Multiple mechanisms underlying the neuroprotective effects of antiepileptic drugs against in vitro ischemia

Cinzia Costa, Giuseppina Martella, Barbara Picconi, Chiara Prosperetti, Antonio Pisani, Massimiliano Di Filippo, Francesco Pisani, Giorgio Bernardi, Paolo Calabresi

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Purpose - The possible neuroprotective effects of classic and new antiepileptic drugs on the electrophysiological changes induced by in vitro ischemia on striatal neurons were investigated. In particular, the aim of the study was to correlate the putative neuroprotective effects with the action of these drugs on fast sodium (Na +) and high-voltage-activated (HVA) calcium (Ca 2+) currents. Methods - Extracellular field potentials were recorded from rat corticostriatal brain-slice preparations. In vitro ischemia was delivered by switching to an artificial cerebrospinal fluid solution in which glucose and oxygen were omitted. Na + and HVA Ca 2+ currents were analyzed by whole-cell patch-clamp recordings from acutely isolated rat striatal neurons. Excitatory postsynaptic potential was measured following synaptic stimulation in corticostriatal slices by sharp intracellular microelectrodes. Results - Neuroprotection against in vitro ischemia was observed in slices treated with carbamazepine (CBZ), valproic acid (VPA), and topiramate (TPM), whereas it was not achieved by using levetiracetam (LEV). Fast Na + conductances were inhibited by CBZ and TPM, whereas VPA and LEV showed no effect. HVA Ca 2+ conductances were reduced by CBZ, TPM, and LEV. VPA had no effect on this current. All antiepileptic drugs induced a small reduction of excitatory postsynaptic potential amplitude at concentrations higher than 100 μm without changes of paired-pulse facilitation. Conclusions - The concomitant inhibition of fast Na + and HVA Ca 2+ conductances is critically important for the neuroprotection, whereas the presynaptic inhibition on glutamate transmission does not seem to play a major role.

Original languageEnglish
Pages (from-to)1319-1326
Number of pages8
JournalStroke
Volume37
Issue number5
DOIs
Publication statusPublished - May 2006

Keywords

  • Antiepileptic drugs
  • Ca
  • Electrophysiology
  • Ischemia
  • Na

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

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