Keller Elena E, Bauer Sophina, Roider Karin, Kleindorfer Michael, Törzsök Peter, Tevini Julia, Felder Thomas, Aigner Ludwig, Lusuardi Lukas
Institute of Molecular and Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020 Salzburg, Austria.
Department of Urology and Andrology, University Hospital Salzburg, Müllner Hauptstrasse 48, 5020 Salzburg, Austria.
Int J Mol Sci. 2025 Jun 11;26(12):5606. doi: 10.3390/ijms26125606.
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.
膀胱功能障碍是脊髓损伤(SCI)后最严重且降低生活质量的病症之一。SCI后下尿路(LUT)的神经炎症可能是神经源性膀胱功能障碍和组织纤维化的关键驱动因素。白三烯是一组高活性脂质介质,是强效炎症介质。在此,我们探讨了早期使用孟鲁司特(MLK)治疗(一种半胱氨酰白三烯受体1拮抗剂)对大鼠严重SCI后四周LUT功能和结构的影响。大鼠(Lewis品系,雌性,n = 50)接受永久性膀胱导管插入术,随后进行T9脊髓完全横断。从损伤后第一天开始每天给予MLK。定期评估膀胱和运动功能。对膀胱组织进行组织学和免疫组织化学分析。SCI后,血浆和脑脊液中的MLK浓度具有临床相关性。MLK改善了膀胱功能。在这个早期SCI时间点,MLK对平滑肌排列和尿路上皮完整性没有影响。这项初步研究首次深入了解了早期、持续口服MLK治疗,取得了保留LUT功能以及可能随后改善组织完整性的首个有前景的结果。