Pioglitazone Enhances Survival and Regeneration of Pelvic Ganglion Neurons After Cavernosal Nerve Injury

Katz, Eric G; Moustafa, Ahmed A.; Heidenberg, Daniel; Haney, Nora M.; Peak, Taylor C.; Lasker, George F.; Knoedler, Margaret; Rittenberg, Daniel; Rezk, Bashir M.; Elmageed, Zakaria Y. Abd; Yafi, Faysal A.; Sikka, Suresh C.; Abdel‐Mageed, Asim B.

doi:10.1016/j.urology.2015.12.021

Cited by 9 publications

(13 citation statements)

References 30 publications

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“…nNOS-positive nerve fibers innervating the penis derive mainly from the MPG [ 23 ]. Our results showed that the nNOS content in both the MPG and the dorsal penile nerve was reduced in the CN traction group, which is consistent with results in other CN injury models [ 9 , 24 , 25 ]. The number of neurofilament-positive nerve fibers in the dorsal penile nerve also declined, indicating that the axon contents were decreased after CN traction, which is also consistent with previous studies [ 26 , 27 ].…”

Section: Discussionsupporting

confidence: 92%

The effect of cavernous nerve traction on erectile function in rats

Chen

Wang

et al. 2017

PLoS ONE

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We performed this study to evaluate the effect of cavernous nerve (CN) traction on erectile function in rats. Thirty-two 8- week-old Sprague–Dawley rats were divided into four groups: control, 1-minute CN traction, 2-minute CN traction, and 2-minute CN crush. CN traction was performed using a glass hook with a tensile force of 0.2 Newton. One month later, the mean arterial pressure (MAP) and intracavernosal pressure (ICP) in response to CN stimulation were measured to assess erectile function. The penis and major pelvic ganglion (MPG) were harvested to explore the expression of neuronal nitric oxide synthase (nNOS) and neurofilament, fibrosis and apoptosis. The ICP/MAP ratio was reduced in the 2-minute CN traction group compared with the control group (P < 0.05). The ICP/MAP ratio in the CN crush group was lower than in the other three groups (P < 0.05, for each). Expression of nNOS in both MPG and dorsal penile nerve was lower in the CN traction group than in the control group, but was higher than in the CN crush group (P < 0.05). Nerve fiber number in the dorsal penile nerve was reduced by 2-minute CN traction (P < 0.05). The ratios of collagen to smooth muscle content and the apoptosis were both increased the in 2-minute CN traction group compared with the control group (P < 0.05). The findings indicate that CN traction is an effective CN injury model and the injury it caused is relatively mild compared with the CN crush model.

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Section: Discussionsupporting

confidence: 92%

The effect of cavernous nerve traction on erectile function in rats

Chen

Wang

et al. 2017

PLoS ONE

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“…Pioglitazone appears to preserve erectile activity when the corporal cavernosum undergoes neuronal failure. This was demonstrated in rats with bilateral cavernosal nerve crush injury [ 124 ]. In particular, when pioglitazone was administered both pre- and post-surgically, both survival and regeneration responses within the neuronal pelvic compartment were activated with an increase in nitrergic penis-projecting neurons and upregulation of key neuroprotective molecules (e.g., neurotrophin, neuturin) [ 124 ].…”

Section: Glucose-lowering Medicationsmentioning

confidence: 97%

“…This was demonstrated in rats with bilateral cavernosal nerve crush injury [ 124 ]. In particular, when pioglitazone was administered both pre- and post-surgically, both survival and regeneration responses within the neuronal pelvic compartment were activated with an increase in nitrergic penis-projecting neurons and upregulation of key neuroprotective molecules (e.g., neurotrophin, neuturin) [ 124 ]. Currently, the mechanism underlying these effects are still poorly investigated, even though some studies have established that the prevention of erectile failure by pioglitazone administration could occur via both anti-inflammatory and insulin-like growth factor I (IGF-I)-mediated pathways.…”

Section: Glucose-lowering Medicationsmentioning

confidence: 97%

Role of Glucose-Lowering Medications in Erectile Dysfunction

Cignarelli

Genchi

D’Oria

et al. 2021

JCM

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Erectile dysfunction (ED) is a long-term complication of type 2 diabetes (T2D) widely known to affect the quality of life. Several aspects of altered metabolism in individuals with T2D may help to compromise the penile vasculature structure and functions, thus exacerbating the imbalance between smooth muscle contractility and relaxation. Among these, advanced glycation end-products and reactive oxygen species derived from a hyperglycaemic state are known to accelerate endothelial dysfunction by lowering nitric oxide bioavailability, the essential stimulus of relaxation. Although several studies have explained the pathogenetic mechanisms involved in the generation of erectile failure, few studies to date have described the efficacy of glucose-lowering medications in the restoration of normal sexual activity. Herein, we will present current knowledge about the main starters of the pathophysiology of diabetic ED and explore the role of different anti-diabetes therapies in the potential remission of ED, highlighting specific pathways whose activation or inhibition could be fundamental for sexual care in a diabetes setting.

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“…Furthermore, a small randomized controlled trial has shown efficacy of this agent for erectile dysfunction refractory to sildenafil [146]. A study by Katz et al investigated the impact of pioglitazone on pelvic ganglion neurons after bilateral cavernosal nerve injury (BCNI) in Sprague-Dawley rats [147]. Four groups were examined: sham surgery, BCNI, BCNI + post-operative pioglitazone, BCNI + pre-and post-operative therapy.…”

Section: Neuroprotective Agentsmentioning

confidence: 99%

“…Four groups were examined: sham surgery, BCNI, BCNI + post-operative pioglitazone, BCNI + pre-and post-operative therapy. Gene expression profiles of neuronal nitric oxide synthase, neurturin, glial cell line-derived neurotrophic factor family receptor alpha-2 (GFRα2), and β-III tubulin were upregulated in the pre-operative therapy group [147]. Further work is necessary to fully explore the utility of this therapy.…”

Section: Neuroprotective Agentsmentioning

confidence: 99%

Preventing Erectile Dysfunction after Radical Prostatectomy: Nerve-Sparing Techniques, Penile Rehabilitation, and Novel Regenerative Therapies

Whalen¹

2019

Prostatectomy

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Erectile dysfunction is a known and much-dreaded functional consequence of radical prostatectomy. Dr. Patrick Walsh pioneered the nerve-sparing radical retropubic prostatectomy in the early 1980s, which has mitigated the morbidity of this surgery. Postoperative potency rates range widely from 20 to 80%, however, and depend on myriad factors including age, preoperative potency, and degree of nerve-sparing during surgery. Over the past four decades several developments have continued to offer hope to patients and clinicians alike, including refined understanding of cavernosal nerve neuroanatomy, beneficial modifications in surgical technique, as well as the advent of robotic surgery. Furthermore, multiple pre-and post-operative penile rehabilitation techniques using mechanotherapy and pharmaceuticals have also improved functional recovery. This paper examines erectile dysfunction as a consequence of radical prostatectomy, including the physiology of erections, the pathophysiology of post-operative erectile dysfunction, novel surgical techniques to enhance neurovascular bundle preservation, and penile rehabilitation strategies involving hyperbaric oxygen, neuroprotective pharmaceuticals, dehydrated human amnion-chorion membrane allografts, and mesenchymal stem cell therapy.

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Pioglitazone Enhances Survival and Regeneration of Pelvic Ganglion Neurons After Cavernosal Nerve Injury

Cited by 9 publications

References 30 publications

The effect of cavernous nerve traction on erectile function in rats

The effect of cavernous nerve traction on erectile function in rats

Role of Glucose-Lowering Medications in Erectile Dysfunction

Preventing Erectile Dysfunction after Radical Prostatectomy: Nerve-Sparing Techniques, Penile Rehabilitation, and Novel Regenerative Therapies

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