Effects of FK1706 on nerve regeneration and bladder recovery after spinal cord injury

Abstract

Objective To investigate the effects of FK1706 on nerve regeneration and bladder function recovery after spinal cord injury in rats. Methods Thirty adult male SD rats weighing 230-250 g were randomly divided into three groups for different treatments: FK1706 group, neurorrhaphy group and control group (10 rats each group). In FK1706 group, the spinal cords were transected in the level of L5 to make rat spinal injury model. Then the distal stump of L6VR was sutured to the lateral face of L4 ventral root (L4VR) in an end-to-side (ETS) fashion under microscope. FK1706 (0.3 mg/kg) was administrated subcutaneously for 5 consecutive days per week for a total of 8 weeks after neurorrhaphy. In neurorrhaphy group, the same operation as FK1706 group was performed but without FK1706 applied after surgery. In control group, left ventral and dorsal roots of L5, L6, S1 and S2 were transected but the left L6VR was preserved as normal control. After four months, FG and FB were injected into left major pelvic ganglion (MPG) and sciatic nerve (SN), respectively, for retrograde nerve tracing to ascertain whether neural pathway was established after surgery. The left L6VR distal to coaptation was harvested for semi-thin sectioning and toluidine blue staining to count the number of myelinated axons. Urodynamic parameters such as maximum detrusor pressure (MDP) and residual urine volume (RUV) were measured in rats through BL-420 biological experimental system. Results The neural pathways were successfully established between left L4VR and L6VR in FK1706 group and neurorrhaphy group through retrograde nerve tracing. The number of regenerated myelinated axons of left L6VR distal to coaptation in FK1706 group and neurorrhaphy group was 535.7±45.2 and 337.4±56.5, respectively, which had a significant difference (P=0.000). The MDP and RUV were (44.6±6.7) mmHg (1 mmHg=0.133 kPa) and (1.16±0.24) ml in FK1706 group, respectively, when the left L4VR proximal to coaptation was stimulated by BL-420 experimental system. The MDP and RUV were (32.5±5.4) mmHg and (2.36±0.34) ml in neurorrhaphy group, respectively. There were statistically significant differences in the MDP and RUV between the two groups (P=0.000). Conclusion The effects of nerve regeneration and bladder function recovery could be evidently enhanced by FK1706 after neurorrhaphy in rat spinal cord injury model. Key words: FK1706; Spinal cord injury; Nerve regeneration; Functional recovery