Zmiany aktywności sieci hipokampa we wczesnej fazie rozwoju epilepsji jako predyktor późniejszego rozwoju padaczki
Hippocampal network activity changes during early epileptogenesis predict subsequent epilepsy
W skrócie
Badacze obserwowali, jak zmienia się aktywność elektryczna mózgu u szczurów po bodźcach, które mogą prowadzić do epilepsji. Okazało się, że zwierzęta, u których później rozwinęła się padaczka, wykazywały charakterystyczne zmiany w równowadze między pobudzeniem a hamowaniem nerwowym w pierwszych dniach po stymulacji. Te wczesne zmiany aktywności mózgu mogą być bardzo dokładnym wskaźnikiem tego, czy u zwierzęcia rozwinie się epilepsja, co daje szansę na wcześniejsze wykrywanie zagrożenia i testowanie nowych sposobów leczenia.
Oryginalny abstract (angielski)
OBJECTIVE: Despite decades of research, the circuit mechanisms that underlie focal epileptogenesis remain incompletely understood. In this study, we aimed to characterize the changes in hippocampal network activity induced by an epileptogenic insult. METHODS: In rats, prolonged electrical perforant pathway stimulation leads in a high percentage of animals to the development of temporal lobe epilepsy. However, a subset of animals remained apparently non-epileptic for unknown reasons. We monitored alterations of neuronal activity by chronically recording the local field potential (LFP) from the hippocampal dentate gyrus before, during, and after the potentially epileptogenic insult and quantifying the time-dependent changes in the periodic and the aperiodic components of the LFP. RESULTS: It is intriguing that animals with epilepsy identified by subsequent spontaneous epileptic seizures were characterized by a transient increase in the aperiodic exponent, suggesting a shift toward a reduced local excitation-to-inhibition (E/I) ratio during the first days after the perforant path stimulation. Furthermore, these animals developed a strong impairment of theta oscillation prevalence and regularity during early epileptogenesis. In contrast, resilient non-epilepsy animals without spontaneous seizures showed neither this modulation in E/I ratio nor a corruption of hippocampal theta activity. In fact, the increase in the aperiodic exponent on the first day after completion of the electrical stimulation paradigm could predict epileptogenesis with very high fidelity (area under the curve [AUC] 0.92) and correlated significantly with later seizure rate. SIGNIFICANCE: The very early phase of epileptogenesis seems to be dominated by a relative dominance of inhibitory synaptic activity in affected circuits. This finding opens the opportunity to dissect mechanisms of epileptogenesis and to test the effectiveness of anti-epileptogenesis treatment in very early disease stages by allowing identification of individuals at high risk. Furthermore, it might offer a potential explanation for the frequently observed failure of anti-epileptogenesis drugs boosting γ-aminobutyric acid (GABA)ergic inhibition.