Overexpression of thioredoxin in transgenic mice attenuates focal ischemicbrain damage

Thioredoxin (TRX) plays important biological roles both in intra- and extra cellular compartments, including in regulation of various intracellular mol ecules via thiol redox control. We produced TRX overexpressing mice and con firmed that there were no anatomical and physiological differences between mild-type (WT) mice and TRX transgenic (Tg) mice. In the present study we s ubjected mice to focal brain ischemia to shed light on the role of TRX in b rain ischemic injury. At 24 hr after middle cerebral artery occlusion, infa rct areas and volume were significantly smaller in Tg mice than in WT mice. Moreover neurological deficit was ameliorated in Tg mice compared with WT mice. Protein carbonyl content, a marker of cellular protein oxidation, in Tg mice showed less increase than did that of WT mice after the ischemic in sult. Furthermore, c-fos expression in Tg mice was stronger than in WT mice I hr after ischemia, Our results suggest that transgene expression of TRX decreased ischemic neuronal injury and that TRX and the redox state modifie d by TRX play a crucial role in brain damage during stroke.