Developmental spinal stenosis: a novel rat model with circumferential compression

Abstract

Introduction: Developmental Spinal Stenosis (DSS) is defined as a pre-existing circumferential narrowing of spinal column originating from dorsal spinal elements mal-development, resulting in neural compression. Despite models exist for degenerative spinal stenosis from a one-directional compression mimicking disc protrusions and ligamentum flavum and facet hypertrophy, lumbar DSS requires a new, reproducible animal model which can create a circumferential compression of the dura sac is desirable for future investigation of this disease condition. This study aims to create and validate a model simulating specific bony canal constriction of DSS. Material and Methods: Ten female Sprague-Dawley rats (13.0-14.5 weeks-old) were operated at L4-L5 with circumferential compression (using stainless-steel wire/silicone sheet); dorsal compression (using overlapping silicone sheets), or as controls. Subjects were assessed preoperatively, postoperative 1, 2, 3, 4 weeks and pre-sacrifice at 2 months. Assessment included rung-ladder walking, swimming and electrophysiological test. Basso, Beatie and Bresnahan (BBB) locomotor rating scale, foot-fault scoring, foot placement accuracy analysis and Louisville Swimming Scale (LSS) were used. Axonal demyelination was evaluated histologically by ratio of myelin sheath area to axon area and g-ratio. Group comparison was performed using one-way ANOVA with Post-hoc analysis and Kruskal-Wallis test where appropriate. Results: For BBB scores at flat-rung ladder walking, there was significant difference among study groups (p < 0.05) at postoperative 3-weeks persisting until sacrifice. The statistical significant difference in BBB was demonstrated earlier at one week postoperatively for sloped rung-ladder. At postoperative 3-weeks, circumferential compression had significantly lower foot-fault scores than dorsal compression for right hindlimb, as well as lower foot placement accuracy scores (p < 0.05). LSS was different (p < 0.05) among all study groups at postoperative one month until end-point. Circumferential group using silicone sheets was the only group with increasing and higher P1 and N1 latency for both hind-paws. The mean area ratio of myelin sheath to axons were significantly different between groups: 0.99 ± 0.43 (circumferential – wire), 0.98 ± 0.58 (circumferential-silicone), 1.23 ± 0.73 (dorsal compression), 2.28 ± 1.61 (control) (p ≤ 0.001). The mean g-ratio was significant larger for the circumferential compression (silicone: 0.73) than dorsal compression (0.69) and control (0.58). Conclusion: Our findings validate this created model with specific properties of DSS. Circumferential (wire/silicone) compression group demonstrated little/no hindlimb movements on walking and swimming, high reliance was on forelimbs for forward motion. Their consistently increasing trend of P1 and Ni latency and larger latency indicated somatosensory system deterioration. Neuromonitoring confirms their worst deterioration of somatosensory system than others. This was consistent with the most axonal demyelination in circumferential (wire/silicone) compression than both the dorsal compression and control. This model has successfully simulated DSS and produces characteristic outcomes required for DSS.