Study on the therapeutic effect of simvastatin by mobilizing the bone marrow-derived stem cells to the injury site in spinal cord injury rat

English Keywords:Spinal cord injury  Simvastatin  Bone marrow-derived stem cells  Homing  Rat

English Abstract:

  【Abstract】 Objectives: To study the effect of simvastatin-mediated mobilization of bone marrow-derived stem cells(BMSCs) on the injured spinal cord and the underlying mechanism. Methods: The transgenic rat GFP-BMSCs were transplanted into rat through the caudal vein. 24 hours after transplantation, animals were randomly divided into 3 groups: sham group(laminectomy only), vehicle treated group(SCI+vehicle) and simvastatin treated group(SCI+simvastatin). Spinal cord injury was introduced by modified Allen′s method (10g·4cm) at T10 level. Simvastatin or vehicle was injected into the subarachnoid space after injury. Hind limb locomotor recovery(BBB scores and inclined plane test) was used for assessment. At 28 days after injury, animals were killed and HE was performed to evaluate the area of spinal cavity. Immunohistochemistry for GFP and cell lineage marker NeuN and GFAP was performed to evaluate simvastatin-mediated mobilization of bone marrow-derived cells into injured spinal cord. Western blot was performed to detect the expression of BDNF and VEGF. Results: The BBB scores and inclined-plated angles of the sham group did not significanlty change during the research. While those in simvastatin treated rats showed significant recovery of hind limb function compared to control rats. HE revealed that simvastatin decreased the cavity of injured spinal cord. Immunohistochemistry revealed that simvastatin increased the number of GFP-positive cells in injured spinal cord, indicating that bone marrow-derived cells were mobilized and migrated into injured spinal cord. The numbers of double positive cells for GFP and NeuN marker or GFAP were more in the simvastatin treated rats than in the control rats, indicating that these GFP-BMSCs differentiated into the neuro or glial cells. The expression levels of BDNF and VEGF were higher in the simvastatin treated group. Conclusions: Simvastatin can mobilize the BMSCs home to the injured spinal cord, which can decrease the spinal cavity, increase the expression of BDNF and VEGF, and improve the functional recovery of spinal cord injury.