Effect of early sacral neuromodulation on bladder function in a rat model of incomplete spinal cord injury due to focal contusion

Jeong S1, Yoon C1, Lee Y1, Lee S2, Kim J1, Yeo C1, Kim J2

Research Type

Basic Science / Translational

Abstract Category

Neurourology

Abstract 205
Neurourology and Interventions
Scientific Podium Short Oral Session 10
Wednesday 4th September 2019
14:45 - 14:52
Hall G3
Animal Study Spinal Cord Injury Neuromodulation Neuropathies: Central
1.Seoul National University Bundang Hospital, 2.Kangwon National University School of Medicine
Presenter
S

Seong Jin Jeong

Links

Abstract

Hypothesis / aims of study
Sacral neuromodulation (SNM) has been reported to modulate the micturition reflex to some extent in studies using a completely spinalized rat model, with several possible mechanisms underlying the action of SNM suggested. In actual clinical practice, however, 66% of all patients with spinal cord injury (SCI) are estimated to have incomplete-type of SCI induced by spinal contusion. Nonetheless, most animal studies that have addressed the effect of SNM on bladder function have used rats with spinal transection. Experiments in a rat model of incomplete SCI, which would reflect more relevant conditions of clinical SCI, are scarce. We aimed to evaluate the effect of early SNM on bladder responses in a rat model of incomplete SCI.
Study design, materials and methods
Altogether, 21 female Sprague-Dawley rats were equally assigned to control (CTR), SCI + sham stimulation (SHAM), and SCI + SNM (SNM) groups. In the SHAM and SNM groups, incomplete SCI was created by producing a moderate contusion with an NYU-MASCIS impactor at the T9-T10 level of the spine, with needle electrodes implanted bilaterally into the S2 or S3 sacral foramen. The exposed cord was contused by a 10 g weight rod being dropped from a height of 25 mm using the impactor, resulting in a moderate degree of incomplete SCI. The dura mater was examined visually after the procedure to determine if any lacerations had occurred. After that, standard stainless-steel needle electrodes were implanted in all the rats in the SHAM and SNM groups on the same day that the SCI was induced. A midline incision was made at the sacral level, and paravertebral muscles were pushed laterally. Stainless-steel needle electrodes (0.5” × 27G) were inserted into the bilateral S2 or S3 foramen, and the response of the underlying nerve was examined to identify hind limb movement. Only SNM group underwent electrical stimulation for 28 days, beginning on day 7 after SCI. Cystometry was performed 35 days after SCI.
Results
Although the interval between voiding contractions was significantly longer in the SHAM group than the CTR group (25.5 ± 1.4 vs 12.5 ± 1.7 min; P < 0.05), there were no significant differences between the SNM group (16.5 ± 1.5 min) and the CTR group. Maximum voiding contraction pressure did not differ among the groups. The SNM group had a significantly lower frequency (3.5 ± 0.5 vs 14.6 ± 2.0; P < 0.05) and maximum pressure (11.4 ± 6.2 vs 21.3 ± 1.8 cmH2O; P < 0.05) of nonvoiding contractions than the SHAM group (Fig. 1).
Interpretation of results
Most of SNM experimental studies were performed in a rat model with spinal transection that causes complete SCI. In clinical practice, however, the most frequent neurologic category of traumatic SCI is incomplete tetraplegia followed by incomplete paraplegia, complete paraplegia, and complete tetraplegia. Thus, 66% of all the patients with SCI are estimated to have an incomplete type of SCI induced by spinal contusion. Given this context, experiments using a rat model of incomplete SCI may represent the situations that would be more similar to those encountered frequently in a clinical practice of SCI and thus be more reasonably applicable to human patients. The effect of SNM on incomplete SCI might be dissimilar to those produced on complete SCI. The present study is the first experimental trial to assess the efficacy of early SNM on bladder function in the incomplete SCI rat model. Our results provide experimental evidence that early SNM may prevent or diminish bladder dysfunction in patients with incomplete SCI, which accounts for most clinical traumatic SCI.
Concluding message
Our results provide experimental evidence that early SNM treatment may prevent or diminish bladder dysfunctions (e.g., detrusor overactivity, abnormal micturition reflex) in a clinical condition of incomplete SCI.
Figure 1
Disclosures
<span class="text-strong">Funding</span> Supported by grant no. 11-2010-005 from the Seoul National University Bundang Hospital Research Fund <span class="text-strong">Clinical Trial</span> No <span class="text-strong">Subjects</span> Animal <span class="text-strong">Species</span> Rat <span class="text-strong">Ethics Committee</span> The Institutional Animal Care and Use Committee of Seoul National University Bundang Hospital