Pd07-08 Improvement of Lower Urinary Tract Dysfunction by a Monoacylglycerol Lipase Inhibitor After Spinal Cord Injury

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction (PD07)1 May 2024PD07-08 IMPROVEMENT OF LOWER URINARY TRACT DYSFUNCTION BY A MONOACYLGLYCEROL LIPASE INHIBITOR AFTER SPINAL CORD INJURY Kang Jun Cho, Mamoru Hashimoto, Kanako Matsuoka, Sergei Karnup, Joon Chul Kim, Stephanie L. Daugherty, Jonathan M. Beckel, and Naoki Yoshimura Kang Jun ChoKang Jun Cho , Mamoru HashimotoMamoru Hashimoto , Kanako MatsuokaKanako Matsuoka , Sergei KarnupSergei Karnup , Joon Chul KimJoon Chul Kim , Stephanie L. DaughertyStephanie L. Daugherty , Jonathan M. BeckelJonathan M. Beckel , and Naoki YoshimuraNaoki Yoshimura View All Author Informationhttps://doi.org/10.1097/01.JU.0001008552.16893.70.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Activation of endocannabinoid system by monoacylglycerol lipase (MAGL) blockade may affect the lower urinary tract function. We investigated the effect of MAGL inhibitor, MJN110, in the mouse with neurogenic lower urinary tract dysfunction (LUTD) after spinal cord injury (SCI). METHODS: Female C57BL/6 mice that underwent spinal cord transection at T8-10 level were divided into three groups; vehicle-treated and 5 or 10 mg/kg of MJN110 groups. MJN110 and vehicle were injected intraperitoneally for seven days from 4 weeks after spinal cord transection. We then conducted awake cystometrograms and compared urodynamic parameters between three groups. In addition, the expression of cannabinoid receptors (CB), transient receptor potential (TRP) channels and inflammatory cytokines in the L6-S1 dorsal root ganglion (DRG) or bladder mucosa were evaluated by qPCR and compared in three groups. RESULTS: In cystometrograms, detrusor overactivity (DO) parameters, such as the number of non-voiding contractions (NVC), a ratio of time to the 1st NVC to intercontraction intervals (ICI) and NVC integrals were improved by MJN110 treatment, and some effects were dose dependent. Also, MJN110 treatment decreased bladder capacity, ICI, and residual urine volume compared to vehicle injection (Table 1), MJN110 treatment groups had lower CB2, TRPV 1, TRPA1 and inflammatory cytokines mRNA levels in DRG and the bladder mucosa. CONCLUSIONS: MAGL inhibition can improve LUTD by attenuation of DO after SCI. MAGL can be a therapeutic target for neurogenic LUTD after SCI. Source of Funding: NIH R01DK129194 © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e170 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Kang Jun Cho More articles by this author Mamoru Hashimoto More articles by this author Kanako Matsuoka More articles by this author Sergei Karnup More articles by this author Joon Chul Kim More articles by this author Stephanie L. Daugherty More articles by this author Jonathan M. Beckel More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement PDF downloadLoading ...