Neuroprotection of ebselen against ischemia/reperfusion injury involves GABA shunt enzymes.

Abstract

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.

• Authors: Jeong Yeol Seo, Choong Hyun Lee, Jun Hwi Cho, Jung Hoon Choi, Ki-Yeon Yoo, Dae Won Kim, Ok Kyu Park, Hua Li, Soo Young Choi, In Koo Hwang, Moo-Ho Won
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 285 Issue 1-2 Pg. 88-94 (Oct 15 2009) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 19576596 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Azoles
• Isoindoles
• Neuroprotective Agents
• Organoselenium Compounds
• ebselen
• Succinate-Semialdehyde Dehydrogenase
• 4-Aminobutyrate Transaminase
• Glutamate Decarboxylase
• glutamate decarboxylase 1

Topics

• 4-Aminobutyrate Transaminase (metabolism)
• Animals
• Azoles (pharmacology)
• Blotting, Western
• Brain Ischemia (drug therapy, enzymology)
• Cell Death (drug effects)
• Gerbillinae
• Glutamate Decarboxylase (metabolism)
• Hippocampus (drug effects, enzymology)
• Immunohistochemistry
• Isoindoles
• Locomotion (drug effects)
• Neurons (drug effects, enzymology)
• Neuroprotective Agents (pharmacology)
• Organoselenium Compounds (pharmacology)
• Pyramidal Cells (drug effects, enzymology)
• Reperfusion Injury (drug therapy)
• Succinate-Semialdehyde Dehydrogenase (metabolism)
• Time Factors