MP30-14 UROTHELIAL HYPERPLASIA AND REGENERATION AFTER SPINAL CORD INJURY

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology II1 Apr 2016MP30-14 UROTHELIAL HYPERPLASIA AND REGENERATION AFTER SPINAL CORD INJURY F. Aura Kullmann, Dennis Clayton, Gerard Apodaca, Irina Zabbarova, Youko Ikeda, Anthony Kanai, and Lori Birder F. Aura KullmannF. Aura Kullmann More articles by this author , Dennis ClaytonDennis Clayton More articles by this author , Gerard ApodacaGerard Apodaca More articles by this author , Irina ZabbarovaIrina Zabbarova More articles by this author , Youko IkedaYouko Ikeda More articles by this author , Anthony KanaiAnthony Kanai More articles by this author , and Lori BirderLori Birder More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1246AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The urothelium (UT) normally functions as an efficient barrier to solutes and pathogens and an integral part of a sensory web that can influence bladder function. Spinal cord injury (SCI) is associated with profound changes of the UT including an initial disruption followed by a UT thickening or hyperplasia. In SCI patients, a number of factors including bladder irritation (i.e. chronic infection; use of indwelling catheters) can cause UT hyperplasia, which increases the risk of bladder cancer. Surprisingly, little is known about the temporal order of events that result in UT proliferation following SCI. Here we investigate the time course of UT hyperplasia after SCI as well as changes in structural/junctional proteins necessary for maintaining epithelial integrity. METHODS Bladders from sham and spinal cord transected C57Bl6 female mice (T8-T9; 1-28 days post SCI) were prepared for histology (hematoxylin and eosin) and immunohistochemistry. Some mice were injected intraperitoneally with bromodeoxyuridine (BrdU; 100mg/kg) prior to sacrificing to assess the extent of UT hyperplasia. RESULTS Histology showed thicker UT, lamina propria and smooth muscle (SM) starting 2-3 days post SCI. BrdU staining indicated that epithelial proliferation was evident as early as day two post SCI and followed a temporal gradient from the UT to the SM. The number of BrdU+ cells in the UT increased dramatically at day 2 post SCI and declined thereafter. In contrast, the number of BrdU+ cells in the SM was maximal 7 days post SCI and decreased thereafter. P63+ progenitor cells, located in the basal and intermediate layers of the UT, were more numerous in the SCI versus sham at all time points. We also found that claudin-8, a marker for epithelial junctional integrity, was expressed as early as one week post SCI. CONCLUSIONS The bladder urothelium possesses a remarkable ability to regenerate after SCI. We find that the process of regeneration starts soon after SCI (>2days) and follows a temporal gradient (over approximately two weeks) from the UT to the SM. Though the structural recovery, as indicated by claudin 8 expression, may be achieved in the first two weeks post SCI, the number of progenitor cells was still elevated one month following SCI, suggesting the potential for further remodeling. Future research will investigate factors involved in SCI-associated urothelial hyperplasia. This is an important issue since epithelial hyperplasia may be a predisposition for bladder cancer, which is a serious oncologic complication in SCI patients associated with significant mortality. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e416 Advertisement Copyright & Permissions© 2016MetricsAuthor Information F. Aura Kullmann More articles by this author Dennis Clayton More articles by this author Gerard Apodaca More articles by this author Irina Zabbarova More articles by this author Youko Ikeda More articles by this author Anthony Kanai More articles by this author Lori Birder More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...