MP80-02 EFFECTS OF ALPHA-1A/D ADRENOCEPTOR ANTAGONIST ON BLADDER OVERACTIVITY AND REMODELING IN RATS WITH SPINAL CORD INJURY

Abstract

INTRODUCTION AND OBJECTIVES: Detrusor overactivity threatens the renal function of patients with spinal cord injury. Suppressing N-methyl-D-aspartate receptors is known to improve detrusor overactivity in rats with spinal cord injury, whereas kynurenic acid, the endogenous antagonist of N-methyl-D-aspartate receptors, is irreversibly synthesized by kynurenine aminotransferases. METHODS: In this study, we evaluated if replication-defective herpes simplex virus vectors mediated gene transfer of human kynurenine aminotransferase II could treat detrusor overactivity by injecting the vectors into the rat bladder wall at one week after spinal cord injury. At three weeks after injection, we evaluated the cystometry and the gene expression of kynurenine aminotransferase II in L6-S1 dorsal root ganglia. RESULTS: The results showed the vectors are transported to L6-S1 dorsal root ganglia and up-regulate the expression of kynurenine aminotransferase II, improve detrusor overactivity and voiding efficiency. We also proved N-methyl-D-aspartate receptors were blocked by the kynurenic acid in the extracellular solution or the vector-mediated gene transfer of kynurenine aminotransferase II in cultured rat neurons of L6-S1 dorsal root ganglia by whole-cell patch clamp to explore the mechanisms of gene therapy. CONCLUSIONS: Therefore, replication-defective herpes simplex virus vectors mediated kynurenine aminotransferase II inhibits detrusor overactivity in spinal cord injured rats, possibly through suppressing N-methyl-D-aspartate receptors in bladder afferent pathways.