Coordination of the Bladder Detrusor and the External Urethral Sphincter in a Rat Model of Spinal Cord Injury: Effect of Injury Severity

Abstract

Recovery of urinary tract function after spinal cord injury (SCI) is important in its own right and may also serve as a model for studying mechanisms of functional recovery after injury in the CNS. Normal micturition requires coordinated activation of smooth muscle of the bladder (detrusor) and striated muscle of the external urethral sphincter (EUS) that is controlled by spinal and supraspinal circuitry. We used a clinically relevant rat model of thoracic spinal cord contusion injury to examine the effect of varying the degree of residual supraspinal connections on chronic detrusor-EUS coordination. Urodynamic evaluation at 8 weeks after SCI showed that detrusor contractions of the bladder recovered similarly in groups of rats injured with a 10 gm weight dropped 12.5, 25, or 50 mm onto the spinal cord. In contrast, the degree of coordinated activation of the EUS varied with the severity of initial injury and the degree of preservation of white matter at the injury site. The 12.5 mm SCI resulted in the sparing of 20% of the white matter at the injury site and complete recovery of detrusor-EUS coordination. In more severely injured rats, the chronic recovery of detrusor-EUS coordination was very incomplete and correlated to decreased innervation of lower motoneurons by descending control pathways and their increased levels of mRNA for glutamate receptor subunits NR2A and GluR2. These results show that the extent of recovery of detrusor-EUS coordination depends on injury severity and the degree of residual connections with brainstem control centers.

Serial Changes in Bladder, Locomotion, and Levels of Neurotrophic Factors in Rats with Spinal Cord Contusion

“…We studied a mild contusion injury because contusion is the most common type of spinal cord trauma in humans, and because spontaneous recovery of gait and bladder function is greater with this form of spinal cord trauma than after moderate or severe contusion (Basso et al, 1996;Pikov and Wrathall, 2001). The recovery mechanisms after mild injury are likely to differ from those that act after more severe types of spinal cord injury, but we do not believe that these mechanisms are relevant only to recovery from spinal shock.…”

“…We did not use the bladder weight to assess bladder hypertrophy or capacity (Vizzard, 2000;Pikov and Wrathall, 2001;Mitsui et al, 2005) because it could vary depending on the amount of residual urine, the water content of the bladder, or the point at which the bladder was sectioned.…”

“…Two weeks after moderate contusion of the rat spinal cord, bladders showed detrusor hyperreflexia (Smith et al, 2002); rats with a mild contusion injury showed complete recovery of coordination between the detrusor and external urethral sphincter. However, in more severely injured rats, detrusorsphincter-dyssynergia continued at 8 weeks (Pikov and Wrathall, 2001). Few experiments have investigated changes in the neurogenic bladder over time.…”

Transplantation and repair: Combined cell implantation and chondroitinase delivery prevents deterioration of bladder function in rats with complete spinal cord injury

“…3 However, the continuous co-contractions of the bladder and the sphincter (bladder-sphincter dyssynergia) lead to inefficient voiding and large residual urine volumes. 4 Other factors contributing to inefficient voiding of the bladder include alterations in bladder size and tissue composition, including the accumulation of collagen type III. 5,6 As a result of continuous vesicular pressure and urine retention in spinalized rats, the phase of restored, but inefficient, bladder function might lead to complete deterioration of bladder compliance/function, infections and other lower urinary tract complications.…”

Up-regulation of 5-HT2 receptors is involved in the increased H-reflex amplitude after contusive spinal cord injury

“…We therefore investigated the role of 5-HT 2 R in the increased H-reflex amplitude observed after a standardized incomplete contusive SCI using a well-characterized rat model of injury (Basso, et al, 1996, Lee, et al, 2005, Pikov and Wrathall, 2001). We employed local intrathecal administration of the 5-HT 2 R antagonists, mianserin and LY53857, and the agonist, DOI, as well as immunohistochemistry of 5-HT 2 R expression on plantar motor neurons and found evidence in support of the hypothesis that increased 5-HT 2 R expression by plantar muscle motoneurons is causally related to the increased H-reflex amplitude of the plantar muscle after contusive SCI.…”