RESUMO
Traumatic brain injury (TBI) is a leading cause of death and disability and is a risk factor for the later development of neuropsychiatric disorders and neurodegenerative diseases. Many models of TBI have been developed, but their further refinement and a more detailed long-term follow-up is needed. We have used the Thy1-YFP-H transgenic mouse line and the parallel rod floor test to produce an unbiased and robust method for the evaluation of the multiple effects of a validated model of controlled cortical injury. This approach reveals short- and long-term progressive changes, including compromised biphasic motor function up to 85 days post-lesion, which correlates with neuronal atrophy, dendrite and spine loss, and long-term axonal pathology evidenced by axon spheroids and fragmentation. Here we present methods for inducing a controlled cortical injury in the Thy1-YFP-H transgenic mouse line and for evaluating the resulting deficits in the parallel rod floor test. This technique constitutes a new, unbiased, and robust method for the evaluation of motor and behavioral alterations after TBI. © 2018 by John Wiley & Sons, Inc.
Assuntos
Lesões Encefálicas Traumáticas , Modelos Animais de Doenças , Animais , Astrócitos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Comportamento Animal , Encéfalo/metabolismo , Encéfalo/patologia , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/fisiopatologia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Exame Neurológico , Neurônios/metabolismo , Neurônios/patologia , Ratos Sprague-DawleyRESUMO
Introducción: Las enfermedades con obstrucción crónica de la vía aérea, como la enfermedad pulmonar obstructiva crónica, asocian alteraciones funcionales de los músculos respiratorios. Los agonistas adrenérgicos ¦Â2 mejoran la fuerza muscular en condiciones fisiológicas y patológicas. Nuestro objetivo ha sido estudiar los efectos del salbutamol sobre la contractilidad diafragmática en un modelo animal de obstrucción crónica de la vía aérea lograda por obstrucción traqueal (OT) extrínseca. Materiales y métodos: Se aleatorizaron 24 ratas Sprague-Dawley en 4 grupos: a) control; b) OT; c) OT+salbutamol agudo, y d) OT+salbutamol crónico. Se estudiaron los gases sanguíneos, el equilibrio ácido-base y la fuerza diafragmática in vitro, a través de las siguientes medidas: tensión máxima (Tmáx), tiempo de contracción (TC), velocidad de contracción (dT/dtmáx), tiempo de relajación media (TR1/2), velocidad de relajación (−dT/dtmáx) y curvas fuerza-frecuencia. Resultados: Los 3 grupos sometidos a OT presentaron una disminución significativa del pH y un incremento de la presión arterial de anhídrido carbónico y del bicarbonato en sangre arterial (p<0,05). El grupo OT experimentó una disminución significativa de Tmáx, de dT/dtmáx y de la curva fuerza-frecuencia en comparación con los otros grupos (p<0,05). La −dT/dtmáx fue mayor en el grupo OT+salbutamol crónico comparado con el grupo OT (p<0,05). Los valores medios (¡À error estándar) de Tmáx fueron: control, 6,46¡À0,90N/cm2; OT, 3,28¡À0,55N/cm2; OT+salbutamol agudo, 6,18¡À0,71N/cm2; OT+salbutamol crónico, 7,09¡À0,59N/cm2. Conclusiones: La disfunción diafragmática asociada a obstrucción crónica de la vía aérea mejora con salbutamol administrado tanto en forma aguda como crónica. Los mecanismos involucrados en la disfunción muscular deben analizarse más profundamente(AU)
Introduction: Chronic airflow obstruction in conditions such as chronic obstructive pulmonary disease is associated with respiratory muscle dysfunction. Our aim was to study the effects of salbutamol¡ªa ¦Â-adrenergic agonist known to improve muscle strength in physiologic and pathologic conditions¡ªon diaphragm contractility in an animal model of chronic airway obstruction achieved by tracheal banding.Materials and Methods: Twenty-four Sprague-Dawley rats were randomized into a control group and 3 tracheal banding groups, 1 that received acute salbutamol treatment, 1 that received chronic salbutamol treatment, and 1 that received nothing. Arterial blood gases, acid-base balance, and in vitro diaphragmatic contractility were evaluated by measuring peak twitch tension, contraction time, contraction velocity, half-relaxation time, relaxation velocity, and force-frequency curves.Results: The 3 study groups had significantly reduced arterial pH and increased PaCO2 and bicarbonate levels compared to the control group (P<.05). The untreated tracheal banding group had significantly reduced peak twitch tension and contraction velocity, and a significantly lower force-frequency curve in comparison with the other groups (P<.05). The chronic treatment group had a higher relaxation velocity than the untreated study group (P<.05). The mean (SE) peak twitch tension values were 6.46 (0.90)N/cm2 for the control group, 3.28 (0.55)N/cm2 for the untreated tracheal banding group, 6.18 (0.71)N/cm2 for the acute treatment group, and 7.09 (0.59)N/cm2 for the chronic treatment group.Conclusions: Diaphragmatic dysfunction associated with chronic airflow obstruction improves with both the acute and chronic administration of salbutamol. The mechanisms involved in respiratory muscle dysfunction warrant further study(AU)
Assuntos
Animais , Ratos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Albuterol/farmacocinética , Obstrução das Vias Respiratórias/fisiopatologia , Diafragma , Obstrução das Vias Respiratórias/tratamento farmacológico , Ratos Sprague-Dawley , Modelos Animais de DoençasRESUMO
INTRODUCTION: Chronic airflow obstruction in conditions such as chronic obstructive pulmonary disease is associated with respiratory muscle dysfunction. Our aim was to study the effects of salbutamol-a beta-adrenergic agonist known to improve muscle strength in physiologic and pathologic conditions-on diaphragm contractility in an animal model of chronic airway obstruction achieved by tracheal banding. MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were randomized into a control group and 3 tracheal banding groups, 1 that received acute salbutamol treatment, 1 that received chronic salbutamol treatment, and 1 that received nothing. Arterial blood gases, acid-base balance, and in vitro diaphragmatic contractility were evaluated by measuring peak twitch tension, contraction time, contraction velocity, half-relaxation time, relaxation velocity, and force-frequency curves. RESULTS: The 3 study groups had significantly reduced arterial pH and increased PaCO2 and bicarbonate levels compared to the control group (P<.05). The untreated tracheal banding group had significantly reduced peak twitch tension and contraction velocity, and a significantly lower force-frequency curve in comparison with the other groups (P<.05). The chronic treatment group had a higher relaxation velocity than the untreated study group (P<.05). The mean (SE) peak twitch tension values were 6.46 (0.90)N/cm(2) for the control group, 3.28 (0.55)N/cm(2) for the untreated tracheal banding group, 6.18 (0.71)N/cm(2) for the acute treatment group, and 7.09 (0.59)N/cm(2) for the chronic treatment group. CONCLUSIONS: Diaphragmatic dysfunction associated with chronic airflow obstruction improves with both the acute and chronic administration of salbutamol. The mechanisms involved in respiratory muscle dysfunction warrant further study.