DeFinis Jaclyn H, Weinberger Jeremy, Hou Shaoping
Marion Murray Spinal Cord Research Center, Department of Neurobiology & Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Biology (Basel). 2021 Jan 19;10(1):68. doi: 10.3390/biology10010068.
Traumatic spinal cord injury (SCI) interrupts spinobulbospinal micturition reflex pathways and results in urinary dysfunction. Over time, an involuntary bladder reflex is established due to the reorganization of spinal circuitry. Previous studies show that manipulation of serotonin 2A (5-HT) receptors affects recovered bladder function, but it remains unclear if this receptor regulates the activity of the external urethral sphincter (EUS) following SCI. To elucidate how central and peripheral serotonergic machinery acts on the lower urinary tract (LUT) system, we employed bladder cystometry and EUS electromyography recordings combined with intravenous or intrathecal pharmacological interventions of 5-HT receptors in female SCI rats. Three to four weeks after a T10 spinal transection, systemic and central blockage of 5-HT receptors with MDL only slightly influenced the micturition reflex. However, delivery of the 5-HT receptor agonist, DOI, increased EUS tonic activity and elicited bursting during voiding. Additionally, subcutaneous administration of DOI verified the enhancement of continence and voiding capability during spontaneous micturition in metabolic cage assays. Although spinal 5HT receptors may not be actively involved in the recovered micturition reflex, stimulating this receptor subtype enhances EUS function and the synergistic activity between the detrusor and sphincter to improve the micturition reflex in rats with SCI.
创伤性脊髓损伤（SCI）会中断脊髓-延髓-脊髓排尿反射通路，导致排尿功能障碍。随着时间的推移，由于脊髓回路的重组，会建立起一种非自主膀胱反射。先前的研究表明，对5-羟色胺2A（5-HT）受体的调控会影响膀胱功能的恢复，但尚不清楚该受体在脊髓损伤后是否调节尿道外括约肌（EUS）的活动。为了阐明中枢和外周5-羟色胺机制如何作用于下尿路（LUT）系统，我们在雌性脊髓损伤大鼠中采用膀胱内压测量和尿道外括约肌肌电图记录，并结合对5-HT受体进行静脉或鞘内药物干预。在T10脊髓横断后三到四周，用MDL对5-HT受体进行全身和中枢阻断仅对排尿反射有轻微影响。然而，给予5-HT受体激动剂DOI会增加尿道外括约肌的紧张性活动，并在排尿时引发阵发活动。此外，在代谢笼试验中，皮下注射DOI证实了在自发排尿过程中尿失禁和排尿能力的增强。虽然脊髓5-HT受体可能未积极参与恢复的排尿反射，但刺激该受体亚型可增强尿道外括约肌功能以及逼尿肌与括约肌之间的协同活动，从而改善脊髓损伤大鼠的排尿反射。
