Evidence of overactive urinary bladder and outflow obstruction in a rat model of centrally induced neuroendocrine stress

Chronic stress is an important risk factor for overactive bladder syndrome; however, theunderlying mechanisms are not fully understood. Variability in the different chronic stressparadigms currently used in the field and the duration of these protocols further complicate theanalysis of contributing factors. Here, we tested urinary bladder dysfunction in a novel, centrallyinduced neuroendocrine stress model. This model is based on our previous findings indicatingthat prolonged upregulation of brain-derived neurotrophic factor (BDNF) in the paraventricularnucleus of the hypothalamus (PVN) induced hypertension and chronically elevated activities ofthe sympathetic nervous system and hypothalamus-pituitary-adrenal axis. Male Sprague Dawleyrats received bilateral PVN injections of AAV2 viral vectors expressing either BDNF or GFP (forcontrol). Bladder catheters were implanted into the bladder dome 16 days after vector injectionsand the catheters were connected to a catheter access button positioned in the interscapularregion. Five days later, 3 weeks after vector injections, bladder function was assessed usingconscious cystometry during intravesical infusion sterile 0.9% NaCl at a rate of 10 ml/h.Urodynamic measurement were continuously recorded and voided volume was measured on ananalytical scale placed under a wire-bottom cage. Void rates were calculated by measuring therate of change of the scale signal during a void (ml/s). Intermicturition interval and voided volumewere significantly lower in BDNF-treatment group (266 ± 19 sec; 0.76 ± 0.07 mL) vs GFP (475 ± 47sec; 1.30 ± 0.14 mL; p < 0.01 for both). Average bladder pressure during the fill cycle was similarin GFP (22.2 ± 1.4 cm H2O) and BDNF rats (24.4 ± 2.3 cm H2O). However, the frequency of non-voiding pressure peaks was significantly higher in BDNF (59.0 ± 4.7/h) vs GFP (34.2 ± 8.5/h).During micturition, the maximum bladder pressures were similar in GFP and BDNF rats; however, average void rate was significantly reduced in the BDNF group (0.12 ± 0.01 mL/s) vs GFP (0.18 ±0.01 mL/s, p < 0.01). In summary, we demonstrated that centrally induced neuroendocrine stressfollowing BDNF overexpression in the PVN lead to significant alterations in bladder function suchthat BDNF-treated rats exhibited a higher number of urinary voids and lower void volumecompared with GFP controls. This overactive bladder phenotype was combined with reducedurinary flow void rates indicating outflow obstructions. These results demonstrate that this novelanimal model can be an important tool for better understanding the mechanisms of stress-induced bladder dysfunction. Funded by R01HL166464, R03AG072016 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.