ObjectiveTo investigate the protective effect of human urine-derived stem cells (USCs) on erectile function and cavernous structure in rats with cavernous nerve injury (CNI).

METHODSSixty adult male SD rats with normal sexual function were randomly divided into four groups of equal number: sham operation, bilateral CNI (BCNI) model control, phosphate buffered saline (PBS), and USC. The BCNI model was established in the latter three groups of rats by clamping the bilateral cavernous nerves. After modeling, the rats in the PBS and USC groups were treated by intracavernous injection of PBS at 200 μl and USCs at 1×106/200 μl PBS respectively for 28 days. Then, the maximum intracavernous pressure (mICP) and the ratio of mICP to mean arterial pressure (mICP/MAP) of the rats were calculated by electrical stimulation of the major pelvic ganglions, the proportion of nNOS- or NF200-positive nerve fibers in the total area of penile dorsal nerves determined by immunohistochemical staining, the levels of endothelial cell marker eNOS, smooth muscle marker α-SMA and collagen I detected by Western blot, and the smooth muscle to collagen ratio and the cell apoptosis rate in the corpus cavernosum measured by Masson staining and TUNEL, respectively.

RESULTSAfter 28 days of treatment, the rats in the USC group, as compared with those in the PBS and BCNI model control groups, showed significant increases in the mICP (［81 ± 9.9］ vs ［31 ± 8.3］ and ［33 ± 4.2］ mmHg, P <0.05), mICP/MAP ratio (0.72 ± 0.05 vs 0.36 ± 0.03 and 0.35 ± 0.04, P <0.05), the proportions of nNOS-positive nerve fibers (［11.31 ± 4.22］% vs ［6.86 ± 3.08］% and ［7.29 ± 4.84］% , P <0.05) and NF200-positive nerve fibers in the total area of penile dorsal nerves (［27.31 ± 3.12］% vs ［17.38 ± 2.87］% and ［19.49 ± 4.92］%, P <0.05), the eNOS/GAPDH ratio (0.52 ± 0.08 vs 0.31 ± 0.06 and 0.33 ± 0.07, P <0.05), and the α-SMA/GAPDH ratio (1.01 ± 0.09 vs 0.36 ± 0.05 and 0.38 ± 0.04, P <0.05), but a remarkable decrease in the collagen I/GAPDH ratio (0.28 ± 0.06 vs 0.68 ± 0.04 and 0.70 ± 0.10, P <0.05). The ratio of smooth muscle to collagen in the corpus cavernosum was significantly higher in the USC than in the PBS and BCNI model control groups (17.91 ± 2.86 vs 7.70 ± 3.12 and 8.21 ± 3.83, P <0.05) while the rate of cell apoptosis markedly lower in the former than in the latter two (3.31 ± 0.83 vs 9.82 ± 0.76, P <0.01; 3.31 ± 0.83 vs 9.75 ± 0.91, P <0.05).

CONCLUSIONSIntracavernous injection of USCs can protect the erectile function of the rat with cavernous nerve injury by protecting the nerves, improving the endothelial function, alleviating fibrosis and inhibiting cell apoptosis in the cavernous tissue.

Actins ; analysis ; Animals ; Arterial Pressure ; Collagen ; analysis ; Disease Models, Animal ; Erectile Dysfunction ; prevention & control ; Male ; Nitric Oxide Synthase Type I ; analysis ; Nitric Oxide Synthase Type III ; analysis ; Penile Erection ; physiology ; Penis ; innervation ; Pudendal Nerve ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Saline Solution ; administration & dosage ; Stem Cell Transplantation ; methods ; Stem Cells ; Urine ; cytology

Objective: To explore the effects of immediate and delayed intracavernous injection of bone marrow mesenchymal stem cells (BM-MSCs) on neurogenic erectile dysfunction (NED) induced by bilateral cavernous nerve injury in Sprague-Dawley (SD) rats. METHODS: BM-MSCs isolated from male SD rats were cultured and identified. Twenty-eight 8-week-old male SD rats were randomly divided into four groups, sham operation, NED model control, BM-MSCs immediate, and BM-MSCs delayed, and NED models were established in the latter three groups by crushing the bilateral cavernous nerves. The rats in the sham operation and model control groups were injected intracavernously with placebo while those in the latter two with BM-MSCs immediately or 2 weeks after modeling. At 12 weeks after operation, the penile function of the rats was assessed according to the penile intracavernous pressure (ICP), mean arterial pressure (MAP), and ICP/MAP ratio obtained from different groups of rats. Then, all the animals were sacrificed and the penile cavernosal tissue collected for histological analysis. RESULTS: At 12 weeks after modeling, both ICP and ICP/MAP were significantly increased in the BM-MSCs immediate and delayed groups as compared with those in the model control (P <0.05), and so were the ratio of smooth muscle to collagen (P <0.05) and the smooth muscle content in the corpus cavernosum (P <0.05), and the number of neurofilament (NF)-positive nerve fibers (P <0.05) and the expression of neuronal nitric oxide synthase (nNOS) in the dorsal nerves of the midshaft penis (P <0.05). CONCLUSIONS Intracavernous injection of BM-MSCs can improve erectile function in rats with bilateral cavernous nerve injury by elevating the smooth muscle-collagen ratio and smooth muscle content in the corpus cavernosum and thus preventing its fibrosis as well as by increasing the number of NF-positive nerve fibers and expression of nNOS in the penile dorsal nerves.
Animals ; Disease Models, Animal ; Erectile Dysfunction ; enzymology ; etiology ; therapy ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Muscle, Smooth ; Nitric Oxide Synthase Type I ; metabolism ; Penile Erection ; physiology ; Penis ; enzymology ; innervation ; Pudendal Nerve ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Recently, with application of evoked potentials technology in the test of somatic and autonomic nerves, quantitative sensory testing in the detection of small nerve fiber function, and functional magnetic resonance imaging in the detection of senior central function, the detection of neural function has become more accurate. This article reviews the progress and application of diagnostic methods about neurogenic erectile dysfunction in order to provide a reference for forensic diagnosis and research in the future.
Autonomic Nervous System/physiopathology* ; Autonomic Pathways/physiopathology* ; Erectile Dysfunction/physiopathology* ; Evoked Potentials/physiology* ; Humans ; Male ; Nervous System Diseases/complications* ; Neural Conduction ; Neurologic Examination/methods* ; Penile Erection/physiology* ; Penis/innervation* ; Sensory Thresholds

The aim of this study was to investigate the effect of platelet-rich plasma (PRP) on cavernous nerve (CN) regeneration and functional status in a nerve-crush rat model. Twenty-four Sprague-Dawley male rats were randomly divided into three equal groups: eight had a sham operation, eight underwent bilateral nerve crushing with no further intervention and eight underwent bilateral nerve crushing with an immediate application of PRP on the site of injury. Erectile function was assessed by CN electrostimulation at 3 months and nerve regeneration was assessed by toluidine blue staining of CN and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining of penile tissue. Three months after surgery, in the group that underwent bilateral nerve crushing with no further intervention, the functional evaluation showed a lower mean maximal intracavernous pressure (ICP) and maximal ICP per mean arterial pressure (MAP) with CN stimulation than those in the sham group. In the group with an immediate application of PRP, the mean maximal ICP and maximal ICP/MAP were significantly higher than those in the injured control group. Histologically, the group with the application of PRP had more myelinated axons of CNs and more NADPH-diaphorase-positive nerve fibres than the injured control group but fewer than the sham group. These results show that the application of PRP to the site of CN-crush injury facilitates nerve regeneration and recovery of erectile function. Our research indicates that clinical application of PRP has potential repairing effect on CN and peripheral nerves.
Animals ; Disease Models, Animal ; Electric Stimulation ; Erectile Dysfunction ; pathology ; physiopathology ; therapy ; Male ; NADPH Dehydrogenase ; metabolism ; Nerve Regeneration ; physiology ; Penile Erection ; physiology ; Penis ; innervation ; Peripheral Nerve Injuries ; Peripheral Nerves ; metabolism ; pathology ; Platelet Transfusion ; Platelet-Rich Plasma ; Radiculopathy ; etiology ; pathology ; physiopathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo assess the clinical significance of electrophysiological tests of bulbocavernosus reflex (BCR), ischiocavernosus reflex (ICR) and pudenda somatosensory evoked potential (PSEP) for patients with erectile dysfunction (ED).

METHODSElectrophysiological tests of BCR, ICR and PSEP were performed for 232 ED patients with IIEF-5 scores of 2-20 (10.39 +/- 5.52), another 21 normal volunteer controls underwent the same tests, and the results were compared.

RESULTSAbnormal results, such as prolonged and advanced latencies, were found in 94 (40.5%) of the patients, which suggested neurotic ED with different degrees of cauda equine nerve injuries.

CONCLUSIONElectrophysiological tests of BCR, ICR and PSEP can objectively reveal the functional state of the cauda equine nerve and offer an important support to the diagnosis of nerve-mediated ED.

Adult ; Aged ; Case-Control Studies ; Electrophysiology ; Erectile Dysfunction ; physiopathology ; Evoked Potentials, Somatosensory ; Humans ; Male ; Middle Aged ; Muscle, Smooth ; physiopathology ; Penis ; innervation ; physiopathology ; Reflex ; physiology

The concept of muscle rehabilitation after nerve injury is not a novel idea and is practiced in many branches of medicine, including urology. Bladder rehabilitation after spinal cord injury is universally practiced. The erectile dysfunction (ED) experienced after radical prostatectomy (RP) is increasingly recognized as being primarily neurogenic followed by secondary penile smooth muscle (SM) changes. There is unfortunately no standard approach to penile rehabilitation after RP because controlled prospective human studies are not available. This article reviews the epidemiology, experimental pathophysiological models, rationale for penile rehabilitation, and currently published rehabilitation strategies.
Alprostadil ; administration & dosage ; Animals ; Erectile Dysfunction ; etiology ; rehabilitation ; Humans ; Male ; Muscle, Smooth ; physiopathology ; Penile Erection ; physiology ; Penis ; innervation ; Peripheral Nerve Injuries ; Phosphodiesterase 5 Inhibitors ; Phosphodiesterase Inhibitors ; administration & dosage ; Prostatectomy ; adverse effects

OBJECTIVETo explicate the spinal nerve source of the rabbit penis cutaneous sensation.

METHODSTwelve adult male rabbits were randomly divided into two groups of equal number. While mechanical stimuli were given to the penis by different von Frey hairs, single fiber activities were recorded in vivo in the left (Group A) and right (Group B) S1-S4 spinal nerves, respectively. The mechanical threshold, adaptability and conduction velocity of the fibers were analyzed.

RESULTSWhen the ipsilateral penis was mechanically stimulated, discharges were detected in S2 and S3 spinal nerve fibers, but not in S1 and S4. The discharge fibers were 39.67 +/- 3.14 (S2) and 21.00 +/- 2.19 (S3) in the left spinal nerve and 40.00 +/- 3.16 (S2) and 19.67 +/- 2.58 (S3) in the right. There was no obvious difference between the numbers of the left spinal nerves and the right ones (P > 0.05).

CONCLUSIONThe rabbit penis cutaneous sensation originates from S2 and S3 spinal nerves.

Animals ; Electrophysiology ; Male ; Neurons, Afferent ; physiology ; Penis ; Rabbits ; Random Allocation ; Sensory Thresholds ; Skin ; innervation ; Spinal Nerves ; physiology

OBJECTIVETo study the relationship between substance P (SP) and/or calcitonin gene-related peptide (CGRP) immunoreactive neurons in dorsal root ganglia (DRG) and the transmission of nociception in the penile frenulum of rats.

METHODSThe fluoro-gold (FG) retrograde tracing method was used to trace the origin of nerve terminals in the penile frenulum of rats. And SP and/or CGRP immunofluorescence labeling was employed to detect the distribution of SP and/or CGRP immunoreactive neurons in DRG.

RESULTSFG retrograde tracing showed that the FG retrolabeled neurons were localized in L6-DRG and S1-DRG. SP and/or CGRP immunofluorescence labeling indicated that a large number of DRG neurons were SP- and CGRP-immunoreactive, different in size, bright red and bright green respectively in color, and arranged in rows or spots among nerve bundles. All the FG/SP and FG/CGRP double-labeled neurons were medium or small-sized. One third of the FG-labeled neurons were SP-immunoreactive, and a half of them CGRP-immunoreactive in L6-DRG and S1-DRG respectively. The FG/SP/CGRP-labeled neurons accounted for one fifth of the FG retro labeled neurons.

CONCLUSIONSP- and CGRP-immunoreactive neurons in L6-DRG and SI-DRG of rats may be involved in the transmission of nociception in rat penile frenulum.

Animals ; Calcitonin Gene-Related Peptide ; analysis ; Ganglia, Spinal ; chemistry ; cytology ; Male ; Microscopy, Fluorescence ; Neurons ; chemistry ; physiology ; Neurons, Afferent ; chemistry ; physiology ; Penis ; innervation ; Rats ; Rats, Sprague-Dawley ; Substance P ; analysis

Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are highly prevalent in aging men and both of the conditions have a significant impact on the quality of life. In the past few years, various epidemiological trials were conducted to assess the association between LUTS and ED. These studies showed that LUTS, particularly the voiding symptoms, nocturia and the others caused by LUTS, independently increased the incidence of ED. There are some factors involved in the link between LUTS and ED: (1) rho-kinase expression/activity increased; (2) nitric oxide release decreased and corpus cavernosum smooth muscle contraction strengthened due to endothelin-1; (3) the composition of myosin isoform altered; (4) sympathetic hyperactivity and innervation of the corpus cavernosum smooth muscles decreased. These findings concerning the relationship between LUTS and ED have offered some new insights into the evaluation and treatment of patients with these conditions. The present paper briefly reviews the recent studies of the association between LUTS and ED.
Adult ; Aged ; Aged, 80 and over ; Endothelin-1 ; physiology ; Erectile Dysfunction ; epidemiology ; etiology ; Humans ; Intracellular Signaling Peptides and Proteins ; Male ; Middle Aged ; Myosins ; metabolism ; Nitric Oxide ; metabolism ; Penis ; innervation ; physiopathology ; Protein-Serine-Threonine Kinases ; biosynthesis ; Urologic Diseases ; complications ; epidemiology ; rho-Associated Kinases

OBJECTIVETo investigate the effects of growth hormone (GH) on the erectile function and the number of neuronal nitric oxide synthase (nNOS) -containing nerve fibers in the penis of aged rats.

METHODSTwenty-four aged male SD rats (18 months) were randomized into 2 groups: GH intervention group and control group. After four and eight weeks, a half of each group were selected and tested for erectile function after apomorphine (APO) injection and then sacrificed for the detection of nNOS-containing nerve fibers in the penis by streptavidin-peroxidase conjugated method (SP method).

RESULTSAfter four weeks, the erectile function and the number of nNOS-containing nerve fibers showed no significant difference between the GH intervention group and the control group (P > 0.05). After eight weeks, the erection frequency was significantly different (P < 0.05) between the two groups, while the erection rate was not. The number of nNOS-containing nerve fibers in the GH intervention group was significantly larger than that in the control group (P < 0.01).

CONCLUSIONGH enhances the regeneration of nNOS-containing nerve fibers in the penis and improves the erectile function of the aged rat.

Animals ; Apomorphine ; pharmacology ; Human Growth Hormone ; pharmacology ; Immunohistochemistry ; Male ; Nerve Fibers ; enzymology ; physiology ; Nerve Regeneration ; drug effects ; Nitric Oxide Synthase Type I ; analysis ; Penile Erection ; drug effects ; Penis ; enzymology ; innervation ; Random Allocation ; Rats ; Rats, Sprague-Dawley