Neuroprotection of ethanol against cerebral ischemia/reperfusion induced brain injury through GABA receptor activation.
In this study we investigated whether ethanol could play neuroprotective effects against ischemic brain injury and the related mechanism. Cresyl violet staining results demonstrated that moderate dose of ethanol administered intracerebroventricularly (i.c.v.) had neuroprotective effect against ischemia-reperfusion induced neuronal cell death. Ethanol also inhibited the phosphorylation of JNK3 induced by cerebral ischemia-reperfusion. Three separate drugs, NS3763 (the selective antagonist of GluR5), GluR5 antisense oligodeoxynucleotides (AS-ODNs) and Bicuculline (an antagonist of GABA receptors), were found to inhibit the neuroprotective effect of ethanol. Moreover, the GABA receptor agonist muscimol could attenuate the JNK3 phosphorylation. Taken together, the results suggest that during ischemia-reperfusion ethanol may activate presynaptic GluR5-KA and postsynaptic GABA receptors continuously, and the activation of GABA receptors inhibits the JNK3 signal pathway. The results show a novel potential mechanism underlying ethanol protective effects.
Qi
Su-Hua
SH
Research Center for Biochemistry and Molecular Biology and Provincial Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou 221002, PR China.
Liu
Yong
Y
Wang
Wei-Wei
WW
Wang
Min
M
Zhang
Guang-Yi
GY
D000818:Animals; D001549:Benzamides / Q000008:administration & dosage; D001640:Bicuculline / Q000008:administration & dosage; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy*; D002545:Brain Ischemia / Q000150:complications; D016923:Cell Death / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage*; D018682:GABA Agents / Q000008:administration & dosage; D008297:Male; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism; D009118:Muscimol / Q000008:administration & dosage; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D015427:Reperfusion Injury / Q000188:drug therapy*
D001549:Benzamides; D001640:Bicuculline; D000431:Ethanol; D018682:GABA Agents; D048057:Mitogen-Activated Protein Kinase 10; D009118:Muscimol; D018696:Neuroprotective Agents; D020319:Oligodeoxyribonucleotides, Antisense; D018079:Receptors, GABA; D018092:Kainic Acid Receptors; C487402:5-carboxyl-2,4-di-benzamidobenzoic acid