Retigabine and flupirtine exert neuroprotective actions in organotypic hippocampal cultures

Francesca Boscia, Lucio Annunziato, Maurizio Taglialatela

Research output: Contribution to journalArticle

Abstract

Retigabine and flupirtine are two structurally related molecules provided of anticonvulsant and analgesic actions. The present study has investigated the neuroprotective potential, as well as the possible underlying molecular mechanisms, exerted by retigabine and flupirtine in rat organotypic hippocampal slice cultures (OHSCs) exposed to N-methyl-d-aspartate (NMDA), oxygen and glucose deprivation followed by reoxygenation (OGD), or serum withdrawal (SW). Region-specific vulnerability of hippocampal subfields occurred with each of these injury models. Specifically, CA1 was the most susceptible region to both NMDA and OGD-induced neurodegeneration, whereas selective cell death in the dentate gyrus (DG) occurred upon OHSCs exposure to SW. The NMDA antagonist MK-801 (10-30 μM), despite blocking NMDA- and OGD-induced cell death, failed to prevent SW-induced neurodegeneration. Interestingly, retigabine (0.01-10 μM) and flupirtine (0.01-10 μM) dose-dependently prevented DG neuronal death induced by SW, with IC50 s of 0.4 μM and 0.7 μM, respectively. By contrast, retigabine and flupirtine (each at 10 μM) were less effective in counteracting NMDA- or OGD-induced toxicity in the CA1 region. Both retigabine and flupirtine (0.1-10 μM) reduced SW-induced ROS production in the DG with IC50 s of ≈1 μM. This suggested that antioxidant actions of these compounds participated in OHSC neuroprotection during SW. By contrast, activation of KCNQ K+ channels seemed not to be involved in retigabine-induced OHSCs neuroprotection during SW, since linopirdine (20 μM) and XE-991 (10 μM), two KCNQ blockers, failed to reverse retigabine-induced neuronal rescue.

Original languageEnglish
Pages (from-to)283-294
Number of pages12
JournalNeuropharmacology
Volume51
Issue number2
DOIs
Publication statusPublished - Aug 2006

Keywords

  • Dentate gyrus
  • Excitotoxicity
  • Flupirtine
  • Neuroprotection
  • Organotypic hippocampal cultures
  • Oxidative stress
  • Retigabine

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Fingerprint Dive into the research topics of 'Retigabine and flupirtine exert neuroprotective actions in organotypic hippocampal cultures'. Together they form a unique fingerprint.

  • Cite this