Sildenafil promotes neuroprotection of the pelvic ganglia neurones after bilateral cavernosal nerve resection in the rat
Article first published online: 6 JUN 2012
© 2012 BJU International
Volume 111, Issue 1, pages 159–170, January 2013
How to Cite
Hlaing, S. M., Garcia, L. A., Kovanecz, I., Martinez, R. A., Shah, S., Artaza, J. N. and Ferrini, M. G. (2013), Sildenafil promotes neuroprotection of the pelvic ganglia neurones after bilateral cavernosal nerve resection in the rat. BJU International, 111: 159–170. doi: 10.1111/j.1464-410X.2012.11278.x
- Issue published online: 20 DEC 2012
- Article first published online: 6 JUN 2012
- bilateral cavernosal nerve resection;
- main pelvic ganglia;
What's known on the subject? and What does the study add?
- Treatment with phosphodiesterase 5 (PDE5) inhibitors preserves penile corporal smooth muscle and inhibits the fibrotic degeneration normally seen after bilateral cavernosal nerve resection (BCNR) in rats. However, the effect of PDE5 inhibitors on the pelvic ganglia neurones affected by BCNR is unknown.
- The present study found that cavernosal nerve damage triggers a cascade of events in pelvic ganglia neurones, including changes in the expression of neurotransmitters, neurotrophic factors and cytokine production. Treatment with sildenafil ameliorates the impact of nerve damage by up-regulating neuronal nitric oxide synthase and neurotrophic factors, promoting a neuroprotective microenvironment that may favour nerve regeneration of the pelvic ganglia neurones affected by BCNR.
- To determine the gene expression profile of pelvic ganglia neurones after bilateral cavernosal nerve resection (BCNR) and subsequent treatment with sildenafil in relation to neurotrophic-related pathways.
Materials and Methods
- Fisher rats aged 5 months were subjected to BCNR or sham operation and treated with or without sildenafil (20 mg/kg body-weight in drinking water) for 7 days.
- Total RNA isolated from pelvic ganglia was subjected to reverse transcription and then to quantitative reverse transcriptase-polymerase chain reaction (PCR) with the RAT-neurotrophic array.
- Results were corroborated by real-time PCR and western blotting.
- Another set of animals were injected with a fluorescent tracer at the base of the penis, 7 days before BCNR or sham operation, and were sacrificed 7 days after surgery.
- Sections of pelvic ganglia were used for immunohistochemistry with antibodies against neurturin, neuronal nitric oxide synthase, tyrosine hydroxylase and glial cell line-derived neurotrophic factor receptor α2.
- A down-regulation of the expression of neuronal nitric oxide synthase accompanied by changes in the level of cholinergic neurotrophic factors, such as neurturin and its receptor glial cell line-derived neurotrophic factor receptor α2, artemin, neurotrophin-4 and cilliary neurotrophic factor, was observed 7 days after BCNR in pelvic ganglia neurones.
- Treatment with sildenafil, starting immediately after surgery, reversed all these changes at a level similar to that in sham-operated animals.
- Sildenafil treatment promotes changes in the neurotrophic phenotype, leading to a regenerative state of pelvic ganglia neurones.
- The present study provides a justification for the use of phosphodiesterase 5 inhibitors as a neuroprotective agent after BCNR.