Effects of pituitary adenylate cyclase-activating polypeptide on facial nerve recovery in the guinea pig

Objectives/Hypothesis. Pituitary adenylate cyclase-activating polypeptide (PACAP) has neurotrophic effects of neural regeneration and gives protection to the nervous system. We investigated whether PACAP had a neurotrophic effect on peripheral motoneurons and whether PACAP could facilitate glial cell line-derived neurotrophic factor (GDNF), a neurotrophin, in nerve regeneration. The presence and distribution of PACAP receptors following facial nerve transection were also investigated. Study Design: Animal experiment. Methods. Unilateral transection of the facial nerve was performed in male Hartley guinea pigs, and PACAP was injected at the site. Saline was substituted as a control. Compound muscle action potentials were recorded to measure the changes of latency. Glial cell line-derived neurotrophic factor (GDNF) content in facial target muscle was measured using enzyme-linked immunosorbent assay. The regenerating site was taken for histological studies. Results. Pituitary adenylate cyclase-activating polypeptide hastened the appearance of compound muscle action potentials and shortened the latency. Pituitary adenylate cyclase-activating polypeptide increased and prolonged the nerve transection-induced GDNF increase in the facial muscles. The number of myelinated fibers at 1 to 4 weeks after the transection was increased. PAC1 receptor or VPAC1 receptor or both were identified in the injury area at 2 to 4 weeks. Conclusions: Pituitary adenylate cyclase-activating polypeptide facilitated the recovery of latency of compound muscle action potentials or the number of myelinated. axons, or both. Pituitary adenylate cyclase-activating polypeptide prolonged the GDNF levels in target organs. These data indicated that PACAP promoted regeneration of the facial nerve.