Alzheimer's disease (AD) is a devastating age-related neurodegenerative disease. Age is the main risk factor for sporadic AD, which is the most prevalent type. Amyloid-beta peptide (Abeta) neurotoxicity is the proposed first step in a cascade of deleterious events leading to AD pathology and dementia. Glial cells play an important role in these changes. Astrocytes provide vital support to neurons and modulate functional synapses. Therefore, the toxic effects of Abeta on astrocytes might promote neurodegenerative changes that lead to AD. Aging reduces astrocyte antioxidant defenses and induces oxidative stress. We studied the effects of Abeta(42) on cultures of human astrocytes in the presence or absence of the following pro-oxidant agents: buthionine sulfoximine (BSO), a glutathione synthesis inhibitor, and FeSO(4), which liberates redox active iron. Pro-oxidant conditions potentiated Abeta toxicity, as shown by the generation of free radicals, inflammatory changes, and apoptosis. Similar treatments were assessed in rats in vivo. A combination of Abeta(40) and Abeta(42) or Abeta(42) alone was infused intracerebroventricularly for 4 weeks. Other animal groups were also infused with BSO and FeSO(4). A long-term analysis that ended 4 months later showed greater cognitive impairment in the Morris water maze task, which was induced by Abeta plus pro-oxidant agent treatments. Pro-oxidant agents also potentiated brain tissue pathology. This was demonstrated in histological studies that showed highly increased astrocyte reactivity in AD-vulnerable areas, Abeta deposits, and oxidative damage of AD-sensitive hippocampal neurons. To increase our understanding of AD, experimental models should be used that mimic age-related brain changes, in which age-related oxidative stress potentiates the effects of Abeta.
Introducción. El estudio diagnóstico de polimicrogiria mediante resonancia magnética ha facilitado la publicación de varias series de pacientes en las que las manifestaciones clínicas predominantes varían considerablemente. Objetivo. Conocer la variabilidad fenotípica de la polimicrogiria basándose en la serie de pacientes atendidos en nuestro servicio y la revisión de la bibliografía. Pacientes y métodos. Estudio retrospectivo de los pacientes diagnosticados de polimicrogiria mediante resonancia magnética y seguidos en consultas durante los años 1989-2011. Resultados. De un total de 44 pacientes, nueve fueron excluidos por no cumplir los criterios diagnósticos radiológicos propuestos por Barkovich. La polimicrogiria fue bilateral en 22/35 pacientes (una frontal, 21 perisilvianas) y unilateral en 13/35 (dos frontales, el resto perisilvianas). Todos los pacientes con polimicrogiria bilateral tenían algún tipo de discapacidad intelectual, un 71% tenía retraso global del desarrollo, un 75% tenía trastorno oromotor y un 40% tenía epilepsia. Los pacientes con polimicrogiria unilateral presentaron discapacidad intelectual (65%), retraso global del desarrollo (55%), trastorno oromotor (55%) y epilepsia (55%), estando asintomáticos dos pacientes (2 años de edad). La presentación clínica de los pacientes dependía de la edad: en el período neonatal, el síntoma guía fue el trastorno oromotor; antes de los 2 años, el retraso global del desarrollo; y partir de los 2 años, la epilepsia. Conclusión. En este estudio, a diferencia de otras series, el síntoma más prevalente fue la discapacidad intelectual (independientemente del tipo de polimicrogiria), seguido del trastorno oromotor y, en menor medida, la epilepsia. Palabras clave. Epilepsia. Malformación cortical. Parálisis pseudobulbar. Polimicrogiria. Resonancia magnética. Síndrome perisilviano.
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