Abstract
Spinal cord injury (SCI) to the terminal segments of the spinal cord causes severe disruption of the neural circuitry of the bladder, resulting in neurogenic underactive bladder (nUAB). We developed a rodent lumbosacral injury model to investigate the effects of bladder function and structure. A severe contusion SCI was performed over the L5-S2 segmental spinal cord (T13/L1 junction, L1 vertebra, L1/L2 junction). The injured spinal cords were scanned by advanced micro-CT imaging. Bladder function was assessed in awake rats before and at 2, 4, 6, and 8 weeks after SCI. Locomotor function was assessed using the BBB Open Field Rating Scale and the Catwalk system. Specific histological staining assessed structural bladder remodelling in control and SCI rats. Contusion SCI at the three respective segmental heights revealed variations in lesion sizes and white and gray matter sparing. However, this did not influence SCI rats’ bladder and locomotor outcomes, whereas the functional deficits were comparable in control and SCI rats. From week 2 onwards, the main functional changes of nUAB in SCI rats were noticeable: a low detrusor strength with a combination of slow maximal flow rate and low leakage volumes with no to incomplete voiding. Histological analyses of bladder tissue underlined the functional outcomes by depicting a thickened bladder wall with ongoing fibrotic and uroepithelial changes. As expected, only mild locomotor impairments were determined. This model of lumbosacral SCI reproduces nUAB with structural and functional outcomes similar to human nUAB, giving future studies a well-defined framework to test therapies for nUAB conditions in a standardized rat model.
Keywords
Rat model, Lumbosacral level, Underactive bladder, Spinal cord injury, Neurogenic bladder