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Seo JY, Lee CH, Cho JH, Choi JH, Yoo KY, Kim DW, Park OK, Li H, Choi SY, Hwang IK, Won MH: Neuroprotection of ebselen against ischemia/reperfusion injury involves GABA shunt enzymes. J Neurol Sci. 2009 Oct 15;285(1-2):88-94. Epub 2009 Jul 2. Seleno-organic compound, ebselen (2-phenyl-1,2-benzisoselenazol-3 (2H)-one), is a substrate with radical-scavenging activity. In this study, we observed the neuroprotective effects of ebselen against ischemic damage and on GABA shunt enzymes such as glutamic acid decarboxylase 67 (GAD67), GABA transaminse (GABA-T) and succinic semialdehyde dehydrogenase (SSADH) in the hippocampal CA1 region after 5 min of transient forebrain ischemia in gerbils. For this, vehicle (physiological saline) or ebselen was administered 30 min before or after ischemia/reperfusion and sacrificed 4 days after ischemia/reperfusion. The administration of ebselen significantly reduced the neuronal death in the CA1 region induced by ischemia/reperfusion. In addition, treatment with ebselen markedly elevated GAD67, GABA-T and SSADH immunoreactivity and their protein levels compared to that in the vehicle-treated group, respectively. These results suggest that ebselen protects neurons from ischemic damage via control of the expressions of GABA shunt enzymes to enter the TCA cycle. |
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