce sprouting, were found in motor neurons of early- versus late-onset ALS patients postmortem. The mevalonate-prenylation pathway therefore constitutes an endogenous brake on axonal growth, and its inhibition provides a potential therapeutic approach to accelerate neuronal regeneration in humans.

  13. Mechanisms of Distal Axonal Degeneration in Peripheral Neuropathies

    Science.gov (United States)

    Cashman, Christopher R.; Höke, Ahmet

    2015-01-01

    Peripheral neuropathy is a common complication of a variety of diseases and treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV, hepatitis C, and Campylobacter jejuni). Despite the fundamental difference between these insults, peripheral neuropathy develops as a combination of just six primary mechanisms: altered metabolism, covalent modification, altered organelle function and reactive oxygen species formation, altered intracellular and inflammatory signaling, slowed axonal transport, and altered ion channel dynamics and expression. All of these pathways converge to lead to axon dysfunction and symptoms of neuropathy. The detailed mechanisms of axon degeneration itself have begun to be elucidated with studies of animal models with altered degeneration kinetics, including the slowed Wallerian degeneration (Wlds) and Sarmknockout animal models. These studies have shown axonal degeneration to occur througha programmed pathway of injury signaling and cytoskeletal degradation. Insights into the common disease insults that converge on the axonal degeneration pathway promise to facilitate the development of therapeutics that may be effective against other mechanisms of neurodegeneration. PMID:25617478

  14. Calpain Inhibition Reduces Axolemmal Leakage in Traumatic Axonal Injury

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    János Sándor

    2009-12-01

    Full Text Available Calcium-induced, calpain-mediated proteolysis (CMSP has recently been implicated to the pathogenesis of diffuse (traumatic axonal injury (TAI. Some studies suggested that subaxolemmal CMSP may contribute to axolemmal permeability (AP alterations observed in TAI. Seeking direct evidence for this premise we investigated whether subaxolemmal CMSP may contribute to axolemmal permeability alterations (APA and pre-injury calpain-inhibition could reduce AP in a rat model of TAI. Horseradish peroxidase (HRP, a tracer that accumulates in axons with APA was administered one hour prior to injury into the lateral ventricle; 30 min preinjury a single tail vein bolus injection of 30 mg/kg MDL-28170 (a calpain inhibitor or its vehicle was applied in Wistar rats exposed to impact acceleration brain injury. Histological detection of traumatically injured axonal segments accumulating HRP and statistical analysis revealed that pre-injury administration of the calpain inhibitor MDL-28170 significantly reduced the average length of HRP-labeled axonal segments. The axono-protective effect of pre-injury calpain inhibition recently demonstrated with classical immunohistochemical markers of TAI was further corroborated in this experiment; significant reduction of the length of labeled axons in the drug-treated rats implicate CMSP in the progression of altered AP in TAI.

  15. 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.

  16. Characterization of patients with head trauma and traumatic axonal injury

    International Nuclear Information System (INIS)

    Mosquera Betancourt, Dra.C. Gretel; Van Duc, Dr. Hanh; Casares Delgado, Dr. Jorge Alejandro; Hernández González, Dr. Erick Héctor

    2016-01-01

    Background: traumatic axonal injury is characterized by multifocal lesions, consequences of primary, secondary and tertiary damage which is able to cause varying degrees of disability. Objective: to characterize patients with traumatic axonal injury. Methods: a cross-sectional analytical study was conducted from January 2014 to December 2015. The target population was composed of 35 patients over age 18 whose diagnosis was traumatic axonal injury type I and IV of the Marshall computed tomographic (CT) classification. With the data collected from medical records revisions and direct observation, a database was created in SPSS for its processing through univariate and multivariate techniques. Results: male patients between 18 and 30 years old without bad habits prevailed. Most of the patients survived and death was associated with the presence of severe traumatic axonal injury, Marshall computed tomographic (CT) classification degree III, complications and presence of trauma in thorax, abdomen and cervical spine. Conclusions: diagnosis of traumatic axonal injury is based on the clinical radiological correlation based on images from tomography and it is confirmed by Magnetic resonance imaging (MRI). Histological study shows injuries that are not demonstrated in the most advanced radiological studies. Its prevention is the most fundamental base in medical assistance, followed by neurocritical attention oriented by neuromonitoring. (author)

  17. Highly effective photonic cue for repulsive axonal guidance.

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    Bryan J Black

    Full Text Available In vivo nerve repair requires not only the ability to regenerate damaged axons, but most importantly, the ability to guide developing or regenerating axons along paths that will result in functional connections. Furthermore, basic studies in neuroscience and neuro-electronic interface design require the ability to construct in vitro neural circuitry. Both these applications require the development of a noninvasive, highly effective tool for axonal growth-cone guidance. To date, a myriad of technologies have been introduced based on chemical, electrical, mechanical, and hybrid approaches (such as electro-chemical, optofluidic flow and photo-chemical methods. These methods are either lacking in desired spatial and temporal selectivity or require the introduction of invasive external factors. Within the last fifteen years however, several attractive guidance cues have been developed using purely light based cues to achieve axonal guidance. Here, we report a novel, purely optical repulsive guidance technique that uses low power, near infrared light, and demonstrates the guidance of primary goldfish retinal ganglion cell axons through turns of up to 120 degrees and over distances of ∼90 µm.

  18. 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.

  19. Estatus de parámetros oxidativos y del gen p53 en sangre de niños en edad escolar de zonas afectadas por el accidente nuclear de Chernobyl.

    OpenAIRE

    García Mora, Mª Carmen

    2004-01-01

    RESUMEN Tras el accidente nuclear de Chernobyl producido el 26 de abril de 1986 se liberaron muchos radioisótopos, produciendo la contaminación del medio ambiente, con la consiguiente implicación sobre la salud de las personas afectadas. La irradiación produce su efecto sobre el material biológico de manera directa, como consecuencia inmediata de la ionización inducida por la irradiación y de manera indirecta, que al interaccionar sobre cualquier estructura celular, esencialmente el agua t...

  20. 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)

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

    Energy Technology Data Exchange (ETDEWEB)

    Goldowitz, D; Cotman, C W [California Univ., Irvine (USA)

    1980-12-01

    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 (/sup 3/H)-labeled proteins in the commissural and associational projections following an entorhinal lesion. Injections of (/sup 3/H)proline, (/sup 3/H)leucine or (/sup 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.

  2. Localization of mRNA in vertebrate axonal compartments by in situ hybridization.

    Science.gov (United States)

    Sotelo-Silveira, José Roberto; Calliari, Aldo; Kun, Alejandra; Elizondo, Victoria; Canclini, Lucía; Sotelo, José Roberto

    2011-01-01

    The conclusive demonstration of RNA in vertebrate axons by in situ hybridization (ISH) has been elusive. We review the most important reasons for difficulties, including low concentration of axonal RNAs, localization in specific cortical domains, and the need to isolate axons. We demonstrate the importance of axon micro-dissection to obtain a whole mount perspective of mRNA distribution in the axonal territory. We describe a protocol to perform fluorescent ISH in isolated axons and guidelines for the preservation of structural and molecular integrity of cortical RNA-containing domains (e.g., Periaxoplasmic Ribosomal Plaques, or PARPs) in isolated axoplasm.

  3. 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

  4. 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.

  5. Chondroitin-4-sulfation negatively regulates axonal guidance and growth

    Science.gov (United States)

    Wang, Hang; Katagiri, Yasuhiro; McCann, Thomas E.; Unsworth, Edward; Goldsmith, Paul; Yu, Zu-Xi; Tan, Fei; Santiago, Lizzie; Mills, Edward M.; Wang, Yu; Symes, Aviva J.; Geller, Herbert M.

    2008-01-01

    Summary Glycosaminoglycan (GAG) side chains endow extracellular matrix proteoglycans with diversity and complexity based upon the length, composition, and charge distribution of the polysaccharide chain. Using cultured primary neurons, we show that specific sulfation in the GAG chains of chondroitin sulfate (CS) mediates neuronal guidance cues and axonal growth inhibition. Chondroitin-4-sulfate (CS-A), but not chondroitin-6-sulfate (CS-C), exhibits a strong negative guidance cue to mouse cerebellar granule neurons. Enzymatic and gene-based manipulations of 4-sulfation in the GAG side chains alter their ability to direct growing axons. Furthermore, 4-sulfated CS GAG chains are rapidly and significantly increased in regions that do not support axonal regeneration proximal to spinal cord lesions in mice. Thus, our findings provide the evidence showing that specific sulfation along the carbohydrate backbone carries instructions to regulate neuronal function. PMID:18768934

  6. Growing axons analysis by using Granulometric Size Distribution

    International Nuclear Information System (INIS)

    Gonzalez, Mariela A; Ballarin, Virginia L; Rapacioli, Melina; CelIn, A R; Sanchez, V; Flores, V

    2011-01-01

    Neurite growth (neuritogenesis) in vitro is a common methodology in the field of developmental neurobiology. Morphological analyses of growing neurites are usually difficult because their thinness and low contrast usually prevent to observe clearly their shape, number, length and spatial orientation. This paper presents the use of the granulometric size distribution in order to automatically obtain information about the shape, size and spatial orientation of growing axons in tissue cultures. The results here presented show that the granulometric size distribution results in a very useful morphological tool since it allows the automatic detection of growing axons and the precise characterization of a relevant parameter indicative of the axonal growth spatial orientation such as the quantification of the angle of deviation of the growing direction. The developed algorithms automatically quantify this orientation by facilitating the analysis of these images, which is important given the large number of images that need to be processed for this type of study.

  7. 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.

  8. 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.

  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. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Studies of axon-glial cell interactions and periaxonal K+ homeostasis--II. The effect of axonal stimulation, cholinergic agents and transport inhibitors on the resistance in series with the axon membrane.

    Science.gov (United States)

    Hassan, S; Lieberman, E M

    1988-06-01

    The small electrical resistance in series with the axon membrane is generally modeled as the intercellular pathway for current flow through the periaxonal glial (Schwann cell) sheath. The series resistance of the medial giant axon of the crayfish, Procambarus clarkii, was found to vary with conditions known to affect the electrical properties of the periaxonal glia. Series resistance was estimated from computer analysed voltage waveforms generated by axial wire-constant current and space clamp techniques. The average series resistance for all axons was 6.2 +/- 0.5 omega cm2 (n = 128). Values ranged between 1 and 30 omega cm2. The series resistance of axons with low resting membrane resistance (less than 1500 omega cm2) increased an average of 30% when stimulated for 45 s to 7 min (50 Hz) whereas the series resistance of high membrane resistance (greater than 1500 omega cm2) axons decreased an average of 10%. Carbachol (10(-7) M) caused the series resistance of low membrane resistance axons to decrease during stimulation but had no effect on high membrane resistance axons. d-Tubocurare (10(-8) M) caused the series resistance of high membrane resistance axons to increase during stimulation but had no effect on low membrane resistance axons. Bumetanide, a Na-K-Cl cotransport inhibitor and low [K+]o, prevented the stimulation-induced increase in series resistance of low membrane resistance axons but had no effect on the high membrane resistance axons. The results suggest that the series resistance of axons varies in response to the activity of the glial K+ uptake mechanisms stimulated by the appearance of K+ in the periaxonal space during action potential generation.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. 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.

  16. 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.

  17. RGM is a repulsive guidance molecule for retinal axons

    DEFF Research Database (Denmark)

    Monnier, Philippe P; Sierra, Ana; Macchi, Paolo

    2002-01-01

    with known guidance cues, and its messenger RNA is distributed in a gradient with increasing concentration from the anterior to posterior pole of the embryonic tectum. Recombinant RGM at low nanomolar concentration induces collapse of temporal but not of nasal growth cones and guides temporal retinal axons...

  18. IFNgamma enhances microglial reactions to hippocampal axonal degeneration

    DEFF Research Database (Denmark)

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

    2000-01-01

    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...

  19. 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)

  20. Chronic severe axonal polyneuropathy associated with hyperthyroidism and multivitamin deficiency.

    Science.gov (United States)

    Sugie, Kazuma; Umehara, Fujio; Kataoka, Hiroshi; Kumazawa, Aya; Ueno, Satoshi

    2012-01-01

    Hyperthyroidism is often associated with various neuromuscular disorders, most commonly proximal myopathy. Peripheral nerve involvement in hyperthyroidism is very uncommon and has rarely been reported. We describe a 29-year-old woman with untreated hyperthyroidism who presented with chronic severe axonal sensory-motor polyneuropathy. Peripheral nerve involvement developed together with other symptoms of hyperthyroidism 2 years before presentation. She also had anorexia nervosa for the past 6 months, resulting in multivitamin deficiency. Electrophysiological and pathological findings as well as clinical manifestations confirmed the diagnosis of severe axonal polyneuropathy. Anorexia nervosa has been considered a manifestation of untreated hyperthyroidism. We considered hyperthyroidism to be an important causal factor in the polyneuropathy in our patient, although peripheral nerve involvement in hyperthyroidism is rare. To our knowledge, this is the first documented case of chronic severe axonal polyneuropathy ascribed to both hyperthyroidism and multivitamin deficiency. Our findings strongly suggest that not only multivitamin deficiency, but also hyperthyroidism can cause axonal polyneuropathy, thus expanding the clinical spectrum of hyperthyroidism.

  1. Impaired Mitochondrial Dynamics Underlie Axonal Defects in Hereditary Spastic Paraplegias.

    Science.gov (United States)

    Denton, Kyle; Mou, Yongchao; Xu, Chong-Chong; Shah, Dhruvi; Chang, Jaerak; Blackstone, Craig; Li, Xue-Jun

    2018-05-02

    Mechanisms by which long corticospinal axons degenerate in hereditary spastic paraplegia (HSP) are largely unknown. Here, we have generated induced pluripotent stem cells (iPSCs) from patients with two autosomal recessive forms of HSP, SPG15 and SPG48, which are caused by mutations in the ZFYVE26 and AP5Z1 genes encoding proteins in the same complex, the spastizin and AP5Z1 proteins, respectively. In patient iPSC-derived telencephalic glutamatergic and midbrain dopaminergic neurons, neurite number, length and branching are significantly reduced, recapitulating disease-specific phenotypes. We analyzed mitochondrial morphology and noted a significant reduction in both mitochondrial length and their densities within axons of these HSP neurons. Mitochondrial membrane potential was also decreased, confirming functional mitochondrial defects. Notably, mdivi-1, an inhibitor of the mitochondrial fission GTPase DRP1, rescues mitochondrial morphology defects and suppresses the impairment in neurite outgrowth and late-onset apoptosis in HSP neurons. Furthermore, knockdown of these HSP genes causes similar axonal defects, also mitigated by treatment with mdivi-1. Finally, neurite outgrowth defects in SPG15 and SPG48 cortical neurons can be rescued by knocking down DRP1 directly. Thus, abnormal mitochondrial morphology caused by an imbalance of mitochondrial fission and fusion underlies specific axonal defects and serves as a potential therapeutic target for SPG15 and SPG48.

  2. Botulinum toxin's axonal transport from periphery to the spinal cord.

    Science.gov (United States)

    Matak, Ivica; Riederer, Peter; Lacković, Zdravko

    2012-07-01

    Axonal transport of enzymatically active botulinum toxin A (BTX-A) from periphery to the CNS has been described in facial and trigeminal nerve, leading to cleavage of synaptosomal-associated protein 25 (SNAP-25) in central nuclei. Aim of present study was to examine the existence of axonal transport of peripherally applied BTX-A to spinal cord via sciatic nerve. We employed BTX-A-cleaved SNAP-25 immunohistochemistry of lumbar spinal cord after intramuscular and subcutaneous hind limb injections, and intraneural BTX-A sciatic nerve injections. Truncated SNAP-25 in ipsilateral spinal cord ventral horns and dorsal horns appeared after single peripheral BTX-A administrations, even at low intramuscular dose applied (5 U/kg). Cleaved SNAP-25 appearance in the spinal cord after BTX-A injection into the sciatic nerve was prevented by proximal intrasciatic injection of colchicine (5 mM, 2 μl). Cleaved SNAP-25 in ventral horn, using choline-acetyltransferase (ChAT) double labeling, was localized within cholinergic neurons. These results extend the recent findings on BTX-A retrograde axonal transport in facial and trigeminal nerve. Appearance of truncated SNAP-25 in spinal cord following low-dose peripheral BTX-A suggest that the axonal transport of BTX-A occurs commonly following peripheral application. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Computed tomography in diagnosis of diffuse axonal injury

    International Nuclear Information System (INIS)

    Iwadate, Yasuo; Ono, Juniti; Okimura, Yoshitaka; Suda, Sumio; Isobe, Katsumi; Yamaura, Akira.

    1990-01-01

    Diffuse axonal injury (DAI) has been described in instances of prolonged traumatic coma on the basis of the neuropathological findings, but the same findings are also found in patients with cerebral concussion. Experimental studies confirm that the quality of survivors following trauma is directly proportional to the amount of primarily injured-axon. When the injured axon lies in a widespread area of the brain, outcome for the patient is always poor. In a series of 260 severely head-injured patients, based on their poor outcome, 69 (27%) were diagnosed as DAI. Because of their relatively good outcome, eighty-two patients (32%) were classified into non-DAI group. The predominant CT finding of DAI patients was intraparenchymal deep-seated hemorrhagic lesion. This was observed in 28 patients (41%). Normal CT was also observed in 11 patients (16%). On the other hand, 8 of the non-DAI group (10%) manifested deep-seated lesions. Diffuse cerebral swelling (DCS) appeared in both groups in the same incidence. Subarachnoid hematoma in the perimesencephalic cistern (SAH (PMC)) and intraventricular hematoma (IVH) were observed in 64% of the DAI group, and in 23% of the non-DAI group. The available evidence indicates that various types of hematoma seen in the deep-seated structures of the brain do not have an absolute diagnostic value, but the frequency of hematoma is thought to increase in proportion to the amount of injured-axon. (author)

  4. Unravelling the incidence and etiology of chronic idiopathic axonal polyneuropathy

    NARCIS (Netherlands)

    Visser, N.A.

    2016-01-01

    Chronic idiopathic axonal polyneuropathy (CIAP) is a sensory or sensorimotor polyneuropathy that has a slowly progressive course without severe disability. CIAP is diagnosed in a significant proportion of patients with polyneuropathy, but precise figures on the incidence of polyneuropathy and CIAP

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  7. 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

    2018-05-01

    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 noninflammatory 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. Because 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. NEW & NOTEWORTHY Many patients with radiating pain lack signs of nerve injury on clinical examination but may have neuritis, which disrupts axonal transport. We have shown that axonal transport disruption does not induce ongoing activity in primary sensory neurons but does cause transient axonal mechanical sensitivity. The present data complete a profile of key axonal sensitivities following axonal transport disruption. Collectively, this profile supports that an active peripheral process is necessary for maintained axonal sensitivities.

  8. 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

  9. 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.

  10. Environmental Subconcussive Injury, Axonal Injury, and Chronic Traumatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Wendy A. Morley

    2018-03-01

    Full Text Available Brain injury occurs in two phases: the initial injury itself and a secondary cascade of precise immune-based neurochemical events. The secondary phase is typically functional in nature and characterized by delayed axonal injury with more axonal disconnections occurring than in the initial phase. Axonal injury occurs across the spectrum of disease severity, with subconcussive injury, especially when repetitive, now considered capable of producing significant neurological damage consistent with axonal injury seen in clinically evident concussion, despite no observable symptoms. This review is the first to introduce the concept of environmental subconcussive injury (ESCI and sets out how secondary brain damage from ESCI once past the juncture of microglial activation appears to follow the same neuron-damaging pathway as secondary brain damage from conventional brain injury. The immune response associated with ESCI is strikingly similar to that mounted after conventional concussion. Specifically, microglial activation is followed closely by glutamate and calcium flux, excitotoxicity, reactive oxygen species and reactive nitrogen species (RNS generation, lipid peroxidation, and mitochondrial dysfunction and energy crisis. ESCI damage also occurs in two phases, with the primary damage coming from microbiome injury (due to microbiome-altering events and secondary damage (axonal injury from progressive secondary neurochemical events. The concept of ESCI and the underlying mechanisms have profound implications for the understanding of chronic traumatic encephalopathy (CTE etiology because it has previously been suggested that repetitive axonal injury may be the primary CTE pathogenesis in susceptible individuals and it is best correlated with lifetime brain trauma load. Taken together, it appears that susceptibility to brain injury and downstream neurodegenerative diseases, such as CTE, can be conceptualized as a continuum of brain resilience. At one end

  11. 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...

  12. 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

  13. 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.

  14. Use of self-complementary adeno-associated virus serotype 2 as a tracer for labeling axons: implications for axon regeneration.

    Directory of Open Access Journals (Sweden)

    Yingpeng Liu

    Full Text Available Various types of tracers are available for use in axon regeneration, but they require an extra operational tracer injection, time-consuming immunohistochemical analysis and cause non-specific labeling. Considerable efforts over the past years have explored other methodologies, especially the use of viral vectors, to investigate axon regeneration after injury. Recent studies have demonstrated that self-complementary Adeno-Associated Virus (scAAV induced a high transduction efficiency and faster expression of transgenes. Here, we describe for the first time the use of scAAV2-GFP to label long-projection axons in the corticospinal tract (CST, rubrospinal tract (RST and the central axons of dorsal root ganglion (DRG in the normal and lesioned animal models. We found that scAAV2-GFP could efficiently transduce neurons in the sensorimotor cortex, red nucleus and DRG. Strong GFP expression could be transported anterogradely along the axon to label the numerous axon fibers from CST, RST and central axons of DRG separately. Comparison of the scAAV2 vector with single-stranded (ss AAV2 vector in co-labeled sections showed that the scAAV2 vector induced a faster and stronger transgene expression than the ssAAV2 vector in DRG neurons and their axons. In both spinal cord lesion and dorsal root crush injury models, scAAV-GFP could efficiently label the lesioned and regenerated axons around the lesion cavity and the dorsal root entry zone (DREZ respectively. Further, scAAV2-GFP vector could be combined with traditional tracer to specifically label sensory and motor axons after spinal cord lesion. Thus, we show that using scAAV2-GFP as a tracer is a more effective and efficient way to study axon regeneration following injury.

  15. Síndrome metabólico y preeclampsia: los aportes realizados por el Instituto de Investigaciones de la Fundación Cardiovascular de Colombia Metabolic syndrome and pre-eclampsia: contributions realized by the research Institute of the Colombian Cardiovascular Foundation

    OpenAIRE

    Patricio López-Jaramillo; Federico Silva; Paul A Camacho; Lina P Pradilla; Ronald García; Christian Rueda-Clausen; Yalil Bracho; Sandra Silva; Ligia Rueda; Narella Rodríguez; Juan G Zarruk; Mayaris Mendoza; Mario Arenas; William Arenas; Isabel C Bolívar

    2006-01-01

    Durante los últimos años, el Instituto de Investigaciones de la Fundación Cardiovascular de Colombia ha centrado sus proyectos en el estudio de las diferencias en los mecanismos etiofisiopatológicos de la hipertensión inducida por el embarazo y del síndrome metabólico en poblaciones de países desarrollados y en vía de desarrollo, así como en el peso específico de los factores de riesgo que determinan la presentación de estas enfermedades. Los resultados obtenidos de las investigaciones realiz...

  16. Antiretroviral Therapy-Associated Acute Motor and Sensory Axonal Neuropathy

    Directory of Open Access Journals (Sweden)

    Kimberly N. Capers

    2011-01-01

    Full Text Available Guillain-Barré syndrome (GBS has been reported in HIV-infected patients in association with the immune reconstitution syndrome whose symptoms can be mimicked by highly active antiretroviral therapy (HAART-mediated mitochondrial toxicity. We report a case of a 17-year-old, HIV-infected patient on HAART with a normal CD4 count and undetectable viral load, presenting with acute lower extremity weakness associated with lactatemia. Electromyography/nerve conduction studies revealed absent sensory potentials and decreased compound muscle action potentials, consistent with a diagnosis of acute motor and sensory axonal neuropathy. Lactatemia resolved following cessation of HAART; however, neurological deficits minimally improved over several months in spite of immune modulatory therapy. This case highlights the potential association between HAART, mitochondrial toxicity and acute axonal neuropathies in HIV-infected patients, distinct from the immune reconstitution syndrome.

  17. Craniocerebral trauma. Magnetic resonance imaging of diffuse axonal injury

    International Nuclear Information System (INIS)

    Mallouhi, A.

    2014-01-01

    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. (orig.) [de

  18. 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.

  19. 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.

  20. 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.

  1. Axonal Control of the Adult Neural Stem Cell Niche

    Science.gov (United States)

    Tong, Cheuk Ka; Chen, Jiadong; Cebrián-Silla, Arantxa; Mirzadeh, Zaman; Obernier, Kirsten; Guinto, Cristina D.; Tecott, Laurence H.; García-Verdugo, Jose Manuel; Kriegstein, Arnold; Alvarez-Buylla, Arturo

    2014-01-01

    SUMMARY The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSC) in the walls of the lateral ventricles of the adult brain. How the adult brain’s neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C. PMID:24561083

  2. Vesicular glutamate release from central axons contributes to myelin damage.

    Science.gov (United States)

    Doyle, Sean; Hansen, Daniel Bloch; Vella, Jasmine; Bond, Peter; Harper, Glenn; Zammit, Christian; Valentino, Mario; Fern, Robert

    2018-03-12

    The axon myelin sheath is prone to injury associated with N-methyl-D-aspartate (NMDA)-type glutamate receptor activation but the source of glutamate in this context is unknown. Myelin damage results in permanent action potential loss and severe functional deficit in the white matter of the CNS, for example in ischemic stroke. Here, we show that in rats and mice, ischemic conditions trigger activation of myelinic NMDA receptors incorporating GluN2C/D subunits following release of axonal vesicular glutamate into the peri-axonal space under the myelin sheath. Glial sources of glutamate such as reverse transport did not contribute significantly to this phenomenon. We demonstrate selective myelin uptake and retention of a GluN2C/D NMDA receptor negative allosteric modulator that shields myelin from ischemic injury. The findings potentially support a rational approach toward a low-impact prophylactic therapy to protect patients at risk of stroke and other forms of excitotoxic injury.

  3. Retinal glia promote dorsal root ganglion axon regeneration.

    Directory of Open Access Journals (Sweden)

    Barbara Lorber

    Full Text Available Axon regeneration in the adult central nervous system (CNS is limited by several factors including a lack of neurotrophic support. Recent studies have shown that glia from the adult rat CNS, specifically retinal astrocytes and Müller glia, can promote regeneration of retinal ganglion cell axons. In the present study we investigated whether retinal glia also exert a growth promoting effect outside the visual system. We found that retinal glial conditioned medium significantly enhanced neurite growth and branching of adult rat dorsal root ganglion neurons (DRG in culture. Furthermore, transplantation of retinal glia significantly enhanced regeneration of DRG axons past the dorsal root entry zone after root crush in adult rats. To identify the factors that mediate the growth promoting effects of retinal glia, mass spectrometric analysis of retinal glial conditioned medium was performed. Apolipoprotein E and secreted protein acidic and rich in cysteine (SPARC were found to be present in high abundance, a finding further confirmed by western blotting. Inhibition of Apolipoprotein E and SPARC significantly reduced the neuritogenic effects of retinal glial conditioned medium on DRG in culture, suggesting that Apolipoprotein E and SPARC are the major mediators of this regenerative response.

  4. 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

  5. Pathophysiologic insights into motor axonal function in Kennedy disease.

    Science.gov (United States)

    Vucic, Steve; Kiernan, Matthew C

    2007-11-06

    Kennedy disease (KD), or spinobulbomuscular atrophy, is a slowly progressive inherited neurodegenerative disorder, marked by prominent fasciculations that typically precede the development of other symptoms. Although the genetic basis of KD relates to triplet (CAG) repeat expansion in the androgen receptor (AR) gene on the X chromosome, the mechanisms underlying the clinical presentation in KD have yet to be established. Consequently, the present study applied axonal excitability techniques to investigate the pathophysiologic mechanisms associated with KD. Peripheral nerve excitability studies were undertaken in 7 patients with KD with compound muscle action potentials (CMAP) recorded from the right abductor pollicis brevis. Strength-duration time constant (KD 0.54 +/- 0.03 msec; controls, 0.41 +/- 0.02 msec, p TEd [90 to 100 msec], 50.75 +/- 1.98%; controls TEd [90 to 100 msec], 45.67 +/- 0.67%, p < 0.01) and hyperpolarizing (KD TEh [90 to 100 msec], 128.5 +/- 6.9%; controls TEh [90 to 100 msec], 120.5 +/- 2.4%) conditioning pulses. Measurements of refractoriness, superexcitability, and late subexcitability changed appropriately for axonal hyperpolarization, perhaps reflecting the effects of increased ectopic activity. In total, the increase in the strength-duration time constant may be the primary event, occurring early in course of the disease, contributing to the development of axonal hyperexcitability in Kennedy disease, and thereby to the generation of fasciculations, a characteristic hallmark of the disease.

  6. In vivo imaging reveals mitophagy independence in the maintenance of axonal mitochondria during normal aging.

    Science.gov (United States)

    Cao, Xu; Wang, Haiqiong; Wang, Zhao; Wang, Qingyao; Zhang, Shuang; Deng, Yuanping; Fang, Yanshan

    2017-10-01

    Mitophagy is thought to be a critical mitochondrial quality control mechanism in neurons and has been extensively studied in neurological disorders such as Parkinson's disease. However, little is known about how mitochondria are maintained in the lengthy neuronal axons in the context of physiological aging. Here, we utilized the unique Drosophila wing nerve model and in vivo imaging to rigorously profile changes in axonal mitochondria during aging. We revealed that mitochondria became fragmented and accumulated in aged axons. However, lack of Pink1 or Parkin did not lead to the accumulation of axonal mitochondria or axonal degeneration. Further, unlike in in vitro cultured neurons, we found that mitophagy rarely occurred in intact axons in vivo, even in aged animals. Furthermore, blocking overall mitophagy by knockdown of the core autophagy genes Atg12 or Atg17 had little effect on the turnover of axonal mitochondria or axonal integrity, suggesting that mitophagy is not required for axonal maintenance; this is regardless of whether the mitophagy is PINK1-Parkin dependent or independent. In contrast, downregulation of mitochondrial fission-fusion genes caused age-dependent axonal degeneration. Moreover, Opa1 expression in the fly head was significantly decreased with age, which may underlie the accumulation of fragmented mitochondria in aged axons. Finally, we showed that adult-onset, neuronal downregulation of the fission-fusion, but not mitophagy genes, dramatically accelerated features of aging. We propose that axonal mitochondria are maintained independently of mitophagy and that mitophagy-independent mechanisms such as fission-fusion may be central to the maintenance of axonal mitochondria and neural integrity during normal aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  7. 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

  8. ¿Hay un mal en morir? Consideraciones éticas y jurídicas sobre la muerte inducida

    Directory of Open Access Journals (Sweden)

    ALEJANDRA ZÚÑIGA F.

    2011-01-01

    Full Text Available Se analizan los dilemas morales asociados a la muerte, para reflexionar sobre los interrogantes que surgen al calificarla como un hecho banal desde la perspectiva de quien muere. Se estudian, además, las consecuencias éticas y jurídicas de reconocer autonomía moral a quienes deciden, en circunstancias extremas, tomar por sí mismos la decisión de cuándo y cómo morir.

  9. El péptido ? A [25-35] y el hierro promueven apoptosis en linfocitos por un mecanismo de estrés oxidativo: contribución del H202,, caspasa 3, fn- kb, p53 y c-Jun

    Directory of Open Access Journals (Sweden)

    Marlene Jiménez

    2001-04-01

    Full Text Available El depósito del beta-amiloide (βA en las placas neuríticas es
    uno de los principales marcadores neuropatológicos de la enfermedad de Alzheimer (EA. Estudios in vitro han demostrado que el fragmento βA25-35, el cual contiene la secuencia funcionalmente citotóxica del péptido amiloide, induce neurotoxicidad y muerte celular por apoptosis (1. A pesar de las intensas investigaciones, no se ha dado una descripción completa de la cascada de eventos moleculares que conducen a muerte inducida por βA25-35 en un modelo celular único. Por lo tanto, nuestro objetivo principal es evidenciar una cascada de eventos moleculares ordenados inducidos por el bA25-35 y el hierro en un modelo celular.

  10. Dynamic Changes of Neuroskeletal Proteins in DRGs Underlie Impaired Axonal Maturation and Progressive Axonal Degeneration in Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Hideki Kamiya

    2009-01-01

    Full Text Available We investigated mechanisms underlying progressive axonal dysfunction and structural deficits in type 1 BB/Wor-rats from 1 week to 10 month diabetes duration. Motor and sensory conduction velocities were decreased after 4 and 6 weeks of diabetes and declined further over the remaining 9 months. Myelinated sural nerve fibers showed progressive deficits in fiber numbers and sizes. Structural deficits in unmyelinated axonal size were evident at 2 month and deficits in number were present at 4 mo. These changes were preceded by decreased availability of insulin, C-peptide and IGF-1 and decreased expression of neurofilaments and β-III-tubulin. Upregulation of phosphorylating stress kinases like Cdk5, p-GSK-3β, and p42/44 resulted in increased phosphorylation of neurofilaments. Increasing activity of p-GSK-3β correlated with increasing phosphorylation of NFH, whereas decreasing Cdk5 correlated with diminishing phosphorylation of NFM. The data suggest that impaired neurotrophic support results in sequentially impaired synthesis and postranslational modifications of neuroskeletal proteins, resulting in progressive deficits in axonal function, maturation and size.

  11. Axonal Spheroid Accumulation In the Brainstem and Spinal Cord of A Young Angus Cow with Ataxia.

    Science.gov (United States)

    Hanshaw, D M; Finnie, J W; Manavis, J; Kessell, A E

    2015-08-01

    An 18-month-old Angus cow presented with rapidly developing ataxia and subsequently died. The finding of large numbers of axonal spheroids in brainstem nuclei and spinal cord grey matter, bilaterally symmetrical in distribution, was consistent with a histopathological diagnosis of neuroaxonal dystrophy (NAD). Most of the axonal swellings were immunopositive to amyloid precursor protein, suggesting that interruption to axonal flow was important in their genesis. The topographical distribution of axonal spheroids in the brain and spinal cord in this bovine case closely resembled that found in the ovine neurodegenerative disorder termed NAD, in which axonal swellings are the major pathological feature. This appears to be the first reported case of this type of NAD in cattle. The aetiology of the spheroidal aggregations in this case was not determined. There was no evidence from the case history or neuropathology to indicate whether the axonal spheroids in this case involved an acquired or heritable aetiology. © 2015 Australian Veterinary Association.

  12. 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.

  13. 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

    Spinal root injuries result in newly formed glial scar formation, which prevents regeneration of sensory axons causing permanent sensory loss. Previous studies showed that delivery of trophic factors or implantation of human neural progenitor cells supports sensory axon regeneration and partly......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...... their level of differentiation. Our data show that (1) the ability of stem cells to migrate into the spinal cord and organize cellular “bridges” in the newly formed interface is crucial for successful sensory axon regeneration, (2) trophic factor mimetics delivered by mesoporous silica may be a convenient...

  14. 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.

  15. REGENERATIVE GROWTH OF CORTICOSPINAL TRACT AXONS VIA THE VENTRAL COLUMN AFTER SPINAL CORD INJURY IN MICE

    OpenAIRE

    Steward, Oswald; Zheng, Binhai; Tessier-Lavigne, Marc; Hofstadter, Maura; Sharp, Kelli; Yee, Kelly Matsudaira

    2008-01-01

    Studies that have assessed regeneration of corticospinal tract (CST) axons in mice following genetic modifications or other treatments have tacitly assumed that there is little if any regeneration of CST axons in normal mice in the absence of some intervention. Here, we document a previously unrecognized capability for regenerative growth of CST axons in normal mice that involves growth past the lesion via the ventral column. Mice received dorsal hemisection injuries at thoracic level 6–7, wh...

  16. Defective Ca2+ channel clustering in axon terminals disturbs excitability in motoneurons in spinal muscular atrophy

    OpenAIRE

    Jablonka, Sibylle; Beck, Marcus; Lechner, Barbara Dorothea; Mayer, Christine; Sendtner, Michael

    2007-01-01

    Proximal spinal muscular atrophy (SMA) is a motoneuron disease for which there is currently no effective treatment. In animal models of SMA, spinal motoneurons exhibit reduced axon elongation and growth cone size. These defects correlate with reduced β-actin messenger RNA and protein levels in distal axons. We show that survival motoneuron gene (Smn)–deficient motoneurons exhibit severe defects in clustering Cav2.2 channels in axonal growth cones. These defects also correlate with a reduced f...

  17. 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

  18. 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.

  19. 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.

  20. The Molecular and Cellular Mechanisms of Axon Guidance in Mossy Fiber Sprouting

    Directory of Open Access Journals (Sweden)

    Ryuta Koyama

    2018-05-01

    Full Text Available The question of whether mossy fiber sprouting is epileptogenic has not been resolved; both sprouting-induced recurrent excitatory and inhibitory circuit hypotheses have been experimentally (but not fully supported. Therefore, whether mossy fiber sprouting is a potential therapeutic target for epilepsy remains under debate. Moreover, the axon guidance mechanisms of mossy fiber sprouting have attracted the interest of neuroscientists. Sprouting of mossy fibers exhibits several uncommon axonal growth features in the basically non-plastic adult brain. For example, robust branching of axonal collaterals arises from pre-existing primary mossy fiber axons. Understanding the branching mechanisms in adulthood may contribute to axonal regeneration therapies in neuroregenerative medicine in which robust axonal re-growth is essential. Additionally, because granule cells are produced throughout life in the neurogenic dentate gyrus, it is interesting to examine whether the mossy fibers of newly generated granule cells follow the pre-existing trajectories of sprouted mossy fibers in the epileptic brain. Understanding these axon guidance mechanisms may contribute to neuron transplantation therapies, for which the incorporation of transplanted neurons into pre-existing neural circuits is essential. Thus, clarifying the axon guidance mechanisms of mossy fiber sprouting could lead to an understanding of central nervous system (CNS network reorganization and plasticity. Here, we review the molecular and cellular mechanisms of axon guidance in mossy fiber sprouting by discussing mainly in vitro studies.

  1. NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD+ depletion

    Science.gov (United States)

    Sasaki, Yo; Nakagawa, Takashi; Mao, Xianrong; DiAntonio, Aaron; Milbrandt, Jeffrey

    2016-01-01

    Overexpression of the NAD+ biosynthetic enzyme NMNAT1 leads to preservation of injured axons. While increased NAD+ or decreased NMN levels are thought to be critical to this process, the mechanism(s) of this axon protection remain obscure. Using steady-state and flux analysis of NAD+ metabolites in healthy and injured mouse dorsal root ganglion axons, we find that rather than altering NAD+ synthesis, NMNAT1 instead blocks the injury-induced, SARM1-dependent NAD+ consumption that is central to axon degeneration. DOI: http://dx.doi.org/10.7554/eLife.19749.001 PMID:27735788

  2. GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules

    Science.gov (United States)

    Hur, Eun-Mi; Saijilafu; Lee, Byoung Dae; Kim, Seong-Jin; Xu, Wen-Lin; Zhou, Feng-Quan

    2011-01-01

    Suppression of glycogen synthase kinase 3 (GSK3) activity in neurons yields pleiotropic outcomes, causing both axon growth promotion and inhibition. Previous studies have suggested that specific GSK3 substrates, such as adenomatous polyposis coli (APC) and collapsin response mediator protein 2 (CRMP2), support axon growth by regulating the stability of axonal microtubules (MTs), but the substrate(s) and mechanisms conveying axon growth inhibition remain elusive. Here we show that CLIP (cytoplasmic linker protein)-associated protein (CLASP), originally identified as a MT plus end-binding protein, displays both plus end-binding and lattice-binding activities in nerve growth cones, and reveal that the two MT-binding activities regulate axon growth in an opposing manner: The lattice-binding activity mediates axon growth inhibition induced by suppression of GSK3 activity via preventing MT protrusion into the growth cone periphery, whereas the plus end-binding property supports axon extension via stabilizing the growing ends of axonal MTs. We propose a model in which CLASP transduces GSK3 activity levels to differentially control axon growth by coordinating the stability and configuration of growth cone MTs. PMID:21937714

  3. 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...

  4. 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

  5. Axon-Schwann cell interaction in the squid nerve fibre.

    Science.gov (United States)

    Villegas, J

    1972-09-01

    The electrical properties of Schwann cells and the effects of neuronal impulses on their membrane potential have been studied in the giant nerve fibre of the squid.1. The behaviour of the Schwann cell membrane to current injection into the cell was ohmic. No impulse-like responses were observed with displacements of 35 mV in the membrane potential. The resistance of the Schwann cell membrane was found to be approximately 10(3) Omega cm(2).2. A long-lasting hyperpolarization is observed in the Schwann cells following the conduction of impulse trains by the axon. Whereas the propagation of a single impulse had little effect, prolonged stimulation of the fibre at 250 impulses/sec was followed by a hyperpolarization of the Schwann cell that gradually declined over a period of several minutes.3. The prolonged effects of nerve impulse trains on the Schwann cell were similar to those produced by depolarizing current pulses applied to the axon by the voltage-clamp technique. Thus, a series of depolarizing pulses in the axon was followed by a long-lasting hyperpolarization of the Schwann cells. In contrast, the application of a series of hyperpolarizing 100 mV pulses at a frequency of 1/sec had no apparent effects.4. Changes in the external potassium concentration did not reproduce the long-lasting effects of nerve excitation.5. The hyperpolarizing effects of impulse trains were abolished by the incubation of the nerve fibre in a sea-water solution containing trypsin.6. These findings are discussed in relation to the possible mechanisms that might be responsible for the long-lasting hyperpolarizations of the Schwann cells.

  6. Excitability properties of motor axons in adults with cerebral palsy

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    Cliff S. Klein

    2015-06-01

    Full Text Available Cerebral Palsy (CP is a permanent disorder caused by a lesion to the developing brain that significantly impairs motor function. The neurophysiological mechanisms underlying motor impairment are not well understood. Specifically, few have addressed whether motoneuron or peripheral axon properties are altered in CP, even though disruption of descending inputs to the spinal cord may cause them to change. In the present study, we have compared nerve excitability properties in seven adults with CP and fourteen healthy controls using threshold tracking techniques by stimulating the median nerve at the wrist and recording the compound muscle action potential (CMAP over the abductor pollicis brevis. The excitability properties in the CP subjects were found to be abnormal. Early and late depolarizing and hyperpolarizing threshold electrotonus was significantly larger (i.e., fanning out, and resting current-threshold (I/V slope was smaller, in CP compared to control. In addition resting threshold and rheobase tended to be larger in CP. According to a modeling analysis of the data, an increase in leakage current under or through the myelin sheath, i.e., the Barrett-Barrett conductance (GBB, combined with a slight hyperpolarization of the resting membrane potential, best explained the group differences in excitability properties. There was a trend for those with greater impairment in gross motor function to have more abnormal axon properties. The findings indicate plasticity of motor axon properties far removed from the site of the lesion. We suspect that this plasticity is caused by disruption of descending inputs to the motoneurons at an early age around the time of their injury.

  7. 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...

  8. Luxación témporo-mandibular recurrente y secundaria a distonía por antipsicóticos.

    OpenAIRE

    Cruzado, Lizardo; Núñez-Moscoso, Patricia; Garibay-Huamaní, Mercibel; Villar-Salas, Alicia

    2016-01-01

    La distonía aguda inducida por antipsicóticos sigue siendo una patología frecuente en los servicios de emergencia psiquiátrica. Sin embargo, la luxación de la articulación témporo-mandibular, como secuela de distonía oromandibular, es una presentación inusual dentro de esta casuística. Presentamos el caso de una paciente mujer de 20 años de edad, quien recibió haloperidol intramuscular tras sendas crisis de agitación psicomotriz y persistencia de riesgo suicida, y que luego desarrolló distoní...

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

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    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.

  10. 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

  11. Neuron-to-neuron transmission of α-synuclein fibrils through axonal transport

    Science.gov (United States)

    Freundt, Eric C.; Maynard, Nate; Clancy, Eileen K.; Roy, Shyamali; Bousset, Luc; Sourigues, Yannick; Covert, Markus; Melki, Ronald; Kirkegaard, Karla; Brahic, Michel

    2012-01-01

    Objective The lesions of Parkinson's disease spread through the brain in a characteristic pattern that corresponds to axonal projections. Previous observations suggest that misfolded α-synuclein could behave as a prion, moving from neuron to neuron and causing endogenous α-synuclein to misfold. Here, we characterized and quantified the axonal transport of α-synuclein fibrils and showed that fibrils could be transferred from axons to second-order neurons following anterograde transport. Methods We grew primary cortical mouse neurons in microfluidic devices to separate soma from axonal projections in fluidically isolated microenvironments. We used live-cell imaging and immunofluorescence to characterize the transport of fluorescent α-synuclein fibrils and their transfer to second-order neurons. Results Fibrillar α-synuclein was internalized by primary neurons and transported in axons with kinetics consistent with slow component-b of axonal transport (fast axonal transport with saltatory movement). Fibrillar α-synuclein was readily observed in the cell bodies of second-order neurons following anterograde axonal transport. Axon-to-soma transfer appeared not to require synaptic contacts. Interpretation These results support the hypothesis that the progression of Parkinson's disease can be caused by neuron-to-neuron spread of α-synuclein aggregates and that the anatomical pattern of progression of lesions between axonally connected areas results from the axonal transport of such aggregates. That the transfer did not appear to be transsynaptic gives hope that α-synuclein fibrils could be intercepted by drugs during the extra-cellular phase of their journey. PMID:23109146

  12. 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.

  13. Nociceptive DRG neurons express muscle lim protein upon axonal injury.

    Science.gov (United States)

    Levin, Evgeny; Andreadaki, Anastasia; Gobrecht, Philipp; Bosse, Frank; Fischer, Dietmar

    2017-04-04

    Muscle lim protein (MLP) has long been regarded as a cytosolic and nuclear muscular protein. Here, we show that MLP is also expressed in a subpopulation of adult rat dorsal root ganglia (DRG) neurons in response to axonal injury, while the protein was not detectable in naïve cells. Detailed immunohistochemical analysis of L4/L5 DRG revealed ~3% of MLP-positive neurons 2 days after complete sciatic nerve crush and maximum ~10% after 4-14 days. Similarly, in mixed cultures from cervical, thoracic, lumbar and sacral DRG ~6% of neurons were MLP-positive after 2 days and maximal 17% after 3 days. In both, histological sections and cell cultures, the protein was detected in the cytosol and axons of small diameter cells, while the nucleus remained devoid. Moreover, the vast majority could not be assigned to any of the well characterized canonical DRG subpopulations at 7 days after nerve injury. However, further analysis in cell culture revealed that the largest population of MLP expressing cells originated from non-peptidergic IB4-positive nociceptive neurons, which lose their ability to bind the lectin upon axotomy. Thus, MLP is mostly expressed in a subset of axotomized nociceptive neurons and can be used as a novel marker for this population of cells.

  14. Profiling biomarkers of traumatic axonal injury: From mouse to man.

    Science.gov (United States)

    Manivannan, Susruta; Makwana, Milan; Ahmed, Aminul Islam; Zaben, Malik

    2018-05-18

    Traumatic brain injury (TBI) poses a major public health problem on a global scale. Its burden results from high mortality and significant morbidity in survivors. This stems, in part, from an ongoing inadequacy in diagnostic and prognostic indicators despite significant technological advances. Traumatic axonal injury (TAI) is a key driver of the ongoing pathological process following TBI, causing chronic neurological deficits and disability. The science underpinning biomarkers of TAI has been a subject of many reviews in recent literature. However, in this review we provide a comprehensive account of biomarkers from animal models to clinical studies, bridging the gap between experimental science and clinical medicine. We have discussed pathogenesis, temporal kinetics, relationships to neuro-imaging, and, most importantly, clinical applicability in order to provide a holistic perspective of how this could improve TBI diagnosis and predict clinical outcome in a real-life setting. We conclude that early and reliable identification of axonal injury post-TBI with the help of body fluid biomarkers could enhance current care of TBI patients by (i) increasing speed and accuracy of diagnosis, (ii) providing invaluable prognostic information, (iii) allow efficient allocation of rehabilitation services, and (iv) provide potential therapeutic targets. The optimal model for assessing TAI is likely to involve multiple components, including several blood biomarkers and neuro-imaging modalities, at different time points. Copyright © 2018. Published by Elsevier B.V.

  15. 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.

  16. Bridging the gap: axonal fusion drives rapid functional recovery of the nervous system

    Directory of Open Access Journals (Sweden)

    Jean-Sébastien Teoh

    2018-01-01

    Full Text Available Injuries to the central or peripheral nervous system frequently cause long-term disabilities because damaged neurons are unable to efficiently self-repair. This inherent deficiency necessitates the need for new treatment options aimed at restoring lost function to patients. Compared to humans, a number of species possess far greater regenerative capabilities, and can therefore provide important insights into how our own nervous systems can be repaired. In particular, several invertebrate species have been shown to rapidly initiate regeneration post-injury, allowing separated axon segments to re-join. This process, known as axonal fusion, represents a highly efficient repair mechanism as a regrowing axon needs to only bridge the site of damage and fuse with its separated counterpart in order to re-establish its original structure. Our recent findings in the nematode Caenorhabditis elegans have expanded the promise of axonal fusion by demonstrating that it can restore complete function to damaged neurons. Moreover, we revealed the importance of injury-induced changes in the composition of the axonal membrane for mediating axonal fusion, and discovered that the level of axonal fusion can be enhanced by promoting a neuron's intrinsic growth potential. A complete understanding of the molecular mechanisms controlling axonal fusion may permit similar approaches to be applied in a clinical setting.

  17. Noninvasive Detection and Differentiation of Axonal Injury/Loss, Demyelination, and Inflammation

    Science.gov (United States)

    2014-10-01

    phosphorylated neurofilament primary antibody (SMI-31; 1:1000, Covance , US) to stain non-injured axons, and in rabbit anti-myelin basic protein (MBP) primary...neurofilament antibody (SMI- 31; 1:1000, Covance , US) to stain non-injured axons or with rabbit anti-myelin basic protein (MBP) antibody (1:1000, Sigma Inc

  18. MuSC is involved in regulating axonal fasciculation of mouse primary vestibular afferents.

    Science.gov (United States)

    Kawauchi, Daisuke; Kobayashi, Hiroaki; Sekine-Aizawa, Yoko; Fujita, Shinobu C; Murakami, Fujio

    2003-10-01

    Regulation of axonal fasciculation plays an important role in the precise patterning of neural circuits. Selective fasciculation contributes to the sorting of different types of axons and prevents the misrouting of axons. However, axons must defasciculate once they reach the target area. To study the regulation of fasciculation, we focused on the primary vestibulo-cerebellar afferents (PVAs), which show a dramatic change from fasciculated axon bundles to defasciculated individual axons at their target region, the cerebellar primordium. To understand how fasciculation and defasciculation are regulated in this system, we investigated the roles of murine SC1-related protein (MuSC), a molecule belonging to the immunoglobulin superfamily. We show: (i) by comparing 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) labelling and anti-MuSC immunohistochemistry, that downregulation of MuSC in PVAs during development is concomitant with the defasciculation of PVA axons; (ii) in a binding assay with cells expressing MuSC, that MuSC has cell-adhesive activity via a homophilic binding mechanism, and this activity is increased by multimerization; and (iii) that MuSC also displays neurite outgrowth-promoting activity in vestibular ganglion cultures. These findings suggest that MuSC is involved in axonal fasciculation and its downregulation may help to initiate the defasciculation of PVAs.

  19. Interaction between the soma and the axon terminal of horizontal cells in carp retina

    NARCIS (Netherlands)

    Kamermans, M.; van Dijk, B. W.; Spekreijse, H.

    1990-01-01

    In teleost retina, the receptive fields of horizontal cell axon terminals have a larger space constant than the receptive fields of the horizontal cell somata. Generally this difference in receptive field size is attributed to the cell coupling which is assumed to be stronger in the horizontal axon

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. 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.

  3. 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.

  4. In silico modeling of axonal reconnection within a discrete fiber tract after spinal cord injury.

    Science.gov (United States)

    Woolfe, Franco; Waxman, Stephen G; Hains, Bryan C

    2007-02-01

    Following spinal cord injury (SCI), descending axons that carry motor commands from the brain to the spinal cord are injured or transected, producing chronic motor dysfunction and paralysis. Reconnection of these axons is a major prerequisite for restoration of function after SCI. Thus far, only modest gains in motor function have been achieved experimentally or in the clinic after SCI, identifying the practical limitations of current treatment approaches. In this paper, we use an ordinary differential equation (ODE) to simulate the relative and synergistic contributions of several experimentally-established biological factors related to inhibition or promotion of axonal repair and restoration of function after SCI. The factors were mathematically modeled by the ODE. The results of our simulation show that in a model system, many factors influenced the achievability of axonal reconnection. Certain factors more strongly affected axonal reconnection in isolation, and some factors interacted in a synergistic fashion to produce further improvements in axonal reconnection. Our data suggest that mathematical modeling may be useful in evaluating the complex interactions of discrete therapeutic factors not possible in experimental preparations, and highlight the benefit of a combinatorial therapeutic approach focused on promoting axonal sprouting, attraction of cut ends, and removal of growth inhibition for achieving axonal reconnection. Predictions of this simulation may be of utility in guiding future experiments aimed at restoring function after SCI.

  5. A developmental timing switch promotes axon outgrowth independent of known guidance receptors.

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    Katherine Olsson-Carter

    2010-08-01

    Full Text Available To form functional neuronal connections, axon outgrowth and guidance must be tightly regulated across space as well as time. While a number of genes and pathways have been shown to control spatial features of axon development, very little is known about the in vivo mechanisms that direct the timing of axon initiation and elongation. The Caenorhabditis elegans hermaphrodite specific motor neurons (HSNs extend a single axon ventrally and then anteriorly during the L4 larval stage. Here we show the lin-4 microRNA promotes HSN axon initiation after cell cycle withdrawal. Axons fail to form in lin-4 mutants, while they grow prematurely in lin-4-overexpressing animals. lin-4 is required to down-regulate two inhibitors of HSN differentiation--the transcriptional regulator LIN-14 and the "stemness" factor LIN-28--and it likely does so through a cell-autonomous mechanism. This developmental switch depends neither on the UNC-40/DCC and SAX-3/Robo receptors nor on the direction of axon growth, demonstrating that it acts independently of ventral guidance signals to control the timing of HSN axon elongation.

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

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    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.

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

    Science.gov (United States)

    Zhang, Yihao; Abiraman, Krithika; Li, He; Pierce, David M; Tzingounis, Anastasios V; Lykotrafitis, George

    2017-02-01

    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.

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

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    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.

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

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    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. Integration of shallow gradients of Shh and Netrin-1 guides commissural axons.

    Science.gov (United States)

    Sloan, Tyler F W; Qasaimeh, Mohammad A; Juncker, David; Yam, Patricia T; Charron, Frédéric

    2015-03-01

    During nervous system development, gradients of Sonic Hedgehog (Shh) and Netrin-1 attract growth cones of commissural axons toward the floor plate of the embryonic spinal cord. Mice defective for either Shh or Netrin-1 signaling have commissural axon guidance defects, suggesting that both Shh and Netrin-1 are required for correct axon guidance. However, how Shh and Netrin-1 collaborate to guide axons is not known. We first quantified the steepness of the Shh gradient in the spinal cord and found that it is mostly very shallow. We then developed an in vitro microfluidic guidance assay to simulate these shallow gradients. We found that axons of dissociated commissural neurons respond to steep but not shallow gradients of Shh or Netrin-1. However, when we presented axons with combined Shh and Netrin-1 gradients, they had heightened sensitivity to the guidance cues, turning in response to shallower gradients that were unable to guide axons when only one cue was present. Furthermore, these shallow gradients polarized growth cone Src-family kinase (SFK) activity only when Shh and Netrin-1 were combined, indicating that SFKs can integrate the two guidance cues. Together, our results indicate that Shh and Netrin-1 synergize to enable growth cones to sense shallow gradients in regions of the spinal cord where the steepness of a single guidance cue is insufficient to guide axons, and we identify a novel type of synergy that occurs when the steepness (and not the concentration) of a guidance cue is limiting.

  11. Brief electrical stimulation accelerates axon regeneration in the peripheral nervous system and promotes sensory axon regeneration in the central nervous system.

    Science.gov (United States)

    Gordon, Tessa; Udina, Esther; Verge, Valerie M K; de Chaves, Elena I Posse

    2009-10-01

    Injured peripheral but not central nerves regenerate their axons but functional recovery is often poor. We demonstrate that prolonged periods of axon separation from targets and Schwann cell denervation eliminate regenerative capacity in the peripheral nervous system (PNS). A substantial delay of 4 weeks for all regenerating axons to cross a site of repair of sectioned nerve contributes to the long period of separation. Findings that 1h 20Hz bipolar electrical stimulation accelerates axon outgrowth across the repair site and the downstream reinnervation of denervated muscles in rats and human patients, provides a new and exciting method to improve functional recovery after nerve injuries. Drugs that elevate neuronal cAMP and activate PKA promote axon outgrowth in vivo and in vitro, mimicking the electrical stimulation effect. Rapid expression of neurotrophic factors and their receptors and then of growth associated proteins thereafter via cAMP, is the likely mechanism by which electrical stimulation accelerates axon outgrowth from the site of injury in both peripheral and central nervous systems.

  12. Transfer of vesicles from Schwann cell to axon: a novel mechanism of communication in the peripheral nervous system

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    María Alejandra eLopez-Verrilli

    2012-06-01

    Full Text Available Schwann cells (SCs are the glial component of the peripheral nervous system, with essential roles during development and maintenance of axons, as well as during regenerative processes after nerve injury. SCs increase conduction velocities by myelinating axons, regulate synaptic activity at presynaptic nerve terminals and are a source of trophic factors to neurons. Thus, development and maintenance of peripheral nerves are crucially dependent on local signalling between SCs and axons. In addition to the classic mechanisms of intercellular signalling, the possibility of communication through secreted vesicles has been poorly explored to date. Interesting recent findings suggest the occurrence of lateral transfer mediated by vesicles from glial cells to axons that could have important roles in axonal growth and axonal regeneration. Here, we review the role of vesicular transfer from SCs to axons and propose the benefits of this means in supporting neuronal and axonal maintenance and regeneration after nerve damage.

  13. 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

    in the cerebellar slice cultures was analyzed through high-resolution respirometry assays and quantification of adenosine triphosphate (ATP) production. RESULTS: Both conditions promoted an increase in the size and complexity of axonal mitochondria evident in electron microscopy images, suggesting a compensatory...... acutely impairs axonal mitochondrial transportation, which would promote an inappropriate delivery of energy throughout axons and, by this way, contribute to axonal damage. Thus, preserving axonal mitochondrial transport might represent a promising avenue to exploit as a therapeutic target...... response. Such compensation was reflected at the tissue level as increased respiratory activity of complexes I and IV and as a transient increase in ATP production in response to acute inflammation. Notably, time-lapse microscopy indicated that mitochondrial transport (mean velocity) was severely impaired...

  14. Golgi bypass for local delivery of axonal proteins, fact or fiction?

    Science.gov (United States)

    González, Carolina; Cornejo, Víctor Hugo; Couve, Andrés

    2018-04-06

    Although translation of cytosolic proteins is well described in axons, much less is known about the synthesis, processing and trafficking of transmembrane and secreted proteins. A canonical rough endoplasmic reticulum or a stacked Golgi apparatus has not been detected in axons, generating doubts about the functionality of a local route. However, axons contain mRNAs for membrane and secreted proteins, translation factors, ribosomal components, smooth endoplasmic reticulum and post-endoplasmic reticulum elements that may contribute to local biosynthesis and plasma membrane delivery. Here we consider the evidence supporting a local secretory system in axons. We discuss exocytic elements and examples of autonomous axonal trafficking that impact development and maintenance. We also examine whether unconventional post-endoplasmic reticulum pathways may replace the canonical Golgi apparatus. Copyright © 2018. Published by Elsevier Ltd.

  15. Nuclear-Encoded Mitochondrial mRNAs: A Powerful Force in Axonal Growth and Development.

    Science.gov (United States)

    Gale, Jenna R; Aschrafi, Armaz; Gioio, Anthony E; Kaplan, Barry B

    2018-04-01

    Axons, their growth cones, and synaptic nerve terminals are neuronal subcompartments that have high energetic needs. As such, they are enriched in mitochondria, which supply the ATP necessary to meet these demands. To date, a heterogeneous population of nuclear-encoded mitochondrial mRNAs has been identified in distal axons and growth cones. Accumulating evidence suggests that the local translation of these mRNAs is required for mitochondrial maintenance and axonal viability. Here, we review evidence that suggests a critical role for axonal translation of nuclear-encoded mitochondrial mRNAs in axonal growth and development. Additionally, we explore the role that site-specific translation at the mitochondria itself may play in this process. Finally, we briefly review the clinical implications of dysregulation of local translation of mitochondrial-related mRNAs in neurodevelopmental disorders.

  16. 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.

  17. BmRobo2/3 is required for axon guidance in the silkworm Bombyx mori.

    Science.gov (United States)

    Li, Xiao-Tong; Yu, Qi; Zhou, Qi-Sheng; Zhao, Xiao; Liu, Zhao-Yang; Cui, Wei-Zheng; Liu, Qing-Xin

    2016-02-15

    Axon guidance is critical for proper wiring of the nervous system. During the neural development, the axon guidance molecules play a key role and direct axons to choose the correct way to reach the target. Robo, as the receptor of axon guidance molecule Slit, is evolutionarily conserved from planarians to humans. However, the function of Robo in the silkworm, Bombyx mori, remained unknown. In this study, we cloned robo2/3 from B. mori (Bmrobo2/3), a homologue of robo2/3 in Tribolium castaneum. Moreover, BmRobo2/3 was localized in the neuropil, and RNAi-mediated knockdown of Bmrobo2/3 resulted in the longitudinal connectives forming closer to the midline. These data demonstrate that BmRobo2/3 is required for axon guidance in the silkworm. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. 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....

  19. 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

  20. Delineating neurotrophin-3 dependent signaling pathways underlying sympathetic axon growth along intermediate targets.

    Science.gov (United States)

    Keeler, Austin B; Suo, Dong; Park, Juyeon; Deppmann, Christopher D

    2017-07-01

    Postganglionic sympathetic neurons detect vascular derived neurotrophin 3 (NT3) via the axonally expressed receptor tyrosine kinase, TrkA, to promote chemo-attraction along intermediate targets. Once axons arrive to their final target, a structurally related neurotrophic factor, nerve growth factor (NGF), also acts through TrkA to promote final target innervation. Does TrkA signal differently at these different locales? We previously found that Coronin-1 is upregulated in sympathetic neurons upon exposure to NGF, thereby endowing the NGF-TrkA complex with new signaling capabilities (i.e. calcium signaling), which dampens axon growth and branching. Based on the notion that axons do not express functional levels of Coronin-1 prior to final target innervation, we developed an in vitro model for axon growth and branching along intermediate targets using Coro1a -/- neurons grown in NT3. We found that, similar to NGF-TrkA, NT3-TrkA is capable of inducing MAPK and PI3K in the presence or absence of Coronin-1. However, unlike NGF, NT3 does not induce calcium release from intracellular stores. Using a combination of pharmacology, knockout neurons and in vitro functional assays, we suggest that the NT3-TrkA complex uses Ras/MAPK and/or PI3K-AKT signaling to induce axon growth and inhibit axon branching along intermediate targets. However, in the presence of Coronin-1, these signaling pathways lose their ability to impact NT3 dependent axon growth or branching. This is consistent with a role for Coronin-1 as a molecular switch for axon behavior and suggests that Coronin-1 suppresses NT3 dependent axon behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. 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.

  2. 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.

  3. Extrinsic and intrinsic regulation of axon regeneration at a crossroads.

    Science.gov (United States)

    Kaplan, Andrew; Ong Tone, Stephan; Fournier, Alyson E

    2015-01-01

    Repair of the injured spinal cord is a major challenge in medicine. The limited intrinsic regenerative response mounted by adult central nervous system (CNS) neurons is further hampered by astrogliosis, myelin debris and scar tissue that characterize the damaged CNS. Improved axon regeneration and recovery can be elicited by targeting extrinsic factors as well as by boosting neuron-intrinsic growth regulators. Our knowledge of the molecular basis of intrinsic and extrinsic regulators of regeneration has expanded rapidly, resulting in promising new targets to promote repair. Intriguingly certain neuron-intrinsic growth regulators are emerging as promising targets to both stimulate growth and relieve extrinsic inhibition of regeneration. This crossroads between the intrinsic and extrinsic aspects of spinal cord injury is a promising target for effective therapies for this unmet need.

  4. The cholinergic ligand binding material of axonal membranes

    International Nuclear Information System (INIS)

    Mautner, H.G.; Coronado, R.; Jumblatt, J.E.

    1986-01-01

    Choline acetyltransferase and acetylcholinesterase, the enzymes responsible for the synthesis and hydrolysis of ACh, are present in nerve fibers. In crustacean peripheral nerves, release of ACh from cut nerve fibers has been demonstrated. Previously closed membrane vesicles have been prepared from lobster walking leg nerve plasma membrane and saturable binding of cholinergic agonsist and antagonists to such membranes have been demonstrated. This paper studies this axonal cholinergic binding material, and elucidates its functions. The binding of tritium-nicotine to lobster nerve plasma membranes was antagonized by a series of cholinergic ligands as well as by a series of local anesthetics. This preparation was capable of binding I 125-alpha-bungarotoxin, a ligand widely believed to be a specific label for nicotinic ACh receptor. The labelling of 50 K petide band with tritium-MBTA following disulfide reduction is illustrated

  5. 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.

  6. 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.

  7. Neuron Morphology Influences Axon Initial Segment Plasticity123

    Science.gov (United States)

    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

  8. 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

  9. Diffuse axonal injury at ultra-high field MRI.

    Directory of Open Access Journals (Sweden)

    Christoph Moenninghoff

    Full Text Available Diffuse axonal injury (DAI is a specific type of traumatic brain injury caused by shearing forces leading to widespread tearing of axons and small vessels. Traumatic microbleeds (TMBs are regarded as a radiological marker for DAI. This study aims to compare DAI-associated TMBs at 3 Tesla (T and 7 T susceptibility weighted imaging (SWI to evaluate possible diagnostic benefits of ultra-high field (UHF MRI.10 study participants (4 male, 6 female, age range 20-74 years with known DAI were included. All MR exams were performed with a 3 T MR system (Magnetom Skyra and a 7 T MR research system (Magnetom 7 T, Siemens AG, Healthcare Sector, Erlangen, Germany each in combination with a 32-channel-receive coil. The average time interval between trauma and imaging was 22 months. Location and count of TMBs were independently evaluated by two neuroradiologists on 3 T and 7 T SWI images with similar and additionally increased spatial resolution at 7 T. Inter- and intraobserver reliability was assessed using the interclass correlation coefficient (ICC. Count and diameter of TMB were evaluated with Wilcoxon signed rank test.Susceptibility weighted imaging revealed a total of 485 TMBs (range 1-190, median 25 at 3 T, 584 TMBs (plus 20%, range 1-262, median 30.5 at 7 T with similar spatial resolution, and 684 TMBs (plus 41%, range 1-288, median 39.5 at 7 T with 10-times higher spatial resolution. Hemorrhagic DAI appeared significantly larger at 7 T compared to 3 T (p = 0.005. Inter- and intraobserver correlation regarding the counted TMB was high and almost equal 3 T and 7 T.7 T SWI improves the depiction of small hemorrhagic DAI compared to 3 T and may be supplementary to lower field strengths for diagnostic in inconclusive or medicolegal cases.

  10. Axonal transport of proteoglycans to the goldfish optic tectum

    International Nuclear Information System (INIS)

    Ripellino, J.A.; Elam, J.S.

    1988-01-01

    The study addressed the question of whether 35 SO 4 labeled molecules that have been delivered to the goldfish optic nerve terminals by rapid axonal transport include soluble proteoglycans. For analysis, tectal homogenates were subfractionated into a soluble fraction (soluble after centrifugation at 105,000 g), a lysis fraction (soluble after treatment with hypotonic buffer followed by centrifugation at 105,000 g) and a final 105,000 g pellet fraction. The soluble fraction contained 25.7% of incorporated radioactivity and upon DEAE chromatography was resolved into a fraction of sulfated glycoproteins eluting at 0-0.32 M NaCl and containing 39.5% of total soluble label and a fraction eluting at 0.32-0.60 M NaCl containing 53.9% of soluble label. This latter fraction was included on columns of Sepharose CL-6B with or without 4 M guanidine and after pronase digestion was found to have 51% of its radioactivity contained in the glycosaminoglycans (GAGs) heparan sulfate and chondroitin (4 or 6) sulfate in the ratio of 70% to 30%. Mobility of both intact proteoglycans and constituent GAGs on Sepharose CL-6B indicated a size distribution that is smaller than has been observed for proteoglycans and GAGs from cultured neuronal cell lines. Similar analysis of lysis fraction, containing 11.5% of incorporated 35 SO 4 , showed a mixture of heparan sulfate and chondroitin sulfate containing proteoglycans, apparent free heparan sulfate and few, if any, sulfated glycoproteins. Overall, the results support the hypothesis that soluble proteoglycans are among the molecules axonally transported in the visual system

  11. Live Imaging of Calcium Dynamics during Axon Degeneration Reveals Two Functionally Distinct Phases of Calcium Influx

    Science.gov (United States)

    Yamagishi, Yuya; Tessier-Lavigne, Marc

    2015-01-01

    Calcium is a key regulator of axon degeneration caused by trauma and disease, but its specific spatial and temporal dynamics in injured axons remain unclear. To clarify the function of calcium in axon degeneration, we observed calcium dynamics in single injured neurons in live zebrafish larvae and tested the temporal requirement for calcium in zebrafish neurons and cultured mouse DRG neurons. Using laser axotomy to induce Wallerian degeneration (WD) in zebrafish peripheral sensory axons, we monitored calcium dynamics from injury to fragmentation, revealing two stereotyped phases of axonal calcium influx. First, axotomy triggered a transient local calcium wave originating at the injury site. This initial calcium wave only disrupted mitochondria near the injury site and was not altered by expression of the protective WD slow (WldS) protein. Inducing multiple waves with additional axotomies did not change the kinetics of degeneration. In contrast, a second phase of calcium influx occurring minutes before fragmentation spread as a wave throughout the axon, entered mitochondria, and was abolished by WldS expression. In live zebrafish, chelating calcium after the first wave, but before the second wave, delayed the progress of fragmentation. In cultured DRG neurons, chelating calcium early in the process of WD did not alter degeneration, but chelating calcium late in WD delayed fragmentation. We propose that a terminal calcium wave is a key instructive component of the axon degeneration program. SIGNIFICANCE STATEMENT Axon degeneration resulting from trauma or neurodegenerative disease can cause devastating deficits in neural function. Understanding the molecular and cellular events that execute axon degeneration is essential for developing treatments to address these conditions. Calcium is known to contribute to axon degeneration, but its temporal requirements in this process have been unclear. Live calcium imaging in severed zebrafish neurons and temporally controlled

  12. 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

  13. Hindsight regulates photoreceptor axon targeting through transcriptional control of jitterbug/Filamin and multiple genes involved in axon guidance in Drosophila.

    Science.gov (United States)

    Oliva, Carlos; Molina-Fernandez, Claudia; Maureira, Miguel; Candia, Noemi; López, Estefanía; Hassan, Bassem; Aerts, Stein; Cánovas, José; Olguín, Patricio; Sierralta, Jimena

    2015-09-01

    During axon targeting, a stereotyped pattern of connectivity is achieved by the integration of intrinsic genetic programs and the response to extrinsic long and short-range directional cues. How this coordination occurs is the subject of intense study. Transcription factors play a central role due to their ability to regulate the expression of multiple genes required to sense and respond to these cues during development. Here we show that the transcription factor HNT regulates layer-specific photoreceptor axon targeting in Drosophila through transcriptional control of jbug/Filamin and multiple genes involved in axon guidance and cytoskeleton organization.Using a microarray analysis we identified 235 genes whose expression levels were changed by HNT overexpression in the eye primordia. We analyzed nine candidate genes involved in cytoskeleton regulation and axon guidance, six of which displayed significantly altered gene expression levels in hnt mutant retinas. Functional analysis confirmed the role of OTK/PTK7 in photoreceptor axon targeting and uncovered Tiggrin, an integrin ligand, and Jbug/Filamin, a conserved actin- binding protein, as new factors that participate of photoreceptor axon targeting. Moreover, we provided in silico and molecular evidence that supports jbug/Filamin as a direct transcriptional target of HNT and that HNT acts partially through Jbug/Filamin in vivo to regulate axon guidance. Our work broadens the understanding of how HNT regulates the coordinated expression of a group of genes to achieve the correct connectivity pattern in the Drosophila visual system. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1018-1032, 2015. © 2015 Wiley Periodicals, Inc.

  14. Glia-axon interactions and the regulation of the extracellular K+ in the peripheral nerve.

    Science.gov (United States)

    Jirounek, P; Robert, A; Kindler, E; Blazek, T

    1998-01-01

    Changes in membrane potential of both axons and Schwann cells were measured simultaneously during electrical activity and during the period of recovery in the rabbit vagus nerve by the use of the sucrose-gap apparatus. During low-frequency stimulation (0.5-1 Hz) the preparation developed a ouabain-sensitive hyperpolarization. This hyperpolarization increased when the inwardly rectifying K+ channels in Schwann cells were blocked with Ba2+, indicating that the hyperpolarization was generated by the electrogenic glial Na(+)-K+ pump. During trains at higher frequencies (15 Hz), the preparation depolarized, but after cessation of the stimulation it developed a posttetanic hyperpolarization (PTH). The PTH was also ouabain-sensitive and was strongly enhanced by Cs+ which is known to block the hyperpolarization-activated inward current (Ih) in axons but not in glial cells. These results show that the PTH reflects mainly the axonal electrogenic pump. Our results indicate that during activity the K+ released from the firing axons is removed from the extracellular space by Schwann cells and that after cessation of the stimulation the K+ surplus returns from Schwann cells back to axons. Both the glial and axonal K+ uptake is mediated by successive activation of the glial and axonal Na(+)-K+ pump. The nature of the signalling mechanisms that control the pumping rates of the respective pumps remain unknown.

  15. Characterization of axon formation in the embryonic stem cell-derived motoneuron.

    Science.gov (United States)

    Pan, Hung-Chuan; Wu, Ya-Ting; Shen, Shih-Cheng; Wang, Chi-Chung; Tsai, Ming-Shiun; Cheng, Fu-Chou; Lin, Shinn-Zong; Chen, Ching-Wen; Liu, Ching-San; Su, Hong-Lin

    2011-01-01

    The developing neural cell must form a highly organized architecture to properly receive and transmit nerve signals. Neural formation from embryonic stem (ES) cells provides a novel system for studying axonogenesis, which are orchestrated by polarity-regulating molecules. Here the ES-derived motoneurons, identified by HB9 promoter-driven green fluorescent protein (GFP) expression, showed characteristics of motoneuron-specific gene expression. In the majority of motoneurons, one of the bilateral neurites developed into an axon that featured with axonal markers, including Tau1, vesicle acetylcholine transporter, and synaptophysin. Interestingly, one third of the motoneurons developed bi-axonal processes but no multiple axonal GFP cell was found. The neuronal polarity-regulating proteins, including the phosphorylated AKT and ERK, were compartmentalized into both of the bilateral axonal tips. Importantly, this aberrant axon morphology was still present after the engraftment of GFP(+) neurons into the spinal cord, suggesting that even a mature neural environment fails to provide a proper niche to guide normal axon formation. These findings underscore the necessity for evaluating the morphogenesis and functionality of neurons before the clinical trials using ES or somatic stem cells.

  16. Target-Derived Neurotrophins Coordinate Transcription and Transport of Bclw to Prevent Axonal Degeneration

    Science.gov (United States)

    Cosker, Katharina E.; Pazyra-Murphy, Maria F.; Fenstermacher, Sara J.

    2013-01-01

    Establishment of neuronal circuitry depends on both formation and refinement of neural connections. During this process, target-derived neurotrophins regulate both transcription and translation to enable selective axon survival or elimination. However, it is not known whether retrograde signaling pathways that control transcription are coordinated with neurotrophin-regulated actions that transpire in the axon. Here we report that target-derived neurotrophins coordinate transcription of the antiapoptotic gene bclw with transport of bclw mRNA to the axon, and thereby prevent axonal degeneration in rat and mouse sensory neurons. We show that neurotrophin stimulation of nerve terminals elicits new bclw transcripts that are immediately transported to the axons and translated into protein. Bclw interacts with Bax and suppresses the caspase6 apoptotic cascade that fosters axonal degeneration. The scope of bclw regulation at the levels of transcription, transport, and translation provides a mechanism whereby sustained neurotrophin stimulation can be integrated over time, so that axonal survival is restricted to neurons connected within a stable circuit. PMID:23516285

  17. A Communication Theoretical Modeling of Axonal Propagation in Hippocampal Pyramidal Neurons.

    Science.gov (United States)

    Ramezani, Hamideh; Akan, Ozgur B

    2017-06-01

    Understanding the fundamentals of communication among neurons, known as neuro-spike communication, leads to reach bio-inspired nanoscale communication paradigms. In this paper, we focus on a part of neuro-spike communication, known as axonal transmission, and propose a realistic model for it. The shape of the spike during axonal transmission varies according to previously applied stimulations to the neuron, and these variations affect the amount of information communicated between neurons. Hence, to reach an accurate model for neuro-spike communication, the memory of axon and its effect on the axonal transmission should be considered, which are not studied in the existing literature. In this paper, we extract the important factors on the memory of axon and define memory states based on these factors. We also describe the transition among these states and the properties of axonal transmission in each of them. Finally, we demonstrate that the proposed model can follow changes in the axonal functionality properly by simulating the proposed model and reporting the root mean square error between simulation results and experimental data.

  18. Microtubule-targeting drugs rescue axonal swellings in cortical neurons from spastin knockout mice

    Directory of Open Access Journals (Sweden)

    Coralie Fassier

    2013-01-01

    Mutations in SPG4, encoding the microtubule-severing protein spastin, are responsible for the most frequent form of hereditary spastic paraplegia (HSP, a heterogeneous group of genetic diseases characterized by degeneration of the corticospinal tracts. We previously reported that mice harboring a deletion in Spg4, generating a premature stop codon, develop progressive axonal degeneration characterized by focal axonal swellings associated with impaired axonal transport. To further characterize the molecular and cellular mechanisms underlying this mutant phenotype, we have assessed microtubule dynamics and axonal transport in primary cultures of cortical neurons from spastin-mutant mice. We show an early and marked impairment of microtubule dynamics all along the axons of spastin-deficient cortical neurons, which is likely to be responsible for the occurrence of axonal swellings and cargo stalling. Our analysis also reveals that a modulation of microtubule dynamics by microtubule-targeting drugs rescues the mutant phenotype of cortical neurons. Together, these results contribute to a better understanding of the pathogenesis of SPG4-linked HSP and ascertain the influence of microtubule-targeted drugs on the early axonal phenotype in a mouse model of the disease.

  19. 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.

  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. 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.

  2. 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

  3. Schwann cell transplantation improves reticulospinal axon growth and forelimb strength after severe cervical spinal cord contusion.

    Science.gov (United States)

    Schaal, S M; Kitay, B M; Cho, K S; Lo, T P; Barakat, D J; Marcillo, A E; Sanchez, A R; Andrade, C M; Pearse, D D

    2007-01-01

    Schwann cell (SC) implantation alone has been shown to promote the growth of propriospinal and sensory axons, but not long-tract descending axons, after thoracic spinal cord injury (SCI). In the current study, we examined if an axotomy close to the cell body of origin (so as to enhance the intrinsic growth response) could permit supraspinal axons to grow onto SC grafts. Adult female Fischer rats received a severe (C5) cervical contusion (1.1 mm displacement, 3 KDyn). At 1 week postinjury, 2 million SCs ex vivo transduced with lentiviral vector encoding enhanced green fluorescent protein (EGFP) were implanted within media into the injury epicenter; injury-only animals served as controls. Animals were tested weekly using the BBB score for 7 weeks postimplantation and received at end point tests for upper body strength: self-supported forelimb hanging, forearm grip force, and the incline plane. Following behavioral assessment, animals were anterogradely traced bilaterally from the reticular formation using BDA-Texas Red. Stereological quantification revealed a twofold increase in the numbers of preserved NeuN+ neurons rostral and caudal to the injury/graft site in SC implanted animals, corroborating previous reports of their neuroprotective efficacy. Examination of labeled reticulospinal axon growth revealed that while rarely an axon was present within the lesion site of injury-only controls, numerous reticulospinal axons had penetrated the SC implant/lesion milieu. This has not been observed following implantation of SCs alone into the injured thoracic spinal cord. Significant behavioral improvements over injury-only controls in upper limb strength, including an enhanced grip strength (a 296% increase) and an increased self-supported forelimb hanging, accompanied SC-mediated neuroprotection and reticulospinal axon growth. The current study further supports the neuroprotective efficacy of SC implants after SCI and demonstrates that SCs alone are capable of supporting

  4. Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade

    Directory of Open Access Journals (Sweden)

    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. Trafficking of cholesterol from cell bodies to distal axons in Niemann Pick C1-deficient neurons.

    Science.gov (United States)

    Karten, Barbara; Vance, Dennis E; Campenot, Robert B; Vance, Jean E

    2003-02-07

    Niemann Pick type C (NPC) disease is a progressive neurodegenerative disorder. In cells lacking functional NPC1 protein, endocytosed cholesterol accumulates in late endosomes/lysosomes. We utilized primary neuronal cultures in which cell bodies and distal axons reside in separate compartments to investigate the requirement of NPC1 protein for transport of cholesterol from cell bodies to distal axons. We have recently observed that in NPC1-deficient neurons compared with wild-type neurons, cholesterol accumulates in cell bodies but is reduced in distal axons (Karten, B., Vance, D. E., Campenot, R. B., and Vance, J. E. (2002) J. Neurochem. 83, 1154-1163). We now show that NPC1 protein is expressed in both cell bodies and distal axons. In NPC1-deficient neurons, cholesterol delivered to cell bodies from low density lipoproteins (LDLs), high density lipoproteins, or cyclodextrin complexes was transported into axons in normal amounts, whereas transport of endogenously synthesized cholesterol was impaired. Inhibition of cholesterol synthesis with pravastatin in wild-type and NPC1-deficient neurons reduced axonal growth. However, LDLs restored a normal rate of growth to wild-type but not NPC1-deficient neurons treated with pravastatin. Thus, although LDL cholesterol is transported into axons of NPC1-deficient neurons, this source of cholesterol does not sustain normal axonal growth. Over the lifespan of NPC1-deficient neurons, these defects in cholesterol transport might be responsible for the observed altered distribution of cholesterol between cell bodies and axons and, consequently, might contribute to the neurological dysfunction in NPC disease.

  6. Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade.

    Science.gov (United States)

    Dumoulin, Alexandre; Ter-Avetisyan, Gohar; Schmidt, Hannes; Rathjen, Fritz G

    2018-04-24

    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.

  7. Current Opportunities for Clinical Monitoring of Axonal Pathology in Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    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. Diffuse axonal injury: detection of changes in anisotropy of water diffusion by diffusion-weighted imaging

    International Nuclear Information System (INIS)

    Chan, J.H.M.; Tsui, E.Y.K.; Yuen, M.K.; Peh, W.C.G.; Fong, D.; Fok, K.F.; Leung, K.M.; Fung, K.K.L.

    2003-01-01

    Myelinated axons of white matter demonstrate prominent directional differences in water diffusion. We performed diffusion-weighted imaging on ten patients with head injury to explore the feasibility of using water diffusion anisotropy for quantitating diffuse axonal injury. We showed significant decrease in diffusion anisotropy indices in areas with or without signal abnormality on T2 and T2*-weighted images. We conclude that the water diffusion anisotropy index a potentially useful, sensitive and quantitative way of diagnosing and assessing patients with diffuse axonal injury. (orig.)

  10. 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...

  11. In vivo electrophysiological measurement of the rat ulnar nerve with axonal excitability testing

    DEFF Research Database (Denmark)

    Wild, Brandon M.; Morris, Renée; Moldovan, Mihai

    2018-01-01

    Electrophysiology enables the objective assessment of peripheral nerve function in vivo. Traditional nerve conduction measures such as amplitude and latency detect chronic axon loss and demyelination, respectively. Axonal excitability techniques "by threshold tracking" expand upon these measures...... by providing information regarding the activity of ion channels, pumps and exchangers that relate to acute function and may precede degenerative events. As such, the use of axonal excitability in animal models of neurological disorders may provide a useful in vivo measure to assess novel therapeutic...... interventions. Here we describe an experimental setup for multiple measures of motor axonal excitability techniques in the rat ulnar nerve. The animals are anesthetized with isoflurane and carefully monitored to ensure constant and adequate depth of anesthesia. Body temperature, respiration rate, heart rate...

  12. Axonal plasticity elicits long-term changes in oligodendroglia and myelinated fibers

    DEFF Research Database (Denmark)

    Drøjdahl, Nina; Nielsen, Helle Hvilsted; Gardi, Jonathan E

    2010-01-01

    Axons are linked to induction of myelination during development and to the maintenance of myelin and myelinated tracts in the adult CNS. Currently, it is unknown whether and how axonal plasticity in adult CNS impacts the myelinating cells and their precursors. In this article, we report that newly...... formed axonal sprouts are able to induce a protracted myelination response in adult CNS. We show that newly formed axonal sprouts, induced by lesion of the entorhino-hippocampal perforant pathway, have the ability to induce a myelination response in stratum radiatum and lucidum CA3. The lesion resulted...... in significant recruitment of newly formed myelinating cells, documented by incorporation of the proliferation marker bromodeoxyuridine into chondroitin sulphate NG2 expressing cells in stratum radiatum and lucidum CA3 early after lesion, and the occurrence of a 28% increase in the number of oligodendrocytes...

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

    Science.gov (United States)

    2014-10-01

    stress, impairments of mitochondrial function, neuroinflammation, altered neurotrophin responses, etc. (reviewed, Soltaninejad and Abdollahi, 2009...Exposure to Chlorpyrifos in Rats: Protracted Effects on Axonal Transport, Neurotrophin Receptors, Cholinergic Markers, and Information Processing

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

    Science.gov (United States)

    2015-10-01

    function, neuroinflammation, al- tered neurotrophin responses, etc. (reviewed, Soltaninejad and Abdollahi, 2009; Banks and Lein, 2012; Terry, 2012). Conflict...JN, Middlemore ML, Williamson LN, et al. Chronic, intermittent exposure to chlorpyrifos in rats: protracted effects on axonal transport, neurotrophin

  15. Effects of X-irradiation on axonal sprouting induced by botulinum toxin

    Energy Technology Data Exchange (ETDEWEB)

    Gomez, S; Duchen, L W [National Hospital, London (UK); Hornsey, S [Hammersmith Hospital, London (UK). M.R.C. Cyclotron Unit

    1982-01-01

    The effect of X-irradiation on axonal sprouting of motor nerves induced by botulinum toxin was examined. Muscles of one leg in the mouse were X-irradiated (15Gy) prior to the injection of a locally paralysing dose of botulinum toxin. It was found that axonal sprouting occurred as expected, but the sprouts remained unmyelinated and many degenerated. Fewer new end-plates were formed, muscles remained more severely atrophied and supersensitive to acetylcholine and recovery of neuromuscular transmission was greatly delayed when compared with the effects of botulinum toxin alone. X-irradiation did not prevent sprouting but, probably by impairing Schwann cell proliferation, altered axon-Schwann cell relationships and prevented the maturation of newly-formed axons and the differentiation of new end-plates.

  16. BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon.

    Science.gov (United States)

    Farías, Ginny G; Guardia, Carlos M; De Pace, Raffaella; Britt, Dylan J; Bonifacino, Juan S

    2017-04-04

    The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly understood. Here we show that an ensemble of BORC, Arl8, SKIP, and kinesin-1, previously shown to mediate centrifugal transport of lysosomes in nonneuronal cells, specifically drives lysosome transport into the axon, and not the dendrites, in cultured rat hippocampal neurons. This transport is essential for maintenance of axonal growth-cone dynamics and autophagosome turnover. Our findings illustrate how a general mechanism for lysosome dispersal in nonneuronal cells is adapted to drive polarized transport in neurons, and emphasize the importance of this mechanism for critical axonal processes.

  17. BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon

    Science.gov (United States)

    Farías, Ginny G.; Guardia, Carlos M.; De Pace, Raffaella; Britt, Dylan J.; Bonifacino, Juan S.

    2017-01-01

    The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly understood. Here we show that an ensemble of BORC, Arl8, SKIP, and kinesin-1, previously shown to mediate centrifugal transport of lysosomes in nonneuronal cells, specifically drives lysosome transport into the axon, and not the dendrites, in cultured rat hippocampal neurons. This transport is essential for maintenance of axonal growth-cone dynamics and autophagosome turnover. Our findings illustrate how a general mechanism for lysosome dispersal in nonneuronal cells is adapted to drive polarized transport in neurons, and emphasize the importance of this mechanism for critical axonal processes. PMID:28320970

  18. 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.

  19. Electrocardiografo por computadora

    OpenAIRE

    Tinoco Hernandez, Rosanna; Paredes Bejarano, Margarita; Romero Chaglia, Norman; Yapur Auad, Miguel Eduardo

    2009-01-01

    El presente trabajo trata sobrees el diseño y la implementación de un graficador de señales cardiacas por computadora, para lo cual diseñamos un circuito electrónico capaz de recibir la senal analógica proveniente de la actividad electrica del corazón , amplificarla, y luego convertirla en una señal digital para ser procesada por software y finalmente ser graficada, siendo posible así observar la señal cardiaca en el monitor de un computador como un tren de pulsos. Cabe destacar que par...

  20. 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

    " pockets. The total number of axons in the sural nerve was unchanged, but a greater proportion was unmyelinated. In addition, we observed large-diameter axons that were in a 1:1 relationship with Schwann cells, surrounded by a basal lamina but not myelinated. There was no evidence of DRG or Schwann cell...... death; the markers of different DRG cell populations and cutaneous innervation were unchanged. These anatomical changes were reflected in a slowing of conduction velocity at the lower end of the A-fiber conduction velocity range and a new population of more rapidly conducting C-fibers that are likely...

  1. 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.

  2. Adenosine: an activity-dependent axonal signal regulating MAP kinase and proliferation in developing Schwann cells

    OpenAIRE

    Stevens, Beth; Ishibashi, Tomoko; Chen, Jiang-Fan; Fields, R. Douglas

    2004-01-01

    Nonsynaptic release of ATP from electrically stimulated dorsal root gangion (DRG) axons inhibits Schwann cell (SC) proliferation and arrests SC development at the premyelinating stage, but the specific types of purinergic receptor(s) and intracellular signaling pathways involved in this form of neuron–glia communication are not known. Recent research shows that adenosine is a neuron–glial transmitter between axons and myelinating glia of the CNS. The present study investigates the possibility...

  3. 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

  4. Regional Retinal Ganglion Cell Axon Loss in a Murine Glaucoma Model.

    Science.gov (United States)

    Schaub, Julie A; Kimball, Elizabeth C; Steinhart, Matthew R; Nguyen, Cathy; Pease, Mary E; Oglesby, Ericka N; Jefferys, Joan L; Quigley, Harry A

    2017-05-01

    To determine if retinal ganglion cell (RGC) axon loss in experimental mouse glaucoma is uniform in the optic nerve. Experimental glaucoma was induced for 6 weeks with a microbead injection model in CD1 (n = 78) and C57BL/6 (B6, n = 68) mice. From epoxy-embedded sections of optic nerve 1 to 2 mm posterior to the globe, total nerve area and regional axon density (axons/1600 μm2) were measured in superior, inferior, nasal, and temporal zones. Control eyes of CD1 mice have higher axon density and more total RGCs than control B6 mice eyes. There were no significant differences in control regional axon density in all mice or by strain (all P > 0.2, mixed model). Exposure to elevated IOP caused loss of RGC in both strains. In CD1 mice, axon density declined without significant loss of nerve area, while B6 mice had less density loss, but greater decrease in nerve area. Axon density loss in glaucoma eyes was not significantly greater in any region in either mouse strain (both P > 0.2, mixed model). In moderately damaged CD1 glaucoma eyes, and CD1 eyes with the greatest IOP elevation exposure, density loss differed by region (P = 0.05, P = 0.03, mixed model) with the greatest loss in the temporal and superior regions, while in severely injured B6 nerves superior loss was greater than inferior loss (P = 0.01, mixed model, Bonferroni corrected). There was selectively greater loss of superior and temporal optic nerve axons of RGCs in mouse glaucoma at certain stages of damage. Differences in nerve area change suggest non-RGC responses differ between mouse strains.

  5. Normal axonal ion channel function in large peripheral nerve fibers following chronic ciguatera sensitization.

    Science.gov (United States)

    Vucic, Steve; Kiernan, Matthew C

    2008-03-01

    Although the acute clinical effects of ciguatera poisoning, due to ingestion of ciguatoxin, are mediated by activation of transient Na+ channels, the mechanisms underlying ciguatera sensitization remain undefined. Axonal excitability studies were performed by stimulating the median motor and sensory nerves in two patients with ciguatera sensitization. Excitability parameters were all within normal limits, thereby arguing against dysfunction of axonal membrane ion channels in large-diameter fibers in ciguatera sensitization.

  6. Hydrogels as scaffolds and delivery systems to enhance axonal regeneration after injuries

    Directory of Open Access Journals (Sweden)

    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

  7. Axonal Elongation into Peripheral Nervous System ``Bridges'' after Central Nervous System Injury in Adult Rats

    Science.gov (United States)

    David, Samuel; Aguayo, Albert J.

    1981-11-01

    The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model. When peripheral nerve segments were used as ``bridges'' between the medulla and spinal cord, axons from neurons at both these levels grew approximately 30 millimeters. The regenerative potential of these central neurons seems to be expressed when the central nervous system glial environment is changed to that of the peripheral nervous system.

  8. Axon-Sorting Multifunctional Nerve Guides: Accelerating Restoration of Nerve Function

    Science.gov (United States)

    2014-10-01

    factor (singly & in selected combinations) in the organotypic model system for preferential sensory or motor axon extension. Use confocal microscopy to...track axon extension of labeled sensory or motor neurons from spinal cord slices (motor) or dorsal root ganglia ( DRG ) (sensory). 20 Thy1-YFP mice...RESEARCH ACCOMPLISHMENTS: • Established a system of color-coded mixed nerve tracking using GFP and RFP expressing motor and sensory neurons (Figure 1

  9. Wnt Signalling Promotes Actin Dynamics during Axon Remodelling through the Actin-Binding Protein Eps8.

    Directory of Open Access Journals (Sweden)

    Eleanna Stamatakou

    Full Text Available Upon arrival at their synaptic targets, axons slow down their growth and extensively remodel before the assembly of presynaptic boutons. Wnt proteins are target-derived secreted factors that promote axonal remodelling and synaptic assembly. In the developing spinal cord, Wnts secreted by motor neurons promote axonal remodelling of NT-3 responsive dorsal root ganglia neurons. Axon remodelling induced by Wnts is characterised by growth cone pausing and enlargement, processes that depend on the re-organisation of microtubules. However, the contribution of the actin cytoskeleton has remained unexplored. Here, we demonstrate that Wnt3a regulates the actin cytoskeleton by rapidly inducing F-actin accumulation in growth cones from rodent DRG neurons through the scaffold protein Dishevelled-1 (Dvl1 and the serine-threonine kinase Gsk3β. Importantly, these changes in actin cytoskeleton occurs before enlargement of the growth cones is evident. Time-lapse imaging shows that Wnt3a increases lamellar protrusion and filopodia velocity. In addition, pharmacological inhibition of actin assembly demonstrates that Wnt3a increases actin dynamics. Through a yeast-two hybrid screen, we identified the actin-binding protein Eps8 as a direct interactor of Dvl1, a scaffold protein crucial for the Wnt signalling pathway. Gain of function of Eps8 mimics Wnt-mediated axon remodelling, whereas Eps8 silencing blocks the axon remodelling activity of Wnt3a. Importantly, blockade of the Dvl1-Eps8 interaction completely abolishes Wnt3a-mediated axonal remodelling. These findings demonstrate a novel role for Wnt-Dvl1 signalling through Eps8 in the regulation of axonal remodeling.

  10. 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.

  11. MRI findings in acute diffuse axonal injured patients

    International Nuclear Information System (INIS)

    Sato, Hidetaka

    2001-01-01

    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)

  12. Structural study of Purkinje cell axonal torpedoes in essential tremor.

    Science.gov (United States)

    Louis, Elan D; Yi, Hong; Erickson-Davis, Cordelia; Vonsattel, Jean-Paul G; Faust, Phyllis L

    2009-02-06

    Essential tremor (ET) is one of the most common neurological diseases. A basic understanding of its neuropathology is now emerging. Aside from Purkinje cell loss, a prominent finding is an abundance of torpedoes (rounded swellings of Purkinje cell axons). Such swellings often result from the mis-accumulation of cell constituents. Identifying the basic nature of these accumulations is an important step in understanding the underlying disease process. Torpedoes, only recently identified in ET, have not yet been characterized ultrastructurally. Light and electron microscopy were used to characterize the structural constituents of torpedoes in ET. Formalin-fixed cerebellar cortical tissue from four prospectively collected ET brains was sectioned and immunostained with a monoclonal phosphorylated neurofilament antibody (SMI-31, Covance, Emeryville, CA). Using additional sections from three ET brains, torpedoes were assessed using electron microscopy. Immunoreactivity for phosphorylated neurofilament protein revealed clear labeling of torpedoes in each case. Torpedoes were strongly immunoreactive; in many instances, two or more torpedoes were noted in close proximity to one another. On electron microscopy, torpedoes were packed with randomly arranged 10-12nm neurofilaments. Mitochondria and smooth endoplasmic reticulum were abundant as well, particularly at the periphery of the torpedo. We demonstrated that the torpedoes in ET represent the mis-accumulation of disorganized neurofilaments and other organelles. It is not known where in the pathogenic cascade these accumulations occur (i.e., whether these accumulations are the primary event or a secondary/downstream event) and this deserves further study.

  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. Bridging Physics and Biology Using Resistance and Axons

    Science.gov (United States)

    Dyer, Joshua M.

    2014-11-01

    When teaching physics, it is often difficult to get biology-oriented students to see the relevance of physics.1 A complaint often heard is that biology students are required to take physics for the Medical College Admission Test (MCAT) as part of a "weeding out" process, but that they don't feel like they need physics for biology. Despite this impression held by students, there have been calls for better physics education for future physicians and life scientists.2,3 Research is being performed to improve physics classes and labs by linking topics in biology and physics.4,5 Described here is a laboratory experiment covering the topics of resistance of materials and circuits/Kirchhoff's laws in a biology context with their direct application to neurons, axons, and electrical impulse transmission within animals. This experiment will also demonstrate the mechanism believed to cause multiple sclerosis. The apparatus was designed with low-cost and readily available materials in mind.

  15. 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.

  16. 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.)

  17. Detection of functional homotopy in traumatic axonal injury

    International Nuclear Information System (INIS)

    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

    2017-01-01

    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.)

  18. Early development of the circumferential axonal pathway in mouse and chick spinal cord.

    Science.gov (United States)

    Holley, J A

    1982-03-10

    The early development of the circumferential axonal pathway in the brachial and lumbar spinal cord of mouse and chick embryos was studied by scanning and transmission electron microscopy. The cellular processes which comprise this pathway grow in the transverse plane and along the lateral margin of the marginal zone (i.e., circumferentially oriented), as typified by the early embryonic commissural axons. The first formative event observed was in the ventrolateral margin of the primitive spinal cord ventricular zone. Cellular processes were found near the external limiting membrane that appeared to grow a variable distance either dorsally or ventrally. Later in development, presumptive motor column neurons migrated into the ventrolateral region, distal to these early circumferentially oriented processes. Concurrently, other circumferentially oriented perikarya and processes appeared along the dorsolateral margin. Due to their aligned sites of origin and parallel growth, the circumferential processes formed a more or less continuous line or pathway, which in about 10% of the scanned specimens could be followed along the entire lateral margin of the embryonic spinal cord. Several specimens later in development had two sets of aligned circumferential processes in the ventral region. Large numbers of circumferential axons were then found to follow the preformed pathway by fasciculation, after the primitive motor column had become established. Since the earliest circumferential processes appeared to differentiate into axons and were found nearly 24 hours prior to growth of most circumferential axons, their role in guidance as pioneering axons was suggested.

  19. 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.

  20. 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.

  1. 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.

  2. Drosophila growth cones: a genetically tractable platform for the analysis of axonal growth dynamics.

    Science.gov (United States)

    Sánchez-Soriano, Natalia; Gonçalves-Pimentel, Catarina; Beaven, Robin; Haessler, Ulrike; Ofner-Ziegenfuss, Lisa; Ballestrem, Christoph; Prokop, Andreas

    2010-01-01

    The formation of neuronal networks, during development and regeneration, requires outgrowth of axons along reproducible paths toward their appropriate postsynaptic target cells. Axonal extension occurs at growth cones (GCs) at the tips of axons. GC advance and navigation requires the activity of their cytoskeletal networks, comprising filamentous actin (F-actin) in lamellipodia and filopodia as well as dynamic microtubules (MTs) emanating from bundles of the axonal core. The molecular mechanisms governing these two cytoskeletal networks, their cross-talk, and their response to extracellular signaling cues are only partially understood, hindering our conceptual understanding of how regulated changes in GC behavior are controlled. Here, we introduce Drosophila GCs as a suitable model to address these mechanisms. Morphological and cytoskeletal readouts of Drosophila GCs are similar to those of other models, including mammals, as demonstrated here for MT and F-actin dynamics, axonal growth rates, filopodial structure and motility, organizational principles of MT networks, and subcellular marker localization. Therefore, we expect fundamental insights gained in Drosophila to be translatable into vertebrate biology. The advantage of the Drosophila model over others is its enormous amenability to combinatorial genetics as a powerful strategy to address the complexity of regulatory networks governing axonal growth. Thus, using pharmacological and genetic manipulations, we demonstrate a role of the actin cytoskeleton in a specific form of MT organization (loop formation), known to regulate GC pausing behavior. We demonstrate these events to be mediated by the actin-MT linking factor Short stop, thus identifying an essential molecular player in this context.

  3. DISCO Interacting Protein 2 regulates axonal bifurcation and guidance of Drosophila mushroom body neurons.

    Science.gov (United States)

    Nitta, Yohei; Yamazaki, Daisuke; Sugie, Atsushi; Hiroi, Makoto; Tabata, Tetsuya

    2017-01-15

    Axonal branching is one of the key processes within the enormous complexity of the nervous system to enable a single neuron to send information to multiple targets. However, the molecular mechanisms that control branch formation are poorly understood. In particular, previous studies have rarely addressed the mechanisms underlying axonal bifurcation, in which axons form new branches via splitting of the growth cone. We demonstrate that DISCO Interacting Protein 2 (DIP2) is required for precise axonal bifurcation in Drosophila mushroom body (MB) neurons by suppressing ectopic bifurcation and regulating the guidance of sister axons. We also found that DIP2 localize to the plasma membrane. Domain function analysis revealed that the AMP-synthetase domains of DIP2 are essential for its function, which may involve exerting a catalytic activity that modifies fatty acids. Genetic analysis and subsequent biochemical analysis suggested that DIP2 is involved in the fatty acid metabolization of acyl-CoA. Taken together, our results reveal a function of DIP2 in the developing nervous system and provide a potential functional relationship between fatty acid metabolism and axon morphogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Wnt3 and Gata4 regulate axon regeneration in adult mouse DRG neurons.

    Science.gov (United States)

    Duan, Run-Shan; Liu, Pei-Pei; Xi, Feng; Wang, Wei-Hua; Tang, Gang-Bin; Wang, Rui-Ying; Saijilafu; Liu, Chang-Mei

    2018-05-05

    Neurons in the adult central nervous system (CNS) have a poor intrinsic axon growth potential after injury, but the underlying mechanisms are largely unknown. Wingless-related mouse mammary tumor virus integration site (WNT) family members regulate neural stem cell proliferation, axon tract and forebrain development in the nervous system. Here we report that Wnt3 is an important modulator of axon regeneration. Downregulation or overexpression of Wnt3 in adult dorsal root ganglion (DRG) neurons enhances or inhibits their axon regeneration ability respectively in vitro and in vivo. Especially, we show that Wnt3 modulates axon regeneration by repressing mRNA translation of the important transcription factor Gata4 via binding to the three prime untranslated region (3'UTR). Downregulation of Gata4 could restore the phenotype exhibited by Wnt3 downregulation in DRG neurons. Taken together, these data indicate that Wnt3 is a key intrinsic regulator of axon growth ability of the nervous system. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Conduction velocity is regulated by sodium channel inactivation in unmyelinated axons innervating the rat cranial meninges.

    Science.gov (United States)

    De Col, Roberto; Messlinger, Karl; Carr, Richard W

    2008-02-15

    Axonal conduction velocity varies according to the level of preceding impulse activity. In unmyelinated axons this typically results in a slowing of conduction velocity and a parallel increase in threshold. It is currently held that Na(+)-K(+)-ATPase-dependent axonal hyperpolarization is responsible for this slowing but this has long been equivocal. We therefore examined conduction velocity changes during repetitive activation of single unmyelinated axons innervating the rat cranial meninges. In direct contradiction to the currently accepted postulate, Na(+)-K(+)-ATPase blockade actually enhanced activity-induced conduction velocity slowing, while the degree of velocity slowing was curtailed in the presence of lidocaine (10-300 microm) and carbamazepine (30-500 microm) but not tetrodotoxin (TTX, 10-80 nm). This suggests that a change in the number of available sodium channels is the most prominent factor responsible for activity-induced changes in conduction velocity in unmyelinated axons. At moderate stimulus frequencies, axonal conduction velocity is determined by an interaction between residual sodium channel inactivation following each impulse and the retrieval of channels from inactivation by a concomitant Na(+)-K(+)-ATPase-mediated hyperpolarization. Since the process is primarily dependent upon sodium channel availability, tracking conduction velocity provides a means of accessing relative changes in the excitability of nociceptive neurons.

  6. p27Kip1 Modulates Axonal Transport by Regulating α-Tubulin Acetyltransferase 1 Stability

    Directory of Open Access Journals (Sweden)

    Giovanni Morelli

    2018-05-01

    Full Text Available Summary: The protein p27Kip1 plays roles that extend beyond cell-cycle regulation during cerebral cortex development, such as the regulation of neuronal migration and neurite branching via signaling pathways that converge on the actin and microtubule cytoskeletons. Microtubule-dependent transport is essential for the maturation of neurons and the establishment of neuronal connectivity though synapse formation and maintenance. Here, we show that p27Kip1 controls the transport of vesicles and organelles along the axon of mice cortical projection neurons in vitro. Moreover, suppression of the p27Kip1 ortholog, dacapo, in Drosophila melanogaster disrupts axonal transport in vivo, leading to the reduction of locomotor activity in third instar larvae and adult flies. At the molecular level, p27Kip1 stabilizes the α-tubulin acetyltransferase 1, thereby promoting the acetylation of microtubules, a post-translational modification required for proper axonal transport. : Morelli et al. report that p27Kip1/Dacapo modulates the acetylation of microtubules in axons via stabilization of ATAT1, the main α-tubulin acetyltransferase. Its conditional loss leads to the reduction of bidirectional axonal transport of vesicles and mitochondria in vitro in mice and in vivo in Drosophila. Keywords: p27Kip1, dacapo, acetylation, axonal transport, ATAT1, alpha-tubulin, HDAC6, Drosophila, mouse, cerebral cortex

  7. Indice por Materias

    Directory of Open Access Journals (Sweden)

    Montoya H Luz Marina

    1982-09-01

    Full Text Available Un índice es una lista de palabras o frases indicadores asociados que permite la ubicación de material al interior de un libro o una publicación, en este caso será por el nombre de la materia.

  8. Polarized axonal surface expression of neuronal KCNQ potassium channels is regulated by calmodulin interaction with KCNQ2 subunit.

    Directory of Open Access Journals (Sweden)

    John P Cavaretta

    Full Text Available KCNQ potassium channels composed of KCNQ2 and KCNQ3 subunits give rise to the M-current, a slow-activating and non-inactivating voltage-dependent potassium current that limits repetitive firing of action potentials. KCNQ channels are enriched at the surface of axons and axonal initial segments, the sites for action potential generation and modulation. Their enrichment at the axonal surface is impaired by mutations in KCNQ2 carboxy-terminal tail that cause benign familial neonatal convulsion and myokymia, suggesting that their correct surface distribution and density at the axon is crucial for control of neuronal excitability. However, the molecular mechanisms responsible for regulating enrichment of KCNQ channels at the neuronal axon remain elusive. Here, we show that enrichment of KCNQ channels at the axonal surface of dissociated rat hippocampal cultured neurons is regulated by ubiquitous calcium sensor calmodulin. Using immunocytochemistry and the cluster of differentiation 4 (CD4 membrane protein as a trafficking reporter, we demonstrate that fusion of KCNQ2 carboxy-terminal tail is sufficient to target CD4 protein to the axonal surface whereas inhibition of calmodulin binding to KCNQ2 abolishes axonal surface expression of CD4 fusion proteins by retaining them in the endoplasmic reticulum. Disruption of calmodulin binding to KCNQ2 also impairs enrichment of heteromeric KCNQ2/KCNQ3 channels at the axonal surface by blocking their trafficking from the endoplasmic reticulum to the axon. Consistently, hippocampal neuronal excitability is dampened by transient expression of wild-type KCNQ2 but not mutant KCNQ2 deficient in calmodulin binding. Furthermore, coexpression of mutant calmodulin, which can interact with KCNQ2/KCNQ3 channels but not calcium, reduces but does not abolish their enrichment at the axonal surface, suggesting that apo calmodulin but not calcium-bound calmodulin is necessary for their preferential targeting to the axonal

  9. 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

    Directory of Open Access Journals (Sweden)

    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

  10. Inducción de la enzima triptófano 2,3 dioxigenasa por glucocorticoides y su papel en la tolerancia materna al feto

    Directory of Open Access Journals (Sweden)

    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.

     

     

  11. Partial Denervation of Subbasal Axons Persists Following Debridement Wounds to the Mouse Cornea

    Science.gov (United States)

    Pajoohesh-Ganji, Ahdeah; Pal-Ghosh, Sonali; Tadvalkar, Gauri; Kyne, Briana M.; Saban, Daniel R.; Stepp, Mary Ann

    2015-01-01

    Although sensory reinnervation occurs after injury in the PNS, poor reinnervation in the elderly and those with diabetes often leads to pathology. Here we quantify subbasal axon density in the central and peripheral mouse cornea over time after three different types of injury. The mouse cornea is highly innervated with a dense array of subbasal nerves that form a spiral called the vortex at the corneal center or apex; these nerves are readily detected within flat mounted corneas. After anesthesia, corneal epithelial cells were removed using either a dulled blade or a rotating burr within an area demarcated centrally with a 1.5 mm trephine. A third wound type, superficial trephination, involved demarcating the area with the 1.5 mm trephine but not removing cells. By 7d after superficial trephination, subbasal axon density returns to control levels; by 28d the vortex reforms. Although axon density is similar to control 14d after dulled blade and rotating burr wounding, defects in axon morphology at the corneal apex remain. After 14d, axons retract from the center leaving the subbasal axon density reduced by 37.2% and 36.8% at 28d after dulled blade and rotating burr wounding, respectively, compared to control. Assessment of inflammation using flow cytometry shows that persistent inflammation is not a factor in the incomplete reinnervation. Expression of mRNAs encoding 22 regeneration associated genes (RAGs) involved in axon targeting assessed by QPCR reveals that netrin-1 and ephrin signaling are altered after wounding. Subpopulations of corneal epithelial basal cells at the corneal apex stop expressing ki67 as early as 7d after injury and by 14d and 28d after wounding, many of these basal cells undergo apoptosis and die. While subbasal axons are restored to their normal density and morphology after superficial trephination, subbasal axon recovery is partial after debridement wounds. The increase in corneal epithelial basal cell apoptosis at the apex observed at 14d

  12. Partial denervation of sub-basal axons persists following debridement wounds to the mouse cornea.

    Science.gov (United States)

    Pajoohesh-Ganji, Ahdeah; Pal-Ghosh, Sonali; Tadvalkar, Gauri; Kyne, Briana M; Saban, Daniel R; Stepp, Mary Ann

    2015-11-01

    Although sensory reinnervation occurs after injury in the peripheral nervous system, poor reinnervation in the elderly and those with diabetes often leads to pathology. Here we quantify sub-basal axon density in the central and peripheral mouse cornea over time after three different types of injury. The mouse cornea is highly innervated with a dense array of sub-basal nerves that form a spiral called the vortex at the corneal center or apex; these nerves are readily detected within flat mounted corneas. After anesthesia, corneal epithelial cells were removed using either a dulled blade or a rotating burr within an area demarcated centrally with a 1.5 mm trephine. A third wound type, superficial trephination, involved demarcating the area with the 1.5 mm trephine but not removing cells. By 7 days after superficial trephination, sub-basal axon density returns to control levels; by 28 days the vortex reforms. Although axon density is similar to control 14 days after dulled blade and rotating burr wounding, defects in axon morphology at the corneal apex remain. After 14 days, axons retract from the center leaving the sub-basal axon density reduced by 37.2 and 36.8% at 28 days after dulled blade and rotating burr wounding, respectively, compared with control. Assessment of inflammation using flow cytometry shows that persistent inflammation is not a factor in the incomplete reinnervation. Expression of mRNAs encoding 22 regeneration-associated genes involved in axon targeting assessed by QPCR reveals that netrin-1 and ephrin signaling are altered after wounding. Subpopulations of corneal epithelial basal cells at the corneal apex stop expressing ki67 as early as 7 days after injury and by 14 and 28 days after wounding, many of these basal cells undergo apoptosis and die. Although sub-basal axons are restored to their normal density and morphology after superficial trephination, sub-basal axon recovery is partial after debridement wounds. The increase in corneal

  13. 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

  14. 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

  15. The Pseudopod System for Axon-Glia Interactions: Stimulation and Isolation of Schwann Cell Protrusions that Form in Response to Axonal Membranes.

    Science.gov (United States)

    Poitelon, Yannick; Feltri, M Laura

    2018-01-01

    In the peripheral nervous system, axons dictate the differentiation state of Schwann cells. Most of this axonal influence on Schwann cells is due to juxtacrine interactions between axonal transmembrane molecules (e.g., the neuregulin growth factor) and receptors on the Schwann cell (e.g., the ErbB2/ErbB3 receptor). The fleeting nature of this interaction together with the lack of synchronicity in the development of the Schwann cell population limits our capability to study this phenomenon in vivo. Here we present a simple Boyden Chamber-based method to study this important cell-cell interaction event. We isolate the early protrusions of Schwann cells that are generated in response to juxtacrine stimulation by sensory neuronal membranes. This method is compatible with a large array of current biochemical analyses and provides an effective approach to study biomolecules that are differentially localized in Schwann cell protrusions and cell bodies in response to axonal signals. A similar approach can be extended to different kinds of cell-cell interactions.

  16. Peripheral nerve injury fails to induce growth of lesioned ascending dorsal column axons into spinal cord scar tissue expressing the axon repellent Semaphorin3A

    NARCIS (Netherlands)

    Pasterkamp, R Jeroen; Anderson, Patrick N; Verhaagen, J

    We have investigated the hypothesis that the chemorepellent Semaphorin3A may be involved in the failure of axonal regeneration after injury to the ascending dorsal columns of adult rats. Following transection of the thoracic dorsal columns, fibroblasts in the dorsolateral parts of the lesion site

  17. beta(2)-ADRENERGIC RECEPTORS PROTECT AXONS DURING ENERGETIC STRESS BUT DO NOT INFLUENCE BASAL GLIO-AXONAL LACTATE SHUTTLING IN MOUSE WHITE MATTER

    NARCIS (Netherlands)

    Laureys, G.; Valentino, M.; Demol, F.; Zammit, C.; Muscat, R.; Cambron, M.; Kooijman, R.; De Keyser, J.

    2014-01-01

    In vitro studies have demonstrated that beta 2-adrenergic receptor activation stimulates glycogen degradation in astrocytes, generating lactate as a potential energy source for neurons. Using in vivo microdialysis in mouse cerebellar white matter we demonstrate continuous axonal lactate uptake and

  18. Channelrhodopsin-2 localised to the axon initial segment.

    Directory of Open Access Journals (Sweden)

    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.

  19. Apendicitis por Paracoccidioides brasiliensis

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    Ana Beatriz MUÑOZ URRIBARRI

    2006-01-01

    Full Text Available La paracoccidioidomicosis es la micosis más prevalente en Sudamérica. La forma aguda afecta el sistema fagocítico mononuclear de niños y personas inmunocomprometidas. El compromiso gastrointestinal es frecuente y su patogenia implica diseminación hematógena y linfática. La linfadenomegalia abdominal causa obstrucción intestinal y abdomen agudo. En este artículo damos a conocer el caso de un niño con compromiso gastrointestinal por apendicitis. Este es el primer caso reportado de apendicitis por esta patología. (Rev Med Hered 2006;17:58-60.

  20. Reprogramación del polen a embriogénesis inducida por estrés: identidad celular, muerte celular programada y papel de la metilación de DNA

    OpenAIRE

    Solís, María Teresa

    2012-01-01

    El desarrollo del grano de polen es un proceso estrictamente regulado a nivel génico que conduce a la formación de un organismo haploide, el gametofito masculino o grano de polen, cuyas células poseen una alta especialización, necesaria para su importante función en la germinación del tubo polínico y doble fecundación de las plantas con flores. Mediante la aplicación de un tratamiento de estrés in vitro en la etapa adecuada del desarrollo, concretamente en la fase de microspora...

  1. Interval for the expression of the adaptive response induced by gamma radiation in leucocytes of mouse In vivo; Intervalo para la expresion de la respuesta adaptativa inducida por radiacion gamma en leucocitos de raton In vivo

    Energy Technology Data Exchange (ETDEWEB)

    Mendiola C, M T; Morales R, P [Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    2002-07-01

    The interval between the adaptive gamma radiation dose (0.01 Gy) and challenge (1.0 Gy) capable to induce the maximum expression of the adaptive response in lymphocytes of mouse In vivo. The animals were exposed to the mentioned doses with different intervals among both (1, 1.5, 5 or 18 hr). By means of the unicellular electrophoresis in gel technique, four damage parameters were analysed. The results showed that from the 1 hr interval an adaptive response was produced since in the pretreated organisms with 0.01 Gy the cells present lesser damage than in those not adapted. The maximum response was induced with the intervals between 2.5 and 5 hr and even though it persisted until 18 hr, the effect was reducing. (Author)

  2. Validation of the technique of kinetic fosforimetria induced by laser for the determination of the concentration of uranium in urine; Validacion de la tecnica de fosforimetria cinetica inducida por laser para la determinacion de la concentracion de uranio en orina

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, C.; Sierra, I.; Benito, P.; Lopez, C.

    2013-07-01

    This paper describes the methodology used to conduct the validation of the method of determination of uranium using the technique of Kinetic Phosphorescence Analyser (KPA) The technical requirements of the standard 17025 stresses the need for validation samples KPA urine of workers exposed to risk of internal contamination. (Author)

  3. Efectos de un preparado probiótico en un modelo de colitis experimental crónica en ratones, inducida por la ingesta de dextrano sulfato sódico (DSS

    Directory of Open Access Journals (Sweden)

    S Bolívar González

    2015-01-01

    Conclusión: La administración del preparado probiótico, previene o retrasa los signos externos de la colitis, así como los niveles proteicos y génicos de marcadores inflamatorios asociados a ella.

  4. Eosinophilic pneumonitis induced by aerosol-administered diesel oil and pyrethrum to mice Neumonía eosinofílica inducida por aerosol de aceite diésel y piretroide en ratones

    Directory of Open Access Journals (Sweden)

    Maria Lúcia B. Garcia

    2009-06-01

    Full Text Available OBJECTIVE: To confirm the episode of eosinophilic pneumonitis that occurred in March 2001 in Manaus, Amazon, northern Brazil, as secondary to home aerosolization with 2% cypermethrin diluted in diesel compared with the more conventional 1% cypermethrin and soybean solution used in prophylaxis of dengue. METHODS: Four groups of Swiss mice were kept in polycarbonate cages aerosolized with one of the following solutions: diesel, diesel and cypermethrin, soy oil and cypermethrin, and saline. Three and 6 days after exposure, resistance and compliance of the respiratory system and white cell kinetics in peripheral blood and lung tissue were analyzed. RESULTS: The group exposed to diesel and cypermethrin showed higher respiratory system resistance (p OBJETIVO: Confirmar el episodio de neumonía eosinofílica ocurrido en marzo de 2001 en Manaus, Amazonas, en el norte de Brasil, secundario al uso de aerosol de cipermetrina diluida al 2% en aceite diésel en las viviendas en comparación con la profilaxis más convencional contra el dengue, basada en cipermetrina al 1% con aceite de soya. MÉTODOS: Se mantuvieron cuatro grupos de ratones suizos en jaulas de policarbonato y se aplicó aerosol con una de las siguientes soluciones: aceite diésel, aceite diésel y cipermetrina, aceite de soya y cipermetrina, y solución salina. Se analizaron la resistencia y el funcionamiento del sistema respiratorio y la cinética de leucocitos en sangre periférica y tejido pulmonar a los tres y seis días después de la exposición. RESULTADOS: El grupo expuesto a aceite diésel y cipermetrina mostró mayor resistencia del sistema respiratorio (P < 0,001, peor funcionamiento (P = 0,03 y más eosinófilos en sangre (P = 0,03 y tejido pulmonar (P = 0,005 que los otros grupos. Se observó un aumento de neutrófilos en sangre en todos los grupos experimentales al tercer día después de la exposición (P < 0,001. CONCLUSIONES: El aceite diésel con cipermetrina indujo una hiperrespuesta pulmonar en este modelo experimental y se asoció con un aumento en las células polimorfonucleares (eosinófilos y neutrófilos en sangre y tejido pulmonar. Este efecto es mayor al tercer día después de la exposición. Estos efectos son similares a los observados en el episodio ocurrido en Manaus en 2001 e indican que se debe reevaluar el uso de aerosol de aceite diésel con cipermetrina para la profilaxis de arbovirus en las viviendas.

  5. Setting-up of the Laser Induced Fluorescence diagnostic. Measurements of Cr density in a neon glow discharge; Puesta a punto del diagnstico de fluorescencia inducida por laser. Medidas de densidad de Cr en Glow discharg de Neon

    Energy Technology Data Exchange (ETDEWEB)

    Tafalla, D.; Cal, E. de la; Tabares, F. L.

    1994-07-01

    A plasma diagnostic based on the Laser Induced Fluorescence (LIF) technique has been set up in the Fusion Division at the CIEMAT. In a preliminary experiment, the density of sputtered chromium atoms produced in a neon glow discharge was measured. Firstly, the laser beam was characterized by calibration of its wavelength, bandwidth and energy profile and Rayleigh scattering in N2 was used for the optical system calibration. An absolute density of Cr atoms of n {approx} 5x10 cm was obtained in discharges at 100 mA and pressure of 15 mTorr and a linear dependence of the LIF signal us. current was found. These values are in agreement with those expected from the tabulated sputtering yields and the thermalization and diffusion of the sputtered atoms into the Ne plasma. (Author) 19 refs.

  6. A review of case histories of induced seismicity caused by hydrocarbon production and storage; Revisión de la casuística sobre sismicidad inducida por producción y almacenamiento de hidrocarburos

    Energy Technology Data Exchange (ETDEWEB)

    Vadillo Fernández, L.; Fernández Naranjo, F.J.; Rodríguez Gómez, V.; López Gutiérrez, J.

    2017-09-01

    In this article we review the stress-strain relationships that take place in the crust during some of the main hydrocarbon production and storage processes: gas extraction; water injection in wells to stimulate the extraction of oil (EOR); unconventional hydrocarbon production by hydraulic fracturing (fracking); disposal of wastewater (saline water) from the extraction of conventional and unconventional hydrocarbons such as saline water return (flowback) of hydraulic fracturing, both with TDS higher than 40000 mg/L. In addition, the type of faults that are more likely to slip and the induced seismicity related to the production and extraction of hydrocarbons are analysed. [Spanish] En este artículo se revisan los procesos de tensión que se producen en la corteza durante: la extracción de gas; en el almacenamiento de gas; en la inyección de fluidos (agua, CO2) para estimular la extracción de hidrocarburos convencionales (EOR); en la extracción de hidrocarburos no convencionales con inyección de agua a presión y fracturación hidráulica (fracking); y en la eliminación, mediante inyección, del agua salina (produced water) procedente de la extracción de hidrocarburos convencionales, así como del agua salina de retorno (flowback) de la fracturación hidráulica de la explotación de hidrocarburos no convencionales, ambas con más de 40000 mg/L de Sólidos Totales Disueltos (TDS). Asimismo se revisa la tipología de fallas más propensas a sufrir deslizamientos y la sismicidad relacionada con cada uno de los casos anteriormente descritos consecuencia del aumento de la presión de poro durante la inyección y la disminución de la presión de poro durante al extracción.

  7. Evaluation of the recombination in somatic cells induced by radiation in different stages of Drosophila larval development; Evaluacion de la recombinacion en celulas somaticas inducida por radiacion en diferentes etapas del desarrollo larvario de Drosophila

    Energy Technology Data Exchange (ETDEWEB)

    Cruces, M P; Morales R, P [Instituto nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    1997-07-01

    The mitotic recombination can happen spontaneously and its frequency is very low, however the recombination rate of a cell can be increased by the exposure to agents which cause damage to DNA. This type of agents are knew commonly as recombinogens. The ionizing radiation and a numerous chemical agents can be mentioned (Vogel, 1992). The objective of this work is to determine if the mutation/recombination rate induced by gamma rays varies with the development stage. In order to realize this investigation it was used the mutation and somatic recombination test of Drosophila wing (Graf and col. 1984). The mwh/ mwh and flr{sup 3}/TM3, Ser stocks were used. (Author)

  8. First Patagonian Course on 'Diagnosis and Therapy of Injuries Induced by Ionizing Radiation'; Primer curso patagonico 'Diagnostico y Tratamiento de Lesiones Inducidas por Radiaciones Ionizantes'

    Energy Technology Data Exchange (ETDEWEB)

    Bellotti, Mariela I., E-mail: bellotti@cab.cnea.gov.ar [Comision Nacional de Energia Atomica (CAB/CNEA), San Carlos de Bariloche (Argentina). Centro Atomico Bariloche. Lab. de Cavitacion y Biotecnologia; Andres, Pablo A., E-mail: andresp@cab.cnea.gov.ar [Comision Nacional de Energia Atomica (CAB/CNEA), San Carlos de Bariloche (Argentina). Centro Atomico Bariloche. Division Proteccion Radiologica; Cascón, Adriana S., E-mail: adrianacascon@yahoo.com [Instituto de Medicina, Radiomedicina y Seguridad (IMERASE SA), Buenos Aires, (Argentina)

    2013-07-01

    In Patagonia there are academic centers, health and industrial facilities that use ionizing radiations in its usual practices. However, they do not have protocols that respond to local needs. For this reason was held from October 5 to November 10, 2012 in Bariloche Atomic Center, a training course for health personnel. The range of topics covered ranged from the definition of dosimetry quantities, types of radiation and biological dosimetry, biological effects, radiation acute syndrome, radiation-induced cutaneous syndrome, internal contamination, screening in radiological emergencies, etc.The course provided a theoretical and practical guide about how to recognize and treat people exposed to radiations, guidelines for acting in radiological emergencies and a perception of the psychosocial impact of the radiation accidents.The result was a pocket book for health personnel that will be used in case of having a patient with radiation induced injury.

  9. Influence of temperature in TL signal induced by gamma radiation in zircon prepared by sol gel via; Influencia de la temperatura en la senal TL inducida por la radiacion gamma en zirconia preparada via solgel

    Energy Technology Data Exchange (ETDEWEB)

    Salas, P.; Castano, V.M. [Instituto de Fisica, UNAM, Laboratorio Juriquilla, A.P. 1-1010, 76001 Queretaro (Mexico); Mendoza A, D.; Gonzalez M, P.R. [ININ, Mexico, D.F. (Mexico); Rosa C, E. de la [Centro de Investigaciones en Optical, Leon, Gto. (Mexico)

    2000-07-01

    In this work, it was realized a study of the temperature effects in thermoluminescent signal (Tl) induced by gamma radiation in zircon, which was prepared by the sol gel method. According to the obtained results, the zircon thermically treated at 500 C or over is sensitive to radiation. This sensitivity is increased when the temperature in study is augmented, moreover, the Tl spectra form also is modified with the temperature increment. The samples thermically treated at 750 C or over present a linear response in the dose interval 27 to 165 Gy; therefore, such materials result promissories for dosimetric purposes. (Author)

  10. Microstructural characteristics of the hydroxyapatite and its influence in the Tl signal induced by gamma radiation; Caracteristicas microestructurales de la hidroxiapatita y su influencia en la senal Tl inducida por la radiacion gamma

    Energy Technology Data Exchange (ETDEWEB)

    Mendoza A, D.; Gonzalez M, P.R.; Hernandez A, M. [ININ, A.P. 18-1027, 11801 Mexico D.F. (Mexico); Estrada G, R. [Depto. de Fisica y Matematicas, Universidad Iberoamericana, Santa Fe, 01000 Mexico D.F. (Mexico); Rodriguez L, V. [Centro Universitario de Vinculacion, BUAP, Puebla (Mexico)

    2003-07-01

    The analysis carried out on different materials has shown that the quantity and type of dopants play an important role in the behaviour thermoluminescent signal induced by the ionizing radiation. More recent studies have also shown that the grain size influences strongly in the thermoluminescent signal. Plus still, the crystal growth habit and the crystalline degree have an important effect in the type and intensity thermoluminescent signal. In this sense, we present this work on the analysis of the thermoluminescent signal induced by the gamma radiation in the hydroxyapatite ceramic. Depending the growth habit, a variation of the peak temperature location, signal intensity and linearity range was observed; in particular cases a lineal relationship between glow curve and radiation dose was in the range from 2 to 1000 Gray. These results are complemented with a microstructural and crystalline degree analysis through scanning electron microscopy and X-ray Diffraction. The dose-response over the whole irradiation range opening up the possibility of employing this bio material as a dosimeter. (Author)

  11. Estudio del receptor 5HT2A y de la vía Akt/GSK3 como mecanismos moleculares de la psicosis inducida por el consumo crónico de cannabis

    OpenAIRE

    Ibarra Lecue, Inés

    2015-01-01

    La esquizofrenia es una enfermedad mental de carácter crónico que afecta aproximadamente al 1% de la población , principalmente con edades comprendidas entre los 15 y 4 5 años . Se trata de una enfermedad de inicio en la adolescencia o comienzo de la madurez y cuyo potencial discapacitante persiste y se agrava a lo largo de la vida. La etiología de la esquizofrenia es multifactorial con evidencias de factores genéticos y ambientales. El carácter hereditario de la...

  12. Mapping axonal density and average diameter using non-monotonic time-dependent gradient-echo MRI

    DEFF Research Database (Denmark)

    Nunes, Daniel; Cruz, Tomás L; Jespersen, Sune N

    2017-01-01

    available in the clinic, or extremely long acquisition schemes to extract information from parameter-intensive models. In this study, we suggest that simple and time-efficient multi-gradient-echo (MGE) MRI can be used to extract the axon density from susceptibility-driven non-monotonic decay in the time...... the quantitative results are compared against ground-truth histology, they seem to reflect the axonal fraction (though with a bias, as evident from Bland-Altman analysis). As well, the extra-axonal fraction can be estimated. The results suggest that our model is oversimplified, yet at the same time evidencing......-dependent signal. We show, both theoretically and with simulations, that a non-monotonic signal decay will occur for multi-compartmental microstructures – such as axons and extra-axonal spaces, which we here used in a simple model for the microstructure – and that, for axons parallel to the main magnetic field...

  13. 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

  14. 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

  15. Phospholipid synthesis in the squid giant axon: incorporation of lipid precursors

    Energy Technology Data Exchange (ETDEWEB)

    Gould, R.M.; Pant, H.; Gainer, H.; Tytell, M.

    1983-05-01

    The squid giant axon and extruded axoplasm from the giant axon were used to study the capacity of axoplasm for phospholipid synthesis. Extruded axoplasm, suspended in chemically defined media, catalyzed the synthesis of phospholipids from all of the precursors tested. /sup 32/P-Labeled inorganic phosphate and gamma-labeled ATP were actively incorporated into phosphatidylinositol phosphate, while (2-/sup 3/H)myo-inositol and L-(/sup 3/H(G))serine were actively incorporated into phosphatidylinositol and phosphatidylserine, respectively. Though less well utilized. (2-/sup 3/H)glycerol was incorporated into phosphatidic acid, phosphatidylinositol, and triglyceride, and methyl-3H)choline and (1-/sup 3/H)ethanolamine were incorporated into phosphatidylcholine and phosphatidylethanolamine, respectively. Isolated squid giant axons were incubated in artificial seawater containing the above precursors. The axoplasm was extruded following the incubations. Although most of the product lipids were recovered in the sheath (composed of cortical axoplasm, axolemma, and surrounding satellite cells), significant amounts (4-20%) were present in the extruded axoplasm. With tritiated choline and myo-inositol, the major labeled phospholipids found in both the extruded axoplasm and the sheath were phosphatidylcholine and phosphatidylinositol, respectively. With both glycerol and phosphate, phosphatidylethanolamine was a major labeled lipid in both axoplasm and sheath. These findings demonstrate that all classes of phospholipids are formed by endogenous synthetic enzymes in axoplasm. In addition, we feel that the different patterns of incorporation by intact axons and extruded axoplasm indicate that surrounding sheath cells contribute lipids to axoplasm. A comprehensive picture of axonal lipid metabolism should include axoplasmic synthesis and glial-axon transfer as pathways complementing the axonal transport of perikaryally formed lipids.

  16. EVOLUCIÓN DEL COMPORTAMIENTO VISCOELÁSTICO DEL ASFALTO INDUCIDA BAJO TERMO-OXIDACIÓN IN SITU EN UN REO-REACTOR

    Directory of Open Access Journals (Sweden)

    XIOMARA VARGAS

    2008-01-01

    Full Text Available En este artículo se presentan los resultados del proceso de termo-oxidación de asfalto realizados por primera vez en un reo-reactor. El comportamiento viscoelástico del asfalto pudo ser representado por una ley de potencia (G'(w - wn, G'' (w - w1. La variación del exponente 'n' reflejó los cambios estructurales del asfalto inducidos por el proceso de termo-oxidación. En el intervalo de frecuencia experimental y a 200 y 250°C, los módulos elástico G' y viscoso G'' mostraron una relación del tipo: G'' (w - wn y G' (w ~ wn, este comportamiento es equivalente a un 'gel-débil' y confirma los cambios estructurales del asfalto inducidos por el envejecimiento termo-oxidativo.

  17. 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...

  18. Axonal transport and incorporation of radioactivity after injection of N-[3H]acetyl-D-mannosamine into rat mesencephalon

    International Nuclear Information System (INIS)

    Loopuijt, L.D.

    1980-01-01

    A study has been performed to demonstrate the possibility of incorporation of sialic acid into nerve endings of the rubrospinal tract after antegrade axonal transport. Young adult rats received injections of N-[ 3 H]acetyl-D-mannosamine into the red nucleus and axonal transport of the tritiated compounds along the axons of afferent and efferent connections of the red nucleus was studied and the transported material was analysed. Light microscopic autoradiography and biochemical methods were used. (Auth./C.F.)

  19. Toxicidad hepática por medicamentos antituberculosos Hepatotoxicity induced by antituberculosis drugs

    Directory of Open Access Journals (Sweden)

    Isabel Eugenia Escobar Toledo

    2008-01-01

    Full Text Available

    El fenómeno de la toxicidad hepática inducida por medicamentos cobró relevancia hace algunos años con el estudio de las reacciones adversas a medicamentos. El daño producido en el hígado por un xenobiótico que altera su función es lo que se conoce como toxicidad hepática. La importancia de reconocer y diagnosticar la toxicidad hepática por medicamentos estriba en su gravedad potencial; no en vano es la causa más frecuente por la que la industria farmacéutica retira medicamentos. La tuberculosis es una pandemia que afecta a gran parte de la población mundial y junto con el VIH es una enfermedad cada vez más frecuente en Colombia. Esta enfermedad se puede considerar como una situación especial porque para su tratamiento es preciso suministrar, por largos períodos, medicamentos con potencial tóxico para el hígado.

     

    El objetivo de este artículo es revisar algunos aspectos relacionados con la toxicidad hepática secundaria a medicamentos antituberculosos, tales como: epidemiología, factores de riesgo, mecanismos de toxicidad, manifestaciones clínicas, diagnóstico, tratamiento y seguimiento.

    Hepatotoxicity is the alteration of liver structure and function induced by either drugs or other substances. The importance of its proper diagnosis rests on its potential severity. It is the most frequent reason by which the pharmaceutical industry withdraws its products. Tuberculosis is a pandemic infection affecting a large proportion of the world population. Together with HIV infection it is becoming ever more frequent in Colombia. Tuberculosis poses

  20. Bergmann glia and the recognition molecule CHL1 organize GABAergic axons and direct innervation of Purkinje cell dendrites.

    Directory of Open Access Journals (Sweden)

    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.

  1. 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

  2. Co-immobilization of semaphorin3A and nerve growth factor to guide and pattern axons.

    Science.gov (United States)

    McCormick, Aleesha M; Jarmusik, Natalie A; Leipzig, Nic D

    2015-12-01

    Immobilization of axon guidance cues offers a powerful tissue regenerative strategy to control the presentation and spatial location of these biomolecules. We use our previously developed immobilization strategy to specifically tether recombinant biotinylated nerve growth factor (bNGF) and biotinylated semaphorin3A (bSema3A) to chitosan films as an outgrowth and guidance platform. DRG neurite length and number for a range of single cues of immobilized bNGF or bSema3A were examined to determine a concentration response. Next single and dual cues of bNGF and bSema3A were immobilized and DRG guidance was assessed in response to a step concentration change from zero. Overall, immobilized groups caused axon extension, retraction and turning depending on the ratio of bNGF and bSema3A immobilized in the encountered region. This response indicated the exquisite sensitivity of DRG axons to both attractive and repulsive tethered cues. bSema3A concentrations of 0.10 and 0.49 ng/mm(2), when co-immobilized with bNGF (at 0.86 and 0.43 ng/mm(2) respectively), caused axons to turn away from the co-immobilized region. Immunocytochemical analysis showed that at these bSema3A concentrations, axons inside the co-immobilized region display microtubule degradation and breakdown of actin filaments. At the lowest bSema3A concentration (0.01 ng/mm(2)) co-immobilized with a higher bNGF concentration (2.16 ng/mm(2)), neurite lengths are shorter in the immobilized area, but bNGF dominates the guidance mechanism as neurites are directed toward the immobilized region. Future applications can pattern these cues in various geometries and gradients in order to better modulate axon guidance in terms of polarity, extension and branching. Nervous system formation and regeneration requires key molecules for guiding the growth cone and nervous system patterning. In vivo these molecules work in conjunction with one another to modulate axon guidance, and often they are tethered to limit spatial

  3. Slow Muscle Precursors Lay Down a Collagen XV Matrix Fingerprint to Guide Motor Axon Navigation.

    Science.gov (United States)

    Guillon, Emilie; Bretaud, Sandrine; Ruggiero, Florence

    2016-03-02

    The extracellular matrix (ECM) provides local positional information to guide motoneuron axons toward their muscle target. Collagen XV is a basement membrane component mainly expressed in skeletal muscle. We have identified two zebrafish paralogs of the human COL15A1 gene, col15a1a and col15a1b, which display distinct expression patterns. Here we show that col15a1b is expressed and deposited in the motor path ECM by slow muscle precursors also called adaxial cells. We further demonstrate that collagen XV-B deposition is both temporally and spatially regulated before motor axon extension from the spinal cord in such a way that it remains in this region after the adaxial cells have migrated toward the periphery of the myotome. Loss- and gain-of-function experiments in zebrafish embryos demonstrate that col15a1b expression and subsequent collagen XV-B deposition and organization in the motor path ECM depend on a previously undescribed two-step mechanism involving Hedgehog/Gli and unplugged/MuSK signaling pathways. In silico analysis predicts a putative Gli binding site in the col15a1b proximal promoter. Using col15a1b promoter-reporter constructs, we demonstrate that col15a1b participates in the slow muscle genetic program as a direct target of Hedgehog/Gli signaling. Loss and gain of col15a1b function provoke pathfinding errors in primary and secondary motoneuron axons both at and beyond the choice point where axon pathway selection takes place. These defects result in muscle atrophy and compromised swimming behavior, a phenotype partially rescued by injection of a smyhc1:col15a1b construct. These reveal an unexpected and novel role for collagen XV in motor axon pathfinding and neuromuscular development. In addition to the archetypal axon guidance cues, the extracellular matrix provides local information that guides motor axons from the spinal cord to their muscle targets. Many of the proteins involved are unknown. Using the zebrafish model, we identified an

  4. Dendrites of cerebellar granule cells correctly recognize their target axons for synaptogenesis in vitro.

    Science.gov (United States)

    Ito, Shoko; Takeichi, Masatoshi

    2009-08-04

    Neural circuits are generated by precisely ordered synaptic connections among neurons, and this process is thought to rely on the ability of neurons to recognize specific partners. However, it is also known that neurons promiscuously form synapses with nonspecific partners, in particular when cultured in vitro, causing controversies about neural recognition mechanisms. Here we reexamined whether neurons can or cannot select particular partners in vitro. In the cerebellum, granule cell (GC) dendrites form synaptic connections specifically with mossy fibers, but not with climbing fibers. We cocultured GC neurons with pontine or inferior olivary axons, the major sources for mossy and climbing fibers, respectively, as well as with hippocampal axons as a control. The GC neurons formed synapses with pontine axons predominantly at the distal ends of their dendrites, reproducing the characteristic morphology of their synapses observed in vivo, whereas they failed to do so when combined with other axons. In the latter case, synaptic proteins could accumulate between axons and dendrites, but these synapses were randomly distributed throughout the contact sites, and also their synaptic vesicle recycling was anomalous. These observations suggest that GC dendrites can select their authentic partners for synaptogenesis even in vitro, forming the synapses with a GC-specific nature only with them.

  5. Immunohistochemical and transcriptome analyses indicate complex breakdown of axonal transport mechanisms in canine distemper leukoencephalitis.

    Science.gov (United States)

    Spitzbarth, Ingo; Lempp, Charlotte; Kegler, Kristel; Ulrich, Reiner; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang; Seehusen, Frauke

    2016-07-01

    CDV-DL (Canine distemper virus-induced demyelinating leukoencephalitis) represents a spontaneously occurring animal model for demyelinating disorders. Axonopathy represents a key pathomechanism in this disease; however, its underlying pathogenesis has not been addressed in detail so far. This study aimed at the characterization of axonal cytoskeletal, transport, and potential regenerative changes with a parallel focus upon Schwann cell remyelination. Immunohistochemistry of canine cerebellar tissue as well as a comparative analysis of genes from an independent microarray study were performed. Increased axonal immunoreactivity for nonphosphorylated neurofilament was followed by loss of cytoskeletal and motor proteins. Interestingly, a subset of genes encoding for neurofilament subunits and motor proteins was up-regulated in the chronic stage compared to dogs with subacute CDV-DL. However, immunohistochemically, hints for axonal regeneration were restricted to up-regulated axonal positivity of hypoxia-inducible factor 1 alpha, while growth-associated protein 43, erythropoietin and its receptor were not or even down-regulated. Periaxin-positive structures, indicative of Schwann cell remyelination, were only detected within few advanced lesions. The present findings demonstrate a complex sequence of axonal cytoskeletal breakdown mechanisms. Moreover, though sparse, this is the first report of Schwann cell remyelination in CDV-DL. Facilitation of these very limited endogenous regenerative responses represents an important topic for future research.

  6. The transmembrane collagen COL-99 guides longitudinally extending axons in C. elegans.

    Science.gov (United States)

    Taylor, Jesse; Unsoeld, Thomas; Hutter, Harald

    2018-06-01

    We have identified the transmembrane collagen, COL-99, in a genetic screen for novel genes involved in axon guidance in the nematode C. elegans. COL-99 is similar to transmembrane collagens type XIII, XXIII and XXV in vertebrates. col-99 mutants exhibit guidance defects in axons extending along the major longitudinal axon tracts, most prominently the left ventral nerve cord (VNC). COL-99 is expressed in the hypodermis during the time of axon outgrowth. We provide evidence that a furin cleavage site in COL-99 is essential for function, suggesting that COL-99 is released from the cells producing it. Vertebrate homologs of COL-99 have been shown to be expressed in mammalian nervous systems and linked to various neurological disease but have not been associated with guidance of extending neurons. col-99 acts genetically with the discoidin domain receptors ddr-1 and ddr-2, which are expressed by neurons affected in col-99 mutants. Discoidin domain receptors are activated by collagens in vertebrates. DDR-1 and DDR-2 may function as receptors for COL-99. Our results establish a novel role for a transmembrane collagen in axonal guidance and asymmetry establishment of the VNC. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Spinal muscular atrophy pathogenic mutations impair the axonogenic properties of axonal-survival of motor neuron.

    Science.gov (United States)

    Locatelli, Denise; d'Errico, Paolo; Capra, Silvia; Finardi, Adele; Colciaghi, Francesca; Setola, Veronica; Terao, Mineko; Garattini, Enrico; Battaglia, Giorgio

    2012-05-01

    The axonal survival of motor neuron (a-SMN) protein is a truncated isoform of SMN1, the spinal muscular atrophy (SMA) disease gene. a-SMN is selectively localized in axons and endowed with remarkable axonogenic properties. At present, the role of a-SMN in SMA is unknown. As a first step to verify a link between a-SMN and SMA, we investigated by means of over-expression experiments in neuroblastoma-spinal cord hybrid cell line (NSC34) whether SMA pathogenic mutations located in the N-terminal part of the protein affected a-SMN function. We demonstrated here that either SMN1 missense mutations or small intragenic re-arrangements located in the Tudor domain consistently altered the a-SMN capability of inducing axonal elongation in vitro. Mutated human a-SMN proteins determined in almost all NSC34 motor neurons the growth of short axons with prominent morphologic abnormalities. Our data indicate that the Tudor domain is critical in dictating a-SMN function possibly because it is an association domain for proteins involved in axon growth. They also indicate that Tudor domain mutations are functionally relevant not only for FL-SMN but also for a-SMN, raising the possibility that also a-SMN loss of function may contribute to the pathogenic steps leading to SMA. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

  8. Assessing the direct effects of deep brain stimulation using embedded axon models

    Science.gov (United States)

    Sotiropoulos, Stamatios N.; Steinmetz, Peter N.

    2007-06-01

    To better understand the spatial extent of the direct effects of deep brain stimulation (DBS) on neurons, we implemented a geometrically realistic finite element electrical model incorporating anisotropic and inhomogenous conductivities. The model included the subthalamic nucleus (STN), substantia nigra (SN), zona incerta (ZI), fields of Forel H2 (FF), internal capsule (IC) and Medtronic 3387/3389 electrode. To quantify the effects of stimulation, we extended previous studies by using multi-compartment axon models with geometry and orientation consistent with anatomical features of the brain regions of interest. Simulation of axonal firing produced a map of relative changes in axonal activation. Voltage-controlled stimulation, with clinically typical parameters at the dorso-lateral STN, caused axon activation up to 4 mm from the target. This activation occurred within the FF, IC, SN and ZI with current intensities close to the average injected during DBS (3 mA). A sensitivity analysis of model parameters (fiber size, fiber orientation, degree of inhomogeneity, degree of anisotropy, electrode configuration) revealed that the FF and IC were consistently activated. Direct activation of axons outside the STN suggests that other brain regions may be involved in the beneficial effects of DBS when treating Parkinsonian symptoms.

  9. Sodium channels in axons and glial cells of the optic nerve of Necturus maculosa.

    Science.gov (United States)

    Tang, C M; Strichartz, G R; Orkand, R K

    1979-11-01

    Experiments investigating both the binding of radioactively labelled saxitoxin (STX) and the electrophysiological response to drugs that increase the sodium permeability of excitable membranes were conducted in an effort to detect sodium channels in glial cells of the optic nerve of Necturus maculosa, the mudpuppy. Glial cells in nerves from chronically enucleated animals, which lack optic nerve axons, show no saturable uptake of STX whereas a saturable uptake is clearly present in normal optic nerves. The normal nerve is depolarized by aconitine, batrachotoxin, and veratridine (10(-6)-10(-5) M), whereas the all-glial preparation is only depolarized by veratridine and at concentrations greater than 10(-3) M. Unlike the depolarization caused by veratridine in normal nerves, the response in the all-glial tissue is not blocked by tetrodotoxin nor enhanced by scorpion venom (Leiurus quinquestriatus). In glial cells of the normal nerve, where axons are also present, the addition of 10(-5) M veratridine does lead to a transient depolarization; however, it is much briefer than the axonal response to veratridine in this same tissue. This glial response to veratridine could be caused by the efflux of K+ from the drug-depolarized axons, and is similar to the glial response to extracellular K+ accumulation resulting from action potentials in the axon.

  10. Formation of compact myelin is required for maturation of the axonal cytoskeleton

    Science.gov (United States)

    Brady, S. T.; Witt, A. S.; Kirkpatrick, L. L.; de Waegh, S. M.; Readhead, C.; Tu, P. H.; Lee, V. M.

    1999-01-01

    Although traditional roles ascribed to myelinating glial cells are structural and supportive, the importance of compact myelin for proper functioning of the nervous system can be inferred from mutations in myelin proteins and neuropathologies associated with loss of myelin. Myelinating Schwann cells are known to affect local properties of peripheral axons (de Waegh et al., 1992), but little is known about effects of oligodendrocytes on CNS axons. The shiverer mutant mouse has a deletion in the myelin basic protein gene that eliminates compact myelin in the CNS. In shiverer mice, both local axonal features like phosphorylation of cytoskeletal proteins and neuronal perikaryon functions like cytoskeletal gene expression are altered. This leads to changes in the organization and composition of the axonal cytoskeleton in shiverer unmyelinated axons relative to age-matched wild-type myelinated fibers, although connectivity and patterns of neuronal activity are comparable. Remarkably, transgenic shiverer mice with thin myelin sheaths display an intermediate phenotype indicating that CNS neurons are sensitive to myelin sheath thickness. These results indicate that formation of a normal compact myelin sheath is required for normal maturation of the neuronal cytoskeleton in large CNS neurons.

  11. Apendicitis por Paracoccidioides brasiliensis.

    OpenAIRE

    MUÑOZ URRIBARRI, Ana Beatriz; CHAPARRO DAMMERT, Eduardo; FERRUFINO LLACH, Juan Carlos; VASQUEZ FLORES, Luciola

    2012-01-01

    La paracoccidioidomicosis es la micosis más prevalente en Sudamérica. La forma aguda afecta el sistema fagocítico mononuclear de niños y personas inmunocomprometidas. El compromiso gastrointestinal es frecuente y su patogenia implica diseminación hematógena y linfática. La linfadenomegalia abdominal causa obstrucción intestinal y abdomen agudo. En este artículo damos a conocer el caso de un niño con compromiso gastrointestinal por apendicitis. Este es el primer caso reportado de apendicitis p...

  12. Meningitis por Streptococcus suis

    OpenAIRE

    Geffner Sclarsky, D. E.; Moreno Muñoz, R.; Campillo Alpera, Mª.S.; Pardo Serrano, F.J.; Gómez Gómez, A.; Martínez-Lozano, Mª.D.

    2001-01-01

    La infección humana por Streptococcus suis (S. suis) es una zoonosis, con un riesgo ocupacional conocido y que suele presentarse como meningitis purulenta, que tiene baja mortalidad y frecuentes secuelas de hipoacusia y ataxia. Se han publicado menos de 150 casos humanos desde el informe original de hace 30 años. Hay una reconocida distribución geográfica viviendo la mayoría de los afectados en el norte de Europa y el sudeste Asiático. En España se han comunicado dos pacientes con enfermedad ...

  13. Por mil devaluados pesos

    Directory of Open Access Journals (Sweden)

    Annie Rodríguez Collázos

    2013-03-01

    Full Text Available El estudio de lo popular y lo urbano hasta ahora se ha centrado en el comportamiento y en algunas relaciones de los habitantes con su entorno. “Por mil devaluados pesos. Publicidad popular y urbana”, pretende explorar las formas de publicidad, dispersas en diferentes espacios populares y urbanos en Bogotá, identificando esquemas y formas características de sus propios códigos comunicativos; se centran en un objeto de estudio consistente en las estrategias publicitarias y los códigos comunicativos en los mensajes publicitarios populares en las subculturas de San Victorino, 7 de Agosto y Sanandresito de San José.

  14. Efecto hipotensor del extracto de ajo (Allium sativum macerado por 18 semanas en un modelo experimental in vivo

    Directory of Open Access Journals (Sweden)

    David Chaupis-Meza

    Full Text Available Objetivos. Determinar si el extracto de ajo (Allium sativum macerado por 18 semanas tiene igual o mejor efecto hipotensor que el captopril en ratas. Materiales y métodos. Se realizó un estudio experimental in vivo con ratas machos Holtzman, clasificados en cinco grupos: 100, 500 y 1000 mg/kg de extracto de ajo, Captopril de 100 mg/kg y un grupo vehículo. El L-NAME (N- -nitro L-arginina-metil-éster administrado vía intraperitoneal 50 mg/kg desde el inicio del experimento, elevó la presión arterial desde el tercer día. El análisis estadístico consistió en las pruebas T de Student para medias pareadas, ANOVA y comparación múltiple de Scheffe. Resultados. El ajo macerado extraído por un proceso hidroalcohólico durante 18 semanas provocó una disminución de la presión arterial en animales de experimentación. El análisis de los tratamientos sobre la presión arterial media (PAM, obtuvieron diferencias significativas desde el tercer día. La comparación sobre la PAM final versus PAM basal (medias no diferentes y el efecto hipotensor (% fueron: ajo-100 (p=0,008, 59,8%; ajo-500 (p=0,021, 80,6%; ajo-1000 (p=0,034, 88,5%, Captopril (p=0,437, 99,9% y vehículo (p=0,001, 0%. Conclusiones. El ajo macerado a un periodo de 18 semanas resultó eficaz para producir un efecto hipotensor en ratas, inducidas a hipertensión arterial por L-NAME

  15. Oxidative stress and proinflammatory cytokines contribute to demyelination and axonal damage in a cerebellar culture model of neuroinflammation.

    Science.gov (United States)

    di Penta, Alessandra; Moreno, Beatriz; Reix, Stephanie; Fernandez-Diez, Begoña; Villanueva, Maite; Errea, Oihana; Escala, Nagore; Vandenbroeck, Koen; Comella, Joan X; Villoslada, Pablo

    2013-01-01

    Demyelination and axonal damage are critical processes in the pathogenesis of multiple sclerosis (MS). Oxidative stress and pro-inflammatory cytokines elicited by inflammation mediates tissue damage. To monitor the demyelination and axonal injury associated with microglia activation we employed a model using cerebellar organotypic cultures stimulated with lipopolysaccharide (LPS). Microglia activated by LPS released pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), and increased the expression of inducible nitric oxide synthase (iNOS) and production of reactive oxygen species (ROS). This activation was associated with demyelination and axonal damage in cerebellar cultures. Axonal damage, as revealed by the presence of non-phosphorylated neurofilaments, mitochondrial accumulation in axonal spheroids, and axonal transection, was associated with stronger iNOS expression and concomitant increases in ROS. Moreover, we analyzed the contribution of pro-inflammatory cytokines and oxidative stress in demyelination and axonal degeneration using the iNOS inhibitor ethyl pyruvate, a free-scavenger and xanthine oxidase inhibitor allopurinol, as well as via blockage of pro-inflammatory cytokines using a Fc-TNFR1 construct. We found that blocking microglia activation with ethyl pyruvate or allopurinol significantly decreased axonal damage, and to a lesser extent, demyelination. Blocking TNFα significantly decreased demyelination but did not prevented axonal damage. Moreover, the most common therapy for MS, interferon-beta, was used as an example of an immunomodulator compound that can be tested in this model. In vitro, interferon-beta treatment decreased oxidative stress (iNOS and ROS levels) and the release of pro-inflammatory cytokines after LPS stimulation, reducing axonal damage. The model of neuroinflammation using cerebellar culture stimulated with endotoxin mimicked myelin and axonal damage mediated by the combination of oxidative stress and pro-inflammatory cytokines

  16. Oxidative Stress and Proinflammatory Cytokines Contribute to Demyelination and Axonal Damage in a Cerebellar Culture Model of Neuroinflammation

    Science.gov (United States)

    di Penta, Alessandra; Moreno, Beatriz; Reix, Stephanie; Fernandez-Diez, Begoña; Villanueva, Maite; Errea, Oihana; Escala, Nagore; Vandenbroeck, Koen; Comella, Joan X.; Villoslada, Pablo

    2013-01-01

    Background Demyelination and axonal damage are critical processes in the pathogenesis of multiple sclerosis (MS). Oxidative stress and pro-inflammatory cytokines elicited by inflammation mediates tissue damage. Methods/Principal Findings To monitor the demyelination and axonal injury associated with microglia activation we employed a model using cerebellar organotypic cultures stimulated with lipopolysaccharide (LPS). Microglia activated by LPS released pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), and increased the expression of inducible nitric oxide synthase (iNOS) and production of reactive oxygen species (ROS). This activation was associated with demyelination and axonal damage in cerebellar cultures. Axonal damage, as revealed by the presence of non-phosphorylated neurofilaments, mitochondrial accumulation in axonal spheroids, and axonal transection, was associated with stronger iNOS expression and concomitant increases in ROS. Moreover, we analyzed the contribution of pro-inflammatory cytokines and oxidative stress in demyelination and axonal degeneration using the iNOS inhibitor ethyl pyruvate, a free-scavenger and xanthine oxidase inhibitor allopurinol, as well as via blockage of pro-inflammatory cytokines using a Fc-TNFR1 construct. We found that blocking microglia activation with ethyl pyruvate or allopurinol significantly decreased axonal damage, and to a lesser extent, demyelination. Blocking TNFα significantly decreased demyelination but did not prevented axonal damage. Moreover, the most common therapy for MS, interferon-beta, was used as an example of an immunomodulator compound that can be tested in this model. In vitro, interferon-beta treatment decreased oxidative stress (iNOS and ROS levels) and the release of pro-inflammatory cytokines after LPS stimulation, reducing axonal damage. Conclusion The model of neuroinflammation using cerebellar culture stimulated with endotoxin mimicked myelin and axonal damage mediated by the combination of

  17. Neurofilament subunit (NFL) head domain phosphorylation regulates axonal transport of neurofilaments.

    LENUS (Irish Health Repository)

    Yates, Darran M

    2009-04-01

    Neurofilaments are the intermediate filaments of neurons and are synthesised in neuronal cell bodies and then transported through axons. Neurofilament light chain (NFL) is a principal component of neurofilaments, and phosphorylation of NFL head domain is believed to regulate the assembly of neurofilaments. However, the role that NFL phosphorylation has on transport of neurofilaments is poorly understood. To address this issue, we monitored axonal transport of phosphorylation mutants of NFL. We mutated four known phosphorylation sites in NFL head domain to either preclude phosphorylation, or mimic permanent phosphorylation. Mutation to preclude phosphorylation had no effect on transport but mutation of three sites to mimic permanent phosphorylation inhibited transport. Mutation of all four sites together to mimic permanent phosphorylation proved especially potent at inhibiting transport and also disrupted neurofilament assembly. Our results suggest that NFL head domain phosphorylation is a regulator of neurofilament axonal transport.

  18. Myosin-Va-dependent cell-to-cell transfer of RNA from Schwann cells to axons.

    Directory of Open Access Journals (Sweden)

    José R Sotelo

    Full Text Available To better understand the role of protein synthesis in axons, we have identified the source of a portion of axonal RNA. We show that proximal segments of transected sciatic nerves accumulate newly-synthesized RNA in axons. This RNA is synthesized in Schwann cells because the RNA was labeled in the complete absence of neuronal cell bodies both in vitro and in vivo. We also demonstrate that the transfer is prevented by disruption of actin and that it fails to occur in the absence of myosin-Va. Our results demonstrate cell-to-cell transfer of RNA and identify part of the mechanism required for transfer. The induction of cell-to-cell RNA transfer by injury suggests that interventions following injury or degeneration, particularly gene therapy, may be accomplished by applying them to nearby glial cells (or implanted stem cells at the site of injury to promote regeneration.

  19. Myosin-Va-dependent cell-to-cell transfer of RNA from Schwann cells to axons.

    Science.gov (United States)

    Sotelo, José R; Canclini, Lucía; Kun, Alejandra; Sotelo-Silveira, José R; Xu, Lei; Wallrabe, Horst; Calliari, Aldo; Rosso, Gonzalo; Cal, Karina; Mercer, John A

    2013-01-01

    To better understand the role of protein synthesis in axons, we have identified the source of a portion of axonal RNA. We show that proximal segments of transected sciatic nerves accumulate newly-synthesized RNA in axons. This RNA is synthesized in Schwann cells because the RNA was labeled in the complete absence of neuronal cell bodies both in vitro and in vivo. We also demonstrate that the transfer is prevented by disruption of actin and that it fails to occur in the absence of myosin-Va. Our results demonstrate cell-to-cell transfer of RNA and identify part of the mechanism required for transfer. The induction of cell-to-cell RNA transfer by injury suggests that interventions following injury or degeneration, particularly gene therapy, may be accomplished by applying them to nearby glial cells (or implanted stem cells) at the site of injury to promote regeneration.

  20. Genetic dysfunction of MT-ATP6 causes axonal Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Pitceathly, Robert D S

    2012-09-11

    Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, affecting 1 in 2,500 individuals. Mitochondrial DNA (mtDNA) mutations are not generally considered within the differential diagnosis of patients with uncomplicated inherited neuropathy, despite the essential requirement of ATP for axonal function. We identified the mtDNA mutation m.9185T>C in MT-ATP6, encoding the ATP6 subunit of the mitochondrial ATP synthase (OXPHOS complex V), at homoplasmic levels in a family with mitochondrial disease in whom a severe motor axonal neuropathy was a striking feature. This led us to hypothesize that mutations in the 2 mtDNA complex V subunit encoding genes, MT-ATP6 and MT-ATP8, might be an unrecognized cause of isolated axonal CMT and distal hereditary motor neuropathy (dHMN).

  1. Action of a diffusible target-derived chemoattractant on cortical axon branch induction and directed growth.

    Science.gov (United States)

    Sato, M; Lopez-Mascaraque, L; Heffner, C D; O'Leary, D D

    1994-10-01

    Cortical axons innervate their brainstem target, the basilar pons, by the initiation and extension of collateral branches interstitially along their length. To address whether a diffusible pons-derived chemoattractant controls these events, we used cocultures in collagen matrices and time-lapse microscopy. Pontine explants enhanced by 5-fold the de novo initiation of transient branches along cortical axons; most branches were directed toward pons. Of the branches extended toward pons, 2%-3% were stabilized; those extended away were not. Pontine explants also enhanced the stable bifurcation of growth cones and prompted directional changes by growth cone turning and collateral extension. These effects were distance dependent and mimicked by pons-conditioned medium. This evidence indicates that the pons activity promotes branch initiation interstitially along cortical axons, a novel property for a chemoattractant, and provides a directional cue for their growth. These findings suggest that the pons chemoattractant serves as a diffusible target-recognition molecule.

  2. Cross-talk between KLF4 and STAT3 regulates axon regeneration

    Science.gov (United States)

    Qin, Song; Zou, Yuhua; Zhang, Chun-Li

    2013-10-01

    Cytokine-induced activation of signal transducer and activator of transcription 3 (STAT3) promotes the regrowth of damaged axons in the adult central nervous system (CNS). Here we show that KLF4 physically interacts with STAT3 upon cytokine-induced phosphorylation of tyrosine 705 (Y705) on STAT3. This interaction suppresses STAT3-dependent gene expression by blocking its DNA-binding activity. The deletion of KLF4 in vivo induces axon regeneration of adult retinal ganglion cells (RGCs) via Janus kinase (JAK)-STAT3 signalling. This regeneration can be greatly enhanced by exogenous cytokine treatment, or removal of an endogenous JAK-STAT3 pathway inhibitor called suppressor of cytokine signalling 3 (SOCS3). These findings reveal an unexpected cross-talk between KLF4 and activated STAT3 in the regulation of axon regeneration that might have therapeutic implications in promoting repair of injured adult CNS.

  3. Cellular and Axonal Diversity in Molecular Layer Heterotopia of the Rat Cerebellar Vermis

    Directory of Open Access Journals (Sweden)

    Sarah E. Van Dine

    2013-01-01

    Full Text Available Molecular layer heterotopia of the cerebellar primary fissure are a characteristic of many rat strains and are hypothesized to result from defect of granule cells exiting the external granule cell layer during cerebellar development. However, the cellular and axonal constituents of these malformations remain poorly understood. In the present report, we use histochemistry and immunocytochemistry to identify neuronal, glial, and axonal classes in molecular layer heterotopia. In particular, we identify parvalbumin-expressing molecular layer interneurons in heterotopia as well as three glial cell types including Bergmann glia, Olig2-expressing oligodendrocytes, and Iba1-expressing microglia. In addition, we document the presence of myelinated, serotonergic, catecholaminergic, and cholinergic axons in heterotopia indicating possible spinal and brainstem afferent projections to heterotopic cells. These findings are relevant toward understanding the mechanisms of normal and abnormal cerebellar development.

  4. 3Tesla magnetic resonance examination of a patient suffering from diffuse axonal injury

    International Nuclear Information System (INIS)

    Bonchev, S.; Zlatareva, D.; Hadjidekov, V.

    2016-01-01

    Diffuse axonal injury has been observed in traumatic brain injury. Both type of lesions - haemorrhagic and non-haemorrhagic, demonstrate on MRI. We would like to introduce you a 24 year old outpatient man, who was examined in our Department with a past medical history of severe traumatic brain injury, followed by two weeks of coma in Intensive care, discharged from hospital with good outcome. Subsequently cognitive impairments have developed and an episode of tonic-clonic seizure have been undergone by the patient. 3Tesla MRI was performed and lesions typical for diffuse axonal injury were found. MRI is the study of choice for demonstrating the lesions of diffuse axonal injury in the acute and chronic period

  5. Effects of laminin blended with chitosan on axon guidance on patterned substrates

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, N; Guan, Y J; Chen, X B [Division of Biomedical Engineering, University of Saskatchewan, Saskatoon S7N 5A9 (Canada); Li, M G [Department of Mechanical Engineering, University of Saskatchewan, Saskatoon S7N 5A9 (Canada); Schreyer, D J, E-mail: niz504@mail.usask.c [Department of Anatomy and Cell Biology, Cameco MS Neuroscience Research Center, University of Saskatchewan, Saskatoon, S7K 0M7 (Canada)

    2010-12-15

    Axon guidance is a crucial consideration in the design of tissue scaffolds used to promote nerve regeneration. Here we investigate the combined use of laminin (a putative axon adhesion and guidance molecule) and chitosan (a leading candidate base material for the construction of scaffolds) for promoting axon guidance in cultured adult dorsal root ganglion (DRG) neurons. Using a dispensing-based rapid prototyping (DBRP) technique, two-dimensional grid patterns were created by dispensing chitosan or laminin-blended chitosan substrate strands oriented in orthogonal directions. In vitro experiments illustrated DRG neurites on these patterns preferentially grew upon and followed the laminin-blended chitosan pathways. These results suggest that an orientation of neurite growth can be achieved in an artificially patterned substrate by creating selectively biofunctional pathways. The DBRP technique may provide improved strategies for the use of biofunctional pathways in the design of three-dimensional scaffolds for guidance of nerve repair.

  6. Retention of retinal axon collateral is responsible for induced ipsilateral retinotectal projections in adult goldfish.

    Science.gov (United States)

    Sharma, S C; Tsai, C

    1991-01-01

    In normal goldfish, optic axons innervate only the contralateral optic tectum. When one eye was enucleated and the optic nerve of the other eye crushed, the regenerating optic axons innervated both optic tecta. We studied the presence of bilaterally projecting retinal ganglion cells by double retrograde cell labeling methods using Nuclear Yellow and True Blue dyes. About 10% of the retinal ganglion cells were double labeled and these cells were found throughout the retina. In addition, HRP application to the ipsilateral tectum revealed retrogradely-labeled retinal ganglion cells of all morphological types. These results suggest that induced ipsilateral projections are formed by regenerating axon collaterals and that all cell types are involved in the generation of normal mirror image typography.

  7. A novel ALS-associated variant in UBQLN4 regulates motor axon morphogenesis

    Science.gov (United States)

    Edens, Brittany M; Yan, Jianhua; Miller, Nimrod; Deng, Han-Xiang; Siddique, Teepu; Ma, Yongchao C

    2017-01-01

    The etiological underpinnings of amyotrophic lateral sclerosis (ALS) are complex and incompletely understood, although contributions to pathogenesis by regulators of proteolytic pathways have become increasingly apparent. Here, we present a novel variant in UBQLN4 that is associated with ALS and show that its expression compromises motor axon morphogenesis in mouse motor neurons and in zebrafish. We further demonstrate that the ALS-associated UBQLN4 variant impairs proteasomal function, and identify the Wnt signaling pathway effector beta-catenin as a UBQLN4 substrate. Inhibition of beta-catenin function rescues the UBQLN4 variant-induced motor axon phenotypes. These findings provide a strong link between the regulation of axonal morphogenesis and a new ALS-associated gene variant mediated by protein degradation pathways. DOI: http://dx.doi.org/10.7554/eLife.25453.001 PMID:28463112

  8. In vivo phosphorylation of axonal proteins in goldfish optic nerve during regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Larrivee, D.C.; Grafstein, B.

    1987-01-01

    In vivo phosphorylation of axonal proteins was investigated in normal and regenerating optic nerves of goldfish by two-dimensional gel electrophoresis. By 6-24 h after intraocular injection of H/sub 3/(32)PO/sub 4/, approximately 20 optic nerve proteins ranging in size from 19 to 180 kilodaltons and in pI from 4.4 to 6.8 were seen to have incorporated radiolabel. Five of these proteins showed a robust increase in incorporation of phosphate during regeneration. Among the latter was an acidic (pI 4.5) 45-kilodalton protein, which has previously been shown to be conveyed by fast axonal transport and to increase dramatically in its rate of synthesis during regeneration of goldfish optic axons.

  9. Effects of laminin blended with chitosan on axon guidance on patterned substrates

    International Nuclear Information System (INIS)

    Zhu, N; Guan, Y J; Chen, X B; Li, M G; Schreyer, D J

    2010-01-01

    Axon guidance is a crucial consideration in the design of tissue scaffolds used to promote nerve regeneration. Here we investigate the combined use of laminin (a putative axon adhesion and guidance molecule) and chitosan (a leading candidate base material for the construction of scaffolds) for promoting axon guidance in cultured adult dorsal root ganglion (DRG) neurons. Using a dispensing-based rapid prototyping (DBRP) technique, two-dimensional grid patterns were created by dispensing chitosan or laminin-blended chitosan substrate strands oriented in orthogonal directions. In vitro experiments illustrated DRG neurites on these patterns preferentially grew upon and followed the laminin-blended chitosan pathways. These results suggest that an orientation of neurite growth can be achieved in an artificially patterned substrate by creating selectively biofunctional pathways. The DBRP technique may provide improved strategies for the use of biofunctional pathways in the design of three-dimensional scaffolds for guidance of nerve repair.

  10. Effects of p-xylene inhalation on axonal transport in the rat retinal ganglion cells

    Energy Technology Data Exchange (ETDEWEB)

    Padilla, S.S.; Lyerly, D.P. (Environmental Protection Agency, Research Triangle Park, NC (USA))

    1989-12-01

    Although the solvent xylene is suspected of producing nervous system dysfunction in animals and humans, little is known regarding the neurochemical consequences of xylene inhalation. The intent of this study was to determine the effect of intermittent, acute, and subchronic p-xylene exposure on the axonal transport of proteins and glycoproteins within the rat retinofugal tract. A number of different exposure regimens were tested ranging from 50 ppm for a single 6-hr exposure to 1600 ppm 6 hr/day, 5 days/week, for a total of 8 exposure days. Immediately following removal from the inhalation chambers rats were injected intraocularly with (35S)methionine and (3H)fucose (to label retinal proteins and glycoproteins, respectively) and the axonal transport of labeled macromolecules to axons (optic nerve and optic tract) and nerve endings (lateral geniculate body and superior colliculus) was examined 20 hr after precursor injection. Only relatively severe exposure regimens (i.e., 800 or 1600 ppm 6 hr/day, 5 days/week, for 1.5 weeks) produced significant reductions in axonal transport; there was a moderate reduction in the axonal transport of 35S-labeled proteins in the 800-ppm-treated group which was more widespread in the 1600 ppm-treated group. Transport of 3H-labeled glycoproteins was less affected. Assessment of retinal metabolism immediately after isotope injection indicated that the rate of precursor uptake was not reduced in either treatment group. Furthermore, rapid transport was still substantially reduced in animals exposed to 1600 ppm p-xylene and allowed a 13-day withdrawal period. These data indicate that p-xylene inhalation decreases rapid axonal transport supplied to the projections of the rat retinal ganglion cells immediately after cessation of inhalation exposure and that this decreased transport is still apparent 13 days after the last exposure.

  11. Effects of p-xylene inhalation on axonal transport in the rat retinal ganglion cells

    International Nuclear Information System (INIS)

    Padilla, S.S.; Lyerly, D.P.

    1989-01-01

    Although the solvent xylene is suspected of producing nervous system dysfunction in animals and humans, little is known regarding the neurochemical consequences of xylene inhalation. The intent of this study was to determine the effect of intermittent, acute, and subchronic p-xylene exposure on the axonal transport of proteins and glycoproteins within the rat retinofugal tract. A number of different exposure regimens were tested ranging from 50 ppm for a single 6-hr exposure to 1600 ppm 6 hr/day, 5 days/week, for a total of 8 exposure days. Immediately following removal from the inhalation chambers rats were injected intraocularly with [35S]methionine and [3H]fucose (to label retinal proteins and glycoproteins, respectively) and the axonal transport of labeled macromolecules to axons (optic nerve and optic tract) and nerve endings (lateral geniculate body and superior colliculus) was examined 20 hr after precursor injection. Only relatively severe exposure regimens (i.e., 800 or 1600 ppm 6 hr/day, 5 days/week, for 1.5 weeks) produced significant reductions in axonal transport; there was a moderate reduction in the axonal transport of 35S-labeled proteins in the 800-ppm-treated group which was more widespread in the 1600 ppm-treated group. Transport of 3H-labeled glycoproteins was less affected. Assessment of retinal metabolism immediately after isotope injection indicated that the rate of precursor uptake was not reduced in either treatment group. Furthermore, rapid transport was still substantially reduced in animals exposed to 1600 ppm p-xylene and allowed a 13-day withdrawal period. These data indicate that p-xylene inhalation decreases rapid axonal transport supplied to the projections of the rat retinal ganglion cells immediately after cessation of inhalation exposure and that this decreased transport is still apparent 13 days after the last exposure

  12. Detection of axonal synapses in 3D two-photon images.

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    Cher Bass

    Full Text Available Studies of structural plasticity in the brain often require the detection and analysis of axonal synapses (boutons. To date, bouton detection has been largely manual or semi-automated, relying on a step that traces the axons before detection the boutons. If tracing the axon fails, the accuracy of bouton detection is compromised. In this paper, we propose a new algorithm that does not require tracing the axon to detect axonal boutons in 3D two-photon images taken from the mouse cortex. To find the most appropriate techniques for this task, we compared several well-known algorithms for interest point detection and feature descriptor generation. The final algorithm proposed has the following main steps: (1 a Laplacian of Gaussian (LoG based feature enhancement module to accentuate the appearance of boutons; (2 a Speeded Up Robust Features (SURF interest point detector to find candidate locations for feature extraction; (3 non-maximum suppression to eliminate candidates that were detected more than once in the same local region; (4 generation of feature descriptors based on Gabor filters; (5 a Support Vector Machine (SVM classifier, trained on features from labelled data, and was used to distinguish between bouton and non-bouton candidates. We found that our method achieved a Recall of 95%, Precision of 76%, and F1 score of 84% within a new dataset that we make available for accessing bouton detection. On average, Recall and F1 score were significantly better than the current state-of-the-art method, while Precision was not significantly different. In conclusion, in this article we demonstrate that our approach, which is independent of axon tracing, can detect boutons to a high level of accuracy, and improves on the detection performance of existing approaches. The data and code (with an easy to use GUI used in this article are available from open source repositories.

  13. Reduced axonal transport in Parkinson's disease cybrid neurites is restored by light therapy

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    De Taboada Luis

    2009-06-01

    Full Text Available Abstract Background It has been hypothesized that reduced axonal transport contributes to the degeneration of neuronal processes in Parkinson's disease (PD. Mitochondria supply the adenosine triphosphate (ATP needed to support axonal transport and contribute to many other cellular functions essential for the survival of neuronal cells. Furthermore, mitochondria in PD tissues are metabolically and functionally compromised. To address this hypothesis, we measured the velocity of mitochondrial movement in human transmitochondrial cybrid "cytoplasmic hybrid" neuronal cells bearing mitochondrial DNA from patients with sporadic PD and disease-free age-matched volunteer controls (CNT. The absorption of low level, near-infrared laser light by components of the mitochondrial electron transport chain (mtETC enhances mitochondrial metabolism, stimulates oxidative phosphorylation and improves redox capacity. PD and CNT cybrid neuronal cells were exposed to near-infrared laser light to determine if the velocity of mitochondrial movement can be restored by low level light therapy (LLLT. Axonal transport of labeled mitochondria was documented by time lapse microscopy in dopaminergic PD and CNT cybrid neuronal cells before and after illumination with an 810 nm diode laser (50 mW/cm2 for 40 seconds. Oxygen utilization and assembly of mtETC complexes were also determined. Results The velocity of mitochondrial movement in PD cybrid neuronal cells (0.175 +/- 0.005 SEM was significantly reduced (p Conclusion The results from this study support our proposal that axonal transport is reduced in sporadic PD and that a single, brief treatment with near-infrared light can restore axonal transport to control levels. These results are the first demonstration that LLLT can increase axonal transport in model human dopaminergic neuronal cells and they suggest that LLLT could be developed as a novel treatment to improve neuronal function in patients with PD.

  14. Tri-partite complex for axonal transport drug delivery achieves pharmacological effect

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    Frederickson Martyn

    2010-01-01

    Full Text Available Abstract Background Targeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy and limit clinical utility for many classes of pharmaceuticals. Axonal transport from the periphery offers a possible selective route, but there has been little progress towards design of agents that can accomplish targeted delivery via this intraneural route. To achieve this goal, we developed a tripartite molecular construction concept involving an axonal transport facilitator molecule, a polymer linker, and a large number of drug molecules conjugated to the linker, then sought to evaluate its neurobiology and pharmacological behavior. Results We developed chemical synthesis methodologies for assembling these tripartite complexes using a variety of axonal transport facilitators including nerve growth factor, wheat germ agglutinin, and synthetic facilitators derived from phage display work. Loading of up to 100 drug molecules per complex was achieved. Conjugation methods were used that allowed the drugs to be released in active form inside the cell body after transport. Intramuscular and intradermal injection proved effective for introducing pharmacologically effective doses into selected populations of CNS neurons. Pharmacological efficacy with gabapentin in a paw withdrawal latency model revealed a ten fold increase in half life and a 300 fold decrease in necessary dose relative to systemic administration for gabapentin when the drug was delivered by axonal transport using the tripartite vehicle. Conclusion Specific targeting of selected subpopulations of CNS neurons for drug delivery by axonal

  15. Ion channel density regulates switches between regular and fast spiking in soma but not in axons.

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    Hugo Zeberg

    2010-04-01

    Full Text Available The threshold firing frequency of a neuron is a characterizing feature of its dynamical behaviour, in turn determining its role in the oscillatory activity of the brain. Two main types of dynamics have been identified in brain neurons. Type 1 dynamics (regular spiking shows a continuous relationship between frequency and stimulation current (f-I(stim and, thus, an arbitrarily low frequency at threshold current; Type 2 (fast spiking shows a discontinuous f-I(stim relationship and a minimum threshold frequency. In a previous study of a hippocampal neuron model, we demonstrated that its dynamics could be of both Type 1 and Type 2, depending on ion channel density. In the present study we analyse the effect of varying channel density on threshold firing frequency on two well-studied axon membranes, namely the frog myelinated axon and the squid giant axon. Moreover, we analyse the hippocampal neuron model in more detail. The models are all based on voltage-clamp studies, thus comprising experimentally measurable parameters. The choice of analysing effects of channel density modifications is due to their physiological and pharmacological relevance. We show, using bifurcation analysis, that both axon models display exclusively Type 2 dynamics, independently of ion channel density. Nevertheless, both models have a region in the channel-density plane characterized by an N-shaped steady-state current-voltage relationship (a prerequisite for Type 1 dynamics and associated with this type of dynamics in the hippocampal model. In summary, our results suggest that the hippocampal soma and the two axon membranes represent two distinct kinds of membranes; membranes with a channel-density dependent switching between Type 1 and 2 dynamics, and membranes with a channel-density independent dynamics. The difference between the two membrane types suggests functional differences, compatible with a more flexible role of the soma membrane than that of the axon membrane.

  16. Optically-Induced Neuronal Activity Is Sufficient to Promote Functional Motor Axon Regeneration In Vivo.

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    Patricia J Ward

    Full Text Available Peripheral nerve injuries are common, and functional recovery is very poor. Beyond surgical repair of the nerve, there are currently no treatment options for these patients. In experimental models of nerve injury, interventions (such as exercise and electrical stimulation that increase neuronal activity of the injured neurons effectively enhance axon regeneration. Here, we utilized optogenetics to determine whether increased activity alone is sufficient to promote motor axon regeneration. In thy-1-ChR2/YFP transgenic mice in which a subset of motoneurons express the light-sensitive cation channel, channelrhodopsin (ChR2, we activated axons in the sciatic nerve using blue light immediately prior to transection and surgical repair of the sciatic nerve. At four weeks post-injury, direct muscle EMG responses evoked with both optical and electrical stimuli as well as the ratio of these optical/electrical evoked EMG responses were significantly greater in mice that received optical treatment. Thus, significantly more ChR2+ axons successfully re-innervated the gastrocnemius muscle in mice that received optical treatment. Sections of the gastrocnemius muscles were reacted with antibodies to Synaptic Vesicle Protein 2 (SV2 to quantify the number of re-occupied motor endplates. The number of SV2+ endplates was greater in mice that received optical treatment. The number of retrogradely-labeled motoneurons following intramuscular injection of cholera toxin subunit B (conjugated to Alexa Fluor 555 was greater in mice that received optical treatment. Thus, the acute (1 hour, one-time optical treatment resulted in robust, long-lasting effects compared to untreated animals as well as untreated axons (ChR2-. We conclude that neuronal activation is sufficient to promote motor axon regeneration, and this regenerative effect is specific to the activated neurons.

  17. Axons Pull on the Brain, But Tension Does Not Drive Cortical Folding

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    Xu, Gang; Knutsen, Andrew K.; Dikranian, Krikor; Kroenke, Christopher D.; Bayly, Philip V.; Taber, Larry A.

    2011-01-01

    During human brain development, the cerebral cortex undergoes substantial folding, leading to its characteristic highly convoluted form. Folding is necessary to accommodate the expansion of the cerbral cortex; abnormal cortical folding is linked to various neurological disorders, including schizophrenia, epilepsy, autism and mental retardation. Although this process requires mechanical forces, the specific force-generating mechanisms that drive folding remain unclear. The two most widely accepted hypotheses are (1) folding is caused by differential growth of the cortex and (2) folding is caused by mechanical tension generated in axons. Direct evidence supporting either theory, however, is lacking. Here we show that axons are indeed under considerable tension in the developing ferret brain, but the patterns of tissue stress are not consistent with a causal role for axonal tension. In particular, microdissection assays reveal that significant tension exists along axons aligned circumferentially in subcortical white matter tracts, as well as those aligned radially inside developing gyri (outward folds). Contrary to previous speculation, however, axonal tension is not directed across developing gyri, suggesting that axon tension does not drive folding. On the other hand, using computational (finite element) models, we show that differential cortical growth accompanied by remodeling of the subplate leads to outward folds and stress fields that are consistent with our microdissection experiments, supporting a mechanism involving differential growth. Local perturbations, such as temporal differences in the initiation of cortical growth, can ensure consistent folding patterns. This study shows that a combination of experimental and computational mechanics can be used to evaluate competing hypotheses of morphogenesis, and illuminate the biomechanics of cortical folding. PMID:20590291

  18. Mouse Intermittent Hypoxia Mimicking Apnea of Prematurity: Effects on Myelinogenesis and Axonal Maturation

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    CAI, JUN; TUONG, CHI MINH; ZHANG, YIPING; SHIELDS, CHRISTOPHER B.; GUO, GANG; FU, HUI; GOZAL, DAVID

    2014-01-01

    Premature babies are at high risk for both infantile apnea and long-term neurobehavioral deficits. Recent studies suggest that diffuse structural changes in brain white matter are a positive predictor of poor cognitive outcomes. Since oligodendrocyte maturation, myelination, axon development and synapse formation mainly occur in the 3rd trimester of gestation and 1st postnatal year, infantile apnea could lead to and/or exaggerate white matter impairments in preterm neonates. Therefore, we investigated oligodendroglia and axon development in a neonatal mouse model of intermittent hypoxia between postnatal days 2 to 10. During critical phases of central nervous system development, intermittent hypoxia induced hypomyelination in the corpus callosum, striatum, fornix and cerebellum, but not the pons or spinal cord. Intermittent hypoxia-elicited alterations in myelin-forming processes were reflected by decreased expression of myelin proteins, including MBP, PLP, MAG and CNPase, possibly due to arrested maturation of oligodendrocytes. Ultra-structural abnormalities were apparent in the myelin sheath and axon. Immature oligodendrocytes were more vulnerable to neonatal intermittent hypoxia exposures than developing axons, suggesting that hypomyelination may contribute, at least partially, to axonal deficits. Insufficient neurofilament synthesis with anomalous components of neurofilament subunits, β-tubulin and MAP2 isoforms indicated immaturity of axons in intermittent hypoxia-exposed mouse brains. In addition, down-regulation of Synapsin I, Synaptophysin and Gap-43 phosphorylation suggested a potential stunt in axonogenesis and synaptogenesis. The region-selective and complex impairment in brain white matter induced by intermittent hypoxia was further associated with electrophysiological changes that may underlie long-term neurobehavioral sequelae. PMID:21953180

  19. Current contribution of diffusion tensor imaging in the evaluation of diffuse axonal injury

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    Daphine Centola Grassi

    Full Text Available ABSTRACT Traumatic brain injury (TBI is the number one cause of death and morbidity among young adults. Moreover, survivors are frequently left with functional disabilities during the most productive years of their lives. One main aspect of TBI pathology is diffuse axonal injury, which is increasingly recognized due to its presence in 40% to 50% of all cases that require hospital admission. Diffuse axonal injury is defined as widespread axonal damage and is characterized by complete axotomy and secondary reactions due to overall axonopathy. These changes can be seen in neuroimaging studies as hemorrhagic focal areas and diffuse edema. However, the diffuse axonal injury findings are frequently under-recognized in conventional neuroimaging studies. In such scenarios, diffuse tensor imaging (DTI plays an important role because it provides further information on white matter integrity that is not obtained with standard magnetic resonance imaging sequences. Extensive reviews concerning the physics of DTI and its use in the context of TBI patients have been published, but these issues are still hazy for many allied-health professionals. Herein, we aim to review the current contribution of diverse state-of-the-art DTI analytical methods to the understanding of diffuse axonal injury pathophysiology and prognosis, to serve as a quick reference for those interested in planning new studies and who are involved in the care of TBI victims. For this purpose, a comprehensive search in Pubmed was performed using the following keywords: “traumatic brain injury”, “diffuse axonal injury”, and “diffusion tensor imaging”.

  20. Neuron-glia signaling and the protection of axon function by Schwann cells.

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    Quintes, Susanne; Goebbels, Sandra; Saher, Gesine; Schwab, Markus H; Nave, Klaus-Armin

    2010-03-01

    The interaction between neurons and glial cells is a feature of all higher nervous systems. In the vertebrate peripheral nervous system, Schwann cells ensheath and myelinate axons thereby allowing rapid saltatory conduction and ensuring axonal integrity. Recently, some of the key molecules in neuron-Schwann cell signaling have been identified. Neuregulin-1 (NRG1) type III presented on the axonal surface determines the myelination fate of axons and controls myelin sheath thickness. Recent observations suggest that NRG1 regulates myelination via the control of Schwann cell cholesterol biosynthesis. This concept is supported by the finding that high cholesterol levels in Schwann cells are a rate-limiting factor for myelin protein production and transport of the major myelin protein P0 from the endoplasmic reticulum into the growing myelin sheath. NRG1 type III activates ErbB receptors on the Schwann cell, which leads to an increase in intracellular PIP3 levels via the PI3-kinase pathway. Surprisingly, enforced elevation of PIP3 levels by inactivation of the phosphatase PTEN in developing and mature Schwann cells does not entirely mimic NRG1 type III stimulated myelin growth, but predominantly causes focal hypermyelination starting at Schmidt-Lanterman incisures and nodes of Ranvier. This indicates that the glial transduction of pro-myelinating signals has to be under tight and life-long control to preserve integrity of the myelinated axon. Understanding the cross talk between neurons and Schwann cells will help to further define the role of glia in preserving axonal integrity and to develop therapeutic strategies for peripheral neuropathies such as CMT1A.