Mitochondrial Oxidative Injury Contributes to Overactive Bladder Neurodegeneration

Deformation of subcellular structures and loss of nerve fibers are documented in human bladder overactivity but mechanistic pathways of these changes remains unknown. Researchers from BUSM led by Kazem Azadzoi, MD, MA, a professor of urology and pathology, and director of urology research, examined mitochondrial integrity and searched for markers of oxidative neural injury in an experimental model of ischemic overactive bladder.

The researchers report that frequent contractions exposed the overactive bladder to cyclical ischemia/reperfusion and hypoxia/reoxygenation leading to oxidative and nitrosative products and upregulation of oxidative stress-sensitive genes. Transmission electron microscopy showed deformed mitochondria with swollen membranes, decreased granules, a total loss of granules and sporadic membrane damage. These changes were associated with sporadic loss of epithelial mucosal membrane, twisted smooth muscle cells, diffused vacuolization and marked neurodegeneration.

The findings suggest free radical mediated ultrastructural damage and neurodegeneration in the overactive bladder. “Mitochondrial stress may contribute to epithelial damage, smooth muscle cell injury and neurodegeneration in the overactive bladder,” explained Azadzoi. “Upregulation of intrinsic defensive mechanisms against free radicals failed to prevent oxidative damage and neurodegeneration. Thus, therapeutic strategies targeting basic mitochondrial processes such as energy metabolism or free radical generation may help better manage wall degeneration and neuropathy in the overactive bladder” he added.