Perfil das crises epiléticas e ritmo circadiano de animais submetidos ao claro constante em modelo experimental de epilepsia do lobo temporal

Abstract

Mesial temporal lobe epilepsy (ELTM) is a chronic condition characterized by the occurrence of spontaneous and recurrent seizures (SRS) due to excessive neuronal activity in limbic regions of the brain. In most cases, the onset of epilepsy is associated with structural and physiological changes that occur progressively in the brain from an epileptogenic insult, such as Status epilepticus (SE). The period of conversion of a normal brain into an epileptic – called epileptogenesis - is variable (months to years) and involves a broad spectrum of biological processes, including neurodegeneration, neurogenesis, inflammation, synaptic plasticity, cell migration, among others. Interestingly, at the end of this period, the individual presents with crises that, although unpredictable, follow a temporal pattern of oscillation (circadian and ultradian). The rhythm of recurrence is maintained even in free-flowing conditions in the dark, which has aroused interest in the involvement of the endogenous clock system in the modulation of the crisis susceptibility threshold. Recently, we observed that the clock genes present their modulated expression in the epileptogenic process induced in the experimental model, providing molecular evidence on the effect of epileptogenesis on circadian rhythmicity. In this study, we investigated the hypothesis that alterations in the circadian rhythm interfere in the epileptogenic process and in the profile of the spontaneous crises. The experimental model used was the induction of SE by the injection of lithium-pilocarpine. Wistar rats were exposed to the constant light (experimental group) or light-dark cycles (control group) throughout the experiment period. The animals were monitored continuously for a period of 55 days from SE induction. We evaluated the frequency and severity of epileptic seizures and the rhythmicity of spontaneous locomotor activity (SLA) prior to SE induction and during the chronic phase of epileptogenesis. Crisis severity was assessed using the Racine scale and SLAwas analyzed by Acrophase and El Temps software. The proportion of animals that developed spontaneous seizures was higher in the group kept in constant clear regime indicating that the interference in the rhythm facilitated epileptogenesis. Animals submitted to constant light had the rhythm of locomotor activity altered, although only 46% completely lost their rhythm at the end of the experiment period (55 days after SE induction). Interestingly, only this subgroup showed a higher frequency and severity in epileptic and spontaneous seizures when compared to animals that did not lose rhythm from the clear or constant light groups. In conclusion, our study suggests that exposure to constant light may facilitate epileptogenesis and that decoupling of the rhythm of locomotor activity may mitigate the severity and frequency of SRS.