Diffusion tensor imaging as a tool to detect presymptomatic axonal degeneration in a preclinical spinal cord model of amyotrophic lateral sclerosis

The G93A-SOD1 mice model and MRI diffusion as a preclinical tool to study amyotrophic lateral sclerosis （ALS）： ALS is a progressive neurological disease characterized primarily by the development of limb paralysis, which eventually leads to lack of control on muscles under voluntary control and death within 3–5 years. Genetic heterogeneity and environmental factors play a critical role in the rate of disease progression and patients display faster declines once the symptoms have manifested. Since its original discovery, ALS has been associated with pathological alterations in motor neurons located in the spinal cord （SC）, where neuronal loss by a mutation in the protein superoxide dismutase in parenthesis （mSOD1） and impairment in axonal connectivity, have been linked to early functional impairments. In addition,mechanisms of neuroinflammation, apoptosis, necroptosis and autophagy have been also implicated in the development of this disease. Among different animal models developed to study ALS, the transgenic G93A-SOD1 mouse has become recognized as a benchmark model for preclinical screening of ALS therapies. Furthermore, the progressive alterations in the locomotor phenotype expressed in this model closely resemble the progressive lower limb dysfunction of ALS patients. Among other imaging tools, MR diffusion tensor imaging （DTI） has emerged as a crucial, noninvasive and real time neuroimaging tool to gather information in ALS. One of the current concerns with the use of DTI is the lack of biological validation of the microstructural information given by this technique. Although clinical studies using DTI can provide a remarkable insight on the targets of neurodegeneration and disease course,they lack histological correlations. To address these shortcomings, preclinical models can be designed to validate the microstructural information unveiled by this particular MRI technique. Thus, the scope of this review is to describe how MRI diffusion and optical microscopy evaluate axonal structural changes at early stages of the disease in a preclinical model of ALS.

Application of molybdenum target X-ray photography in imaging analysis of caudal intervertebral disc degeneration in rats

BACKGROUND Conventional plain X-ray images of rats,the most common animals used as degeneration models,exhibit unclear vertebral structure and blurry intervertebral disc spaces due to their small size,slender vertebral bodies.AIM To apply molybdenum target X-ray photography in the evaluation of caudal intervertebral disc(IVD)degeneration in rat models.METHODS Two types of rat caudal IVD degeneration models(needle-punctured model and endplate-destructed model)were established,and their effectiveness was verified using nuclear magnetic resonance imaging.Molybdenum target inspection and routine plain X-ray were then performed on these models.Additionally,four observers were assigned to measure the intervertebral height of degenerated segments on molybdenum target plain X-ray images and routine plain X-ray images,respectively.The degeneration was evaluated and statistical analysis was subsequently conducted.RESULTS Nine rats in the needle-punctured model and 10 rats in the endplate-destructed model were effective.Compared with routine plain X-ray images,molybdenum target plain X-ray images showed higher clarity,stronger contrast,as well as clearer and more accurate structural development.The McNemar test confirmed that the difference was statistically significant(P=0.031).In the two models,the reliability of the intervertebral height measured by the four observers on routine plain X-ray images was poor(ICC<0.4),while the data obtained from the molybdenum target plain X-ray images were more reliable.CONCLUSIONMolybdenum target inspection can obtain clearer images and display fine calcification in the imaging evaluation of caudal IVD degeneration in rats,thus ensuring a more accurate evaluation of degeneration.

Biomechanical analysis of bone mesoscopic structure and mechanical properties of vertebral endplates of degenerated intervertebral discs in rabbits

In previous studies of disc degeneration,the structural and mechanical properties of the endplate were often neglected.In this paper,the station legislation was used to construct an animal model of minor trauma disc degeneration,and the mechanism of disc degeneration was further investigated by observing the changes of mesoscopic structure and developing the mechanical properties of endplate bone.Twenty-eight 6-month-old Japanese white rabbits were divided into two groups:control group and experimental group.An animal model of intervertebral disc degeneration was established by upright experiment in the experimental group.The bone mesoscopic structures in different areas of each endplate were observed by histological and imaging methods,and the mechanical properties of the endplates were measured by indentation method.The two groups of data were compared by one-way ANOVA.After the experimental animals stood for 17 weeks,The experimental group showed the characteristics of early disc degeneration.The microstructure of the degenerative group showed that the end plate mineralization degree was higher,the bone mass was larger,and the number and thickness of bone trabeculae were larger.The results of indentation test showed that the mechanical properties of the degeneration group were enhanced,and the lower endplate was obviously enhanced.We successfully established a model of human disc degeneration with non invasive trauma and more consistent with the process of human disc degeneration through the standing experiment.In the experimental group,the internal structure of the endplate was dense and pore distance was reduced.The change of bone mesoscopic structure further affects the endplate,resulting in the enhancement of the mechanical properties of the endplate after intervertebral disc degeneration.The reduction of the pore distance and the narrowing of the internal channel structure of the endplate also hinder the nutrition supply of the intervertebral disc,which may be the key reason affecting the degeneration of the intervertebral disc.A biomechanical method for investigating the mechanism of intervertebral disc degeneration can be provided in this paper.