Dataset Information

Non-invasive voiding assessment in conscious mice.

ABSTRACT: OBJECTIVE:To review available options of assessing murine bladder function and to evaluate a non-invasive technique suitable for long-term recording. METHODS:We reviewed previously described methods to record rodent bladder function. We used modified metabolic cages to capture novel recording tracings of mouse micturition. We evaluated our method in a pilot study with female mice undergoing partial bladder outlet obstruction or sham operation, respectively; half of the partial obstruction and sham group received treatment with an S6K-inhibitor, targeting the mTOR pathway, which is known to be implicated in bladder response to obstruction. RESULTS:Our non-invasive method using continuous urine weight recording reliably detected changes in murine bladder function resulting from partial bladder outlet obstruction or treatment with S6K-inhibitor. We found obstruction as well as treatment with S6K-inhibitor to correlate with a hyperactive voiding pattern. CONCLUSIONS:While invasive methods to assess murine bladder function largely disturb bladder histology and intrinsically render post-cystometry gene expression analysis of questionable value, continuous urine weight recording is a reliable, inexpensive, and critically non-invasive method to assess murine bladder function, suitable for a long-term application.

SUBMITTER: Sidler M

PROVIDER: S-EPMC7401987 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Non-invasive voiding assessment in conscious mice.

Sidler Martin M Aitken Karen J KJ Forward Sarah S Vitkin Alex A Bagli Darius J DJ

Bladder (San Francisco, Calif.) 20180402 2

<h4>Objective</h4>To review available options of assessing murine bladder function and to evaluate a non-invasive technique suitable for long-term recording.<h4>Methods</h4>We reviewed previously described methods to record rodent bladder function. We used modified metabolic cages to capture novel recording tracings of mouse micturition. We evaluated our method in a pilot study with female mice undergoing partial bladder outlet obstruction or sham operation, respectively; half of the partial obs ...[more]

PMID: 32775475

Similar Datasets

Project description:BackgroundBuruli ulcer (BU) caused by Mycobacterium ulcerans is the world's third most common mycobacterial infection. There is no vaccine against BU and surgery is needed for patients with large ulcers. Although recent experience indicates combination chemotherapy with streptomycin and rifampin improves cure rates, the utility of this regimen is limited by the 2-month duration of therapy, potential toxicity and required parenteral administration of streptomycin, and drug-drug interactions caused by rifampin. Discovery and development of drugs for BU is greatly hampered by the slow growth rate of M. ulcerans, requiring up to 3 months of incubation on solid media to produce colonies. Surrogate markers for evaluating antimicrobial activity in real-time which can be measured serially and non-invasively in infected footpads of live mice would accelerate pre-clinical evaluation of new drugs to treat BU. Previously, we developed bioluminescent M. ulcerans strains, demonstrating proof of concept for measuring luminescence as a surrogate marker for viable M. ulcerans in vitro and in vivo. However, the requirement of exogenous substrate limited the utility of such strains, especially for in vivo experiments.Methodology/principal findingFor this study, we engineered M. ulcerans strains that express the entire luxCDABE operon and therefore are autoluminescent due to endogenous substrate production. The selected reporter strain displayed a growth rate and virulence similar to the wild-type parent strain and enabled rapid, real-time monitoring of in vitro and in vivo drug activity, including serial, non-invasive assessments in live mice, producing results which correlated closely with colony-forming unit (CFU) counts for a panel of drugs with various mechanisms of action.Conclusions/significanceOur results indicate that autoluminescent reporter strains of M. ulcerans are exceptional tools for pre-clinical evaluation of new drugs to treat BU due to their potential to drastically reduce the time, effort, animals, compound, and costs required to evaluate drug activity.

Project description:BackgroundVoiding dysfunction (VD) is a common neurogenic lower urinary tract dysfunction (NLUTD) in multiple sclerosis (MS) patients. Currently, the only effective management for VD and urinary retention in MS patients is catheterization, prompting us to look for novel therapeutic options beyond the bladder, such as the brain. Transcranial rotating permanent magnet stimulator (TRPMS) is a non-invasive, portable, multifocal neuromodulator that simultaneously modulates multiple cortical regions, enhancing or attenuating strengths of functional connections between these regions. The objective of this pilot clinical trial is to evaluate the feasibility of a TRPMS trial to address lower urinary tract symptoms in MS patients, through investigating the therapeutic effects of TRPMS in modulating brain regions during voiding initiation and mitigating VD in female MS individuals.MethodsTen adult female MS patients with VD (defined as having %post-void residual/bladder capacity (%PVR/BC) ≥ 40% or Liverpool nomogram percentile < 10%) will be recruited for this study. Concurrent urodynamic and functional MRI evaluation with a bladder filling/emptying task repeated three to four times will be performed at baseline and post-treatment. Predetermined regions of interest and their blood-oxygen-level-dependent (BOLD) activation at voiding initiation will be identified on each patient's baseline anatomical and functional MRI scan, corresponding to the microstimulators placement on their individualized TRPMS treatment cap to either stimulate or inhibit these regions. Patients will receive 10 40-min treatment sessions. Non-instrumented uroflow and validated questionnaires will also be collected at baseline and post-treatment to evaluate clinical improvement.DiscussionDespite the crucial role of the central nervous system in urinary control and its sensitivity to MS, there has been no treatment for urinary dysfunction targeting the brain centers that are involved in proper bladder function. This trial, to our knowledge, will be the first of its kind in humans to consider non-invasive and individualized cortical modulation for treating VD in MS patients. Results from this study will provide a better understanding of the brain control of neurogenic bladders and lay the foundation for a potential alternative therapy for VD in MS patients and other NLUTD in a larger neurogenic population in the future.Trial registrationThis trial is registered at ClinicalTrials.Gov ( NCT03574610 , 2 July 2018.) and Houston Methodist Research Institute IRB (PRO00019329).

Project description:BACKGROUND:Although placement of an intra-cerebral catheter remains the gold standard method for measuring intracranial pressure (ICP), several non-invasive techniques can provide useful estimates. The aim of this study was to compare the accuracy of four non-invasive methods to assess intracranial hypertension. METHODS:We reviewed prospectively collected data on adult intensive care unit (ICU) patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), or intracerebral hemorrhage (ICH) in whom invasive ICP monitoring had been initiated and estimates had been simultaneously collected from the following non-invasive indices: optic nerve sheath diameter (ONSD), pulsatility index (PI), estimated ICP (eICP) using transcranial Doppler, and the neurological pupil index (NPI) measured using automated pupillometry. Intracranial hypertension was defined as an invasively measured ICP >?20?mmHg. RESULTS:We studied 100 patients (TBI?=?30; SAH?=?47; ICH?=?23) with a median age of 52?years. The median invasively measured ICP was 17 [12-25] mmHg and intracranial hypertension was present in 37 patients. Median values from the non-invasive techniques were ONSD 5.2 [4.8-5.8] mm, PI 1.1 [0.9-1.4], eICP 21 [14-29] mmHg, and NPI 4.2 [3.8-4.6]. There was a significant correlation between all the non-invasive techniques and invasive ICP (ONSD, r?=?0.54; PI, r?=?0.50; eICP, r?=?0.61; NPI, r?=?-?0.41-p?<?0.001 for all). The area under the curve (AUC) to estimate intracranial hypertension was 0.78 [CIs?=?0.68-0.88] for ONSD, 0.85 [95% CIs 0.77-0.93] for PI, 0.86 [95% CIs 0.77-0.93] for eICP, and 0.71 [95% CIs 0.60-0.82] for NPI. When the various techniques were combined, the highest AUC (0.91 [0.84-0.97]) was obtained with the combination of ONSD with eICP. CONCLUSIONS:Non-invasive techniques are correlated with ICP and have an acceptable accuracy to estimate intracranial hypertension. The multimodal combination of ONSD and eICP may increase the accuracy to estimate the occurrence of intracranial hypertension.

Dataset Information

Non-invasive voiding assessment in conscious mice.

Publications

Non-invasive voiding assessment in conscious mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets