Journal
EXPERIMENTAL NEUROLOGY
Volume 348, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2021.113937
Keywords
Spinal cord injury; Neurogenic lower urinary tract dysfunction; (NLUTD); C-fiber bladder afferents; Serotonin; Corticotropin-releasing factor; GABA; Interneurons
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Funding
- Spinal Cord Consortium of the Christopher and Dana Reeve Foundation
- Santa Casa da Misericordia de Lisboa (Premio Mello e Castro - 2016)
- UZH Foundation (University of Zurich)
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Neurogenic lower urinary tract dysfunction commonly occurs after spinal cord injury, characterized by detrusor overactivity and detrusor-sphincter-dyssynergia. Changes in spinal cord anatomy, including increased C-fiber afferents and decreased CRF-positive and 5-HT-positive neuronal projections, contribute to the development of lower urinary tract symptoms.
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 mal-function of the important physiological pathway of lower urinary tract control.
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