Rolipram prevents detrusor underactivity related to pelvic nerve injury in rats by promoting regeneration of nerve axons.

PURPOSE: Evaluation of the effects of rolipram, a phosphodiesterase 4 (PDE4) inhibitor, on detrusor underactivity in a rat model of pelvic nerve crush (PNC) injury.

MATERIALS AND

METHODS

Female Sprague-Dawley rats (12 weeks old) were divided into sham, PNC, PNC with saline (PNC/Vehicle) and PNC with oral rolipram (1.0 mg/kg/day) treatment (PNC/Rolipram) groups. Cystometrograms, organ bath studies and histological examinations were performed 10 days later.

RESULTS

Micturition interval, bladder capacity and residual volume were significantly increased, and voiding efficiency was significantly decreased in the PNC and PNC/Vehicle groups as compared with the sham group (P < 0.01 each). In organ bath studies, the responses of muscle strips to electrical field stimulation, which activates nerves, were significantly weaker in the PNC and PNC/Vehicle groups than the sham group. Significant improvements in cystometric parameters and muscle strip contractility were seen in the PNC/Rolipram group as compared with the PNC and PNC/Vehicle groups. Immunohistochemical staining demonstrated a significantly increased density of GAP-43-positive nerves, a marker of nerve regeneration, in the detrusor layer of PNC (P = 0.01) and PNC/Vehicle (P = 0.01) groups compared with the sham group. Moreover, the PNC/Rolipram group showed a further significant increase in GAP-43 expression compared with both the PNC group (P = 0.04) and the PNC/Vehicle group (P = 0.04).

CONCLUSIONS

Chronic rolipram treatment might prevent detrusor underactivity by promoting regeneration of nerve axons in a rat PNC model.