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

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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

6 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)424-430
Numero di pagine7
RivistaNeuropharmacology
Volume135
DOI
Stato di pubblicazionePubblicato - 2018

Keywords

  • Animals
  • Brain Ischemia
  • CA1 Region, Hippocampal
  • Corpus Striatum
  • Hippocampus
  • In vitro ischemia
  • Lacosamide
  • Long-Term Potentiation
  • Male
  • Membrane Potentials
  • Mice, Inbred C57BL
  • Neurons
  • Neuroprotection
  • Neuroprotective Agents
  • Oxygen and glucose deprivation
  • Striatum
  • Synapses
  • Synaptic Transmission
  • Synaptic plasticity
  • Tissue Culture Techniques

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