Possible Effect of Intramural Botulinum Neurotoxin A Injection Versus Oral Resveratrol on Minimizing Hypertrophy, Fibrosis and Ultrastructural Changes of Detrusor Muscle Occurring Secondary to Partial Urethral Obstruction in Overactive Bladder Rat Model and Perspective on Their effect on TNFα, TGβ, PCNA, α-SMA and iNOS

Introduction: The clinical condition of overactive bladder affects billions of individuals. The most prevalent cause is excessive detrusor activity. Patients whose symptoms are resistant to conventional treatment must be provided with novel treatment options.
Aim of the Work: Evaluation of effect of botulinum neurotoxin A injection compared to oral resveratrol on histopathological changes occurring secondary to partial urethral obstruction and evaluation of their effect on TNFα, TGβ, PCNA, α-SMA and iNOS.
Materials and Methods: 40 adult rats were included in the study. Group I (Sham group). GroupⅡ: Partial urethral obstruction(PUO)-model was established and rats left for 6weeks. Group III: 10mg/kg resveratrol given by oral gavage for two weeks (from the sixth after PUO to the end of eighth week). Group IV: after PUO.50 ml botulinum neurotoxin A (BoNT-A) was injected in different walls of the bladder. Rats were left for another 2 weeks then sacrificed.
Results: Group II showed disrupted muscular bundles of muscularis propria. Muscle fibers appeared with extensive cytoplasmic vacuolations and abnormal shape of their nuclei. Masson's trichrome sections showed extensive collagen deposition in the bladder wall. Extensive reaction to PAS and deep staining of the muscle fibers. Transmission electron microscope showed irregular cell boundaries and bizarre shape of cell membrane. The myofibroblasts appeared extensively invading the intermuscular septa. Some muscle fibers appeared degenerated with extensive infiltrate by mast cells and fibroblasts. Besides, extremely dilated nerve endings with clustered degenerated bodies at their lower ends. Congested, dilated blood vessels could also be detected. There was marked increase in the oxidative stress markers and proinflammatory cytokines. All previous Changes greatly improved in groups III and IV and the best results were observed in group IV.
Conclusion: Resveratrol and botulinum neurotoxin are new lines of management to patients suffering from refractory symptoms of overactive bladder