Inhibition of GSK-3 reduces infarct volume and improves neurobehavioral functions.
In the present study, we have investigated the effects of glycogen synthase kinase-3 (GSK-3) inhibition on infarct volume and neurobehavioral functions in a focal cerebral ischemia model. To achieve our goals, GSK-3 inhibitor II or VIII was injected at several time points and in varing dosages. GSK-3 inhibitor VIII was more effective than inhibitor II, and infarct volume and water content in the VIII group were significantly decreased 24h after the onset of ischemic stroke, as compared with the control group. These protective effects were associated with reductions of TUNEL-positive cells, neutrophil infiltration, glucose levels after ischemia, and GSK-3 enzyme activity. In addition, expressions of death and inflammation-related signals decreased and those of survival-related signals increased. Lastly, neurobehavioral functions were restored to a greater extent in the VIII group than in the control group. Together, these results suggest that GSK-3 inhibition reduces infarct volume and restores neurobehavioral functions.
Koh
Seong-Ho
SH
Department of Neurology, College of Medicine, Hanyang University, #17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Republic of Korea.
Yoo
A Rum
AR
Chang
Dae-Il
DI
Hwang
Se J
SJ
Kim
Seung H
SH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D001929:Brain Edema / Q000201:enzymology / Q000209:etiology / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000032:analysis; D053148:Caspase 3 / Q000032:analysis; D002544:Cerebral Infarction / Q000150:complications / Q000201:enzymology / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000032:analysis; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D038362:Glycogen Synthase Kinase 3 / Q000032:analysis / Q000037:antagonists & inhibitors*; D008840:Microfilament Proteins; D010069:Oxadiazoles / Q000008:administration & dosage; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000008:administration & dosage; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives
C529548:2-thio(3-iodobenzyl)-5-(1-pyridyl)-(1,3,4)oxadiazole; C100745:Aif1 protein, rat; D001786:Blood Glucose; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D010069:Oxadiazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D013844:Thiazoles; C479831:N-(4-methoxybenzyl)-N'-(5-nitro-1,3-thiazol-2-yl)urea; D014508:Urea; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D011065:Poly(ADP-ribose) Polymerases; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3