430 A STUDY OF AGE-RELATED IMPAIRMENTS IN REGENERATIVE CAPACITY USING THE RODENT BLADDER

Abstract

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology1 Apr 2011430 A STUDY OF AGE-RELATED IMPAIRMENTS IN REGENERATIVE CAPACITY USING THE RODENT BLADDER David Burmeister, Tamer Aboushwareb, Sean D'Souza, Maja Herco, KArl-Erik Andersson, and George Christ David BurmeisterDavid Burmeister Winston-Salem, NC More articles by this author , Tamer AboushwarebTamer Aboushwareb Winston-Salem, NC More articles by this author , Sean D'SouzaSean D'Souza Winston-Salem, NC More articles by this author , Maja HercoMaja Herco Winston-Salem, NC More articles by this author , KArl-Erik AnderssonKArl-Erik Andersson Winston-Salem, NC More articles by this author , and George ChristGeorge Christ Winston-Salem, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.520AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Models of organ regeneration in lower vertebrates (e.g., salamanders) have been utilized to identify key mechanisms involved in regenerative processes. Although information obtained with these models may be leveraged to help restore tissue function, more relevant models in animals closer to humans phylogenetically are lacking. We have previously reported on a rodent model of bladder regeneration, where removal of ∼70% of the bladder (subtotal cystectomy; STC) induces a robust regenerative response in 12 week old female rats, such that normal volume and function are restored within 8 weeks. Herein we report on the impact of age on the remodeling/regenerative response of the bladder after STC in 12 month old females. METHODS 12 month and 12 week old Fisher F344 female rats underwent trigone-sparing STC with subsequent urodynamic assessment performed up to 8 weeks post-STC. After euthanasia, routine H&E was performed on excised bladders and kidneys. Additionally, bladders were immunostained for Hypoxia Inducible Factor (HIF-1á) to examine oxidative stress, and myeloperoxidase and CD68 to look at neutrophil and macrophage infiltration respectively. RESULTS Cystometric studies revealed that bladder capacity 8 weeks post-STC was 0.54 +/-0.06mL, or 60% of age-matched controls (0.9+/−0.05mL). Pressures generated in bladders 8 weeks post-STC also remained low (33.28 +/−4.46 cmH2O) compared to controls (56.72 +/− 4.75cmH2O). H&E staining of excised kidneys revealed damage consistent with hydronephrosis in animals that underwent STC compared to controls, and was accompanied by a significant increase in kidney weight in STC animals (1.10 +/− 0.03g) compared to controls (0.99+/− 0.02g). Immunostaining revealed that an increased monocyte infiltration at 2 weeks post-STC may inhibit functional recovery during the regenerative response. CONCLUSIONS These data clearly demonstrate an age-related diminution in regenerative capacity, potentially leading to end stage renal disease. This is demonstrated by low capacities and pressures 8 weeks after surgery, which is sufficient time for young adult rats to recover. Fully elucidating the mechanistic basis for impaired regeneration is of the highest priority for future studies. In summary, the rodent bladder not only provides an excellent model for studying the regenerative process in adult mammals, but may also shed mechanistic insight on the salient features of impaired regeneration, perhaps pointing toward new therapeutic possibilities for tissue repair/regeneration. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e173-e174 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information David Burmeister Winston-Salem, NC More articles by this author Tamer Aboushwareb Winston-Salem, NC More articles by this author Sean D'Souza Winston-Salem, NC More articles by this author Maja Herco Winston-Salem, NC More articles by this author KArl-Erik Andersson Winston-Salem, NC More articles by this author George Christ Winston-Salem, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...