Altered Glutamate Receptor Function during Recovery of Bladder Detrusor-External Urethral Sphincter Coordination in a Rat Model of Spinal Cord Injury

Abstract

Coordination of the bladder detrusor and the external urethral sphincter is a supraspinally controlled reflex that is essential for efficient micturition. This coordination is permanently lost after spinal cord transection but can recover chronically after incomplete spinal cord injury (SCI). As glutamatergic transmission plays a key role in all levels of detrusor-external urethral sphincter coordination, we examined the role of potential alterations in glutamatergic control in its recovery after SCI. Rats were subjected to standardized incomplete contusion injury. Detrusorexternal urethral sphincter coordination was evaluated urodynamically at 5 days (subacute) and 8 weeks (chronic) after SCI. Sensitivity of coordinated activation of the external urethral sphincter in response to bladder distension to the ␣ -amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid/kainate antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo(f)quinoxaline-7-sulfonamide disodium (NBQX) and to the N-methyl-Daspartate (NMDA) antagonist R(Ϫ-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP) was determined by intrathecal application at the L6 spinal cord level during urodynamic recordings. We found that while detrusor contractions recovered at 5 days after SCI, coordinated activation of the external urethral sphincter was significantly impaired at 5 days and recovered only by 8 weeks. There was no difference in sensitivity of detrusor-external urethral sphincter coordination to NBQX at the subacute or chronic time points. However, external urethral sphincter response to bladder distension was sensitive to a 50% lower dose of CPP at 5 days compared with uninjured rats or chronic recovered SCI rats. Thus, alterations in NMDA receptor function appeared to be involved in recovery of detrusor-external urethral sphincter coordination after incomplete SCI.

17β-Estradiol Is Protective in Spinal Cord Injury in Post- and Pre-Menopausal Rats

“…We found that average days to recovery of spontaneous voiding was approximately 6 days for post-menopausal animals and 5 days for pre-menopausal animals, which was similar to other reports (Nout et al, 2005;Pikov et al, 1998). Although previous work has shown that daily urine volume and/or days to spontaneous voiding are sensitive indicators of lower urinary tract function (Pikov et al, 1998;Pikov and Wrathall, 2002), we did not find significant differences between treatment groups or ages (Fig. 6).…”

Animal models of sacral neuromodulation for detrusor overactivity

“…33 Moreover, there are reversible changes in NMDA and AMPA receptor subunit composition and activity during acontractile detrursor and during recovery of voiding reflex in the rat. 34,35 In humans suffering from spasticity and pain, a similar change in the ratio of excitation and inhibition is observed. 36 An acute period of acontractile detrursor is followed by detrusor overactivity.…”

Effect of Endogenous Androgens on 17β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats

“…Previous work has shown that preservation of white matter is highly correlated with the recovery of hindlimb and lower urinary-tract function in the rodent mid-thoracic spinal cord injury model (Basso, 2000;Fehlings and Tator, 1995;Noble and Wrathall, 1987;Pikov and Wrathall, 2002). Consequently, we evaluated the effect of post-SCI E2 administration on the percentage of white-matter area present in the injury epicenter at 28 days after SCI.…”