Neuroprotective Effects of Adipose-Derived Stem Cells Are Maintained for 3 Weeks against Ischemic Damage in the Rabbit Spinal Cord

In the previous study, we demonstrated that adipose-derived stem cells (ASCs) have neuroprotective effects against ischemic damage in the ventral horn of L5-6 levels at 3 days after ischemia/reperfusion. In the present study, we expanded our observations for 3 weeks after ischemia/reperfusion to rule out the possibility of delayed neuronal death in several days after ischemia/reperfusion. Transient spinal cord ischemia was induced by a 15 min aortic artery occlusion in the subrenal region and rabbit ASCs were administered intrathecally into recipient rabbits (2 × 10(5)) immediately after reperfusion. Transplantation of ASCs improved the neurological motor functions of the hindlimb 3 weeks after ischemia/reperfusion. Similarly, the cresyl violet-positive neurons were significantly increased at 3 weeks after ischemia/reperfusion compared to that in the vehicle (artificial cerebrospinal fluid)-treated group. The transplantation of ASCs significantly reduced reactive microglia induced by ischemia at 3 weeks after ischemia/reperfusion. In addition, transplantation of ASCs maintained the brain-derived neurotrophic factor (BDNF) levels 3 weeks after ischemia/reperfusion. These results suggest that the neuroprotective effects of ASCs are maintained 3 weeks after ischemia/reperfusion by modulating microgliosis and BDNF levels in the spinal cord.