Neurturin enhances the recovery of erectile function following bilateral cavernous nerve crush injury in the rat.
BACKGROUND
The molecular mechanisms responsible for the survival and preservation of function for adult parasympathetic ganglion neurons following injury remain incompletely understood. However, advances in the neurobiology of growth factors, neural development, and prevention of cell death have led to a surge of clinical interest for protective and regenerative neuromodulatory strategies, as surgical therapies for prostate, bladder, and colorectal cancers often result in neuronal axotomy and debilitating loss of sexual function or continence. In vitro studies have identified neurturin, a glial cell line-derived neurotrophic factor, as a neuromodulator for pelvic cholinergic neurons. We present the first in vivo report of the effects of neurturin upon the recovery of erectile function following bilateral cavernous nerve crush injury in the rat.


METHODS
In these experiments, groups (n = 8 each) consisted of uninjured controls and animals treated with injection of albumin (blinded crush control group), extended release neurotrophin-4 or neurturin to the site of cavernous nerve crush injury (100 mug per animal). After 5 weeks, recovery of erectile function (treatment effect) was assessed by cavernous nerve electrostimulation and peak aortic pressures were measured. Investigators were unblinded to specific treatments after statistical analyses were completed.


RESULTS
Erectile dysfunction was not observed in the sham group (mean maximal intracavernous pressure [ICP] increase of 117.5 +/- 7.3 cmH2O), whereas nerve injury and albumin treatment (control) produced a significant reduction in ICP elevation of 40.0 +/- 6.3 cmH2O. Neurturin facilitated the preservation of erectile function, with an ICP increase of 55% at 62.0 +/- 9.2 cmH2O (p < 0.05 vs control). Extended release neurotrophin-4 did not significantly enhance recovery of erectile function with an ICP change of 46.9 +/- 9.6. Peak aortic blood pressures did not differ between groups. No significant pre- and post-treatment weight differences were observed between control, neurotrophin-4 and neurturin cohorts. All animals tolerated the five-week treatment course.


CONCLUSIONS
Treatment with neurturin at the site of cavernous nerve crush injury facilitates recovery of erectile function. Results support further investigation of neurturin as a neuroprotective and/or neuroregenerative agent facilitating functional recovery after cavernous or other pelvic autonomic nerve injuries.
Bella
Anthony J
AJ
Knuppe Molecular Urology Laboratory and Department of Urology, University of California, San Francisco, USA.
Fandel
Thomas M
TM
Knuppe Molecular Urology Laboratory and Department of Urology, University of California, San Francisco, USA.
Tantiwongse
Kavirach
K
Knuppe Molecular Urology Laboratory and Department of Urology, University of California, San Francisco, USA.
Brant
William O
WO
Knuppe Molecular Urology Laboratory and Department of Urology, University of California, San Francisco, USA.
Klein
Robert D
RD
Rinat Neuroscience, South San Francisco, USA.
Garcia
Carlos A
CA
Rinat Neuroscience, South San Francisco, USA.
Lue
Tom F
TF
Knuppe Molecular Urology Laboratory and Department of Urology, University of California, San Francisco, USA.