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 24 h 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. (C) 2008 Elsevier Inc. All rights reserved