Histomorphometric Analysis of Experimental Disc Degeneration

摘要

Symptomatic disc degeneration is a complex pathological condition that involves a cascade of events and is not totally understood. In this context, animal models gain an important role, allowing for better understanding of the degenerative process and therapeutic interventions. There are several models with different methods of evaluation of experimental disc degeneration (EDD), including imaging, biochemical, genetics, and histological approaches, but no real gold standard has been set. The authors aim to evaluate EDD by means of automated morphometric analysis and to determine values for differentiating normal and degenerated discs by this method. The criteria mean and total cellular area, mean and total cytoplasm area, and total nuclear area of cells in the nucleus pulposus were able to differentiate the condition of degeneration ( p 1 once the degenerative process itself is part of physiological aging. 2 There are several definitions to symptomatic disc degeneration, all referring to a cascade process affecting not only the IVD itself but the vertebral end plate and facet joints. 3 Although there is constant evolution on the understanding of this process, several pathological steps of this cascade remain obscure. 4 5 This leads to a poor understanding of the clinical correlation, with a lack of efficient and standardized clinical management of its symptoms. 6 7 8 9 10 Animal models of disc degeneration have allowed for a better understanding of the pathological mechanisms and for testing of therapeutic interventions. 11 12 There are several models of experimental injury available, including stab wounds to the disc, needle punctures, enzyme injection, mechanical torsion and distraction, among others. 13 14 15 One of the most reproducible and most commonly used methods is multiple needle punctures to the IVD. 16 Evaluation of experimental disc degeneration (EDD) is far from standardized with studies using radiographs, tomography, magnetic resonance imaging, and biochemical and histological analysis, 11 14 15 16 17 limiting comparison between different experiments and combination of efforts among research centers. Histological evaluation could be considered a gold standard for EDD evaluation and grading. Imaging studies only give indirect evaluation, and biochemical analysis has a great range of variations that limits its cost-effectiveness. 18 Even in histological analysis, there is great variation in preparing and reading the IVDs specimens, with several studies using subjective methods that are examiner-dependent and have low reproducibility. 19 20 There is a lack of standardized evaluation that could give absolute values to EDD and allow for an efficient, reliable way to evaluate therapeutic interventions. This study aims to: Develop a standardized and automated way to evaluate EDD, thus eliminating the subjectivity of previous grading methods for EDD; Determine the specificity and sensitivity of such measurements.