Abstracts

Rationale: We have attempted to explore the neuroprotective effectiveness of levetiracetam (LEV) by measuring in vivo anti-oxidant effect in the hippocampus of rats in a freely moving state. Methods: Male Wistar rats (n=24) were used for the estimation of in vivo anti-oxidant effect utilizing microdialysis combined with electron spin resonance spectroscopy. Anti-oxidant effect was examined utilizing the principle that systemic administered blood-brain barrier-permeable nitroxide radical (PCAM) decreases in an exponential decay correlated with anti-oxidant in the brain. PCAM decay ratio during normal Ringer solution perfusion was compared with that during 100μM LEV co-perfusion(at 2μl/ml). In addition to examination of in vivo anti-oxidant effect, expression of cystine/glutamate exchanger (xCT) and inducible nitric oxide synthase (iNOS) protein related with redox regulation was measured in the hippocampus of rats after 14 days administration of LEV at dose of 54mg/day i.p.Results: Half-life of PCAM was statistically shortened when perfused with 100μM LEV compared with control (Fig.1A, B). While expression of pro-oxidant protein iNOS was decreased, anti-oxidant protein xCT was statistically increased (Fig2). Conclusions: Role of xCT is to transport of cystine into the cell, which is internal material of glutathione. Shorten half-life of nitroxide radical when co-perfused of LEV with increased xCT and decreased iNOS expression revealed the enhancement of endogenous anti-oxidant effect or free radical scavenging activity. Our findings suggested that LEV synergistically enhances the increased basal endogenous anti-oxidant effect in the hippocampus with ascorbic acid and α-tocopherol.