RESUMEN
Although epilepsy afflicts numerous people worldwide, its dynamics are still controversial. Especially seizure termination is relatively unidentified. Here we suggest a coherent explanation to all stages of epilepsy, its genesis, seizure initiation and termination. We present biophysical features that could account for the phenomenon: all phases of epilepsy can be related to the brain's "waste disposal" systems. Although problems in the astrocytic system have already been suggested as a major player in this malfunction, the termination phase is not really understood. Here it is assumed to arise from a G-lymphatic clearance system. Our biophysical mechanism provides a coherent explanation of the phenomenon, offers support for the previously published mathematical model, and can shed light on the conflicting results encountered in norepinephrine measurements in epilepsy treatment.
Asunto(s)
Astrocitos/fisiología , Encéfalo/metabolismo , Epilepsia/fisiopatología , Ácido Glutámico/metabolismo , Sistema Glinfático/fisiopatología , Modelos Neurológicos , Neuroglía/fisiología , Potasio/metabolismo , Anestesia , Animales , Ritmo Circadiano/fisiología , Epilepsia/etiología , Epilepsia/metabolismo , Humanos , Neuronas/metabolismo , Norepinefrina/fisiología , Sueño/fisiología , Privación de Sueño/fisiopatología , InconscienciaRESUMEN
Cardiac fibrillation is a major clinical and societal burden. Rotors may drive fibrillation in many cases, but their role and patterns are often masked by complex propagation. We used Singular Value Decomposition (SVD), which ranks patterns of activation hierarchically, together with Wiener-Granger causality analysis (WGCA), which analyses direction of information among observations, to investigate the role of rotors in cardiac fibrillation. We hypothesized that combining SVD analysis with WGCA should reveal whether rotor activity is the dominant driving force of fibrillation even in cases of high complexity. Optical mapping experiments were conducted in neonatal rat cardiomyocyte monolayers (diameter, 35 mm), which were genetically modified to overexpress the delayed rectifier K+ channel IKr only in one half of the monolayer. Such monolayers have been shown previously to sustain fast rotors confined to the IKr overexpressing half and driving fibrillatory-like activity in the other half. SVD analysis of the optical mapping movies revealed a hierarchical pattern in which the primary modes corresponded to rotor activity in the IKr overexpressing region and the secondary modes corresponded to fibrillatory activity elsewhere. We then applied WGCA to evaluate the directionality of influence between modes in the entire monolayer using clear and noisy movies of activity. We demonstrated that the rotor modes influence the secondary fibrillatory modes, but influence was detected also in the opposite direction. To more specifically delineate the role of the rotor in fibrillation, we decomposed separately the respective SVD modes of the rotor and fibrillatory domains. In this case, WGCA yielded more information from the rotor to the fibrillatory domains than in the opposite direction. In conclusion, SVD analysis reveals that rotors can be the dominant modes of an experimental model of fibrillation. Wiener-Granger causality on modes of the rotor domains confirms their preferential driving influence on fibrillatory modes.