Neuroprotection of ebselen against ischemia/reperfusion injury involves GABA shunt enzymes.
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.
Seo
Jeong Yeol
JY
Department of Emergency Medicine, College of Medicine, Hallym University, Chuncheon 200-702, South Korea.
Lee
Choong Hyun
CH
Cho
Jun Hwi
JH
Choi
Jung Hoon
JH
Yoo
Ki-Yeon
KY
Kim
Dae Won
DW
Park
Ok Kyu
OK
Li
Hua
H
Choi
Soo Young
SY
Hwang
In Koo
IK
Won
Moo-Ho
MH
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000818:Animals; D001393:Azoles / Q000494:pharmacology*; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology; D016923:Cell Death / Q000187:drug effects; D005849:Gerbillinae; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D007150:Immunohistochemistry; D054833:Isoindoles; D008124:Locomotion / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000201:enzymology; D015427:Reperfusion Injury / Q000188:drug therapy*; D050644:Succinate-Semialdehyde Dehydrogenase / Q000378:metabolism; D013997:Time Factors
D001393:Azoles; D054833:Isoindoles; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; C042986:ebselen; D050644:Succinate-Semialdehyde Dehydrogenase; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1