NEUROPROTECTION WITH FELBAMATE - A 7 AND 28-DAY STUDY IN TRANSIENT FOREBRAIN ISCHEMIA IN GERBILS

The use of glutamate antagonists and GABA agonists may protect neurons from the effects of transient ischemia. Felbamate is a new antiepilep tic drug with glutamate antagonist and GABA agonist properties. We tes ted the efficacy of felbamate in a gerbil model of transient forebrain ischemia. Damage assessment was done with silver staining at 7 and 28 days after 5 min of bilateral carotid occlusion. Cerebral cortex, hip pocampus (CA1 and CA4), thalamus and striatum were evaluated on a 4-po int scoring system. The animals sacrificed at 28 days were also tested in a water-maze task to assess recovery of function. The initial dose of felbamate (300 mg/kg) was given 30 min before the ischemic insult in one set of animals and 30 min after the insult in another set of an imals. There were 8 animals tested per group (total: 48 animals). Ther e was significant neuronal protection with the use of felbamate, both before and after ischemia in all regions of the brain. Protection was seen in animals sacrificed at 7 and 28 days. Protection was moderate w hen felbamate was used before ischemia. It was highly significant when felbamate was given 30 min after the insult. Behavioral studies howev er did not show any difference in the felbamate treated animals versus the saline treated controls. The structural protection with felbamate was very significant when used in the post-ischemic period. This wind ow for protection merits further evaluation in relation to the clinica l setting of stroke.