scholarly journals Validation of an efficient and continuous urodynamic monitoring system for awake, unrestrained, chronic rodent studies

2020 ◽  
Vol 318 (1) ◽  
pp. F86-F95
Author(s):  
D. Angoli ◽  
A. Geramipour ◽  
Z. C. Danziger

The postvoid residual (PVR) is an important measure of bladder function, but obtaining PVR is burdensome because bladder volume must be measured at the time of voiding. The PVR measurement problem has led to experimental tricks in animal studies (infusing the bladder at supraphysiological rates and limiting animal observation windows) to keep the number of observed voids statistically robust while reducing the time an experimenter must be present. Our solution to the PVR measurement problem is a system called Automatic Monitoring for Efficient, Awake, Sensitive, Urine Residual Estimation (AMEASURE). AMEASURE combines metabolic cages and optimization algorithms to estimate continuously PVR for every voiding event 24 h/day for multiple weeks, without artificial bladder infusion, continuous experimenter supervision, anesthesia, or restraints. Using AMEASURE, we obtained voided volumes, PVRs, and other urodynamic parameters continuously for 21 days in 10 healthy female Sprague-Dawley rats. Importantly, this required only one manual measurement of animals’ bladder volume every 12 h. We validated the accuracy of the system experimentally and in simulation. We detected marked differences in voiding frequency and efficiency between light and dark cycles and found that voiding frequency increased over time during the dark cycle (but not the light cycle), due to surgical recovery, cage acclimation, and socialization. This tool enhances the relevance of rodent models to the study of human lower urinary tract by expanding observation periods and obviating the need to infuse the bladder and facilitates the study of conditions for which behavioral, social, or circadian factors play essential roles.

2007 ◽  
Vol 293 (4) ◽  
pp. E977-E985 ◽  
Author(s):  
Patricia Silveyra ◽  
Victoria Lux-Lantos ◽  
Carlos Libertun

Orexins are peptides controlling feeding, sleep, and neuroendocrine functions. They are synthesized by the hypothalamus with projections throughout the brain. Orexins and their orexin 1 (OX1) and orexin 2 receptors (OX2) are present outside the central nervous system. Here the expression of preproorexin (PPO), OX1, and OX2 was studied in rat ovaries. PPO, OX1, and OX2 were determined by quantitative real-time RT-PCR in ovaries of cycling Sprague-Dawley rats on all days of the cycle. Serum hormones and food consumption were determined. Ovarian OX1 and OX2 expression was then studied after ovulation blockade with Cetrorelix or Nembutal. Finally, proestrous rats were treated at 1400 and 1900 with a selective OX1 antagonist (SB-334867-A) and/or a selective OX2 antagonist (JNJ-10397049), and hormone levels, ovulation, and ovarian histology were studied. Both receptors' expression increased in the ovary between 1700 and 2300 of proestrus exclusively, in coincidence with hormone peaks, but not with the dark-light cycle or food intake. PPO was not detected. Cetrorelix or Nembutal prevented the increases of OX1 and OX2 while blunting gonadotropin peaks. SB-334867-A and JNJ-10397049, alone or combined, decreased serum gonadotropins and reduced ova number the following morning; ovaries showed a bloody (hyperemic and/or hemorrhagic) reaction with more preovulatory follicles and less corpora lutea. Here we demonstrate for the first time an increased ovarian expression of both OX1 and OX2, only during proestrous afternoon, and its hormone dependence but not dependence on the dark-light cycle. Two new receptor antagonists reduced proestrous gonadotropins and/or ova number while producing ovarian structural changes.


2021 ◽  
Vol 18 (5) ◽  
pp. 1049-1056
Author(s):  
Qinghong Fan ◽  
Wei Xiao ◽  
Xiaomeng Chai ◽  
Zhe Zhang ◽  
Tao Zhu ◽  
...  

Purpose: To investigate the effect of Kang fu yan capsule (KFYC) on phenol mucilage-induced intrauterine adhesion (IUA) in a rat model, and the underlying mechanisms. Methods: An IUA model was established by injecting 0.06 mL of 25 % phenol mucilage into the uterus of female Sprague-Dawley rats. The IUA model rats (n=59) were randomly divided into 5 groups: IUA group, fuke qianjin tablet group (FKQJT, 0.22 mg/kg), and 3 KFYC groups given different doses of the drug i.e. 0.13, 0.39and 1.17 mg/kg. A group of 10 healthy female rats served as control. After 19 days treatment, blood samples were collected for determination of IL-2 and IL-10 by ELISA, while uterine tissues were subjected to histological examination using hematoxylin and eosin staining (H&E) and Masson staining. Expressions of Notch1, recombination signal binding protein-JK (RBP-JK), a disintegrin and metalloprotease (ADAM)-12, ADAM-15, matrix metalloprotein-9 (MMP-9), and inhibitor of NF-κB (IĸB) in uterine tissues were determined using RT-qPCR and western blot analysis. Results: Compared to IUA group, histological results showed reduced inflammatory cell infiltration in rat uterine tissue of KFYC group. Moreover, KFYC significantly reversed uterine fibrosis (p < 0.05). Serum concentrations of IL-2 significantly decreased in KFYC groups (p < 0.05 or p < 0.01), and there was significant increases the serum concentrations of IL-10 in KFYC groups (p < 0.05 or < 0.01), when compared to IUA group. The mRNA and protein expressions of Notch1, RBP-JK, ADAM-12, ADAM-15, MMP-9 were also significantly down-regulated (p < 0.05), while protein expression of IĸB was upregulated in KFYC group, when compared to IUA group. Conclusion: KFYC exerts an anti-IUA effect via amelioration of uterine inflammation and fibrosis, probably via a mechanism involving regulation of Notch1/ADAM pathway.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Pardeep Kaur ◽  
Rajbir Kaur ◽  
Rohit Arora ◽  
Saroj Arora

3β, hydroxy-lup-20(29)-en-28-oic acid (Betulinic acid), a pentacyclic lupane-type triterpene has diverse pharmacological functions both in vitro and in vivo. The present study focuses its protective effect on polycyclic aromatic hydrocarbon (7,12- Dimethylbenz(a)anthracene or DMBA) induced alterations in membrane bound ATPases, detoxification enzymes and antioxidant enzymes in stomach and lungs of female Sprague Dawley rats. Healthy female Sprague Dawley rats were randomly assorted into six groups and the treatments were given orally for 7 weeks on alternate days. It was observed that betulinic acid facilitated the downregulation of elevated membrane bound ATPases (Na+/K+- ATPase, Ca2+-ATPase and Mg2+-ATPase) in DMBA administered rats. Likewise, the detoxification enzymes as well as antioxidant enzymes were modulated to normalcy in rats. Overall, betulinic acid was seen to be effective modulator of DMBA induced alterations in biochemical parameters.


2004 ◽  
Vol 4 ◽  
pp. 91-99 ◽  
Author(s):  
Daniela Quaglino ◽  
Miriam Capri ◽  
Luigi Zecca ◽  
Claudio Franceschi ◽  
Ivonne P. Ronchetti

Thymus plays an important role in the immune system and can be modulated by numerous environmental factors, including electromagnetic fields (EMF). The present study has been undertaken with the aim to investigate the role of long-term exposure to extremely low frequency electric and magnetic fields (ELF-EMF) on thymocytes of rats housed in a regular dark/light cycle or under continuous light. Male Sprague-Dawley rats, 2 months old, were exposed or sham exposed for 8 months to 50-Hz sinusoidal EMF at two levels of field strength (1 kV/m, 5 μT and 5 kV/m, 100 μT, respectively). Thymus from adult animals exhibits signs of gradual atrophy mainly due to collagen deposition and fat substitution. This physiological involution may be accelerated by continuous light exposure that induces a massive death of thymocytes. The concurrent exposure to continuous light and to ELF-EMF did not change significantly the rate of mitoses compared to sham-exposed rats, whereas the amount of cell death was significantly increased, also in comparison with animals exposed to EMF in a 12-h dark-light cycle. In conclusion, long-term exposure to ELF-EMF, in animals housed under continuous light, may reinforce the alterations due to a photic stress, suggesting that,in vivo, stress and ELF-EMF exposure can act in synergy determining a more rapid involution of the thymus and might be responsible for an increased susceptibility to the potentially hazardous effects of ELF-EMF.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samantha L. Baglot ◽  
Catherine Hume ◽  
Gavin N. Petrie ◽  
Robert J. Aukema ◽  
Savannah H. M. Lightfoot ◽  
...  

AbstractUp to a third of North Americans report using cannabis in the prior month, most commonly through inhalation. Animal models that reflect human consumption are critical to study the impact of cannabis on brain and behaviour. Most animal studies to date utilize injection of delta-9-tetrahydrocannabinol (THC; primary psychoactive component of cannabis). THC injections produce markedly different physiological and behavioural effects than inhalation, likely due to distinctive pharmacokinetics. The current study directly examined if administration route (injection versus inhalation) alters metabolism and central accumulation of THC and metabolites over time. Adult male and female Sprague–Dawley rats received either an intraperitoneal injection or a 15-min session of inhaled exposure to THC. Blood and brains were collected at 15, 30, 60, 90 and 240-min post-exposure for analysis of THC and metabolites. Despite achieving comparable peak blood THC concentrations in both groups, our results indicate higher initial brain THC concentration following inhalation, whereas injection resulted in dramatically higher 11-OH-THC concentration, a potent THC metabolite, in blood and brain that increased over time. Our results provide evidence of different pharmacokinetic profiles following inhalation versus injection. Accordingly, administration route should be considered during data interpretation, and translational animal work should strongly consider using inhalation models.


2018 ◽  
Vol 34 (09) ◽  
pp. 742-748
Author(s):  
Yooseok Ha ◽  
Seung Song ◽  
Nak Kang ◽  
Sang-Ha Oh

Background Reconstruction using supermicrosurgery, a technique of microneurovascular anastomosis for smaller vessels (< 0.8 mm), has become popular. Experimental animal studies for supermicrosurgery training have been reported; however, there have been few studies performed according to vessel diameter and pedicle length. In this study, the external diameters of four vessels (femoral, superficial epigastric, axillary, and common thoracic) and pedicle length of two flaps (superficial epigastric and common thoracic–long thoracic) were measured. Methods The inguinal and pectoral regions of Sprague-Dawley rats (n = 19) were dissected anatomically, and the external diameters of the four vessels were measured (right and left, artery and vein measured separately). After elevating the superficial epigastric and common thoracic–long thoracic flaps, the pedicle length of the flaps was also measured. Results Among the 16 vessels examined, the external diameters of 11 and 5 vessels were above and below 0.8 mm, respectively. The external diameters of the superficial epigastric vessel and common thoracic vessel (both arteries and veins) were below 0.8 mm. The external diameters of the femoral and axillary vessels (veins) were above 0.8 mm. The length of the common thoracic–long thoracic pedicle was approximately10 mm longer than that of the superficial epigastric pedicle. Conclusions The external diameters of the superficial epigastric vessel and common thoracic vessel are small enough for supermicrosurgery training. The pedicle lengths of both the superficial epigastric and common thoracic–long thoracic flaps are sufficient to perform free flap experiments. Supermicrosurgical free flaps using these two vessels and a study of the physiology and pharmacology of the flaps will likely be possible in the future.


2021 ◽  
Author(s):  
Samantha L Baglot ◽  
Catherine Hume ◽  
Gavin N. Petrie ◽  
Robert J Aukema ◽  
Savannah HM Lightfoot ◽  
...  

Up to a third of North Americans over 16 years old report using cannabis in the prior month, most commonly through inhalation. Animal models that reflect human cannabis consumption are critical to study its impacts on brain and behaviour. Nevertheless, most animal studies to date examine effects of cannabis through injection of delta-9-tetrahydrocannabinol (THC; primary psychoactive component of cannabis). THC injections produce markedly different physiological and behavioural effects than inhalation, likely due to distinctive pharmacokinetics of each administration route. The current study directly examined if administration route (injection versus inhalation), with dosing being matched on peak THC blood levels, alters the metabolism of THC, and the central accumulation of THC and its metabolites over time. Adult male and female Sprague-Dawley rats received either a single intraperitoneal injection of THC (2.5 mg/kg) or a single (15 min) session of inhaled exposure to THC distillate (100 mg/mL) vapour. Blood and brains were collected at 15, 30, 60, 90 and 240 minutes post-exposure for analysis of THC and metabolites through mass spectrometry-liquid chromatography. Inhalation results in immediate hypothermia, whereas injection results in delayed hypothermia. Despite achieving comparable peak concentrations of blood THC in both groups, our results indicate higher initial brain THC concentration following inhalation, whereas injection resulted in dramatically higher 11-OH-THC concentrations, a potent THC metabolite, in blood and brain that increased over time. Our results provide evidence that THC and its metabolites exhibit different pharmacokinetic profiles following inhalation versus injection, which could have significant impacts for data interpretation and generalizability. Accordingly, we suggest that translational work in the realm of THC and cannabis strongly consider using inhalation models over those that employ injection.


2019 ◽  
Author(s):  
Ronghua Yu ◽  
Gang Yin ◽  
Jianguo Zhao ◽  
Huihao Chen ◽  
Depeng Meng ◽  
...  

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.


2011 ◽  
Vol 301 (4) ◽  
pp. R896-R904 ◽  
Author(s):  
Long-Hu Jin ◽  
Karl-Erik Andersson ◽  
Jeong-Uk Han ◽  
Yong-Hyun Kwon ◽  
Chang-Shin Park ◽  
...  

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.


2021 ◽  
Vol 9 ◽  
Author(s):  
Stéphane Personne ◽  
Céline Brochot ◽  
Paulo Marcelo ◽  
Aurélie Corona ◽  
Sophie Desmots ◽  
...  

Biomonitoring studies have highlighted the exposure of pregnant women to pyrethroids based on the measurement of their metabolites in urine. Pyrethroids can cross the placental barrier and be distributed in the fetus as some pyrethroids were also measured in the meconium of newborns. Prenatal exposure to pyrethroids is suspected to alter the neurodevelopment of children, and animal studies have shown that early life exposure to permethrin, one of the most commonly used pyrethroid in household applications, can alter the brain development. This study aimed to characterize the fetal permethrin exposure throughout gestation in rats. We developed a pregnancy physiologically based pharmacokinetic (pPBPK) model that describes the maternal and fetal kinetics of the cis- and trans- isomers of permethrin during the whole gestation period. Pregnant Sprague–Dawley rats were exposed daily to permethrin (50 mg/kg) by oral route from the start of gestation to day 20. Permethrin isomers were quantified in the feces, kidney, mammary gland, fat, and placenta in dams and in both maternal and fetal blood, brain, and liver. Cis- and trans-permethrin were quantified in fetal blood and tissues, with higher concentrations for the cis-isomer. The pPBPK model was fitted to the toxicokinetic maternal and fetal data in a Bayesian framework. Several parameters were adjusted, such as hepatic clearances, partition coefficients, and intestinal absorption. Our work allowed to estimate the prenatal exposure to permethrin in rats, especially in the fetal brain, and to quantitatively estimate the placental transfer. These transfers could be extrapolated to humans and be incorporated in a human pPBPK model to estimate the fetal exposure to permethrin from biomonitoring data.


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