Combination effect of p-hydroxybenzyl alcohol and mesenchymal stem cells on the recovery of brain damage in a rat model of brain ischemia

Abstract

p-Hydroxybenzyl alcohol (HBA), an active component of Gastrodia elata blume, has been reported to provide neuroprotection by preventing brain damage. Transplantation of mesenchymal stem cell (MSC) has been shown to ameliorate ischemic brain injury in animals. To explore a way that might enhance neuroprotection after brain stroke, we investigated whether the transplantation of neural progenitor cells (NPCs) derived from MSCs from adipose tissue combined with HBA may enhance neuroprotective effects in an animal model of brain stroke. Intracarotid injection of combination therapy groups showed a significant reduction of infarct volume by 2,3,5-triphenyltetrazolium chloride staining and an improvement of neurological functions were observed at 3 days after middle cerebral artery occlusion (MCAO), compared to monotherapy groups. In our studies, immunohistochemistry showed that NPCs are more likely to enter a damaged brain than a contralateral nonischemic brain. Coadministration of HBA and NPCs enhanced the anti-apoptotic effect and reduced the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic cells compared to the vehicle and NPCs at 7 days after MCAO. HBA and the combination of HBA +NPCs induced the expression of genes encoding antioxidant proteins, including PDI, Nrf2, endogenous neurotrophic factor gene brain-derived neurotrophic factor, NGF, and VEGF, which enhances angiogenesis in an ischemic brain. These effects might be responsible for the survival of NPCs and improved functional behavior. Our finding indicates that combination therapy of HBA and NPCs enhances neuroprotection against ischemic brain injury.