Neuroprotection Afforded by GABA Against Oxygen-Glucose Deprivation-Induced Injury in Rat Cortical Brain Slices: An Hormetic Dose-Response Effect
Lorenzo Ricci, Massimo Valoti, Giampietro Sgaragli and Maria Frosini
DOI : 10.3844/ajptsp.2008.160.167
American Journal of Pharmacology and Toxicology
Volume 3, 2008
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 Î¼M 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.
© 2008 Lorenzo Ricci, Massimo Valoti, Giampietro Sgaragli and Maria Frosini. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.