Female Urinary Bladder Research Articles

Neonatal Cystitis Makes Adult Female Rat Urinary Bladders More Sensitive to Low Concentration Microbial Antigens.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder. Patients with IC/BPS often experience "flares" of symptom exacerbation throughout their lifetime, initiated by triggers, such as urinary tract infections. This study sought to determine whether neonatal bladder inflammation (NBI) alters the sensitivity of adult rat bladders to microbial antigens. Female NBI rats received intravesical zymosan treatments on postnatal days P14-P16 while anesthetized; Neonatal Control Treatment (NCT) rats were anesthetized. In adults, bladder and spinal cord Toll-like receptor type 2 and 4 (TLR2, TLR4) contents were determined using ELISAs. Other rats were injected intravesically with lipopolysaccharide (LPS; mimics an E. coli infection; 25, 50, 100, or 200 μg/mL) or Zymosan (mimics yeast infection; 0.01, 0.1, 1, and 10 mg/mL) solutions on the following day. Visceromotor responses (VMRs; abdominal contractions) to graded urinary bladder distention (UBD, 10-60 mm Hg, 20s) were quantified as abdominal electromyograms (EMGs). Bladder TLR2 and TLR4 protein levels increased in NBI rats. These rats displayed statistically significant, dose-dependent, robustly augmented VMRs following all but the lowest doses of LPS and Zymosan tested, when compared with their adult treatment control groups. The NCT groups showed minimal responses to LPS in adults and minimally increased EMG measurements following the highest dose of Zymosan. The microbial antigens LPS and Zymosan augmented nociceptive VMRs to UBD in rats that experienced NBI but had little effect on NCT rats at the doses tested. The greater content of bladder TLR2 and TLR4 proteins in the NBI group was consistent with increased responsiveness to their agonists, Zymosan and LPS, respectively. Given that patients with IC/BPS have a higher incidence of childhood urinary tract infections, this increased responsiveness to microbial antigens may explain the flares in symptoms following "subclinical" tract infections.

Draft genomes of Lactobacillus delbrueckii and Klebsiella pneumoniae coexisting within a female urinary bladder.

Here, we present the draft genome sequences of Lactobacillus delbrueckii and Klebsiella pneumoniae, both isolated from the urinary bladder of an asymptomatic post-menopausal female patient with a diagnosis of recurrent urinary tract infections. These genomes will facilitate analyses of interbacterial interactions in the urinary microbiome.

The Clinical Features and Predictive Factors of Nocturnal Enuresis in Adult Women.

ObjectiveOur current knowledge on nocturnal enuresis (NE) in adults is scarce due to its uncommon nature. The present study was designed to investigate symptom characteristics and risk factors of NE in adult women to improve the current clinical understanding and management of this rare disease.MethodsOver a 3-year period, we enrolled 70 adult women who complained of bedwetting, with a frequency of at least once per week and a symptom duration of 3 months or longer. Patients were excluded if they had known pregnancy, current urinary tract infection, untreated malignancies, anatomical abnormalities, and irregular sleep cycle. The International Consultation on Incontinence Modular Questionnaire—female lower urinary tract symptoms and bladder diary were employed to appraise lower urinary tract symptoms and voiding behavior. Urodynamics was performed to assess the bladder function. A linear regression analysis was applied to determine potential risk factors for NE frequency.ResultsAmong the recruited subjects, comorbidities and lower urinary tract symptoms were frequently reported. On bladder diary, patients commonly presented with nocturnal polyuria (NP), reduced nocturnal voided volumes (RNVVs), or both. Urodynamics revealed multiple dysfunctions, namely, detrusor overactivity (DO), urodynamic stress incontinence (USI), reduced compliance, bladder outlet obstruction, detrusor underactivity (DU), and simultaneous DO and DU. Patients with more frequent NE (≥4/week) demonstrated markedly increased body mass index, more comorbid conditions, worse incontinence symptoms, NP or NP plus RNVVs, reduced compliance, and poorer voiding possibly owing to DU. Whereas, RNVVs alone and worse overactive bladder-related parameters were associated with milder NE. Multivariate analysis indicated that frequency/urgency quality of life, incontinence symptom, NP + RNVVs, poor flow, increased bladder sensation, USI, and simultaneous detrusor overactivity plus DU were independent risk factors for NE severity.ConclusionNE in adult women may have both urological and non-urological pathophysiology. Imbalanced circadian urine production, jeopardized continence mechanisms, overactive bladder, and DU-induced poor voiding are major factors that contribute to the pathogenesis of NE in adult women. Focused treatments on restoring these functions should be individually considered.

Dual Primary Cancer Patients With Lung Cancer as a Second Primary Malignancy: A Population-Based Study.

BackgroundResearch on patients with lung cancer as a second primary malignancy (LCSPM) remains limited. This study aims to determine the clinical characteristics, prognosis, and temporal relationship of other cancers to lung cancer in these patients.MethodsThis study retrospectively analyzed 3465 patients with dual primary cancers from the 5253 patients with LCSPM retrieved from the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2015.Results2285 eligible patients were further analyzed in this study cohort with 59.3% of 1-year OS, 34.7% of 3-year OS, and 25.2% of 5-year OS. The most common first primary cancer (FPC) in dual primary cancer patients with LCSPM was prostate cancer, followed by female breast cancer and urinary bladder cancer. In the entire study population, the median interval between the two primary malignancies was 21 months (range: 3.5–52 months). Age, sex, FPC location, surgery, stage, and histology of lung cancer were regarded as independent prognostic factors for these patients. The prognosis of patients with urinary bladder cancer as FPC was the worst in the univariate (p = 0.024) and multivariate (p < 0.001) Cox analyses. Lung cancer-directed surgery could significantly improve long-term survival (HR = 0.22, p < 0.001). Additionally, the C-index of the established nomogram with acceptable calibration curves was 0.760 (95% CI: 0.744–0.776) in the training cohort and was 0.759 (95% CI: 0.737–0.781) in the validation cohort, showing an ideal model discrimination ability. The corresponding decision curve analysis (DCA) indicated the nomogram had relatively ideal clinical utility.ConclusionsCancer patients still have the risk of developing a new primary lung cancer. Close, lifelong follow-up is recommended for all these patients. Early detection for surgical treatment will significantly improve the prognosis of dual primary cancer patients with LCSPM. The nomogram developed to predict 1-, 3-, and 5-year OS rates has relatively good performance.

To casuistry foreign bodies of the female urinary bladder

Alexandra Ermolaeva, a peasant woman from the Smolensk district, Spasskaya volost, 22 years old, was admitted to the Smolensk Provincial Zemsky Hospital on February 2, 1890, complaining of complete urinary incontinence, severe pain in the lower abdomen, in the lower back, and external genital organs, constipation and pain.

Levothyroxine treatment is associated with an increased relative risk of overall and organ specific incident cancers – a cohort study of the Swedish population

High thyroid hormone values have been associated with an increased risk of incident cancers, especially breast cancer but also lung cancer and any solid cancers. We explored whether there is an increased risk of overall and cause-specific cancers in those receiving levothyroxine treatment.We included all individuals ≥ 18 years in Sweden (N = 8,573,313) on January 1 2009, and identified patients with two or more dispensed prescriptions of levothyroxine 2005–2006 (n = 253,193, 3.0 %). A cancer diagnosis in the Swedish Cancer Register 2009–2015 was used as outcome. We excluded patients with a cancer diagnosis before 2005. Cox regression was used (hazard ratios, HRs, and 95 % confidence intervals, CI) with adjustments for age, socioeconomic/neighborhood factors and co-morbidities.Totally 399,751 cases of incident cancer were identified, with a slight increased overall risk associated with levothyroxine treatment for both men, adjusted HR 1.06 (95 % CI 1.03–1.10), and women, adjusted HR 1.08 (95 % CI 1.07–1.10). For men, increased risks were found for cancers of the thyroid gland and other endocrine glands. For women, increased risks were found for cancers of the breast, endometrium, other female genitals (ovaries not included), stomach, colon, liver, pancreas, urinary bladder, skin, leukemia, and unspecified primary tumor. Unlike men, for women, no increased risk was found for cancer of the thyroid gland.In conclusions, levothyroxine treatment was associated with an excess cancer risk, including many different types of cancer, especially among women. Our results need confirmation by other studies, but levothyroxine is recommended to be prescribed only on approved indications.

Bacteriophages of the lower urinarytract.

The discovery of bacteria in the female urinary bladder has fundamentally changed current dogma regarding the urinary tract and related urinary disorders. Previous research characterized many of the bacterial components of the female urinary tract, but the viral fraction of this community is largely unknown. Viruses within the human microbiota far outnumber bacterial cells, with the most abundant viruses being those that infect bacteria (bacteriophages). Similar to observations within the microbiota of the gut and oral cavity, preliminary surveys of the urinary tract and bladder microbiota indicate a rich diversity of uncharacterized bacteriophage (phage) species. Phages are vital members of the microbiota, having critical roles in shaping bacterial metabolism and community structure. Although phages have been discovered in the urinary tract, such as phages that infect Escherichia coli, sampling them is challenging owing to low biomass, possible contamination when using non-invasive methods and the invasiveness of methods that reduce the potential for contamination. Phages could influence bladder health, but an understanding of the association between phage communities, bacterial populations and bladder health is in its infancy. However, evidence suggests that phages can defend the host against pathogenic bacteria and, therefore, modulation of the microbiome using phages has therapeutic potential for lower urinary tract symptoms. Furthermore, as natural predators of bacteria, phages have garnered renewed interest for their use as antimicrobial agents, for instance, in the treatment of urinary tract infections.

HIF-1 as a Marker of Age-Related Diseases Associated with Tissue Hypoxia

The data on the role of hypoxia-inducible factor, HIF-1, in the development of immunopathology (infectious, inflammatory, and autoimmune diseases), cancer (of the lung, brain, female reproductive system, urinary bladder, and pancreas), diabetes mellitus, and Alzheimer’s disease are analyzed. The data on the genes involving cell differentiation, apoptosis, and proliferation, the expression of which is regulated by HIF-1, are described. HIF-1 activates the expression of the telomerase gene and increases the replicative lifetime of human lung fibroblasts under hypoxic conditions. HIF-1 may be a molecular marker of cell aging and metabolism, as well as a potential therapeutic target for the treatment of age-related diseases.

Solitary fibrous tumor of urinary bladder in a female patient and transurethral enucleation of tumor

Solitary fibrous tumors are rare neoplasms, initially defined in visceral pleura. Recently, they have been noticed to have ubiquitous distribution of human body. Solitary fibrous tumor of bladder is extremely rare especially in the females. We are presenting a bladder solitary fibrous tumor case of 62-years-old female patient who underwent transurethral enucleation instead of conventional transurethral resection of bladder tumor. According to our research, this is the fourth case of solitary fibrous tumor in a female urinary bladder in the literature.

Female urinary microbiota.

The newly discovered female urinary microbiota has the potential to deepen our understanding of urinary tract health and disease, including common lower urinary tract conditions such as urinary incontinence and urinary tract infection. The spectrum of painful bladder disorders and other less common conditions also may benefit from additional research that includes consideration of the resident bacterial community of the female bladder. The present review provides a clinical context for the rapidly emerging research regarding the female urinary microbiota and its relationships with urinary tract conditions of interest. Studies using culture-independent techniques confirm prior reports of bacteria that reside in the female urinary bladder. These resident communities, the female urinary microbiota, possess characteristics that differ between women affected by urgency urinary incontinence and matched, unaffected controls. Enhanced urine culture techniques permit cultivation of organisms, including uropathogens, missed by standard urine culture, but detected by culture-independent sequencing techniques. New technology is available. Clinical laboratories can modify traditional standard urine culture methods to enhance detection of uropathogens. However, given the existence of the female urinary microbiota, the simple presence of bacteria in the lower urinary tract should not be taken as evidence of infection.

Characterization of axons expressing the artemin receptor in the female rat urinary bladder: a comparison with other major neuronal populations.

Artemin is a member of the glial cell line-derived neurotrophic factor (GDNF) family that has been strongly implicated in development and regeneration of autonomic nerves and modulation of nociception. Whereas other members of this family (GDNF and neurturin) primarily target parasympathetic and nonpeptidergic sensory neurons, the artemin receptor (GFRα3) is expressed by sympathetic and peptidergic sensory neurons that are also the primary sites of action of nerve growth factor, a powerful modulator of bladder nerves. Many bladder sensory neurons express GFRα3 but it is not known if they represent a specific functional subclass. Therefore, our initial aim was to map the distribution of GFRα3-immunoreactive (-IR) axons in the female rat bladder, using cryostat sections and whole wall thickness preparations. We found that GFRα3-IR axons innervated the detrusor, vasculature, and urothelium, but only part of this innervation was sensory. Many noradrenergic sympathetic axons innervating the vasculature were GFRα3-IR, but the noradrenergic innervation of the detrusor was GFRα3-negative. We also identified a prominent source of nonneuronal GFRα3-IR that is likely to be glial. Further characterization of bladder nerves revealed specific structural features of chemically distinct classes of axon terminals, and a major autonomic source of axons labeled with neurofilament-200, which is commonly used to identify myelinated sensory axons within organs. Intramural neurons were also characterized and quantified. Together, these studies reveal a diverse range of potential targets by which artemin could influence bladder function, nerve regeneration, and pain, and provide a strong microanatomical framework for understanding bladder physiology and pathophysiology.

Migrated Contraceptive Devices in Female Urinary Bladder

Foreign bodies in the urinary bladder are not uncommon, however, only few cases have been reported in recent literature. This is not a fatal disease, however, it may lead to serious complications , This is a report of four cases of Intrauterine contraceptive devices ( IUCD) which migrated into the urinary bladder and complicated by stone formation around the devices and cystoscopy was the main management route

Effect of estrogen and ovariectomy on response of the female rabbit urinary bladder to two forms of in vitro oxidative stress

There are several lower urinary tract dysfunctions (LUTD) that are more common in women than in men including incontinence, interstitial cystitis, and recurrent urinary tract infection. There is increasing evidence that these dysfunctions are associated with reduced blood flow, ischemia, hypoxia, and reperfusion resulting in free radical generation and oxidative damage. The goal of the current study was to determine if the level of circulating estrogen affects the response of the bladder muscle and mucosa to two in vitro models of oxidative stress: Incubation in the presence of hydrogen peroxide (H(2)O(2)) is the first model; the second is ischemia followed by reperfusion which results in the direct production of damaging free radicals. The motivation for this study is the current literature linking female-related LUTD with oxidative stress. Eighteen female New Zealand white rabbits were divided into three groups: control, ovariectomized, and ovariectomized receiving continuous estrogen. Eight bladder strips from each of three rabbits per group were taken for in vitro ischemia/reperfusion (I/R) physiological experiments, while eight strips from the three remaining rabbit bladders per group were taken for in vitro H(2)O(2) experiments. All tissue was analyzed for total antioxidant activity (AA) and malondialdehyde (MDA) levels. In addition, the organ bath buffer was also analyzed for AA. In vitro H(2)O(2) was found to target the nerve, muscarinic receptor, and membrane equally causing more damage to bladder tissue than in vitro I/R. Ovariectomy resulted in lower contractility and higher lipid peroxidation. However, estrogen supplementation following ovariectomy protected the bladder against both models of oxidative stress by maintaining contractile responses to stimulation and decreasing lipid peroxidation. The primary conclusion from this study is high estrogen protects the bladder from oxidative stress, whereas low estrogen makes the bladder more susceptible.

Effect of Ovariectomy on External Urethral Sphincter Activity in Anesthetized Female Rats

The postmenopausal hypoestrogen condition is associated with various lower urinary tract dysfunctions, including frequency, urgency, stress urinary incontinence and recurrent urinary infection. We determined whether hypoestrogen induced lower urinary tract dysfunction after ovariectomy is also associated with an alteration in external urethral sphincter activity. Bilateral ovariectomy was performed in female Sprague-Dawley® rats and sham operated rats served as controls. Transvesical cystometry and external urethral sphincter electromyogram activity were monitored 4, 6 and 12 weeks after sham operation or bilateral ovariectomy and at 6 weeks in bilaterally ovariectomized rats treated with estrogen. The micturition reflex was elicited in sham operated and bilaterally ovariectomized, urethane anesthetized animals. Post-void residual urine increased and voiding efficiency decreased in rats with 4 to 12 weeks of bilateral ovariectomy. The silent period of external urethral sphincter electromyogram activity was shortened significantly and progressively at increased times after bilateral ovariectomy. These effects were prevented by estradiol treatment. As evidenced by shortening of the external urethral sphincter electromyogram silent period in ovariectomized rats, the disruption of coordination between the external urethral sphincter and the detrusor muscle could decrease urine outflow and in turn voiding efficiency. Estrogen replacement reverses these changes, suggesting that the central pathways responsible for detrusor-sphincter coordination are modulated by gonadal hormones.

Origins and distribution of nerves to the female urinary bladder: New anatomical findings in the sex differences

The development of nerve-sparing procedures is important in preventing bladder dysfunction following radical hysterectomy. In this study, we dissected 14 halves of 7 female pelvises (age range: 46-86 years; mean age: 74 years) to examine the origins, courses, and distributions of nerve branches to the bladder in females in detail, and 6 halves of 3 male pelvises (age range: 71-85 years, mean age: 78 years) to compare with the female specimens. Nerve branches to the bladder originated mainly from the inferior hypogastric plexus, but independent direct branches running along the ureter from the hypogastric nerve were also distributed particularly to the trigone in all female specimens. We classified these independent branches into four types according to their relationship to the ureter. In males the numbers of the independent branches were small and they were difficult to find. The present observations indicate that nerve distribution patterns to the bladder differ between females and males. In nerve sparing procedures for radical hysterectomy, the area between the ureter and the hypogastric nerve is important.

Dynamics analysis of bladder-urethra system based on CFD

A mathematical model for a bladder-urethra system can provide basic analysis for the disabled urethra closure of stress urinary incontinence (SUI) patients in a clinic. Based on computational fluid dynamics (CFD), we developed a three-dimensional urodynamic bladder-urethra system, which includes bladder, bladder neck, prostate, and urethra. The realistic recirculation process of the urinary bladder during the physiologic voiding process in conjunction with a flow simulation through the female urinary bladder and urethra is presented. The computational results show that a dead-water zone and the zone of secondary flow occur, independent of the shape of the prostatic urethra. For the pathological prostata, the extreme constriction of the prostatic urethra results in an additional wide-stretched dead-water zone. The simulation results does not only improve urinary incontinence surgery for clinicians, but can also provide a basis for theoretical analysis.

Effect of Estrogen on Bladder Nociception in Rats

We assessed the effect of ovariectomy and estrogen replacement on nociceptive responses to bladder distention in a rat model. Female Sprague-Dawley rats (Harlan) underwent ovariectomy or sham surgery. Visceromotor responses (abdominal contractions) to bladder distention were determined 3 to 4 weeks later under isoflurane anesthesia. In rat subsets estrogen was chronically replaced with a subcutaneous estrogen pellet vs a placebo pellet or acutely replaced by subcutaneous injection 24 hours before testing. Effects of estrogen withdrawal were examined in another group of rats by implanting a pellet and explanting the pellet 24 hours before testing. Uterine weight was measured to assess the estrogen dose. Visceromotor responses to bladder distention were significantly less vigorous in ovariectomized rats vs controls. Acute estrogen replacement increased visceromotor responses in these rats but chronic estrogen replacement did not. Sudden chronic estrogen withdrawal resulted in increased visceromotor responses. Uterine weight was consistent with the physiological estrogen dose. Estrogen alone was not sufficient to produce increased nociceptive responses but an acute decrease in estrogen resulted in increased visceromotor responses. These data suggest that the pronociceptive effects of estrogen may be due to a mismatch between peripheral vs central and/or genomic vs nongenomic effects of the hormone, which occur during rapidly decreasing estrogen levels.

Reply

I first thank the person writing the commentary for their excellent comments. A question was asked regarding the reversibility of the changes observed after bilateral ovariectomy. We published an interesting study 1 Palmieri K. Mannikarottu A. Chicester P. et al. The effects of cyclical estrogen on bladder and urethral structure and function. Br J Urol. 2007; 99: 171-176 Crossref Scopus (23) Google Scholar in which after 2 weeks of bilateral ovariectomy, we administered estrogen for 2 weeks by implanting a slow-release estrogen tablet in the subscapular area. After 2 weeks on estrogen, we removed the tablet for a period of 2 weeks, followed by 2 weeks on estrogen. Thus, we cycled estrogen every 2 weeks. We found that bladder weight, smooth muscle to collagen ratio, and blood vessel density, all cycled with estrogen such that all detrimental effects of ovariectomy were fully reversed during the estrogen administration periods. We have recently extended these studies on cyclical estrogen and have demonstrated that during low estrogen periods, blood flow decreases and the level of oxidized and nitrated proteins (reactions to increased free radicals) increase. During high estrogen periods, these changes are reversed and blood flow increases and the level of oxidized and nitrated proteins are reduced to control levels. Editorial CommentUrologyVol. 74Issue 3PreviewEstrogen replacement treatment (ERT) of postmenopausal incontinence has been the topic of extensive debate and research over the past years. Several studies have demonstrated the presence of estrogen receptors throughout the genitourinary tract, and for many years it was postulated that estrogen replacement had therapeutic benefits on postmenopausal urinary continence. However, recent data from large prospective studies, including randomized trials, have shown an increased incidence of urinary incontinence and worsening symptoms among women using hormone therapy. Full-Text PDF The Effect of 2- and 4-Week Ovariectomy on Female Rabbit Urinary Bladder FunctionUrologyVol. 74Issue 3PreviewTo evaluate the effect ovariectomy (OVX) after 2 and 4 weeks on bladder function and biochemistry of the adult female rabbit urinary bladder. Full-Text PDF Editorial CommentUrologyVol. 74Issue 3PreviewThe authors have nicely shown that the decreased contractility of the detrusor muscle in female rabbits after ovariectomy is mediated by decreased mitochondrial and SR function. This study has also revealed some interesting findings on the concentrations of Rho-kinase (ROK) alpha, ROK-beta, and myosin light chain kinase (MLCK) in bladder muscle wall. After ovariectomy, no significant effects were observed on ROKα or ROKβ at 14 days. However, at 28 days the expression of ROKα increased and that of ROKβ decreased significantly. Full-Text PDF

The Effect of 2- and 4-Week Ovariectomy on Female Rabbit Urinary Bladder Function

To evaluate the effect ovariectomy (OVX) after 2 and 4 weeks on bladder function and biochemistry of the adult female rabbit urinary bladder. Twelve mature female rabbits were divided into 3 groups: control, 2-week ovariectomized, and 4-week ovariectomized. At the end of the experimental period, the following studies were performed: contractile studies on isolated strips; examinations of the activity of citrate synthase (a marker for mitochondrial function) and thapsigargin-sensitive calcium ATPase (a marker for sarcoplasmic reticular calcium uptake function); and quantification of Rho-kinase (ROK) alpha and beta and myosin light chain kinase by Western blot analyses. By 28 days after OVX, there were significant decreases in bladder weight, contractile responses, and citrate synthase and sarcoplasmic reticular calcium uptake activity. In addition, by 28 days following OVX the relative concentration of ROK alpha was significantly increased, whereas ROK beta concentration was significantly decreased. Myosin light chain kinase was significantly reduced. Our study demonstrated that OVX contributed significantly to chronically decreased contractile function in the detrusor muscle of the female rabbit bladder, and this decrease, in turn, was mediated by decreased mitochondrial and sarcoplasmic reticulum function. These specific bladder dysfunctions could be related to the demonstrated decreased blood flow to the bladder muscle and mucosa and the increased generation of free radicals. Changes in smooth muscle regulatory proteins, especially myosin light chain kinase, may also play a role in contractile dysfunctions.

Effects of 17ββ‐estradiol on rat urinary bladder: Gender differences in anoxia–glucopenia and reperfusion damage

To study the effect of 17beta-estradiol (E(2)) as a neuroprotective agent in male and female rat urinary bladders subjected to anoxia-glucopenia and reperfusion (A/G-R) damage. Rat urinary bladders were exposed to 1 hour of A-G and 2 hours of reperfusion (R). Intrinsic nerves underwent electrical field stimulation. The effect of E(2) on the contractile response and its recovery in R phase, was monitored by adding it to the bath medium, at different concentrations, 60 min before A-G, during the A-G and the first 30 min of R. Furthermore, on both genders, in vivo treatments with E(2), testosterone, IC1 182,780 and anastrozole were performed. After A-G the recovery of the nerve function in female bladders were significantly higher than in male. E(2) given both in vivo (increased of E(2) plasma levels were monitored) and in vitro, resulted to be neuroprotective in male bladder subjected to A-G/R damage. When rats were treated with anastrozole, a lower recovery of nerve responses both in male and female bladders was observed. Finally, treatments with E2 receptor antagonist ICI 182,780 increased E(2) plasma levels and showed to abolished E(2) neuroprotection, thus suggesting that E2 promotes neuronal survival likely through a rapid estrogen receptor mediated response. Male rat urinary bladder serves are more susceptible to A-G/R damage than female. E(2) exhibits neuroprotective properties and could be a lead for novel agents capable to protect the urinary bladder from ischaemia/reperfusion damage associated with urinary bladder disorders.