Animal models and their use in understanding lower urinary tract dysfunction

Fry, Christopher; Daneshgari, Firouz; Thor, Karl B.; Drake, Marcus; Eccles, Rachel; Birder, Lori A.

doi:10.1002/nau.20903

Cited by 55 publications

(47 citation statements)

References 70 publications

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“…Rodents have been used extensively to investigate mechanisms underlying LUTS in humans (4,9). Rodents provide the opportunity for more invasive investigation of the pathophysiology underlying LUTS than studies in patients, but differences in anatomy and basic physiology must be kept in mind, as well as differences between spontaneous and induced disorders resulting in LUTS.…”

mentioning

confidence: 99%

Evaluation of voiding assays in mice: impact of genetic strains and sex

Bjorling

Wang

Vezina

et al. 2015

American Journal of Physiology-Renal Physiology

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Void spot assays (VSA) and cystometry are two of the most common tests performed in mice to assess lower urinary tract function. Assay protocols and methodology vary greatly among laboratories, and little is known about reproducibility of results generated by different laboratories. We performed VSA in four mouse strains, comparing males with females and comparing results between two independent laboratories. Unique aspects of the current study include direct comparison of results of VSA performed in a similar manner in two locations and comparison of cystometry performed using two different rates of infusion in these two laboratories. Both assays were performed in male and female 129S1/SvImJ, C57BL/6J, NOD/ShiLtJ, and CAST/EiJ mice, and cystometry was performed under urethane anesthesia (10/group). Assays were performed and results analyzed as previously described. Results obtained in female mice were compared with previously reported values. Results of lower urinary tract function testing in mice vary in a consistent manner with strain and sex. Variables in husbandry, testing techniques, and analysis of results can significantly affect conclusions, particularly those obtained by cystometry. Although VSA results were remarkably similar between the two laboratories, consistent methods for performing lower urinary tract function testing in mice are required to compare results among studies with confidence.

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mentioning

confidence: 99%

Evaluation of voiding assays in mice: impact of genetic strains and sex

Bjorling

Wang

Vezina

et al. 2015

American Journal of Physiology-Renal Physiology

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“…Animal models offer the opportunities for detailed investigation of specific mechanistic aspects of the micturition cycle (17), with genetically modified mouse models offering the additional prospect of implicating specific genes. The influence of age on the micturition cycle has been previously studied using in vivo rodent cystometric models (8,9,62), with mixed results regarding urine storage and voiding characteristics.…”

mentioning

confidence: 99%

Detrusor expulsive strength is preserved, but responsiveness to bladder filling and urinary sensitivity is diminished in the aging mouse

Smith

DeAngelis

Kuchel

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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The prevalence of urinary symptoms increases with age and is a significant source of distress, morbidity, and expense in the elderly. Recent evidence suggests that symptoms in the aged may result from sensory dysfunction, rather than abnormalities of detrusor performance. Therefore, we employed a pressure/flow multichannel urethane-anesthetized mouse cystometry model to test the hypothesis that in vivo detrusor performance does not degrade with aging. Secondarily, we sought to evaluate sensory responsiveness to volume using pressure-volume data generated during bladder filling. Cystometric data from 2-, 12-, 22-, and 26-mo-old female C57BL6 mice were compared. All 2- and 12-mo-old mice, 66% of 22-mo-old mice, and 50% of 26-mo-old mice responded to continuous bladder filling with periodic reflex voiding. Abdominal wall contraction with voiding had a minimal contribution to expulsive pressure, whereas compliance pressure was a significant contributor. Maximum bladder pressure, estimated detrusor pressure, detrusor impulse (pressure-time integral), as well as indices of detrusor power and work, did not decrease with aging. Bladder precontraction pressures decreased, compliance increased, and nonvoiding contraction counts did not change with increasing age. Intervoid intervals, per-void volumes, and voiding flow rates increased with age. Calculations approximating wall stress during filling suggested loss of bladder volume sensitivity with increasing age. We conclude that aging is associated with an impaired ability to respond to the challenge of continuous bladder filling with cyclic voiding, yet among responsive animals, voiding detrusor contraction strength does not degrade with aging in this murine model. Furthermore, indirect measures suggest that bladder volume sensitivity is diminished. Thus, changes in homeostatic reserve and peripheral and/or central sensory mechanisms may be important contributors to aging-associated changes in bladder function.

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“…As investigações em pesquisa translacional com animais devem ser integradas com perguntas decorrentes das observações em humanos e os achados pré--clínicos validados (42).…”

Section: Dmg E As Repercussões Maternas Neonatais E Placentárias Nosunclassified

Pesquisa translacional em diabetes melito gestacional e hiperglicemia gestacional leve: conhecimento atual e nossa experiência

Rudge

Pículo

Marini

et al. 2013

Arq Bras Endocrinol Metab

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RESUMOO diabetes materno constitui um ambiente desfavorável para o desenvolvimento embrionário e feto--placentário. É uma repercussão de importância na obstetrícia moderna, visto que está associado a um risco aumentado de morbidade materna e neonatal e continua a ser um desafio médico significativo. O aumento mundial na incidência do diabetes, o aumento do diabetes tipo 2 em mulheres em idade reprodutiva e a geração cruzada da programação intrauterina do diabetes tipo 2 são as bases para o interesse crescente na utilização de modelos experimentais diabéticos, a fim de obter conhecimento sobre os mecanismos que induzem as alterações de desenvolvimento no diabetes gestacional. Vários estudos têm demonstrado os benefícios da prevenção do diabetes com intervenções no estilo de vida, melhora metabólica e controle de fator de risco cardiovascular para evitar substancialmente as complicações devastadores da doença. Apesar desses achados e a revolução recente no conhecimento científico e infinidade de novas terapias do diabetes, continua a haver uma grande lacuna entre o que foi aprendido por meio da pesquisa e o que é feito na prática da saúde pública, clínica e comunitária. O iminente impacto econômico negativo dessa complacência nos indivíduos, nas famílias e nas economias nacionais é alarmante. Espera-se que a pesquisa translacional no binômio diabetes-gravidez seja implementada em centros de excelência tanto de pesquisa básica como aplicada e complementada por estudos clínicos multicêntricos, conduzidos de forma pragmá-tica para aumentar o nível de evidência científica com recursos diagnósticos e propedêuticos mais confiáveis. Arq Bras Endocrinol Metab. 2013;57(7):497-508 Descritores Diabetes; gestação; modelos animais; pesquisa translacional; incontinência urinária ABSTRACT Maternal diabetes constitutes an unfavorable environment for fetal-placental and embryonic development. It is has important repercussion in modern obstetrics, since it is associated to an increased risk of neonatal and maternal morbidity, and it still is a significant medical challenge. The increased occurrence of diabetes worldwide, the increase in diabetes type 2 in women at reproductive age and the crossed generation of intrauterine programming for diabetes type 2 are the bases for the growing interest in utilization of diabetic experimental samples, with the aim to acquire knowledge about the mechanisms that induce development alterations in gestational diabetes. Several studies have shown the benefits of diabetes prevention, with interventions in lifestyle, metabolic improvement and control of cardiovascular risk factors to substantially prevent the complications of this devastating disease. Despite these findings, the recent revolution in the scientific knowledge, and the infinite number of new therapies for diabetes, there is still a large gap between what was learned through research and what is really done in public, clinical and community health. The negative economic impact of this complacency in people, families, and national econom...

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Animal models and their use in understanding lower urinary tract dysfunction

Cited by 55 publications

References 70 publications

Evaluation of voiding assays in mice: impact of genetic strains and sex

Evaluation of voiding assays in mice: impact of genetic strains and sex

Detrusor expulsive strength is preserved, but responsiveness to bladder filling and urinary sensitivity is diminished in the aging mouse

Pesquisa translacional em diabetes melito gestacional e hiperglicemia gestacional leve: conhecimento atual e nossa experiência

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