Figure 1 Nerve reroute illustration. Crossover nerve surgery was conceptualized by Basil Kilvington in 1907, although his experiment on 3 dogs did not demonstrate any bladder contraction. Afterward, positive results have been reported by bladder reinnervation, establishing new connections by rerouting of lumbar spinal ventral roots or peripheral motor nerves of the hypogastric, obturator, genitofemoral, or intercostal nerves into the bladder. According to Dr. de Groat, there

are some basic principles of nerve rerouting: (1) following peripheral nerve injury, axons distal to the injury degenerate and the surviving central axon terminals produce growth cones, (2) denervated target Inhibitors,research,lifescience,medical cells express neurotrophic factors that attract regenerating axons, and (3) cholinergic motor axons can innervate FAK inhibitor decentralized autonomic ganglion cells in the bladder and may directly innervate bladder smooth muscle to establish new excitatory pathways between the spinal cord and the bladder. In 1989, Xiao and coworkers planned to establish an artificial skincentral nervous system (CNS)-bladder reflex pathway to restore Inhibitors,research,lifescience,medical controllable micturition after spinal cord injury. The new concept Inhibitors,research,lifescience,medical was tested in rats, cats, and humans. They grafted a lumbar ventral root containing motor fibers projecting to the hind limb to a transected sacral ventral root carrying the efferent axons to the bladder, creating

a new pathway that could evoke bladder contractions. The new reflex pathway, which is basically Inhibitors,research,lifescience,medical a somatic reflex arc,

was activated by electrical or tactile stimulation of cutaneous afferent axons that normally excite motoneurons in the lumbar spinal cord (Figure 1). Axonal-tracing studies conducted in animals showed that, after spinal root anastomosis, lumbar motoneurons that normally innervate limb-striated muscles send axons to the bladder. Pharmacological experiments were conducted and showed suppression of the new skin-CNS-bladder reflex by a ganglionic blocking agent or by atropine, indicating that the motor axons established cholinergic synapses with bladder Inhibitors,research,lifescience,medical parasympathetic ganglion cells that release acetylcholine which then activates muscarinic receptors in bladder smooth muscle. In 1995, clinical trials began of the artificial somatic-CNS-autonomic reflex arc procedure on adult male patients with upper motoneuron almost lesions and in children with spina bifida. The reflex arc was realized by unilateral anastomosis of the L5 and sacral 2–3 spinal ventral roots. Electrical or tactile stimulation of the cutaneous receptors in the leg ipsilateral to the spinal root anastomosis resulted in voiding. Patients underwent urodynamic evaluation which exhibited improvement in neurogenic detrusor overactivity, detrusor sphincter dyssynergia, and postvoid residual volumes. The results appeared approximately 12 to 18 months after the procedure. Bladder capacity increased and incontinence was reduced in children suffering from spina bifida.