Effects of FTY720 on neurological function and blood-spinal cord barrier of rats with acute spinal cord injury / 解放军医学杂志

ABSTRACT

Objective To investigate the effects of a novel immunomodulator FTY720 (Fingolimod) on nerve function and blood-spinal cord barrier (BSCB) of rats with acute spinal cord injury. Methods One hundred and forty-four adult Sprague- Dawley (SD) rats were randomly divided into four groups with 36 each normal control group (NG Group) rats without any treatment; sham-operated group (SO Group) rats' spinal cords were exposed by laminectomy without injury; hemisection group (HS Group) rats underwent spinal cord hemisection followed by intraperitoneal injection of normal saline; FTY720 treatment group (FTY720 Group) rats underwent spinal cord hemisection followed by intraperitoneal injection of FTY720 [1mg/(kg.d)] for 7 days. The neurological function was assessed by Basso Beatlie Bresnahan (BBB) scores, grid walking, N1 and P1 delay of motor evoked potential (MEP) and somatosensory evoked potentials (SEP), histological evaluation with light microscope with HE staining, and determination of blood-spinal cord barrier permeability with EB at different time points after injury. Results The nerve function of rats in HS group and FTY720 group was impaired after hemisection injury without signs of recovery up to Day 28 after damage as compared with NG group or SO group. The recovery of motor function in FTY720 treatment group was earlier than in HS group. The BBB scores, the results of grid walking test, and the latent period of SEP-P1 showed statistically significant difference between FTY720 group and HS group from Day 7 to 28 after injury (P<0.05). Comparing the pathological picture at Day 14 and Day 28 after injury, the number of chronic inflammatory cells, the degree of glial cell reaction, and the size of syringomyelia cavities in gray matter in FTY720 group were significantly less than those in HS group. In addition, the leakage of EB from the damaged BSCB increased in HS group and FTY720 group than in NG group and SO group through 7 days after injury (P<0.01), while at each time point the leakage of EB was less in FTY720 group than in HS group (P<0.05), and the most significant difference was observed on Day 3 after injury. Conclusion FTY720 can lower the permeability of blood-spinal cord barrier at acute phase of spinal cord injury, effectively promotes the recovery of nerve function after acute injury phase, and it provides certain potential neuroprotective effects.