Ilexonin A Promotes Neuronal Proliferation and Regeneration via Activation of the Canonical Wnt Signaling Pathway after Cerebral Ischemia Reperfusion in Rats

Aims. Ilexonin A (IA), a component of the Chinese medicine Ilex pubescens, has been shown to be neuroprotective during ischemic injury. However, the specific mechanism underlying this neuroprotective effect remains unclear. Methods. In this study, we employed a combination of immunofluorescence staining, western blotting, RT-PCR, and behavioral tests, to investigate the molecular mechanisms involved in IA regulation of neuronal proliferation and regeneration after cerebral ischemia and reperfusion in rodents. Results. Increases in beta-catenin protein and LEF1 mRNA and decreases in GSK3 beta protein and Axin mRNA observed in IA-treated compared to control rodents implicated the canonical Wnt pathway as a key signaling mechanism activated by IA treatment. Furthermore, rodents in the IA treatment group showed less neurologic impairment and a corresponding increase in the number of Brdu/nestin and Brdu/NeuN double positive neurons in the parenchymal ischemia tissue following middle cerebral artery occlusion compared to matched controls. Conclusion. Altogether, our data indicate that IA can significantly diminish neurological deficits associated with cerebral ischemia reperfusion in rats as a result of increased neuronal survival via modulation of the canonical Wnt pathway.