Combination effect of memantine and mesenchymal stem cells on the recovery of brain damage in a rat model of brain ischemia

Whether the transplantation of neural progenitor cells (NPCs) derived from mesenchymal stem cells combined with memantine enhanced neuroprotective effects in an animal model of stroke was investigated. In combination therapy groups, significant reduction of infarct volume and improvement of neurological functions were observed at 3 days after middle cerebral artery occlusion (MCAO) compared to monotherapy. Co-administration of memantine and NPCs enhanced the antiapoptotic effect and reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells compared to the NPCs alone group at 7 days after MCAO. Intracarotid transplanted NPCs were localized to the ischemic boundary zone. Moreover, the number of transplanted NPCs on day 7 with combination therapy was significantly higher than those of NPCs monotherapy. Memantine and the combination of memantine + NPCs induced the expression of endogenous neurotrophic factor genes brain-derived neurotrophic factor, nerve growth factor, and glia-derived neurotrophic factor and also upregulated Arc (activity-regulated cytoskeleton associated protein). These effects might be responsible for the induced survival of NPCs and improved functional behavior. These finding indicates that combination therapy of memantine and NPCs enhances neuroprotection against ischemic brain injury.