Al-Khayat Noor, Cates Lindsay N, Valenti Benjamin R, Hudson Mark P, Yang Claire C, Khaing Zin Z
Department of Neurological Surgery, University of Washington, Seattle, Washington, USA.
Department of Neurobiology and Biophysics, University of Washington, Seattle, Washington, USA.
Neurourol Urodyn. 2025 Jul 30. doi: 10.1002/nau.70124.
Despite modern bladder management methods, lower and upper urinary tract complications still contribute significantly to morbidity and diminished quality of life in persons with spinal cord injuries (SCI). Neurogenic overactive bladders often develop after SCI and this can result in loss of compliance, with concomitant urinary tract complications. Currently, there is no treatment available to prevent the development of neurogenic bladder.
In this study, we tested whether acute application of botulinum toxin A (BoNT-A) to the detrusor can limit the development of poorly compliant neurogenic bladders.
Rats sustained contusion type spinal cord injury at T8 and either received intradetrusor saline or BoNT-A injections immediately (acute) or at 4-weeks post injury (wpi)(chronic). Cystometry studies were performed at 6-8 wpi for all animals.
We found that acute BoNT-A treatment after SCI resulted in animals normalized bladder capacity, improved compliance, and reduction in non-voiding contractions compared to control animals. Only acute BoNT-A treatment, but not chronic BoNT-A treatment, resulted in improving bladder compliance, retaining micturition reflexes, and reducing non-voiding contractions. These bladder physiological changes in acute BoNT-A treated SCI animals were accompanied by significant decreases in calcitonin gene related peptide (CGRP)-positive sensory fibers in the dorsal horn and growth associated protein (GAP)-43 expression, a marker for regenerating axons, compared to SCI animals.
Acute application of BoNT-A to the detrusor muscle after SCI can reduce pathophysiological bladder alterations and limits aberrant bladder afferent sprouting in the L5/S1 dorsal horn after SCI in a rat model.
尽管有现代膀胱管理方法，但下尿路和上尿路并发症仍然是脊髓损伤（SCI）患者发病和生活质量下降的重要原因。脊髓损伤后常出现神经源性膀胱过度活动症，这会导致膀胱顺应性丧失，并伴有泌尿系统并发症。目前，尚无预防神经源性膀胱发展的治疗方法。
在本研究中，我们测试了向逼尿肌急性注射肉毒杆菌毒素A（BoNT-A）是否能限制顺应性差的神经源性膀胱的发展。
大鼠在T8水平遭受挫伤性脊髓损伤，分别在损伤后立即（急性）或4周后（慢性）接受膀胱内注射生理盐水或BoNT-A。在损伤后6 - 8周对所有动物进行膀胱测压研究。
我们发现，与对照动物相比，脊髓损伤后急性BoNT-A治疗可使动物膀胱容量正常化、顺应性提高且无排尿收缩减少。只有急性BoNT-A治疗而非慢性BoNT-A治疗能改善膀胱顺应性、保留排尿反射并减少无排尿收缩。与脊髓损伤动物相比，急性BoNT-A治疗的脊髓损伤动物的这些膀胱生理变化伴随着背角降钙素基因相关肽（CGRP）阳性感觉纤维和轴突再生标志物生长相关蛋白（GAP）-43表达的显著降低。
在大鼠模型中，脊髓损伤后向逼尿肌急性注射BoNT-A可减少膀胱病理生理改变，并限制脊髓损伤后L5/S1背角异常膀胱传入神经的发芽生长。
