Bladder dysfunction is among the most drastic and quality-of-life-reducing conditions after spinal cord injury (SCI). Neuroinflammation in the lower urinary tract (LUT) after SCI could be a key driver of neurogenic bladder dysfunction and tissue fibrosis. Leukotrienes, a group of highly active lipid mediators, are potent inflammatory mediators. Here, we explored the potential of early montelukast (MLK) therapy, a cysteinyl leukotriene receptor 1 antagonist, on LUT function and structure four weeks after severe SCI in rats. Rats (strain Lewis, female, n = 50) received a permanent bladder catheter, followed by a complete T9 spinal cord transection. MLK was given daily, starting on day one post-injury. Bladder and locomotor function were regularly assessed. Bladder tissue was histologically and immunhistochemically analyzed. Post-SCI, MLK concentrations in plasma and cerebrospinal fluid were clinically relevant. MLK improved bladder functionality. MLK had no impact on smooth muscle alignment and uroepithelial integrity at this early SCI time point. This pilot study gave first insights into early, continuous oral MLK treatment with the first promising results of preserved LUT function and possible subsequent improved tissue integrity.

Spinal cord injury (SCI) frequently leads to neurogenic lower urinary tract dysfunction, for which appropriate bladder management is essential. While clinical care relies on continuous low-pressure drainage in the acute phase, rat models commonly use twice-daily manual bladder expression—a method known to generate high intravesical pressures and retention. This study evaluated the impact of this standard practice on bladder tissue remodeling by comparing it to continuous drainage via high vesicostomy in a rat SCI model. 32 female Lewis rats underwent thoracic contusion SCI and were assigned to either manual expression or vesicostomy-based bladder management. Over eight weeks, locomotor recovery, wound healing, and bladder histology were assessed. Vesicostomy proved technically simple but required tailored wound care and calibration. Results showed significantly greater bladder wall thickness, detrusor muscle hypertrophy, urothelial thickening, collagen deposition, and mast cell infiltration in the manual expression group compared to both vesicostomy and controls. In contrast, vesicostomy animals exhibited near-control levels across most parameters. These findings highlight that commonly used bladder emptying protocols in rat SCI models may overestimate structural bladder changes and inflammatory responses. Refined drainage strategies such as vesicostomy can minimize secondary damage and improve the translational relevance of preclinical SCI research.