Institute for Regenerative Medicine, University of Zürich, Switzerland; Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland; Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland.
Institute for Regenerative Medicine, University of Zürich, Switzerland; Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland.
Exp Neurol. 2022 Feb;348:113937. doi: 10.1016/j.expneurol.2021.113937. Epub 2021 Nov 24.
Neurogenic lower urinary tract dysfunction typically develops after spinal cord injury. We investigated the time course and the anatomical changes in the spinal cord that may be causing lower urinary tract symptoms following injury. Rats were implanted with a bladder catheter and external urethral sphincter electromyography electrodes. Animals underwent a large, incomplete spinal transection at the T8/9 spinal level. At 1, 2-3, and 4 weeks after injury, the animals underwent urodynamic investigations. Urodynamic investigations showed detrusor overactivity and detrusor-sphincter-dyssynergia appearing over time at 3-4 weeks after injury. Lower urinary tract dysfunction was accompanied by an increase in density of C-fiber afferents in the lumbosacral dorsal horn. CRF-positive Barrington's and 5-HT-positive bulbospinal projections drastically decreased after injury, with partial compensation for the CRF fibers at 3-4 weeks. Interestingly, a decrease over time was observed in the number of GABAergic neurons in the lumbosacral dorsal horn and lamina X, and a decrease of glutamatergic cells in the dorsal horn. Detrusor overactivity and detrusor-sphincter-dyssynergia might therefore arise from a discrepancy in inhibitory/excitatory interneuron activity in the lumbosacral cord as well as input changes which develop over time after injury. The processes point to spinal plastic changes leading to malfunction of the important physiological pathway of lower urinary tract control.
神经原性下尿路功能障碍通常在脊髓损伤后发展。我们研究了脊髓的时间进程和解剖变化,这些变化可能是导致损伤后下尿路症状的原因。大鼠被植入膀胱导管和尿道外括约肌肌电图电极。动物在 T8/9 脊髓水平接受了大的、不完全的脊髓横断。在损伤后 1、2-3 和 4 周,动物进行了尿动力学研究。尿动力学研究显示,逼尿肌过度活动和逼尿肌-尿道外括约肌协同失调在损伤后 3-4 周逐渐出现。下尿路功能障碍伴随着腰骶部背角 C 纤维传入密度的增加。损伤后,CRF 阳性的 Barrington 氏和 5-HT 阳性的球脊髓投射明显减少,在 3-4 周时有部分补偿纤维。有趣的是,腰骶部背角和 lamina X 中的 GABA 能神经元数量随时间减少,背角中的谷氨酸能细胞减少。因此,逼尿肌过度活动和逼尿肌-尿道外括约肌协同失调可能是由于腰骶髓抑制/兴奋中间神经元活动的差异以及损伤后随时间发展的输入变化所致。这些过程表明,脊髓的可塑性变化导致下尿路控制这一重要生理途径的功能障碍。