MP62-13 BDNF IS ESSENTIAL FOR PUDENDAL NERVE MOTOR BRANCH FUNCTIONAL RECOVERY

Abstract

INTRODUCTION AND OBJECTIVES: Stress Urinary Incontinence (SUI) in women is highly associated with childbirth which could injury the pudendal nerve (PN) during delivery. Increased motor latency in post-partum incontinent women indicates the key role of the PN is to maintain continence. Brain derived neurotrophin factor (BDNF) and its receptor tyrosine kinase B (TrkB) has been shown to be important in motoneuron regeneration. In this experiment, we hypothesized that BDNF is essential to PN functional recovery and tested the hypothesis by administering its receptor, TrkB, to reduce active BDNF in an animal model of SUI. METHODS: Female rats received bilateral PN crush (PNC) and osmotic pumps containing saline (PNC + S) or Fc-TrkB chimera (PNC + TrkB) or received bilateral sham PNC and osmotic pumps containing saline (Sham PNC + S). Three weeks after injury, the rats underwent leak point pressure (LPP) testing with simultaneous PN motor branch potential (PNMBP) recording, followed by PN sensory branch potential (PNSBP) recording during clitoral brushing. One-way ANOVA on Ranks followed by a Dunn's test indicated significant differences (p<0.05). After functional testing, rats were euthanized and plasma was collected. The urethras were harvested and stained with Masson's Trichrome and neuromuscular junction (NMJ) immuno-stain, followed by semi-quantitatively evaluation. BDNF and neurotrophin factor 4 (NT4) plasma levels were measured using ELISAs. NT4 is also a receptor for BDNF, so we tested for it to confirm that our Fc-Trk B was specific to just BDNF. A t-test was used to determine significant difference (p<0.05). RESULTS: BDNF plasma concentration was significantly decreased in the TrkB treated group (1321 ± 278 pg/ml) compared to PNC + Saline (2053 ± 211 pg/ml). NT4 plasma concentrations were not significantly different between PNC + Saline (713 ± 29 pg/ml) and PNC + TrkB (792 ± 55 pg/ml). PNMBP (motor) firing rate was significantly decreased in PNC + TrkB (54.0 ± 9.5 Hz) compared to PNC + S (120.4 ±17.1 Hz), while PNC + S was not significantly different from Sham PNC + S (121.8 ± 26.6 Hz). PNSBP (sensory) firing rate was not significantly different between groups. LPP was not significantly different between the groups: Sham PNC + S (26.4 ± 3.5 cm H20), PNC + S (18.1 ± 1.7 cm H20), and PNC + TrkB (20.1 ± 1.9 cm H20). Masson's staining showed no differences in morphology between the groups. The PNC + TrkB group had fewer innervated NMJ than the other groups. CONCLUSIONS: This study demonstrates that administration of TrkB successfully decreases the expression of BDNF and leads to reduced recovery of PNMBP in a SUI animal model. BDNF is essential to PN functional recovery in a PNC SUI model.