MP17-11 INHIBITION OF P2X7 RECEPTORS AFTER DORSAL-HORN TRANSECTION IMPROVES NEUROGENIC BLADDER DYSFUNCTION IN FEMALE RATS

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology1 Apr 2014MP17-11 INHIBITION OF P2X7 RECEPTORS AFTER DORSAL-HORN TRANSECTION IMPROVES NEUROGENIC BLADDER DYSFUNCTION IN FEMALE RATS Timothy B. Boone and Alvaro Munoz Timothy B. BooneTimothy B. Boone More articles by this author and Alvaro MunozAlvaro Munoz More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.532AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder dysfunction is a common complication affecting patients with spinal cord injury (SCI), making restoration of efficient micturition a clinical priority. Animal models of regeneration after SCI suggest that amelioration of damage at the SCI site could improve visceral function and urine storage, but the extent of bladder sensory restoration remains unclear. In addition to promoting locomotor recovery, our main objective was to determine whether the specific inhibition of P2X7R after a SCI decrease the levels of nerve growth factor (NGF) in the bladder METHODS Female Sprague-Dawley rats were implanted with subcutaneous osmotic pumps filled with either saline or the P2X7 antagonist brilliant blue-G (BBG). A continuous infusion of 30 μg/kg/hr was started at the time of performing a dorsal-horn transection at the T8/T9 level. Spinal cord expression of P2X7R and Iba1 (microglia marker) was verified with immunohistochemistry. Locomotor effects were determined with the Basso, Beattie and Bresnahan (BBB) score and the standing capacity index (standings on rear paws in one minute) at 0, 1, 7, 14 or 28 days. After manual bladder expression, urine samples were stored for determination of residual volume (ml); creatinine (Cr; Jaffe’ reaction); and NGF (ELISA) at 0, 1, 7 or 28 days. Cystometry was done via a suprapubic catheter in urethane anesthetized rats. Data were analyzed with ANOVA and Tukey’s post test. Values are mean+/- SEM. P<0.05 was considered statistically significant. RESULTS SCI increased the number of P2X7R+ cells in the rostral & caudal (to the SCI site) dorsal-horn area, while promoting the appearance of Iba1+ microglia. Systemic BBG treatment accelerated locomotion recovery while significantly improving standing capacity. The residual urine was 0.19+/-0.03 ml in intact rats (n=6), 1.22+/-0.15 ml in SCI rats (n=6; p<0.01 vs intact) and 0.23+/-0.07 ml in BBG-treated SCI animals (n=2). Urine NGF levels (pg NGF/mg Cr) were 45.8+/-7.1 in control rats; 568.8+/-138.4 in SCI-animals (p<0.01 vs intact), and 112.8+/-6.4 in SCI rats receiving BBG (p<0.01 vs SCI rats). Cystometric studies showed a higher frequency of non-voiding contractions in SCI than in BBG-treated SCI rats. CONCLUSIONS Inhibition of P2X7R at the SCI site may be a therapeutic target to improve bladder function by promoting neuroregeneration and decreasing urine NGF, a biomarker for neurogenic bladder. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e139-e140 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Timothy B. Boone More articles by this author Alvaro Munoz More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...