Assessment of the MRI and behavioral test results in a focal cerebral ischemia-reperfusion model in the rat after separate and combined use of mouse-derived neural progenitor cells, human-derived neural progenitor cells and atorvastatin

Abstract

AIM: To assess the efficacy of Neural progenitor cell (NPC) transplantation in ischemic stroke, and to investigate whether atorvastatin enhances therapeutic potency of NPC after stroke. MATERIAL and METHODS: The focal cerebral ischemia-reperfusion model was performed by transient occlusion of middle cerebral artery. Rats were assigned randomly to receive intracerebral transplantation of mouse NPC alone (mNPC), human NPC alone (hNPC), mouse NPC plus oral atorvastatin (mNPC+A), human NPC plus oral atorvastatin (hNPC+A), oral atorvastatin alone, or intracerebral Dulbecco's Modified Eagle's medium injection (control group). Adhesive removal, rotarod, cylinder tests, and magnetic resonance imaging (MRI) were used for assessment of rats during 4 weeks. After sacrification on 28th day, rats were investigated by immunofluorescent staining. RESULTS: The hNPC and mNPC groups showed significantly improved functional outcome and reduced infarct area ratio compared with the control group. The hNPC group had significantly better performance and lower infarct area ratio than the mNPC group. Addition of atorvastatin to stem cell therapy significantly improved functional outcome, although it did not affect the infarct area ratio on MRI. Anti-inflammatory response in the infarct area was higher in the mNPC group. NPC transplantation significantly reduced the amount of microglia and a significant increase in the amount of astrocytes. CD8a+ T lymphocyte and granzyme B activities were not detected in any of the subjects. CONCLUSION: Both hNPC and mNPC treatments significantly improved functional outcome, and reduced infarct area ratio after stroke. Atorvastatin enhanced the therapeutic potency of NPCs, including neurological improvement.