Authors: Lorenzo Ricci Massimo Valoti Giampietro Sgaragli Maria Frosini
Publish Date: 2011/06/12
Volume: 42, Issue: 6, Pages: 2139-2147
Abstract
The activation of the GABAergic system has been shown to protect brain tissues against the damage that occurs after cerebral ischaemia On the other hand the taurine analogues ±Piperidine3sulphonic PSA 2aminoethane phosphonic AEP 2Nacetylamino cyclohexane sulfonicacids ATAHS and 2aminobenzene sulfonateacids ANSA have been reported to block GABA metabolism by inhibiting rabbit brain GABA aminotransferase and to increase GABA content in rabbit brain slices The present investigation explored the neuroprotection provided by GABA Vigabatrin VIGA and taurine analogues in the course of oxygen–glucose deprivation and reperfusion induced damage of rabbit brain slices Tissue damage was assessed by measuring the release of glutamate and lactate dehydrogenase LDH during reperfusion and by determining final tissue water gain measured as the index of cell swelling GABA 30–300 μM and VIGA 30–300 μM significantly antagonised LDH and glutamate release as well as tissue water gain caused by oxygen–glucose deprivation and reperfusion Lower 1–10 μM or higher concentrations up to 3000 μM were ineffective ANSA PSA and ATAHS significantly reduced glutamate and LDH release and tissue water gain in a range of concentrations between 30 and 300 μM Lower 0–10 μM or higher up to 3000 μM concentrations were ineffective Both mechanisms suggest hormetic “Ushaped” effects These results indicate that the GABAergic system activation performed directly by GABA or indirectly through GABA aminotransferase inhibition is a promising approach for protecting the brain against ischemia and reperfusioninduced damageThis work was supported by University of Siena PAR Progetti The authors thank Dr M Ulivelli for supplying Vigabatrin and Dr F Machetti for the synthesis of some taurine analogues The authors thanks Prof Steven Loiselle for his critical reading of the manuscript
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