Activation of signal transducer and activator of transcription 3 signaling attenuates neurogenesis in a rat model of intracerebral hemorrhage.

Abstract

Neurogenesis plays an important role in promoting neurologic function after intracerebral hemorrhage (ICH). Signal transducer and activator of transcription 3 (STAT3) activation has been reported to negatively regulate neurogenesis. Previous studies have also demonstrated that activation of STAT3 signaling exerted a detrimental effect on ICH. In this study, we investigated the effect of STAT3 signaling on neurogenesis following ICH. A rat model of ICH was induced via the stereotaxic injection of 100 µL autologous blood into the right globus pallidus. AG490 (0.25 mg/kg) was injected into the lateral ventricle after ICH to block STAT3 signaling. Brains were perfused to identify proliferating cell nuclear antigen (PCNA)+/ doublecortin (DCX) + nuclei by immunohistochemistry. In addition, the distribution and expression of phosphorylated STAT3 [p-STAT3 (Tyr705)] were evaluated by immunohistochemistry and western blot, respectively. An enhanced level of p-STAT3 (Tyr705) was observed in neurons in the perihematomal region. An increase in DCX-positive cells and PCNA+/DCX+ nuclei was detected after ICH. Blocking STAT3 signaling with AG490 further increased the numbers of DCX-positive cells and PCNA+/DCX+ nuclei after ICH. These results suggest that activation of STAT3 signaling attenuates ICH-induced neurogenesis and may delay neural recovery following hemorrhagic cerebral injury.