In a rat model of neurogenic bladder (NB) created by bilateral L6-S1 spinal nerve transection, resveratrol demonstrably reduced residual urine volume, improved bladder compliance, attenuated fibrosis, and mitigated secondary renal injury. Mechanistically, it suppressed epithelial-mesenchymal transition markers (↓α-SMA, ↑E-cadherin), reduced apoptotic signals (Bax, cleaved caspase-3), and curtailed pyroptosis via NLRP3/IL-1β/Caspase-1 downregulation — all linked to inhibition of the AKT/mTOR/S6K signaling axis. Re-activating mTOR with MHY1485 in vitro partially reversed these benefits, establishing pathway causality.
Neurogenic bladder remains a significant quality-of-life burden in spinal cord injury and pediatric spina bifida populations, with current management largely symptomatic. Resveratrol's pleiotropic biology — SIRT1 activation, antioxidant activity, and now AKT/mTOR suppression — makes it an attractive investigational candidate, but this work carries important caveats. The animal model is acute denervation, not the chronic progressive neuropathy typical in humans. Resveratrol's notorious bioavailability challenges (rapid hepatic metabolism, low plasma concentrations) are unaddressed here. Dosing and pharmacokinetic data are absent from the abstract. The pyroptosis angle is genuinely novel in the NB context and adds mechanistic nuance beyond classical fibrosis frameworks. Overall, this is solid mechanistic groundwork — incremental rather than paradigm-shifting — that identifies AKT/mTOR/S6K as a credible therapeutic target, warranting bioavailability-optimized formulations and eventual human translational studies.
