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 antiepileptic drug with glutamate antagonist and GABA agonist properties. We tested 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, hippocampus (CA1 and CA4), thalamus and striatum were evaluated on a 4-point 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 animals. There were 8 animals tested per group (total: 48 animals). There 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 when felbamate was used before ischemia. It was highly significant when felbamate was given 30 min after the insult. Behavioral studies however 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 window for protection merits further evaluation in relation to the clinical setting of stroke.

Acetyl-L-carnitine attenuates neuronal damage in gerbils with transient forebrain ischemia only when given before the insult.

The underlying mechanisms leading to neuronal damage in cerebral ischemia are multifactoral. In this study, we evaluated the neuroprotective effects of acetyl-L-carnitine, a medication that may enhance metabolic recovery after cerebral ischemia. The 5-minute transient forebrain ischemia model in gerbils was used. Acetyl-L-carnitine was given 30 minutes before the insult in one set of animals and 30 minutes after the insult in a second set of animals with histological evaluation at 7 days (Group A) and 28 days (Group B). Damage assessment was done using a 4-point damage score and Mann-Whitney U test was used for statistical analysis. Compared to the controls, there was significant protection in the cerebral cortex, hippocampus and the striatum in animals treated with the medication before the insult in Group A and Group B. Post-ischemic therapy showed little evidence of neuronal protection in either group. Behavioral tests in the Group B animals showed no significant differences between the treated or the saline controls. Our study shows, that pre-ischemic treatment with acetyl-L-carnitine results in neuronal protection. This may have clinical significance in situations (such as bypass surgery) where treatment could be initiated prior to the insult.