Réplica. Receptores de glutamato de tipo kainato y epilepsia / Reply. Kainate-type glutamate receptors and epilepsy

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[The neurochemistry of epilepsy, inhibitory neurotransmission and experimental models: new perspectives]. / Neuroquímica de la epilepsia, neurotransmisión inhibitoria y modelos experimentales: nuevas perspectivas.

AIMS: The biological mechanisms of epilepsy allow pathophysiological patterns to be established which are essential for the selection of new therapeutic targets. The identification of these mechanisms also provides us with knowledge about the dynamics of neuronal arrangement, synaptogenesis, synaptic transmission and the receptors involved, and even the development of the brain. DEVELOPMENT: Recent advances in neurobiology regarding the GABAergic system point to it as playing a leading role in the pathophysiology of epilepsy. We evaluate the different functional formats of the ionotropic (GABAA) and metabotropic (GABAB) gamma-aminobutyric (GABA) receptors. Although the main function posited is inhibitory, owing to the variability of their location, subunits and neuronal physiology/maturation they can even end up expressing excitatory functions. We discuss the anomalies in the GABAergic system identified in animal models with epilepsy and in brain tissue samples from patients submitted to surgery due to epilepsy. The mechanism inhibiting the activation of GABA receptors is performed by hyperpolarisation achieved by entry of Cl- into the neuron--a process mediated by the cotransporter KCC2, typically expressed in the neuron. Mutations in the KCC2 gene produce mice that are susceptible to seizures. In some animal models it has been found that loop diuretics (furosemide) suppress seizures. Mutations in genes that code for ion channels have been identified in numerous epileptic syndromes and this pushes epilepsy ever further inside the broad group of disorders known as channelopathies. The origin could be polygenetic in many cases. CONCLUSIONS: The GABAergic system seems to situate itself as the main system implicated in the pathophysiology of epilepsy, although conditions that have been considered to be idiopathic up till now could have a polygenic nature.

Neuroquímica de la epilepsia, neurotransmisión inhibitoria y modelos experimentales: nuevas perspectivas / The neurochemistry of epilepsy, inhibitory neurotransmission and experimental models: new perspectives

Objetivo. Los mecanismos biológicos de la epilepsia permiten establecer patrones fisiopatológicos clave para la selección de nuevas dianas terapéuticas. La identificación de estos mecanismos aporta además conocimiento sobre la dinámica de ordenación neuronal, la sinaptogénesis, la transmisión sináptica y los receptores implicados e incluso el desarrollo cerebral. Desarrollo. Los recientes avances neurobiológicos sobre el sistema gabérgico identifican a éste como un agente principal implicado en la fisiopatología de la epilepsia. Evaluamos los distintos formatos funcionales de los receptores g-aminobutíricos ionotrópicos (GABAA) y metabotrópicos (GABAB): aunque se postula una función inhibitoria principalmente, con la variabilidad en su localización, las subunidades y la maduración/fisiología neuronal pueden acabar expresando funciones incluso excitadoras. Se discuten las anomalías en el sistema gabérgico identificadas en modelos animales con epilepsia y muestras cerebrales de pacientes sometidos a cirugía a causa de la epilepsia. El mecanismo inhibitorio de la activación de receptores GABA se lleva a cabo por la hiperpolarización obtenida mediante la entrada de Cl– a la neurona, mediada por el cotransportador KCC2, de expresión típicamente neuronal. Mutaciones en el gen de KCC2 producen ratones susceptibles a crisis. En algunos modelos animales se ha comprobado una supresión de las convulsiones con diuréticos de asa (furosemida). La identificación en múltiples síndromes epilépticos de mutaciones en genes que codifican canales iónicos sitúan a la epilepsia dentro del cada vez más amplio grupo de trastornos conocidos como canalopatías. El origen podría ser poligenético en numerosos casos. Conclusión. El sistema gabérgico parece postularse como el principal sistema implicado en la fisiopatología de la epilepsia, aunque los cuadros hasta ahora considerados idiopáticos podrían tener un carácter poligénico (AU)

Aims. The biological mechanisms of epilepsy allow pathophysiological patterns to be established which are essential for the selection of new therapeutic targets. The identification of these mechanisms also provides us with knowledge about the dynamics of neuronal arrangement, synaptogenesis, synaptic transmission and the receptors involved, and even the development of the brain. Development. Recent advances in neurobiology regarding the GABAergic system point to it as playing a leading role in the pathophysiology of epilepsy. We evaluate the different functional formats of the ionotropic (GABAA) and metabotropic (GABAB) gamma-aminobutyric (GABA) receptors. Although the main function posited is inhibitory, owing to the variability of their location, subunits and neuronal physiology/maturation they can even end up expressing excitatory functions. We discuss the anomalies in the GABAergic system identified in animal models with epilepsy and in brain tissue samples from patients submitted to surgery due to epilepsy. The mechanism inhibiting the activation of GABA receptors is performed by hyperpolarisation achieved by entry of Cl¨C into the neuron ¨Ca process mediated by the cotransporter KCC2, typically expressed in the neuron. Mutations in the KCC2 gene produce mice that are susceptible to seizures. In some animal models it has been found that loop diuretics (furosemide) suppress seizures. Mutations in genes that code for ion channels have been identified in numerous epileptic syndromes and this pushes epilepsy ever further inside the broad group of disorders known as channelopathies. The origin could be polygenetic in many cases. Conclusions. The GABAergic system seems to situate it self as the main system implicated in the pathophysiology of epilepsy, although conditions that have been considered to beidiopathic up till now could have a polygenic nature (AU)

Hepatitis por ticlopidina. Presentación de un nuevo caso / Hepatitis by ticlopidine. Report of a new case

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