Background
Adult hippocampal neurogenesis is crucial for the improvement of cognitive function following cerebral ischemia (CI). Sulfuretin, a flavonoid extracted from Rhus verniciflua, has been found to exert neuroprotection in cerebral disease. Here, we studied the effects of sulfuretin on cognitive function and hippocampal neurogenesis in mice with CI.
Methods
CI was induced in adult mice using the middle cerebral artery occlusion (MCAO) method. Mice were injected with sulfuretin (300 μg/kg, i.p.) from day 1 to day 28 after MCAO and 5-bromo-2′-deoxyuridine (BrdU) (50 mg·kg, i.p.) from day 1 to day 6, and sacrificed on days 7 and 14. Cerebral infarct and neuronal survival in the hippocampal dentate gyrus (DG) were examined using triphenyltetrazolium chloride staining and Nissl staining, respectively. Immunofluorescence staining of BrdU and doublecortin (DCX) was performed to evaluate neurogenesis in the hippocampal DG. The levels of neurotrophic factors including BDNF, TrkB, and CREB in the hippocampus were measured using western blotting. Spatial learning and memory were assessed using the Morris water maze test.
Results
Sulfuretin significantly mitigated cerebral infarct and increased neuronal survival following CI. Sulfuretin promoted hippocampal neurogenesis and increased the number of immature neurons. Sulfuretin significantly enhanced the protein levels of BDNF, phosphorylated TrkB, and phosphorylated CREB in the hippocampus. Moreover, sulfuretin effectively improved spatial learning and memory ability post-CI.
Conclusion
Overall, sulfuretin can improve cognitive dysfunction induced by CI in mice by improving hippocampal neurogenesis, suggesting that sulfuretin might be a candidate drug to treat CI.
