Mecanismos fisiopatológicos de las crisis de ausencia en modelos animales
Resumen
Las crisis de ausencia son un tipo de epilepsia generalizada caracterizada por una breve pérdida de conciencia y descargas espiga-onda en el electroencefalograma. Estas crisis resultan de una disfunción en el sistema GABAérgico, donde una disminución en la actividad de los receptores GABAA fásicos en la corteza somatosensitiva, junto con un aumento en la inhibición por receptores GABAA tónicos en el circuito tálamo-cortical, facilita estas descargas. En este circuito, el núcleo reticular del tálamo desempeña un papel esencial en el inicio y control de las descargas espiga-onda. Se realizó una búsqueda en bases de datos científicas sobre los mecanismos de generación de estas crisis, el acoplamiento del circuito tálamo-cortical y los modelos animales disponibles. Los modelos genéticos sin daño estructural, como las ratas GAERS y WAG/Rij, han sido fundamentales para el estudio de crisis en circuitos intactos. Sin embargo, los modelos genéticos desmielinizantes, como las ratas tremor y taiep, permiten observar cómo la pérdida de mielina afecta la duración y sincronización de las descargas. La desmielinización no solo incrementa la duración de las descargas, sino que también modifica la dinámica del circuito, subrayando la importancia de estudiar tanto factores estructurales como funcionales en la epilepsia de ausencia y abriendo vías para enfoques terapéuticos más completos. La presente revisión analiza la fisiopatología de las crisis de ausencia, centrándose en los cambios funcionales del circuito tálamo-cortical y la influencia de la desmielinización.
Abstract
Absence seizures are a type of generalized epilepsy characterized by a brief loss of consciousness and spike-and-wave discharges on the electroencephalogram. These seizures result from dysfunction in the GABAergic system, where a decrease in the activity of phasic GABAA receptors in the somatosensory cortex, along with an increase in tonic inhibition by GABAA receptors in the thalamocortical circuit, facilitates these discharges. In this circuit, the thalamic reticular nucleus plays an essential role in the initiation and control of spike-and-wave discharges. A search in scientific databases was conducted to examine the mechanisms underlying these seizures, the coupling of the thalamocortical circuit, and the available animal models. Genetic models without structural damage, such as GAERS and WAG/Rij rats, have been fundamental in studying seizures in intact circuits. However, demyelinating genetic models, like tremor and taiep rats, allow for observation of how myelin loss affects the duration and synchronization of discharges. Demyelination not only increases the duration of discharges but also modifies the circuit's dynamics, highlighting the importance of studying both structural and functional factors in absence epilepsy and opening pathways for more comprehensive therapeutic approaches. This review analyzes the pathophysiology of absence seizures, focusing on functional changes in the thalamocortical circuit and the influence of demyelination.
Keywords: Thalamo-cortical circuit, absence seizures, demyelination, spike-wave discharges, taiep rat, GABAA receptor.
Palabras clave
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DOI: https://doi.org/10.25009/eb.v16i40.2638
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