Development of a Unique Mouse Intervertebral Disc Degeneration Model Using a Simple Novel Tool

Abstract

Study Design: Animal case control study.Purpose: To create a simple, reproducible disc degeneration model for mouse coccygeal vertebrae. Overview of Literature: Back pain due to disc degeneration is probably the most common problem encountered in neurosurgical practice. An easily reproducible animal model for disc degeneration will help in understanding its pathophysiology, and serve as a platform for examining various therapeutic options.Methods: A total of 18 mice were divided into injured (n=12) and non-injured (n=6) groups. The disc height index (DHI%) at coccygeal 4–5 level was measured by computed tomography (CT) scan for all mice. Coccygeal 4–5 discs of the injury group were injured using a 32G needle fixed to a novel tool and confirmed by CT. The non-injury group underwent no procedure. DHI% was measured by CT at 2-, 4-, and 6-week post-injury, and all mice tails were sectioned for histopathology grading of disc degeneration at the respective time intervals.Results: The injured group showed significant variation in DHI% at 2, 4, and 6 weeks, whereas there was no change in the noninjured group. Histopathologic evaluation with Safranin O stain showed a worsening of the disc degeneration score at 2, 4, and 6 weeks in the injured group, but in the non-injured group there was no change. Percutaneous needle injury technique with our novel tool provided 100% accuracy and uniform degeneration.Conclusions: A simple, easily reproducible mouse model for disc degeneration was created using a simple, cost-effective, novel tool and technique, its advantage being high precision and user friendly.

In vivo Mouse Intervertebral Disc Degeneration Models and Their Utility as Translational Models of Clinical Discogenic Back Pain: A Comparative Review

“…For collagen content, Hydroxyproline or Sircol assays are used, although the specific collagen type is indistinguishable. Structural tissue level assessments are commonly assessed via histological staining such as H&E for overall tissue organization, Safranin O (with/without Fast green) or alcian blue (AB) for proteoglycans, picrosirius red (PSR) or Elastica van Gieson for collagen, Azan trichrome and Goldner's Masson's for more general cartilage and bone, and Weigert's Resorcin Fuchsin for elastin (50,73,82,102,(118)(119)(120)(121). Multichromatic staining (i.e., FAST) can enhance visualization of tissue-level changes (122,123).…”

“…Multichromatic staining (i.e., FAST) can enhance visualization of tissue-level changes ( 122 , 123 ). Histological grading schemes can be used to determine the degree or severity of IVD degeneration ( 82 , 102 , 123 ).…”

“…In addition to histology, in vivo and ex vivo imaging methods including, radiographs, micro-computed tomography (microCT), and magnetic resonance imaging (MRI) are widely used for characterizing gross characteristics of tissue integrity/structure such as tissue hydration, disc height, grade of degeneration, and bone mineral density ( 50 , 54 – 56 , 69 , 73 , 76 , 84 , 86 , 101 , 102 ). DHI and Disc wedging index (DWI) can be derived from image analyses where DHI is the thickness/height of the IVD relative to vertebrae length and DWI is a measure of the anterior vs. posterior angulation, or wedging, in the sagittal plane ( 88 , 124 ).…”

Circular RNAs in Intervertebral Disc Degeneration: An Updated Review

“…IDD is a chronic process resulting in structural failure of the intervertebral disc, with accelerated or advanced signs of aging. Etiologically, IDD may be hastened by co-morbidities (e.g., diabetes and obesity), certain lifestyles (e.g., smoking, occupation, alcohol consumption), aging, and genetic predisposition ( Tang et al, 2020 ; Tsingas et al, 2020 ; Yang et al, 2021a ; Baldia et al, 2021 ; Shao et al, 2021 ; Zhao et al, 2021 ). The mainstay of treatment for IDD-related diseases is surgical intervention.…”

Application of mesenchymal stem cell-derived exosomes from different sources in intervertebral disc degeneration

“…Based on the tissue engineering, stem cells have been widely used in regenerative medicine owing to their advantages of self-proliferation and directed differentiation at degeneration sites (Moeinabadi-Bidgoli et al, 2021). Mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and adipose stem cells can differentiate into NP cells (NPCs) and synthesize new ECM for IVDD regeneration (Baldia et al, 2021;Ekram et al, 2021). Moreover, stem cells also reduce the inflammatory environment around IVDD through paracrine secretion of anti-inflammatory factors and chemokines (Zhang et al, 2022).…”