Abstract
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 μg 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.
Conclusion 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.
