Pelvic Ganglion Research Articles

Neuroprotective effects of melatonin on erectile dysfunction in streptozotocin-induced diabetic rats.

To explore the neuroprotective effects and its possible mechanisms of melatonin (MT) on erectile dysfunction in streptozotocin-induced diabetic rats. Twenty-eight Sprague-Dawley rats received intraperitoneal injection of streptozotocin and 8weeks later, the determined diabetic rats randomly got intraperitoneal injection of phosphate buffer solution (PBS) or MT. Another 12 normal rats received PBS treatment. Four weeks later, intracavernous pressure, mean arterial pressure, pathological changes in penis, and major pelvic ganglion (MPG) were measured. Malondialdehyde, superoxide dismutase, p38 and p-p38 levels in penis were detected. Diabetic rats showed significant decreases of erectile function accompanied with serious neuropathy in dorsal penile nerve (DPN) and MPG, meanwhile collagen deposition, oxidative stress, and p-p38 levels in penis were elevated. Melatonin treatment partially but significantly improved the erectile function, ameliorated neuropathy in DPN and MPG, and decreased collagen deposition, oxidative stress, and p-p38 levels in diabetic rats. Melatonin treatment helps improve erectile function and ameliorate neuropathy and fibrosis in diabetic rats. These may be associated with reductions in oxidative stress, p38MAPK signaling pathway, and neuropathy.

Advillin Is Expressed in All Adult Neural Crest-Derived Neurons.

Promoter-based genetic recombination (via, e.g., Cre-lox) is most useful when all cells of interest express a particular gene. The discovery that the actin-binding protein advillin is expressed in all somatic sensory neurons has been exploited repeatedly to drive DNA recombination therein, yet specificity of expression has not been well demonstrated. Here, we characterize advillin expression amongst sensory neurons and in several other neural and non-neural tissues. We first validate an advillin antibody against advillin knock-out tissue, advillin promoter-driven EGFP, and advillin mRNA expression. In the dorsal root ganglion (DRG), advillin is enriched in non-peptidergic nociceptors. We also show that advillin expression, and advillin promotor-driven EGFP and Cre-recombinase expression, occurs in multiple tissues including the dorsal habenula of the epithalamus, endocrine cells of the gut, Merkel cells in the skin, and most strikingly, throughout the autonomic nervous system (sympathetic, parasympathetic, and enteric neurons) in mice, rats, and non-human primates. In the mouse pelvic ganglion, advillin immunoreactivity is most intense in pairs of small neurons, and concentrated in spine-like structures on the axon initial segment contacted by sympathetic preganglionic axons. In autonomic targets (iris and blood vessels), advillin is distributed along cholinergic parasympathetic axons and in sympathetic varicosities. Developmentally, advillin expression is absent from sympathetics at postnatal day 4 but begins to emerge by day 7, accounting for previous reports (based on embryonic expression) of advillin’s specificity to sensory neurons. These results indicate that caution is warranted in interpreting previous studies in which advillin-driven genomic editing is either constitutive or performed after postnatal day 4.

Pioglitazone's beneficial effects on erectile function preservation after cavernosal nerve injury in the rat are negated by inhibition of the insulin-like growth factor-1 receptor: a preclinical study.

To determine if the insulin-like growth factor-1 (IGF-1) pathway is involved in the improvement in erectile function recovery in rats after nerve crush injury treated with pioglitazone (Pio). Sprague-Dawley rats were divided into four groups. The first group received sham operation (n = 5). The second group underwent bilateral cavernous nerve injury (BCNI, n = 7). The third group received BCNI and Pio treatment (BCNI + Pio, n = 7), whereas the fourth group underwent BCNI with Pio treatment and IGF-1 inhibition (BCNI + Pio + JB-1, n = 7). The IGF-1 receptor (IGF-1R) was inhibited by JB-1, a small molecular antagonist of the receptor. After 14 days of treatment, erectile function was measured via intracorporal pressure normalized to mean arterial pressure (ICP/MAP) and the major pelvic ganglion and cavernous nerve harvested for western blot and immunohistochemistry (IHC) of phosphorylated-IGF-1Rβ (p-IGF-1Rβ), phosphorylated-ERK1/2 (p-ERK1/2), and neuronal NOS (nNOS). BCNI + Pio animals exhibited improvements in ICP/MAP, similar to Sham animals, and BCNI + Pio + JB-1 rats demonstrated a reduced ICP/MAP similar to BCNI-only rats at all measured voltages. Western blot results showed upregulation of p-IGF-1Rβ was observed in the BCNI + Pio group. Low levels of p-ERK1/2 were seen in the JB-1-treated animals. The immunoblot results were supported by IHC findings. Intense IHC staining of nNOS was detected in the BCNI + Pio group. The group treated with JB-1 showed minimal protein expression of p-ERK1/2, nNOS, and p-IGF-1Rβ. Pio improves erectile function in rats undergoing BCNI via an IGF-1-mediated pathway.

Exosomes derived from mesenchymal stem cells exert therapeutic effect in a rat model of cavernous nerves injury.

Postradical prostatectomy erectile dysfunction (pRP-ED) is a major health issue. There has been a shortage of an effective treatment method until now. In this study, a total of 48 adult male Sprague-Dawley (SD) rats were randomly equally divided into four groups, including group 1-sham surgery with cavernous nerve exposure plus vehicle, group 2-bilateral cavernous nerve injury (BCNI) plus vehicle, group 3-BCNI plus adipose-derived mesenchymal stem cells (ADSCs)-derived exosomes (ADSC-Exo), and group 4-BCNI plus bone marrow-derived mesenchymal stem cell (BMSCs)-derived exosomes (BMSC-Exo). Twenty-one days following surgery, erectile function was measured before tissue harvest. Histologic and Western blot analyses were then performed. Exosomes were capable of internalization into human umbilical vein endothelial cells (HUVEC) invitro and could be detected in the corpus cavernosum invivo. The nNOS expression in the penile dorsal nerves (DN) and major pelvic ganglion (MPG), protein level of neurofilament in the DN, endothelial markers vWF, alpha smooth muscle actin (α-SMA), the ratio of smooth muscle to collagen content were obviously lower in BCNI group compared with the sham group, while ADSC-Exo and BMSC-Exo groups resulted in significant restoration of the above histopathological changes. Moreover, BCNI treated with ADSC-Exo or BMSC-Exo had significantly higher mean intracavernous pressure/mean arterial pressure ratio compared with BCNI group. The results demonstrated that both ADSC-Exo and BMSC-Exo treatment could significantly alleviate pathological changes and improve the erectile function in BCNI-related rats. Exosomes derived from ADSCs and BMSCs may be a potential agent for pRP-ED treatment.

217 Neuropraxia following nerve sparing radical prostatectomy is associated with increased expression of markers of inflammation and Fidgetin-2 like protein

Radical prostatectomy (RP) carries a high risk of erectile dysfunction (ED) as a result of neuropraxia. Neuropraxia also occurs when nerve sparing procedures are utilized. Preliminary data from our group has demonstrated that a previously uncharacterized microtubule severing enzyme that controls axonal growth in vitro, called Fidgetin-like 2 protein (FL2), is rapidly upregulated in the major pelvic ganglion (MPG) following cavernous nerve (CN) transection. Interestingly, animals that undergo surgical procedures without CN transection (SHAM), also had increased FL2 protein and mRNA expression. The objective of the present study was to test the hypothesis that even in the absence of direct damage to the CN, trauma associated with nerve sparing RP triggers an inflammatory and FL2 response which results in neuropraxia and thereby ED. ∼300g Sprague Dawley Rats were subjected to bilateral nerve transection surgery (CNI) or (SHAM). Animals were sacrificed at 6h, 2days and 3 days post-surgery and both MPG removed and total protein and RNA isolated. FL2 expression was assessed by western Blot and RT-qPCR. Immune factors were assayed by RT-qPCR.

020 Prostatic radiation therapy increases neuronal apoptosis, decreases nitrergic neurons and markedly impairs neuritogenesis in the major pelvic ganglion

020 Prostatic radiation therapy increases neuronal apoptosis, decreases nitrergic neurons and markedly impairs neuritogenesis in the major pelvic ganglion

323 Stromal derived factor-1 treatment results in stem cell pathway activation in penile tissues and increased neurotrophins in major pelvic ganglion

323 Stromal derived factor-1 treatment results in stem cell pathway activation in penile tissues and increased neurotrophins in major pelvic ganglion

025 Dickkopf2 reprograms damaged erectile tissue toward neurovascular repair through an angiopoietin-1-Tie2 pathway in mice with diabetes mellitus or cavernous nerve injury

Erectile dysfunction(ED) due to diabetes mellitus(DM) or radical prostatectomy often responds poorly to oral phosphodiesterase-5 inhibitors. Dickkopf2(DKK2), a Wnt antagonist, was recently found to mature vessel formation and promote angiogenesis. We investigated DKK2-mediated signal transduction in the corpus cavernosum and whether and how DKK2 restores penile erection in mouse models of refractory ED. DM or cavernous nerve injury(CNI) was induced in wild type or DKK2-Tg mice. We evaluated erectile function by cavernous nerve stimulation, cavernous histology and biochemistry. To further evaluate the role of DKK2-mediated signal transduction, primary (co-)culture of endothelial cell(EC), pericyte and major pelvic ganglion (MPG) were performed from the mouse penis of normal or pathological conditions. DKK2 was mainly expressed in cavernous pericytes and decreased in both DM and CNI condition. ECs treated with conditioned medium derived from pericytes showed enhanced tube formation, which was impaired by the treatment of DKK2 depleted medium. DKK2-Tg mice or those with intracavernous delivery of DKK2 protein(5μg/20μl) restored erectile function in DM and CNI mice. This recovery by DKK2 in those were accompanied by enhanced proliferation of cavernous ECs and pericytes, evidenced by the increase of CD31(+) with Brdu(+) or p-eNOS(+) and PDGFRc-(+) areafrom the cavernous tissue and by the increase of tube formations from cultured ECs and pericytes. DKK2 treatment also reduced EC permeability by restoration of EC junction proteins in pathologic conditions. Moreover, DKK2 restored nNOS(+) or III tubulin(+) area of corpus cavernosum and promoted neurite sprouting from MPG by enhanced NGF, BDNF, neurotophin3 and TrkA level in pathologic conditions. Transcriptome analysis of ECs revealed that DKK2 treatment upregulates angiopoietin-1 and downregulates angiopoietin-2. Inhibition of this signal with intracavernous delivery of soluble Tie-2 attenuated DKK2-mediated EC proliferation, neurite sprouting and erectile function recovery in those with DM.

428 The effect of cavernous nerve traction on erectile function in rats

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).

Colonization of the Lower Urinary Tract by Neural Crest and Development of Pelvic Autonomic Innervation

The development of organs occurs concurrently with the formation of nerves that are essential for normal function. In the lower urinary tract, comprised of the bladder and urethra, appropriate innervation is essential for storage and coordinated release of urine at socially acceptable times. Understanding how the innervation of the lower urinary tract develops and the signaling pathways that regulate this process is likely to provide insight into congenital problems and offers a means to regenerate neural inputs in cases of damage or disease. The bladder and urethra receive both sensory and autonomic neural inputs that are derived from the neural crest during development. Sensory innervation of the bladder originates from neural crest‐derived dorsal root ganglia at thoracic and sacral spinal levels. Pelvic autonomic sympathetic and parasympathetic neurons that provide motor effects and play a principle role in coordinating bladder contractility are located within the discrete ganglia that lie near the neck of the bladder and proximal urethra. Formation of these mixed pelvic ganglia from neural crest, the routes of neural crest migration into the fetal urogenital sinus, timing of pelvic ganglia neural differentiation, and signaling pathways that regulate these processes are active areas of investigation that are being rapidly advanced through the use of mouse models. An overview of studies undertaken in transgenic mice to derive a spatiotemporal map of neural crest derivatives in the developing lower urinary tract as well as a timeline of differentiation of pelvic ganglia neurons and initial analysis of signaling pathways active during pelvic ganglia neuron differentiation will be presented.Support or Funding InformationThis work was supported by National Institutes of Health grants R01‐DK078158, RC1‐DK086594, and U01‐DK101038.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Clarification of the Innervation of the Bladder, External Urethral Sphincter and Clitoris: A Neuronal Tracing Study in Female Mongrel Hound Dogs.

Many studies examining the innervation of genitourinary structures focus on either afferent or efferent inputs, or on only one structure of the system. We aimed to clarify innervation of the bladder, external urethral sphincter (EUS) and clitoris. Retrograde dyes were injected into each end organ in female dogs. Spinal cord, mid-bladder, and spinal, caudal mesenteric, sympathetic trunk and pelvic plexus ganglia were examined for retrograde dye-labeled neurons. Neurons retrogradely labeled from the bladder were found primarily in L7-S2 spinal ganglia, spinal cord lateral zona intermedia at S1-S3 levels, caudal mesenteric ganglia, T11-L2 and L6-S2 sympathetic trunk ganglia, and pelvic plexus ganglia. The mid-bladder wall contained many intramural ganglia neurons labeled anterogradely from the pelvic nerve, and intramural ganglia retrogradely labeled from dye labeling sites surrounding ureteral orifices. Neurons retrogradely labeled from the clitoris were found only in L7 and S1 spinal ganglia, L7-S3 spinal cord lateral zona intermedia, and S1 sympathetic trunk ganglia, and caudal mesenteric ganglia. Neurons retrogradely labeled from the EUS were found in primarily at S1 and S2 spinal ganglia, spinal cord lamina IX at S1-S3, caudal mesenteric ganglia, and S1-S2 sympathetic trunk ganglia. Thus, direct inputs from the spinal cord to each end organ were identified, as well as multisynaptic circuits involving several ganglia, including intramural ganglia in the bladder wall. Knowledge of this complex circuitry of afferent and efferent inputs to genitourinary structures is necessary to understand and treat genitourinary dysfunction. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.

Galanin Administration Partially Restores Erectile Function After Cavernous Nerve Injury and Mediates Endogenous Nitrergic Nerve Outgrowth In Vitro

BackgroundPreviously, we found that the neuropeptide galanin was strongly upregulated soon after bilateral cavernous nerve injury (BCNI) and that galanin and its receptors were expressed in nitrergic erectile innervation. Galanin has been observed to exert neuroregenerative effects in dorsal root ganglion neurons, but evidence for these effects in the major pelvic ganglion (MPG) after BCNI is lacking. AimTo evaluate the neurotropic effects of galanin receptor agonists and antagonists in vitro in nitrergic neurons and MPG and in vivo in rats after BCNI. MethodsMale Sprague-Dawley rats underwent BCNI and sham surgery. Organ culture and single-cell neuron culture of the MPG were performed. Osmotic pump treatment with the galanin agonist in vivo and measurement of erectile response to electrostimulation after BCNI, immunohistochemical localization of galanin and receptors in the human neurovascular bundle, and myographic analysis of rat corpus cavernosum smooth muscle relaxation to galanin receptor agonists were investigated. OutcomesNeurite outgrowth in vitro and erectile response to electrostimulation after BCNI in vivo, immunohistochemical localization of galanin and receptors, and penile muscle relaxation in vitro. ResultsGalanin showed neurotrophic action in vitro and inhibition of endogenous galanin significantly impaired neurite outgrowth in nitrergic but not in sympathetic MPG neurons. In vivo administration of a selective galanin receptor-2 agonist, M1145, resulted in partial recovery of erectile function (EF) after BCNI. Galanin did not act as a direct vasodilator on corpus cavernosum muscle strips. Clinical TranslationEndogenous neurotrophins such as galanin could be used as a strategy to improve EF for patients after BCNI from radical prostatectomy. Strengths and LimitationsWe evaluated the effect of galanin on nerve regeneration and EF recovery in vivo and in vitro. Limitations include the lack of washout period for the in vivo experiment and absence of differences in the expression of neuronal markers between treatment groups. ConclusionsWe identified galanin as a potential endogenous mechanism for nerve regeneration after BCNI, which could play a physiologic role in EF recovery after radical prostatectomy. In vivo treatment with exogenous galanin was beneficial in enhancing EF recovery after BCNI, but further research is necessary to understand the underlying mechanisms.Weyne E, Hannan JL, Gevaert T, et al. Galanin Administration Partially Restores Erectile Function After Cavernous Nerve Injury and Mediates Endogenous Nitrergic Nerve Outgrowth In Vitro. J Sex Med 2018;15:480–491.

980 - Major pelvic ganglion neurons express CXCR4, which binds stromal derived factor-1 and enhances neurotrophin protein levels and neurogenesis

980 - Major pelvic ganglion neurons express CXCR4, which binds stromal derived factor-1 and enhances neurotrophin protein levels and neurogenesis

Combined Transplantation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Restores Cavernous Nerve Injury-Related Erectile Dysfunction

BackgroundWhether combined transplantation of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) is more effective than transplantation of a single cell type in the restoration of erectile function is unknown. AimTo investigate the effect of combined transplantation of MSCs and EPCs on restoration of erectile function in rats with cavernous nerve injury (CNI). MethodsMSCs were isolated from human bone marrow and EPCs were isolated from human umbilical cord blood. MSCs and EPCs were identified by flow cytometry and in vitro differentiation or immunofluorescence staining. 25 8-week-old male Sprague-Dawley rats were allocated to 1 of 5 groups: sham operation group, bilateral CNI group receiving periprostatic implantation of MSCs plus EPCs, MSCs, EPCs, or phosphate buffered saline (control group). 2 weeks after CNI and treatment, erectile function of rats was measured by electrically stimulating the CN. The penis and major pelvic ganglia were harvested for histologic examinations. RNA and protein levels of neurotrophin factors (vascular endothelial growth factor, nerve growth factor, and brain-derived neurotrophic factor) in mono- or coculture MSCs and EPCs were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. OutcomesIntracavernous pressure and mean arterial pressure were measured to evaluate erectile function. Histologic examinations of the penis and major pelvic ganglia and RNA and protein levels of neurotrophin factors in MSCs and EPCs were performed. ResultsMSCs and EPCs expressed the specified cell markers and exhibited the typical appearance and characteristics. Treatments using MSCs and/or EPCs could increase endothelial and smooth muscle contents of the corpus cavernosum, decrease caspase-3 expression and increase penile neuronal nitric oxide synthase expression, and restore the neural component of the major pelvic ganglia in rats with CNI. Combined transplantation of MSCs and EPCs had a better effect on improving erectile function than single transplantation of MSCs or EPCs. Expression levels of vascular endothelial growth factor and nerve growth factor in coculture MSCs and EPCs were significantly higher than those of primary MSCs or EPCs. Clinical TranslationCombined transplantation of MSCs and EPCs was more effective in restoring erectile function in CNI-related erectile dysfunction models. Strengths and LimitationsThe study, for the 1st time, proved that combined transplantation of MSCs and EPCs was more effective in restoring erectile function in rats with CNI. The rat model might not represent the human condition. ConclusionCombined periprostatic transplantation of MSCs and EPCs could restore erectile function in rats with CNI more effectively. MSCs might restore CN fibers by secreting neurotrophin factors such as vascular endothelial growth factor and nerve growth factor, and EPCs could enhance the paracrine activity of MSCs.Fang J-f, Huang X-n, Han X-y, et al. Combined Transplantation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Restores Cavernous Nerve Injury-Related Erectile Dysfunction. J Sex Med 2018;15:284–295.

018 TNF-alpha Inhibition Improves Parasympathetic Nerve Function and is Associated with Altered Macrophage Infiltration of the Major Pelvic Ganglion following Nerve Injury

018 TNF-alpha Inhibition Improves Parasympathetic Nerve Function and is Associated with Altered Macrophage Infiltration of the Major Pelvic Ganglion following Nerve Injury

161 Low Intensity Extracorporeal Shock Wave Therapy Activates Endogenous Progenitor/Stem Cells as Indicated by Histone 3 Phosphorylation

Low Intensity Extracorporeal Shock Wave Therapy (Li-ESWT) has been employed for many years to treat ED yet its mechanism of action remains poorly defined. We have previously demonstrated that the therapeutic effects from Li-ESWT may be partially related to the activation of endogenous progenitor/stem cells and we are endeavoring to further describe these pathways. To determine the mechanism by which Li-ESWT activates endogenous stem cells by interrogating histone 3 phosphorylation, which occurs only during the mitotic phase of the cell cycle. Male Sprague-Dawley (SD) rats were treated with 5-ethynyl-2'-deoxyuridine (EdU) pulse followed by Li-ESWT, and cohort analysis was performed. Additionally, rat adipose derived stem cells (RADSCs) and rat penile cavernous smooth muscle cells (RCSMCs) were also treated with Li-ESWT. Fifty male SD rats at 12 weeks old were grouped into three cohorts: 1). Sham; 2). Sub-acute: the animals underwent bilateral cavernous nerve injury (BCNI) then were separated into control and Li-ESWT groups. One week after BCNI, the Li-ESWT group were injected with EdU (50mg/kg, i.p) 30 minutes before Li-ESWT (0.02mJ/mm2, 3 Hz, 300 pulses). One week later, ICP/MAP were measured. 3). Chronic: the animals underwent BCNI then grouped into control and Li-ESWT groups. One week after BCNI, the animals were treated with Li-ESWT (0.02mJ/mm2, 3 Hz, 300 pulses) twice a week for 4 weeks. EdU was injected 30 min before the first and last Li-ESWT. One week after the last Li-ESWT, ICP/MAP were measured. The penile erectile tissues and major pelvic ganglion (MPG) were harvested for histological study to assess smooth muscle/collagen content and endothelium content in the corpora cavernosa. EdU as marker of cell activation and phosphorylated histone 3 (H3P) as marker of the mitotic phase of the cell cycle were also assessed. To confirm the effect of Li-ESWT on the phosphorylation of H3 in vitro, RADSCs and RCSMCs were treated with Li-ESWT (0.02mJ/mm2, 3 Hz, 100 pulses), and EdU incorporation rate and the expression of H3P was assessed.

017 Differential Effects on MPG Neurons and Penile Vasculature after Conformal Prostate Radiation in Rats

Prostatic radiation therapy (RT) is presumed to cause erectile dysfunction (ED) through damage to the vasculature and the nerves supplying the penis. This study examined the impact of prostatic RT on 1) vascular function in the internal pudendal artery (IPA) and penis and 2) the effect of in vivo prostate RT on the ex vivo survival and growth of major pelvic ganglia (MPG) neurons. Adult male Sprague-Dawley rats underwent conformal single fraction 25Gy RT using kilovoltage small animal microirradiator to the prostate or sham treatment. Erectile function was assessed by electrical stimulation of the cavernous nerve and ICP/MAP measurement at 2 or 10 weeks post-RT (n=10/grp). MPG were then excised; neurons were dissociated and cultured. Axon length and branching, and neuronal nitric oxide synthase (nNOS), tyrosine hydroxylase (TH) and TUNEL assay expression were measured in neuronal cultures at 72h. IPA and penises were excised and mounted in myograph tissue bath. Concentration response curves to phenylephrine (PE), acetylcholine (ACh), DEA NONOate, or sodium nitroprusside (SNP), and electrical field stimulated (EFS) contraction and NANC relaxation were assessed.

164 The Effects of Multiple Adipose-Derived Stem Cell Intracorporeal Injections on Erectile Dysfunction in a Rat Model of Cavernosal Nerve Injury

Nerve injury after radical prostatectomy leads to erectile dysfunction in over half of treated patients. Despite contemporary advancements, current therapies are inefficient. Recently, experiments utilizing stem cell therapy have shown promising outcomes. In this study, using a rat model of cavernosal nerve injury (CNI), we sought to discover the effect of intracorporal injection (IC) of adipose-derived stem cells (ADSC) on erectile function (EF). Sprague-Dawly rats were randomized into four groups of rats (n=8/group): 1) EXP-1 group in which the animals underwent laparotomy (Lap) with CNI and IC injection of ADSC at the time of surgery. 2) EXP-2 group in which the rats underwent Lap with CNI and IC injection of ADSC both at the time of surgery and three weeks post CNI. 3) Crush group underwent Lap with CNI, and 4) The Sham control group underwent Lap and immediate closure. Six weeks after CNI, all four groups received EF evaluation via cavernosal nerve stimulation at 2.5V, 5V, and 7.5V and measurement of the intracorporal pressure response. Penile and major pelvic ganglion tissue was harvested for immunohistochemical (IHC) analysis.

Ganglion cardiacum or juxtaductal body of human fetuses.

The ganglion cardiacum or juxtaductal body is situated along the left recurrent laryngeal nerve in the aortic window and is an extremely large component of the cardiac nerve plexus. This study was performed to describe the morphologies of the ganglion cardiacum or juxtaductal body in human fetuses and to compare characteristics with intracardiac ganglion. Ganglia were immunostained in specimens from five fetuses of gestational age 12–16 weeks and seven fetuses of gestational age 28–34 weeks. Many ganglion cells in the ganglia were positive for tyrosine hydroxylase (TH; sympathetic nerve marker) and chromogranin A, while a few neurons were positive for neuronal nitric oxide synthase (NOS; parasympathetic nerve marker) or calretinin. Another ganglion at the base of the ascending aorta carried almost the same neuronal populations, whereas a ganglion along the left common cardinal vein contained neurons positive for chromogranin A and NOS but no or few TH-positive neurons, suggesting a site-dependent difference in composite neurons. Mixtures of sympathetic and parasympathetic neurons within a single ganglion are consistent with the morphology of the cranial base and pelvic ganglia. Most of the intracardiac neurons are likely to have a non-adrenergic non-cholinergic phenotype, whereas fewer neurons have a dual cholinergic/noradrenergic phenotype. However, there was no evidence showing that chromogranin A- and/or calretinin-positive cardiac neurons corresponded to these specific phenotypes. The present study suggested that the ganglion cardiacum was composed of a mixture of sympathetic and parasympathetic neurons, which were characterized the site-dependent differences in and near the heart.

Intravenous Infusion of Bone Marrow-Derived Mesenchymal Stem Cells Reduces Erectile Dysfunction Following Cavernous Nerve Injury in Rats.

IntroductionIntravenous preload (delivered before cavernous nerve [CN] injury) of bone marrow–derived mesenchymal stem cells (MSCs) can prevent or decrease postoperative erectile dysfunction (J Sex Med 2015;12:1713–1721). In the present study, the potential therapeutic effects of intravenously administered MSCs on postoperative erectile dysfunction were evaluated in a rat model of CN injury.MethodsMale Sprague-Dawley rats were randomized into 2 groups after electric CN injury. Intravenous infusion of bone marrow–derived MSCs (1.0 × 106 cells in Dulbecco's modified Eagle's medium 1 mL) or vehicle (Dulbecco's modified Eagle's medium 1 mL) was performed 3 hours after electrocautery-induced CN injury.Main Outcome MeasuresTo assess erectile function, we measured intracavernous pressure at 4 weeks after MSC or vehicle infusion. Histologic examinations were performed to investigate neuronal innervation and inhibition of smooth muscle atrophy. Green fluorescent protein–positive bone marrow–derived MSCs were used for cell tracking. To investigate mRNA expression levels of neurotrophins in the major pelvic ganglia (MPGs), quantitative real-time polymerase chain reaction was performed.ResultsThe decrease of intracavernous pressure corrected for arterial pressure and area under the curve of intracavernous pressure in the bone marrow–derived MSC group was significantly lower than that in the vehicle group at 4 weeks after infusion (P < .05). Retrograde neuronal tracing indicated that the MSC group had a larger number of FluoroGold-positive neurons in the MPGs compared with the vehicle group. The ratio of smooth muscle to collagen in the MSC group was significantly higher than in the vehicle group. Green fluorescent protein–positive bone marrow–derived MSCs were detected in the MPGs and injured CNs using confocal microscopy, indicating homing of cells to the MPGs and injured CNs. Brain-derived neurotrophic factor and glial cell-derived neurotrophic factor expression levels in the MPGs were significantly higher in the MSC group than in the vehicle group (P < .01).ConclusionIntravenous infusion of bone marrow–derived MSCs after CN injury might have therapeutic efficacy in experimental erectile dysfunction.Matsuda Y, Sasaki M, Kataoka-Sasaki Y, et al. Intravenous Infusion of Bone Marrow–Derived Mesenchymal Stem Cells Reduces Erectile Dysfunction Following Cavernous Nerve Injury in Rats. Sex Med 2018;6:49–57.