Research Article Open Access

Neuroprotection Afforded by GABA Against Oxygen-Glucose Deprivation-Induced Injury in Rat Cortical Brain Slices: An Hormetic Dose-Response Effect

Lorenzo Ricci1, Massimo Valoti1, Giampietro Sgaragli1 and Maria Frosini1
  • 1 Università di Siena, Italy

Abstract

The aim of the present investigation was to assess neuroprotection exerted by GABA (100 nM-100 mM) in rat cortical brain slices subjected to oxygen-glucose deprivation and reoxygenation. Neuronal injury and neuroprotection were assessed by measuring the release of glutamate and lactate dehydrogenase and tissue water content. Results demonstrate that GABA exerted neuroprotective effects according to a U-shaped, hormetic-like, concentration-response curve, with an efficacy window of 10-100 µM concentration. In order to verify whether GABA-neuroprotective effects were GABAA- or GABAB-mediated, Muscimol (GABAA agonist) and Baclofen (GABAB agonist) were tested. Results demonstrated that only Muscimol exerted neuroprotection according to a U-shaped, hormetic-like, concentration-response curve, while baclofen was ineffective. In conclusion, the hormetic response of GABA or GABAA agonists should be taken into consideration when designing experiments aimed at assessing neuroprotection by these agents against ischemia/reoxygenation injury.

American Journal of Pharmacology and Toxicology
Volume 3 No. 1, 2008, 160-167

DOI: https://doi.org/10.3844/ajptsp.2008.160.167

Submitted On: 2 March 2008 Published On: 31 March 2008

How to Cite: Ricci, L., Valoti, M., Sgaragli, G. & Frosini, M. (2008). Neuroprotection Afforded by GABA Against Oxygen-Glucose Deprivation-Induced Injury in Rat Cortical Brain Slices: An Hormetic Dose-Response Effect. American Journal of Pharmacology and Toxicology, 3(1), 160-167. https://doi.org/10.3844/ajptsp.2008.160.167

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Keywords

  • Brain ischemia
  • GABA
  • hormesis
  • GABA agonist/antagonist
  • neuroprotection