Objective  To investigate whether Danhong injection can enhance the therapeutic effect of neural stem cell (NSC) transplantation in repairing cerebral ischemia injury by regulating the nuclear factor E2-related factor 2 (Nrf2) signaling pathway.

  Methods  Forty male SD rats were randomly divided into the NSC transplantation group (NSC group), Danhong injection group (DH group), NSC+ Danhong injection group (N+D group), NSC+ Danhong injection group +ML385 group(N+D+M group) and PBS control group (PBS group), 8 rats in each group. All rat models of cerebral ischemia were established by embolization of the middle cerebral artery. Reperfusion was performed at 1.5 h after embolization. All rats in each group received corresponding interventions at 3 d after reperfusion. The neurological function score was evaluated before and 1, 2, 4 weeks after NSC transplantation. All rats were sacrificed at 4 weeks after NSC transplantation. The parameters related to oxidative stress were detected. The expression levels of neuron-specific nuclear protein (NeuN) and von Willebrand factor (vWF) were determined by immunofluorescence staining.

  Results  Before NSC transplantation, the neurological function scores did not significantly differ among different groups (all P > 0.05). At postoperative 1, 2 and 4 weeks, the neurological function scores in the NSC, DH and N+D groups were significantly lower than those in the PBS and N+D+M groups (all P < 0.05). Compared with the PBS and N+D+M groups, the malondialdehyde (MDA) levels were significantly decreased, whereas the superoxide dismutase (SOD) and glutathione peroxidase (GPX) levels were considerably increased in the NSC, DH and N+D groups (all P < 0.05). The GPX level in the N+D+M group was significantly lower than that in the PBS group (P < 0.05). Immunofluorescence staining showed that the transplant NSC in the rat brain migrated to the surrounding area of cerebral infarction and survived, and expressed neuronal marker NeuN and neovascularization marker vWF. However, the number of living NSC in the N+D+M group was significantly lower compared with those in the remaining groups.

  Conclusions  Danhong injection may improve the microenvironment of stem cell transplantation, enhance the survival rate of transplant NSC and improve the therapeutic effect of NSC transplantation for cerebral ischemia injury probably by regulating the Nrf2 signaling pathway.