Abstract:

BACKGROUND: Studies have confirmed that tacrolimus not only inhibits T cell proliferation and activation, but also suppresses microglia, macrophages and other inflammatory cells to aggregate, activate and release associated inflammatory cytokines in injuries, which can reduce the damage of secondary inflammation to surrounding normal tissue, thus, provide protective effect to nerves in injuries. 
OBJECTIVE: To observe the effect of tacrolimus on spinal cord regeneration and injury repair following neural stem cells (NSCs) transplantation in rats.
METHODS: NSCs were isolated form 13-day-pregnant SD rats. Aneurysm clipping folder was used to clip T8 spinal cord of rats under microscope to establish animal model of spinal cord compression injury. At 7 days after injury, all rats were randomly divided into 3 groups: rats in the control group were injected with normal saline at the injury center orientation; those in the cell transplantation group received center directional injection of neural stem cells (NSCs); those in the tacrolimus (FK506) group received directional injection of NSCs combined with intraperitoneal injection of immunosuppressant FK506, 1 mm/kg per day for 7 continuous days. The spinal cord tissue regeneration and neuronal changes were observed using BDA anterograde tracer, haematoxylin-eosin staining, immunohistochemistry and electron microscopy at 1, 2, 4 and 8 weeks after operation.
RESULTS AND CONCLUSION: There were no fibers passing through the distal end of the injury center in the control group. However, some nerve fibers in the cell transplantation and FK506 groups passed at 1 week after treatment. Parts of regenerating BDA-positive corticospinal tract passed through the site of spinal cord injury in the cell transplantation and FK506 groups at 8 weeks after treatment, especially in the FK506 group, which may be continued to 1.7 cm of the injury center. Hematoxylin-eosin staining showed that, the necrotic foci began to shrink, and the foam cells decreased in the cell transplantation group and FK506 group at 2 weeks after treatment. Electron microscopy results showed that, in the FK506 group, more normal microfilament and microtubule structure appeared at 1 week, the astrocytes, Schwann cells, and myelin sheaths were commonly seen at 8 weeks after treatment, nerve axons of excitatory terminals had more excitatory transmitter and non-typical tree-axis connections, and there were more normal myelin sheaths. It illustrated that, NSCs transplantation combined with FK506 can reduce the early post-acute inflammatory response, ensure the survival of nerve cells, exhibit neuroprotective and neurotrophic roles, as well as speed up the recovery of neurological function.