Nerve Growth Factor Modulation of the Cavernous Nerve Response to Injury

Overview

Journal J Sex Med

Publisher Oxford University Press

Specialties Gynecology & Obstetrics
Reproductive Medicine
Urology

Date 2009 Mar 10

PMID 19267859

Citations 20

Authors

Anthony J Bella

Guiting Lin

Ching-Shwun Lin

Duane R Hickling

Christopher Morash

Tom F Lue

Affiliations

Soon will be listed here.

Abstract

Introduction: Surgical therapies for prostate cancer and other pelvic malignancies often result in neuronal damage and debilitating loss of sexual function due to cavernous nerve (CN) trauma. Advances in the neurobiology of growth factors have heightened clinical interest in the development of protective and regenerative neuromodulatory strategies targeting CN recovery following injury.

Aim: The aim of this review was to offer an examination of current and future nerve growth factor (NGF) modulation of the CN response to injury with a focus on brain-derived nerve growth factor (BDNF), growth differentiation factor-5 (GDF-5), and neurturin (NTN).

Methods: Information for this presentation was derived from a current literature search using the National Library of Medicine PubMed Services producing publications relevant to this topic. Search terms included neuroprotection, nerve regeneration, NGFs, neurotrophic factors, BDNF, GDF-5, NTN, and CNs.

Main Outcome Measures: Basic science studies satisfying the search inclusion criteria were reviewed.

Results: In this session, BDNF, atypical growth factors GDF-5 and NTN, and their potential influence upon CN recovery after injury are reviewed, as are the molecular pathways by which their influence is exerted.

Conclusions: Compromised CN function is a significant cause of erectile dysfunction development following prostatectomy and serves as the primary target for potential neuroprotective or regenerative strategies utilizing NGFs such as BDNF, GDF-5, and NTN, and/or targeted novel therapeutics modulating signaling pathways.

Citing Articles

Molecular pathogenesis and treatment of cavernous nerve injury-induced erectile dysfunction: A narrative review.

Song G, Hu P, Song J, Liu J, Ruan Y Front Physiol. 2022; 13:1029650.

PMID: 36277218 PMC: 9582663. DOI: 10.3389/fphys.2022.1029650.

Characterization of atherosclerotic plaques in blood vessels with low oxygenated blood and blood pressure (Pulmonary trunk): role of growth differentiation factor-15 (GDF-15).

Bonaterra G, Struck N, Zuegel S, Schwarz A, Mey L, Schwarzbach H BMC Cardiovasc Disord. 2021; 21(1):601.

PMID: 34920697 PMC: 8684150. DOI: 10.1186/s12872-021-02420-9.

Cytokines, Chemokines, and Inflammation in Pulmonary Arterial Hypertension.

Liang S, Desai A, Black S, Tang H Adv Exp Med Biol. 2021; 1303:275-303.

PMID: 33788198 DOI: 10.1007/978-3-030-63046-1_15.

Adipose-derived stem cells modified by gene rescue erectile dysfunction after cavernous nerve injury.

Yang M, Sun J, Ying C, Wang Y, Guo Y Neural Regen Res. 2019; 15(1):120-127.

PMID: 31535660 PMC: 6862402. DOI: 10.4103/1673-5374.264464.

Epalrestat, an Aldose Reductase Inhibitor, Restores Erectile Function in Streptozocin-induced Diabetic Rats.

Yang B, Hong Z, Zhang Z, Yu W, Song T, Zhu L Int J Impot Res. 2018; 31(2):97-104.

PMID: 30214006 PMC: 6462873. DOI: 10.1038/s41443-018-0075-x.

References

Nangle M, Keast J . Reduced efficacy of nitrergic neurotransmission exacerbates erectile dysfunction after penile nerve injury despite axonal regeneration. Exp Neurol. 2007; 207(1):30-41. DOI: 10.1016/j.expneurol.2007.05.011. View

Bella A, Lin G, Tantiwongse K, Garcia M, Lin C, Brant W . Brain-derived neurotrophic factor (BDNF) acts primarily via the JAK/STAT pathway to promote neurite growth in the major pelvic ganglion of the rat: part I. J Sex Med. 2006; 3(5):815-820. DOI: 10.1111/j.1743-6109.2006.00291.x. View

Farkas L, Scheuermann S, Pohl J, Unsicker K, Krieglstein K . Characterization of growth/differentiation factor 5 (GDF-5) as a neurotrophic factor for cultured neurons from chicken dorsal root ganglia. Neurosci Lett. 1997; 236(2):120-2. DOI: 10.1016/s0304-3940(97)00773-8. View

Walsh P . Anatomic radical prostatectomy: evolution of the surgical technique. J Urol. 1998; 160(6 Pt 2):2418-24. DOI: 10.1097/00005392-199812020-00010. View

Chen K, Minor T, Rahman N, Ho H, Nunes L, Lue T . The additive erectile recovery effect of brain-derived neurotrophic factor combined with vascular endothelial growth factor in a rat model of neurogenic impotence. BJU Int. 2005; 95(7):1077-80. DOI: 10.1111/j.1464-410X.2005.05470.x. View

Bella A, Lin G, Cagiannos I, Lue T . Emerging neuromodulatory molecules for the treatment of neurogenic erectile dysfunction caused by cavernous nerve injury. Asian J Androl. 2007; 10(1):54-9. DOI: 10.1111/j.1745-7262.2008.00368.x. View

Ng B, Chen L, Mandemakers W, Cosgaya J, Chan J . Anterograde transport and secretion of brain-derived neurotrophic factor along sensory axons promote Schwann cell myelination. J Neurosci. 2007; 27(28):7597-603. PMC: 6672611. DOI: 10.1523/JNEUROSCI.0563-07.2007. View

Wang R . Penile rehabilitation after radical prostatectomy: where do we stand and where are we going?. J Sex Med. 2007; 4(4 Pt 2):1085-97. DOI: 10.1111/j.1743-6109.2007.00482.x. View

Canguven O, Burnett A . Cavernous nerve injury using rodent animal models. J Sex Med. 2008; 5(8):1776-85. DOI: 10.1111/j.1743-6109.2008.00955.x. View

10.

Hotten G, Neidhardt H, JACOBOWSKY B, Pohl J . Cloning and expression of recombinant human growth/differentiation factor 5. Biochem Biophys Res Commun. 1994; 204(2):646-52. DOI: 10.1006/bbrc.1994.2508. View

11.

Mitsui T, Fischer I, Shumsky J, Murray M . Transplants of fibroblasts expressing BDNF and NT-3 promote recovery of bladder and hindlimb function following spinal contusion injury in rats. Exp Neurol. 2005; 194(2):410-31. DOI: 10.1016/j.expneurol.2005.02.022. View

12.

Wanigasekara Y, Keast J . Neurturin has multiple neurotrophic effects on adult rat sacral parasympathetic ganglion neurons. Eur J Neurosci. 2005; 22(3):595-604. DOI: 10.1111/j.1460-9568.2005.04260.x. View

13.

Kessler T, Burkhard F, Perimenis P, Danuser H, Thalmann G, Hochreiter W . Attempted nerve sparing surgery and age have a significant effect on urinary continence and erectile function after radical cystoprostatectomy and ileal orthotopic bladder substitution. J Urol. 2004; 172(4 Pt 1):1323-7. DOI: 10.1097/01.ju.0000138249.31644.ec. View

14.

Niere M, Braun B, Gass R, Sturany S, Volkmer H . Combination of engineered neural cell adhesion molecules and GDF-5 for improved neurite extension in nerve guide concepts. Biomaterials. 2006; 27(18):3432-40. DOI: 10.1016/j.biomaterials.2006.01.037. View

15.

Lin G, Chen K, Hsieh P, Yeh C, Lue T, Lin C . Neurotrophic effects of vascular endothelial growth factor and neurotrophins on cultured major pelvic ganglia. BJU Int. 2003; 92(6):631-5. DOI: 10.1046/j.1464-410x.2003.04439.x. View

16.

Lin G, Bella A, Lue T, Lin C . Brain-derived neurotrophic factor (BDNF) acts primarily via the JAK/STAT pathway to promote neurite growth in the major pelvic ganglion of the rat: part 2. J Sex Med. 2006; 3(5):821-829. DOI: 10.1111/j.1743-6109.2006.00292.x. View

17.

Bella A, Fandel T, Tantiwongse K, Brant W, Klein R, Garcia C . Neurturin enhances the recovery of erectile function following bilateral cavernous nerve crush injury in the rat. J Brachial Plex Peripher Nerve Inj. 2007; 2:5. PMC: 1820781. DOI: 10.1186/1749-7221-2-5. View

18.

Hiltunen J, Laurikainen A, Klinge E, Saarma M . Neurotrophin-3 is a target-derived neurotrophic factor for penile erection-inducing neurons. Neuroscience. 2005; 133(1):51-8. DOI: 10.1016/j.neuroscience.2005.01.019. View

19.

Sanicola M, Hession C, Worley D, Carmillo P, Ehrenfels C, Walus L . Glial cell line-derived neurotrophic factor-dependent RET activation can be mediated by two different cell-surface accessory proteins. Proc Natl Acad Sci U S A. 1997; 94(12):6238-43. PMC: 21033. DOI: 10.1073/pnas.94.12.6238. View

20.

Bakircioglu M, Lin C, Fan P, Sievert K, Kan Y, Lue T . The effect of adeno-associated virus mediated brain derived neurotrophic factor in an animal model of neurogenic impotence. J Urol. 2001; 165(6 Pt 1):2103-9. DOI: 10.1097/00005392-200106000-00078. View