Induction of phosphorylated-Stat3 following focal cerebral ischemia in mice.

It has been shown that Stat3 is induced following transient cerebral ischemia in rat. However there is no evidence that cerebral ischemia stimulates the expression of phosphorylated-Stat3 (p-Stat3), which can activate cytokine-mediated signal transduction from the membrane to the nucleus. In the present study, we investigated the changes in p-Stat3 expression following middle cerebral artery occlusion in mice. Western blot analysis revealed a significant increase in the p-Stat3 protein in the peripheral part of the ischemic area, starting from 6 h after ischemia. p-Stat3 immunoreactivity was detected only in neurons, but not in astrocytes or microglia, and p-Stat3-positive neurons were increased in number in the peripheral part of the ischemic area at 24 h after ischemia. Double staining with aTdT-mediated biotinylated UTP nick end labeling (TUNEL) kit and the p-Stat3 antibody indicated that p-Stat3-positive neurons were also TUNEL-positive. Subsequent immuno-electron microscopic observations showed that p-Stat3-positive neurons were at different stages of degeneration. The present findings suggest that the increased expression of p-Stat3 after cerebral ischemia could play a crucial role in ischemia-induced neuron death.