The amygdala lesioning due to status epilepticus – Changes in mechanisms controlling chloride homeostasis

Objective: Amygdala has been demonstrated as one of the brain sites involved in the control of cardiorespiratory functioning. The structural and physiological alterations induced by epileptic activity are also present in the amygdala and reflect functional changes that may be directly associated with a sudden unexpected death. Seizures are always associated with neuronal damage and changes in the expression of cation-chloride cotransporters and Na/K pumps. In this study, the authors aimed to investigate if these changes are present in the amygdala after induction of status epilepticus with pilocarpine, which may be directly correlated with Sudden Unexpected Death in Epilepsy (SUDEP). Methods: Pilocarpine-treated wistar rats 60 days after Status Epilepticus (SE) were compared with control rats. Amygdala nuclei of brain slices immunostained for NKCC1, KCC2 and α1-Na+/K+-ATPase, were quantified by optical densitometry. Results: The amygdaloid complex of the animals submitted to SE had no significant difference in the NKCC1 immunoreactivity, but KCC2 immunoreactivity reduced drastically in the peri-somatic sites and in the dendritic-like processes. The α1-Na+/K+-ATPase peri-somatic immunoreactivity was intense in the rats submitted to pilocarpine SE when compared with control rats. The pilocarpine SE also promoted intense GFAP staining, specifically in the basolateral and baso-medial nuclei with astrogliosis and cellular debris deposition. Interpretation: The findings revealed that SE induces lesion changes in the expression of KCC2 and α1-Na+/K+-ATPase meaning intense change in the chloride regulation in the amygdaloid complex. These changes may contribute to cardiorespiratory dysfunction leading to SUDEP

Herramienta de modelado y análisis estocástico de sistemas biológicos

Los sistemas híbridos cuentan con la atención de gran parte de la comunidad científica por lo atractivo del estudio de sus dinámicas, las continuas y las discretas, y la comprensión de sus interacciones. Entre las más comunes se encuentran aquellas que cambian de estado entre diferentes procesos continuos. También se pueden encontrar formas de interacción que incluyen transiciones discretas supeditadas a evoluciones continuas, u otras como resultados de una decisión, o por la ocurrencia de determinados eventos. El estudio de la distribución probabilísticas de la dinámica discreta y la continua se lleva a cavo por medio del análisis del sistema híbrido estocástico (SHE) que lo modela. Debido a que el modelo numérico, de un SH, es afectado por el problema de la explosión de estados y de ser sumamente exigente en lo que a recursos se refiere, aparece como una opción aceptable la formulación del mismo sistema por medio de un SHP. Estos tipos de sistemas pueden ser analizados por medio de herramientas informáticas con solida base matemática como son los Model Checkers Probabilísticos. Los sistemas biológicos encuadran perfectamente en la clasificación de SHE. En el ámbito de estudio de SB no se cuenta con herramientas que permitan una traducción directa de un SHE, como por ejemplo un sistema de reacciones, a un modelo estocástico factible de ser analizado por herramientas informáticas disponibles en la actualidad como son los model checkers antes mencionados. En nuestra línea de investigación proponemos el estudio de factibilidad y de propuesta de desarrollo de una herramienta de análisis de SB basado en su formulación estocástica. Tenemos como hipótesis de trabajo que el desarrollo de este prototipo de herramienta que permite la obtención de un modelo estocástico a partir de su formulación por medio de reacciones que permitirá analizar el sistema e incrementar la productividad en el estudio de SBs habilitando a su verificación y validación con herramientas novedosas en el área biológica. En una primera etapa se centrará en la obtención de modelos estocásticos de un sistema de reacciones para luego habilitar el análisis basado en probabilidades y en simulaciones probabilísticas basadas en su semántica estocástica.Eje: Innovación en Sistemas de Software.Red de Universidades con Carreras en Informática (RedUNCI

Congenital short QT syndrome: Landmarks of the newest arrhythmogenic cardiac channelopathy

Congenital or familial short QT syndrome is a genetically heterogeneous cardiac channelopathy without structural heart disease that has a dominant autosomal or sporadic pattern of transmission affecting the electric system of the heart. Patients present clinically with a spectrum of signs and symptoms including irregular palpitations due to episodes of paroxysmal atrialfibrillation, dizziness and fainting (syncope) and/or sudden cardiac death due to polymorphic ventricular tachycardia and ventricular fibrillation. Electrocardiographic (ECG) findings include extremely short QTc intervals (QTc interval ≤ 330 ms) not significantly modified with heart rate changes and T waves of great voltage witha narrow base. Electrophysiologic studies are characterized by significant shortening of atrial and ventricular refractory periods and arrhythmias induced by programmed stimulation. A few families have been identified with specific genotypes: 3 with mutations in potassium channels called SQT1 (Iks), SQT2 (Ikr) and SQT3 (Ik1). These 3 potassium channel variants are the “genetic mirror image” of long QT syndrome type 2, type 1 and Andersen-Tawil syndrome respectively because they exert opposite gain-of-function effects on the potassium channels in contrast to the loss-of-function of the potassium channels in the long QT syndromes. Three new variants with overlapping phenotypes affecting the slow inward calcium channels havealso been described. Finally, another variant with mixed phenotype affecting the sodium channel was reported. This review focuses the landmarks of this newest arrhythmogenic cardiac channelopathy on the main clinical, genetic, and proposed ECG mechanisms. In addition therapeutic options and the molecular autopsy of this fascinating primary electrical heart disease are discussed

Sudden unexpected death in Parkinson's disease: Insights from clinical practice

Classified as the second most common neurodegenerative disorder associated with aging after Alzheimer's disease, Parkinson's disease (PD) is the most common movement disorder. In the last decade, despite advances in treatment, mortality rates linked with PD continued to reach significant figures. Available studies have shown that compared with healthy controls, patients with PD are accompanied by high rates of premature death. This is usually caused by factors such as pneumonia and cerebrovascular and cardiovascular diseases. Recently, it has been demonstrated that a significant proportion of patients with PD die suddenly. This is referred to as a sudden and unexpected death in PD (SUDPAR). Here, we focus on the magnitude of SUDPAR. Finally, it is important to learn more about SUDPAR for the implementation of effective prevention strategies