Coactivation of GABAA and GABAB Receptor Results in Neuroprotection during In Vitro Ischemia

Cinzia Costa, Giorgia Leone, Emilia Saulle, Francesco Pisani, Giorgio Bernardi, Paolo Calabresi

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Purpose - The possible neuroprotective effect of endogenous γ-aminobutyric acid (GABA) on the irreversible electrophysiological changes induced by in vitro ischemia on striatal neurons was investigated. In particular, the aim of the study was the characterization of the neuroprotective action of 2 antiepileptic drugs increasing GABAergic transmission such as tiagabine, a GABA transporter inhibitor, and vigabatrin, an irreversible inhibitor of GABA transaminase. Methods - Extracellular field potential recordings were obtained from rat corticostriatal slice preparations . In vitro ischemia was delivered by switching to an artificial cerebrospinal fluid solution in which glucose was omitted and oxygen was replaced with N 2. Results - An irreversible loss of the field potentials recorded from striatal neurons was observed after 10 minutes of ischemia in control solution. Conversely, tiagabine and vigabatrin partially prevented the ischemia-induced field potential loss. Surprisingly, both GABAA and GABAB receptor antagonists blocked these effects. Accordingly, neuroprotection could be obtained only when GABAA and GABA B receptor agonists were coapplied, but not when a single agonist was given in isolation. Conclusions - Antiepileptic drugs targeting GABAergic transmission can exert neuroprotective effects against ischemia by increasing endogenous GABA levels and via the activation of both GABAA and GABAB receptors.

Original languageEnglish
Pages (from-to)596-600
Number of pages5
JournalStroke
Volume35
Issue number2
DOIs
Publication statusPublished - Feb 2004

Keywords

  • Anticonvulsants
  • Corpus striatum
  • Electrophysiology
  • GABA
  • Ischemia
  • Receptors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

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