Persistent detrusor overactivity in rats after relief of partial urethral obstruction

Detrusor overactivity (DO) persists after prostatectomy in 20% to 25% of patients with benign disease. Assuming that nonvoiding contractions (NVCs) can be used as a surrogate for DO in humans, the rat model of obstruction/deobstruction may allow us to study the pathophysiology of persistent DO after deobstruction. We investigated bladder function, with a special focus on NVCs, in rats by use of a new, modified method of obstruction and deobstruction and compared these results with those obtained by use of the conventional method. Seventy female Sprague-Dawley rats underwent 1) sham operation ( n = 10), 2) obstruction by a modified method (Modif-Obs; n = 12), 3) obstruction/deobstruction by the conventional method (Conv-Obs/Deobs; n = 13), or 4) obstruction/deobstruction by the modified method (Modif-Obs/Deobs; n = 35). The Modif-Obs/Deobs animals were divided into subgroups with (DO+) and without (DO−) NVCs. Two weeks after partial urethral obstruction, the animals were deobstructed, and 1 wk later cystometry was performed with recording of intravesical and intra-abdominal pressures. NVCs were shown in all groups: Modif-Obs (80%), Conv-Obs/Deobs (100%), and Modif-Obs/Deobs (40%). In the Modif-Obs/Deobs group, bladder weight and the muscle-to-collagen ratio were higher in DO+ than in DO− rats. The Modif-Obs/Deobs group showed no mortality compared with 25% mortality in the Conv-Obs/Deobs group. The modified method may be more adequate for studying persistent DO after deobstruction, because it resulted in pressure/volume- and DO-related parameters similar to those found in the clinical situation. The persistence of DO after deobstruction may partly be due to irreversible changes in the bladder caused during the period of obstruction.

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Ammonia reduction with ornithine phenylacetate restores brain eNOS activity via the DDAH-ADMA pathway in bile duct-ligated cirrhotic rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00097.2011 ◽

2012 ◽

Vol 302 (1) ◽

pp. G145-G152 ◽

Cited By ~ 29

Author(s):

Vairappan Balasubramaniyan ◽

Gavin Wright ◽

Vikram Sharma ◽

Nathan A. Davies ◽

Yalda Sharifi ◽

...

Keyword(s):

Bile Duct ◽

Protein Expression ◽

Ammonia Concentration ◽

Sham Operation ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Duct Ligation ◽

Tnf Α ◽

No Signaling ◽

Brain Water

Ammonia is central in the pathogenesis of hepatic encephalopathy, which is associated with dysfunction of the nitric oxide (NO) signaling pathway. Ornithine phenylacetate (OP) reduces hyperammonemia and brain water in cirrhotic animals. This study aimed to determine whether endothelial NO synthase activity is altered in the brain of cirrhotic animals, whether this is associated with changes in the endogenous inhibitor, asymmetric-dimethylarginine (ADMA) and its regulating enzyme, dimethylarginine-dimethylaminohydrolase (DDAH-1), and whether these abnormalities are restored by ammonia reduction using OP. Sprague-Dawley rats were studied 4-wk after bile duct ligation (BDL) ( n = 16) or sham operation ( n = 8) and treated with placebo or OP (0.6 g/kg). Arterial ammonia, brain water, TNF-α, plasma, and brain ADMA were measured using standard techniques. NOS activity was measured radiometrically, and protein expression for NOS enzymes, ADMA, DDAH-1, 4-hydroxynonenol (4HNE), and NADPH oxidase (NOX)-1 were measured by Western blotting. BDL significantly increased arterial ammonia ( P < 0.0001), brain water ( P < 0.05), and brain TNF-α ( P < 0.01). These were reduced significantly by OP treatment. The estimated eNOS component of constitutive NOS activity was significantly lower ( P < 0.05) in BDL rat, and this was significantly attenuated in OP-treated animals. Brain ADMA levels were significantly higher and brain DDAH-1 significantly lower in BDL compared with sham ( P < 0.01) and restored toward normal following treatment with OP. Brain 4HNE and NOX-1 protein expression were significantly increased in BDL rat brain, which were significantly decreased following OP administration. We show a marked abnormality of NO regulation in cirrhotic rat brains, which can be restored by reduction in ammonia concentration using OP.

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Effects of Electroacupuncture on Uterine Morphology and Expression of Oestrogen Receptors in Ovariectomised Rats

Acupuncture in Medicine ◽

10.1136/acupmed-2016-011093 ◽

2017 ◽

Vol 35 (3) ◽

pp. 208-214 ◽

Cited By ~ 4

Author(s):

Shulan Ma ◽

Dongju Li ◽

Yi Feng ◽

Jianwei Jiang ◽

Bo Shen

Keyword(s):

Steroid Receptors ◽

Endometrial Thickness ◽

Serum Levels ◽

Sham Operation ◽

Sprague Dawley ◽

Sham Operation Group ◽

Reverse Transcription Pcr ◽

Ovx Rats ◽

Sprague Dawley Rats ◽

Unique Effect

Aim To observe the effects of electroacupuncture (EA) on uterine morphology and expression of oestrogen receptor (ER) α and β in ovariectomised (OVX) rats. Methods Thirty female Sprague-Dawley rats with regular 4-day oestrus cycles were divided into a sham operation group (Control, n=10) and two OVX groups that remained untreated (OVX group, n=10) or received EA treatment (OVX+EA group, n=10). In the latter group, EA was applied at CV4, CV3, SP6 and bilateral Zigong (30 min per day) for 3 days. The effects of EA on uterine morphology were observed by H&E staining. Quantitative real-time reverse transcription-PCR (qRT-PCR) and Western blotting were used to measure ERα and ERβ mRNA and protein expression, respectively. Results Relative to the (untreated) OVX group, EA treatment significantly increased the uterine wet weight to body weight (UWW/BW) ratio (0.47±0.04 vs 0.31±0.03 g/kg, p=0.04), and myometrial thickness (109.39±10.71 vs 60.81±8.1 μm, p=0.016) of OVX rats. Similarly, the total number of endometrial glands per cross section and endometrial thickness in the OVX +EA group was significantly increased compared to the (untreated) OVX group. EA treatment also increased protein (but not mRNA) expression of both ERα and ERβ in the uteri of OVX rats. Conclusions This study has demonstrated that EA treatment decreases uterine atrophy in OVX rats. This unique effect of EA on the uterus may be due to upregulation of serum levels of E2 and differential regulation of sex steroid receptors ERα and ERβ.

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The vagus nerve mediates the suppressing effects of peripherally administered oxytocin on methamphetamine self-administration and seeking in rats

10.1101/2019.12.18.880914 ◽

2019 ◽

Author(s):

Nicholas A. Everett ◽

Anita J Turner ◽

Priscila A Costa ◽

Sarah J. Baracz ◽

Jennifer L. Cornish

Keyword(s):

Clinical Trials ◽

Vagus Nerve ◽

Drug Withdrawal ◽

Sham Operation ◽

Sprague Dawley ◽

Self Administration ◽

Male And Female ◽

Functional Interactions ◽

Sprague Dawley Rats ◽

Suppressant Effect

AbstractBackgroundThe neuropeptide oxytocin has emerged as a promising pharmacotherapy for methamphetamine (METH) addiction, and clinical trials of intranasal oxytocin are underway. However, there is debate as to how peripherally administered oxytocin alters brain signaling to modulate addiction processes. Interestingly, there is evidence for functional interactions between peripheral oxytocin administration and the vagus nerve. Therefore, this study investigated whether the effects of peripherally administered oxytocin require vagal signaling to reduce METH self-administration and reinstatement of METH-seeking behaviours.MethodsMale and female Sprague-Dawley rats underwent surgery for jugular catheterization and either subdiaphragmatic vagotomy (SDV) or a sham operation. Rats were trained to self-administer METH, and the effect of peripherally administered oxytocin on METH intake was assessed. Rats then underwent extinction, and effects of oxytocin were assessed on cue- and METH-induced reinstatement of METH-seeking.ResultsOxytocin treatment robustly attenuated METH intake in both sexes. Strikingly, SDV entirely prevented the suppressant effect of oxytocin (0.3 mg/kg) on METH intake, and partially prevented the effects of 1 mg/kg oxytocin in both sexes. After extinction, SDV impaired the suppressing effects of oxytocin on cue- and METH-primed reinstatement in males, but not females. SDV was functionally confirmed by measuring food intake following administration of the vagal dependent peptide, cholecyostokin-8.ConclusionOur data suggest that vagus nerve signaling is required for the anti-addiction effects of peripherally administered oxytocin, and that this vagal dependency is partially mediated by sex and drug withdrawal. This study has considerable implications for the applicability of oxytocin as a therapy for METH use disorder for both sexes.

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Effect of adrenodemedullation on decline in muscle malonyl-CoA during exercise

Journal of Applied Physiology ◽

10.1152/jappl.1993.74.5.2548 ◽

1993 ◽

Vol 74 (5) ◽

pp. 2548-2551 ◽

Cited By ~ 10

Author(s):

W. W. Winder ◽

R. W. Braiden ◽

D. C. Cartmill ◽

C. A. Hutber ◽

J. P. Jones

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Treadmill Running ◽

Acid Oxidation ◽

Sham Operation ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Malonyl Coa ◽

Exercise Induced ◽

Rate Limiting

Malonyl-CoA is an inhibitor of carnitine palmitoyltransferase, a rate-limiting enzyme of fatty acid oxidation. Previous studies have indicated that muscle malonyl-CoA declines in rats during treadmill running. This decrease may be important for allowing an increased rate of fatty acid oxidation during prolonged exercise. This study was designed to determine whether epinephrine is essential for inducing the decline in muscle malonyl-CoA during exercise. Male Sprague-Dawley rats underwent adrenodemedullation (ADM) or sham operation. After allowing 3 wk for recovery, rats were killed (pentobarbital anesthesia) at rest or after running at 21 m/min up a 15% grade for 60 min. Red quadriceps malonyl-CoA decreased from 2.6 +/- 0.3 to 0.8 +/- 0.07 nmol/g in sham-operated rats and from 2.2 +/- 0.3 to 0.8 +/- 0.1 nmol/g in ADM rats. White quadriceps malonyl-CoA decreased to similar levels during exercise in both sham-operated and ADM rats. A second experiment on 24-h fasted rats also showed no impairment in the exercise-induced decline in red quadriceps malonyl-CoA as a result of adrenodemedullation. The hormones of the adrenal medulla are therefore unessential for inducing the decline in malonyl-CoA during exercise.

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Estrogen Modulates Expression of Tight Junction Proteins in Rat Vagina

BioMed Research International ◽

10.1155/2016/4394702 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Kyung-Jin Oh ◽

Hyun-Suk Lee ◽

Kyuyoun Ahn ◽

Kwangsung Park

Keyword(s):

Tight Junctions ◽

Cellular Localization ◽

Superficial Layer ◽

Control Group ◽

Sham Operation ◽

Female Rat ◽

Sprague Dawley ◽

Bilateral Ovariectomy ◽

Sprague Dawley Rats ◽

Vaginal Lubrication

Background. The objectives of this study were to investigate the localization of tight junctions and the modulation of zonula occludens- (ZO-) 1, occludin and claudin-1 expression by estrogen in castrated female rat vagina. Female Sprague-Dawley rats (230–240 g,n=45) were divided into three groups and subjected to a sham operation (control group,n=15), bilateral ovariectomy (Ovx group,n=15), or bilateral ovariectomy followed by daily subcutaneous injection of 17β-estradiol (50 μg/kg/day, Ovx + Est group,n=15). The cellular localization and expression of ZO-1, occludin, and claudin-1 were determined in each group by immunohistochemistry and western blot.Results. Expression of ZO-1 was diffuse in all groups, with the highest intensity in the superficial epithelium in the control group. Occludin was localized in the intermediate and basal epithelium. Claudin-1 was most intense in the superficial layer of the vaginal epithelium in the control group. Expression of ZO-1, occludin, and claudin-1 was significantly decreased after ovariectomy and was restored to the level of the control after estrogen replacement.Conclusions. Tight junctions are distinctly localized in rat vagina, and estrogen modulates the expression of tight junctions. Further researches are needed to clarify the functional role of tight junctions in vaginal lubrication.

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Endothelialization after arterial and venous micro-anastomosis

Canadian Journal of Plastic Surgery ◽

10.1177/229255039500300304 ◽

1995 ◽

Vol 3 (3) ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Patrick G Harris ◽

Sharon Chase ◽

Bang Kao Hong ◽

Jon B Loftus ◽

John F Mosher

Keyword(s):

Clinical Situation ◽

Initial Time ◽

Sprague Dawley ◽

Microsurgical Technique ◽

Small Vessels ◽

Sprague Dawley Rats ◽

Endothelial Surface ◽

Thrombogenic Potential ◽

Time Required ◽

Arteries And Veins

Knowledge of the initial time required to repair the endothelial surface of small vessels after microsurgical vascular anastomosis of veins and arteries is required to determine the preferable duration of antiplatelet prophylaxis and anticoagulation after emergency or elective microsurgery. To determine this, the femoral arteries and veins of 16 Sprague-Dawley rats were isolated, sectioned and repaired with microsurgical technique. The animals were then killed at one day intervals from the first to the 16th postoperative day. Femoral veins and arteries were harvested, sectioned and prepared for scanning electron microscopy. The results show that endothelialization of the repair line is begun by day 3 and completed by day 7 in the veins and arteries. Endothelialization of the intraluminal protruding sutures takes nine days in the veins while it is only starting at day 15 in the arteries. If this model can be extended to the human clinical situation, antiplatelet prophylaxis or anticoagulation should be administered for at least seven days. Further study is required to evaluate the thrombogenic potential of intraluminal protruding sutures.

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Neuropathic Allodynia Involves Spinal Neurexin-1β-dependent Neuroligin-1/Postsynaptic Density-95/NR2B Cascade in Rats

Anesthesiology ◽

10.1097/aln.0000000000000809 ◽

2015 ◽

Vol 123 (4) ◽

pp. 909-926 ◽

Cited By ~ 10

Author(s):

Tzer-Bin Lin ◽

Cheng-Yuan Lai ◽

Ming-Chun Hsieh ◽

Jian-Lin Jiang ◽

Jen-Kun Cheng ◽

...

Keyword(s):

Dorsal Horn ◽

Small Interfering Rna ◽

Postsynaptic Density ◽

Spinal Nerve ◽

Sham Operation ◽

Sprague Dawley ◽

Withdrawal Threshold ◽

Sprague Dawley Rats ◽

Rna Targeting ◽

Interfering Rna

Abstract Background: Neuroligin-1 (NL1) forms a complex with the presynaptic neurexin-1β (Nrx1b), regulating clustering of N-methyl-d-aspartate receptors with postsynaptic density-95 (PSD-95) to underlie learning-/memory-associated plasticity. Pain-related spinal neuroplasticity shares several common features with learning-/memory-associated plasticity. The authors thereby investigated the potential involvement of NL1-related mechanism in spinal nerve ligation (SNL)–associated allodynia. Methods: In 626 adult male Sprague–Dawley rats, the withdrawal threshold and NL1, PSD-95, phosphorylated NR2B (pNR2B) expressions, interactions, and locations in dorsal horn (L4 to L5) were compared between the sham operation and SNL groups. A recombinant Nrx1b Fc chimera (Nrx1b Fc, 10 μg, 10 μl, i.t., bolus), antisense small-interfering RNA targeting to NL1 (10 μg, 10 μl, i.t., daily for 4 days), or NR2B antagonist (Ro 25-6981; 1 μM, 10 μl, i.t., bolus) were administered to SNL animals to elucidate possible cascades involved. Results: SNL-induced allodynia failed to affect NL1 or PSD-95 expression. However, pNR2B expression (mean ± SD from 13.1 ± 2.87 to 23.1 ± 2.52, n = 6) and coexpression of NL1–PSD-95, pNR2B–PSD-95, and NL1-total NR2B were enhanced by SNL (from 10.7 ± 2.27 to 22.2 ± 3.94, 11.5 ± 2.15 to 23.8 ± 3.32, and 8.9 ± 1.83 to 14.9 ± 2.27 at day 7, n = 6). Furthermore, neuron-localized pNR2B PSD-95–pNR2B double-labeled and NL1/PSD-95/pNR2B triple-labeled immunofluorescence in the ipsilateral dorsal horn was all prevented by Nrx1b Fc and NL1-targeted small-interfering RNA designed to block and prevent NL1 expression. Without affecting NL1–PSD-95 coupling, Ro 25-6981 decreased the SNL-induced PSD-95–pNR2B coprecipitation (from 18.7 ± 1.80 to 14.7 ± 2.36 at day 7, n = 6). Conclusion: SNL-induced allodynia, which is mediated by the spinal NL1/PSD-95/pNR2B cascade, can be prevented by blockade of transsynaptic Nrx1b–NL1 interactions.

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Volatile Organic Compounds during Inflammation and Sepsis in Rats

Anesthesiology ◽

10.1097/aln.0000000000000420 ◽

2015 ◽

Vol 122 (1) ◽

pp. 117-126 ◽

Cited By ~ 21

Author(s):

Tobias Fink ◽

Alexander Wolf ◽

Felix Maurer ◽

Frederic W. Albrecht ◽

Nathalie Heim ◽

...

Keyword(s):

Hemorrhagic Shock ◽

Volatile Compounds ◽

Organic Compounds ◽

Cecal Ligation ◽

Volatile Components ◽

Sham Operation ◽

Exhaled Breath ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Observation Period

Abstract Background: Multicapillary column ion-mobility spectrometry (MCC-IMS) may identify volatile components in exhaled gas. The authors therefore used MCC-IMS to evaluate exhaled gas in a rat model of sepsis, inflammation, and hemorrhagic shock. Methods: Male Sprague–Dawley rats were anesthetized and ventilated via tracheostomy for 10 h or until death. Sepsis was induced by cecal ligation and incision in 10 rats; a sham operation was performed in 10 others. In 10 other rats, endotoxemia was induced by intravenous administration of 10 mg/kg lipopolysaccharide. In a final 10 rats, hemorrhagic shock was induced to a mean arterial pressure of 35 ± 5 mmHg. Exhaled gas was analyzed with MCC-IMS, and volatile compounds were identified using the BS-MCC/IMS-analytes database (Version 1209; B&S Analytik, Dortmund, Germany). Results: All sham animals survived the observation period, whereas mean survival time was 7.9 h in the septic animals, 9.1 h in endotoxemic animals, and 2.5 h in hemorrhagic shock. Volatile compounds showed statistically significant differences in septic and endotoxemic rats compared with sham rats for 3-pentanone and acetone. Endotoxic rats differed significantly from sham for 1-propanol, butanal, acetophenone, 1,2-butandiol, and 2-hexanone. Statistically significant differences were observed between septic and endotoxemic rats for butanal, 3-pentanone, and 2-hexanone. 2-Hexanone differed from all other groups in the rats with shock. Conclusions: Breath analysis of expired organic compounds differed significantly in septic, inflammation, and sham rats. MCC-IMS of exhaled breath deserves additional study as a noninvasive approach for distinguishing sepsis from inflammation.

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Potential involvement of P2Y2 receptor in diuresis of postobstructive uropathy in rats

AJP Renal Physiology ◽

10.1152/ajprenal.00382.2009 ◽

2010 ◽

Vol 298 (3) ◽

pp. F634-F642 ◽

Cited By ~ 18

Author(s):

Yue Zhang ◽

Donald E. Kohan ◽

Raoul D. Nelson ◽

Noel G. Carlson ◽

Bellamkonda K. Kishore

Keyword(s):

Mrna Expression ◽

Collecting Duct ◽

Receptor Activation ◽

Receptor Expression ◽

Urinary Concentration ◽

Sham Operation ◽

Protein Abundance ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Relative Mrna Expression

AVP resistance of the medullary collecting duct (mCD) in postobstructive uropathy (POU) has been attributed to increased production of PGE2. P2Y2 receptor activation causes production of PGE2 by the mCD. We hypothesize that increased P2Y2 receptor expression and/or activity may contribute to the diuresis of POU. Sprague-Dawley rats were subjected to bilateral ureteral obstruction for 24 h followed by release (BUO/R, n = 17) or sham operation (SHM/O, n = 15) and euthanized after 1 wk or 12 days. BUO/R rats developed significant polydipsia, polyuria, urinary concentration defect, and increased urinary PGE2 and decreased aquaporin-2 protein abundance in the inner medulla compared with SHM/O rats. After BUO/R, the relative mRNA expression of P2Y2 and P2Y6 receptors was increased by 2.7- and 4.9-fold, respectively, without significant changes in mRNA expression of P2Y1 or P2Y4 receptor. This was associated with a significant 3.5-fold higher protein abundance of the P2Y2 receptor in BUO/R than SHM/O rats. When freshly isolated mCD fractions were challenged with different types of nucleotides (ATPγS, ADP, UTP, or UDP), BUO/R and SHM/O rats responded to only ATPγS and UTP and released PGE2, consistent with involvement of the P2Y2, but not P2Y6, receptor. ATPγS- or UTP-stimulated increases in PGE2 were much higher in BUO/R (3.20- and 2.28-fold, respectively, vs. vehicle controls) than SHM/O (1.68- and 1.30-fold, respectively, vs. vehicle controls) rats. In addition, there were significant 2.4- and 2.1-fold increases in relative mRNA expression of prostanoid EP1 and EP3 receptors, respectively, in the inner medulla of BUO/R vs. SHM/O rats. Taken together, these data suggest that increased production of PGE2 by the mCD in POU may be due to increased expression and activity of the P2Y2 receptor. Increased mRNA expression of EP1 and EP3 receptors in POU may also help accentuate PGE2-induced signaling in the mCD.

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Reducing neuronal apoptosis in pontine micturition center by nerve root transfer to reconstruct bladder function after spinal cord injury

10.21203/rs.2.17382/v1 ◽

2019 ◽

Author(s):

Ronghua Yu ◽

Gang Yin ◽

Jianguo Zhao ◽

Huihao Chen ◽

Depeng Meng ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Nerve Root ◽

Neuronal Apoptosis ◽

Nerve Transfer ◽

Bladder Function ◽

Sprague Dawley ◽

Nerve Roots ◽

Sprague Dawley Rats ◽

Cord Injury

Abstract Background: The neuronal apoptosis is increased after spinal cord injury (SCI), but anastomosing the normal nerve roots above SCI level to the injury sacral nerve roots can enhance functional recovery of neurons. Therefore, we evaluated the effect of sacral nerve root transfer after SCI on pontine neuronal survival and restoration of bladder function. Methods: Adult female Sprague Dawley rats (N = 90, 9–10 weeks old, 240-260 grams weight) were randomly divided into three groups (N = 30). We anastomosed the dorsal and ventral roots of proximal L4 and distal S2 to reconstruct the rat bladder–spinal cord–cerebral nerve afferent and efferent pathways in Sprague Dawley rats after spinal cord transection. We examined pontine neuronal morphology and apoptosis using hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) at different time points (1 day, 1 week, and 1, 3, or 6 months) after SCI and nerve transfer. Bcl-2 and Bax protein expression changes in the pontine micturition center were quantified by immunohistochemistry. Results: After nerve roots reconstruction, Group A compared with Group B, Bcl-2 expression increased significantly, Bax expression decreased significantly, Bcl-2/Bax ratio increased, the number of apoptotic neurons decreased, and the number of apoptotic bodies within neurons decreased significantly as observed by TEM.Conclusion: These findings demonstrate that lumbosacral nerve transfer can reduce neuronal apoptosis in the pontine micturition center and enhance functional recovery of neurons. This method can be used as a new approach for reconstructing bladder function after spinal cord injury.

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