Spinal implants of olfactory ensheathing cells promote axon regeneration and bladder activity after bilateral lumbosacral dorsal rhizotomy in the adult rat.

摘要

PURPOSE: We performed spinal implantation of olfactory ensheathing cells to demonstrate dorsal root afferent regeneration as well as bladder activity restoration after lumbosacral L6 to S2 rhizotomy. MATERIALS AND METHODS: Spinal segments receiving bladder innervation, usually L6, S1 and S2, were identified by bipolar stimulation of the ventral roots. Bilateral section of the identified dorsal roots L6 to S2 was performed in 18 male Wistar rats. Immediately after rhizotomy olfactory ensheathing cells or vehicle was unilaterally injected in the vicinity of the sacral parasympathetic nucleus in 9 rats each using a glass micropipette and air pulse system. The severed roots were reattached to the cord with fibrin glue and the animals recovered under antibiotic prophylaxis. RESULTS: Anatomical regeneration of bladder wall primary afferents was demonstrated by the presence of labeled wheat germ agglutinin-horseradish peroxidase fibers in the dorsal horn and sacral parasympathetic nucleus in 8 of 9 cases of olfactory ensheathing cell implantation but not in the 9 controls injected with vehicle. One week after surgery all rats had an atonic bladder on cystometrography. At 6 weeks 8 of the 9 olfactory ensheathing cell implanted rats had recovered bladder activity. No recovery was observed in controls, in which vehicle was injected instead of olfactory ensheathing cells. CONCLUSIONS: Regenerated primary afferent fibers from the bladder project to the sacral parasympathetic nucleus, where they presumably form synapses mediating the recovery of bladder activity. Thus, olfactory ensheathing cell implants in the adult rat promote sensory axon regeneration, target reinnervation and bladder activity restoration.