Unethical research relating to Helicobacter pylori?

Abstract

<h3>Abstract</h3> Spike and wave discharges (SWDs) of absence epilepsy are considered as pathologic alterations of sleep spindles; however, their network-level relationship has never been convincingly revealed. In order to observe the development and generalization of the thalamocortical SWDs and the concomitant alterations of sleep related oscillations, we performed local field potential and single unit recordings in rats for 3 months during their maturation. We found that while SWDs and spindles look similar in young, they become different with maturation and shift to appear in different brain states. Thus, despite being generated by the same network, they are likely two distinct manifestations of the thalamocortical activity. We show that while spindles are already mainly global oscillations, SWDs appear mainly only focally in young. They become capable to generalize later with maturation, when the out-of-focus brain regions develop a decreased inhibitory/excitatory balance. These results suggest that a hyperexcitable focus is not sufficient alone to drive generalized absence seizures. Importantly, we also found the gradual age dependent disappearance of sleep spindles coinciding with the simultaneous gradual emergence of spike-and-waves, which both could be reversed by the proper dosing of ethosuximide. Based on these observations we conclude that the absence seizure development might be a multi-step process, which might involve the functional impairment of cortical interneurons and network-level changes that negatively affect sleep quality. <b>Significance statement</b> Absence seizure development parallels with the deterioration of slow wave sleep, which might be reversible with ethosuximide in a narrow therapeutic range, but not with early electrical seizure abruption. Thus, by proper dosing, spindles can be pharmaceutically recovered while epileptic activity is suppressed and absence related sleep and learning disturbances may be counterbalanced. We further found that despite the characteristic high voltage rhythmic global ictal EEG patterns the absence seizures are not accompanied with widespread phase-locking of neuronal activities.