Tiagabine and vigabatrin reduce the severity of NMDA-induced excitotoxicity in chick retina.
The possible neuroprotective effects of two GABAergic drugs, tiagabine (TGB) and vigabatrin (VGB), against N-methyl-D-aspartate (NMDA)-induced excitotoxicity have been investigated in the isolated chick embryo retina model. Retina segments were incubated either with NMDA alone (100 microM) or with NMDA and TGB or VGB (10-1,000 microM, added 5 min before NMDA). Retina damage was assessed after 24 h by measuring lactate dehydrogenase (LDH) activity present in the medium and by histological analysis. Both drugs reduced LDH release in a dose-dependent manner with comparable mean maximal values of 56.6-63.7% achieved at concentration of 1 mM. Histological analysis of retina slices was in line with the biochemical assays and showed partial preservation of drug exposed retina structure with reduced edema especially in the inner plexiform layer. The present data provide pharmacological evidence that both TGB and VGB reduce the severity of NMDA-induced excitotoxic damage. Although an increase in GABAergic transmission might play a role, this in itself is insufficient to explain the neuroprotective effect of the two drugs and the exact mechanism remains to be elucidated.
Pisani
Francesco
F
Department of Neurosciences, Psychiatric and Anesthesiological Sciences, First Neurological Clinic, University of Messina, Messina, Italy. pisanif@unime.it
Costa
Cinzia
C
Caccamo
Daniela
D
Mazzon
Emanuela
E
Gorgone
Gaetano
G
Oteri
Giancarla
G
Calabresi
Paolo
P
Ientile
Riccardo
R
D000704:Analysis of Variance; D000818:Animals; D002642:Chick Embryo; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016202:N-Methylaspartate / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009557:Nipecotic Acids / Q000494:pharmacology*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000078308:Tiagabine; D020888:Vigabatrin / Q000494:pharmacology*
D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D009557:Nipecotic Acids; D016202:N-Methylaspartate; D007770:L-Lactate Dehydrogenase; D020888:Vigabatrin; D000078308:Tiagabine