• Gabriela Lazzarotto, Klippel Zanona Querusche Q Neurophysiology and Neurochemistry of Neuronal Excitability and Synaptic Plasticity Laboratory (NNNESP Lab.), Department of Biochemistry, Insti, Cagliari Zenki Kamila K Graduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Br, and Maria Elisa Calcagnotto.
• Neurophysiology and Neurochemistry of Neuronal Excitability and Synaptic Plasticity Laboratory (NNNESP Lab.), Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Graduate Program in Neuroscience, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
• Neuroscience. 2021 Mar 1; 457: 114-124.

AbstractDevelopmental cortical malformations (DCM) are one of the main causes of refractory epilepsy. Many are the mechanisms underlying the hyperexcitability in DCM, including the important contribution of N-methyl-D-aspartate receptors (NMDAR). NMDAR blockers are shown to abolish seizures and epileptiform activity. Memantine, a NMDAR antagonist used to treat Alzheimeŕs disease, has been recently investigated as a possible treatment for other neurological disorders. However, the effects on preventing or diminishing seizures are controversial. Here we aimed to evaluate the effects of memantine on pentylenetetrazole (PTZ)-induced seizures in the freeze-lesion (FL) model. Bilateral cortical microgyria were induced (FL) or not (Sham) in male Wistar neonate rats. At P30, subdural electrodes were implanted and 7 days later, video-EEG was recorded in animals receiving either memantine (FL-M or Sham-M) or saline (FL-S or Sham-S), followed by PTZ. Seizures were evaluated by video-EEG during one hour and scored according to Racine scale. The video-EEG analyses revealed that the number of seizures and the total duration of stage IV-V seizures developed during the 1 h-period increased after memantine application in all groups. The EEG power spectral density (PSD) analysis showed an increased PSD of pre-ictal delta in Sham-M animals and increased PSD of slow, middle and fast gamma oscillations after memantine injection that persists during the pre-ictal period in all groups. Our findings suggested that memantine was unable to control the PTZ-induced seizures and that the associated enhancement of PSD of gamma oscillations may contribute to the increased probability of seizure development in these animals.Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

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