Functional, morphological and molecular characteristics in a novel rat model of spinal sacral nerve injury-surgical approach, pathological process and clinical relevance

Abstract

Spinal sacral nerve injury represents one of the most serious conditions associated with many diseases such as sacral fracture, tethered cord syndrome and sacral canal tumor. Spinal sacral nerve injury could cause bladder denervation and detrusor underactivity. There is limited clinical experience resolving spinal sacral nerve injury associated detrusor underactivity patients, and thus the treatment options are also scarce. In this study, we established a spinal sacral nerve injury animal model for deeper understanding and further researching of this disease. Forty 8 w (week) old Sprague Dawley rats were included and equally divided into sham (n = 20) and crush group (n = 20). Bilateral spinal sacral nerves of rats were crushed in crush group, and sham group received same procedure without nerve crush. Comprehensive evaluations at three time points (1 w, 4 w and 6 w) were performed to comprehend the nature process of this disease. According to urodynamic test, ultrasonography and retrograde urography, we could demonstrate severe bladder dysfunction after spinal sacral nerve injury along the observation period compared with sham group. These functional changes were further reflected by histological examination (hematoxylin-eosin and Masson’s trichrome staining) of microstructure of nerves and bladders. Immunostaining of nerve/bladder revealed schwann cell death, axon degeneration and collagen remodeling of bladder. Polymerase Chain Reaction results revealed vigorous nerve inflammation and bladder fibrosis 1 week after injury and inflammation/fibrosis returned to normal at 4 w. The CatWalk gait analysis was performed and there was no obvious difference between two groups. In conclusion, we established a reliable and reproducible model for spinal sacral nerve injury, this model provided an approach to evaluate the treatment strategies and to understand the pathological process of spinal sacral nerve injuries. It allowed us to understand how nerve degeneration and bladder fibrosis changed following spinal sacral nerve injury and how recovery could be facilitated by therapeutic options for further research.

Transcriptomics Reveals Molecular Features of the Bilateral Pelvic Nerve Injury Rat Model of Detrusor Underactivity

“…In addition, leukocyte migration, immune receptor activity, cytokine-cytokine receptor interaction, and Toll-like receptor signaling pathways were significantly enriched three days after BPNI, which may be related to the inflammatory response that occurs in the acute phase after bladder denervation. Li et al reported a rat model of sacral nerve injury that showed a significant increase in bladder volume and residual urine at one and four weeks after modeling [ 30 ]. PCR results showed that one week after injury, the expression of pro-inflammatory factors IL-1β, IL-6, and TNF-a in the bladder was significantly elevated.…”