Amniotic fluid stem cell-derived extracellular vesicles enhance functional recovery of neurogenic bladder and neurovascular plasticity after cerebral ischemia in rats.

BACKGROUND Post-stroke neurogenic bladder dysfunction impairs patients' quality of life, yet current treatments offer limited effectiveness. This study investigated the therapeutic effects and underlying mechanisms of human amniotic fluid stem cell-derived extracellular vesicle (hAFSC-EV) on bladder dysfunction and neurovascular plasticity after cerebral ischemia.

METHODS Thirty-six female rats underwent bilateral ovariectomy and were assigned to sham-operated or 90-min middle cerebral artery occlusion (MCAO) groups, with or without a single injection of hAFSC-EVs. Magnetic resonance imaging (MRI), cystometry, blood-brain barrier (BBB) permeability, and markers of neurogenesis and angiogenesis in ischemic brain were assessed. Bladder levels of brain-derived neurotrophic factor (BDNF), β3-adrenoceptor, adenylate cyclase, and M2- and M3-muscarinic receptors were evaluated at 7 and 28 days post-MCAO or sham-operation.

RESULTS Compared with untreated rats, hAFSC-EV treatment significantly reduced cerebral infarct volume and BBB leakage, and enhanced microvessel and vascular density, along with angiogenesis. Neural markers such as BDNF, nestin, and doublecortin were significantly upregulated at 7 and/or 28 days post-MCAO. hAFSC-EV treatment ameliorated MCAO-induced bladder dysfunction by reducing peak voided volume, intercontraction interval, and bladder capacity, along with improving residual urine volume. hAFSC-EV treatment significantly increased bladder expression of BDNF and M3-muscarinic receptors, and recovers the expressions of M2, β3-adrenoceptor, and adenylate cyclase to near control levels at 7 and 28 days post-MCAO.

CONCLUSION hAFSC-EV treatment improves neurogenic bladder dysfunction and cerebral ischemia post-MCAO, potentially through reducing infarct volume and BBB disruption, enhancing neurogenesis and angiogenesis in the ischemic brain, and modulating the expression of bladder BDNF, β3-adrenoceptor, adenylate cyclase and muscarinic receptors.