Lacosamide protects striatal and hippocampal neurons from in vitro ischemia without altering physiological synaptic plasticity

Petra Mazzocchetti, Michela Tantucci, Guendalina Bastioli, Valeria Calabrese, Massimiliano Di Filippo, Alessandro Tozzi, Paolo Calabresi, Cinzia Costa

Research output: Contribution to journalArticle

Abstract

Lacosamide ([(R)-2-acetamido-N-benzyl-3-methoxypropanamide], LCM), is an antiepileptic that exerts anticonvulsant activity by selectively enhancing slow sodium channel inactivation. By inhibiting seizures and neuronal excitability it might therefore be a good candidate to stabilize neurons and protect them from energetic insults. Using electrophysiological analyses, we have investigated in mice the possible neuroprotective effect of LCM against in vitro ischemia obtained by oxygen and glucose deprivation (ODG), in striatal and hippocampal tissues, two brain structures particularly susceptible to ischemic injury and of pivotal importance for different form of learning and memory. We also explored in these regions the influence of LCM on firing discharge and on long-term synaptic plasticity. We found that in both areas LCM reduced the neuronal firing activity in a use-dependent manner without influencing the physiological synaptic transmission, confirming its anticonvulsant effects. Moreover, we found that this AED is able to protect, in a dose dependent manner, striatal and hippocampal neurons from energy metabolism failure produced by OGD. This neuroprotective effect does not imply impairment of long-term potentiation of striatal and hippocampal synapses and suggests that LCM might exert additional beneficial therapeutic effects beyond its use as antiepileptic.

Original languageEnglish
Pages (from-to)424-430
Number of pages7
JournalNeuropharmacology
Volume135
DOIs
Publication statusPublished - Jun 1 2018

Keywords

  • Hippocampus
  • In vitro ischemia
  • Lacosamide
  • Neuroprotection
  • Oxygen and glucose deprivation
  • Striatum
  • Synaptic plasticity

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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