Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (3): 634-642.doi: 10.4103/1673-5374.350210

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Chronic spinal cord compression associated with intervertebral disc degeneration in SPARC-null mice

Zhuo-Yao Li1, 2, #, Ai-Fang Zhou1, 2, #, Gan Li1, 2, Long-Yun Zhou3, Pei-Min Pu1, 2, Ke Zhu1, 2, Zhong Zheng1, 2, Yong-Jun Wang1, 2, Qian-Qian Liang1, 2, *, Min Yao1, 2, *, Xue-Jun Cui1, 2, *   

  1. 1Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 2Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 3Rehabilitation Medicine Center, Jiangsu Province Hospital, Nanjing, Jiangsu Province, China
  • Online:2023-03-15 Published:2022-08-28
  • Contact: Xue-Jun Cui, PhD, 13917715524@139.com; Min Yao, PhD, yaomin19871223@126.com; Qian-Qian Liang, PhD, liangqianqiantcm@126.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 82074454 (to XJC), 82174409 (to MY), 81930116 (to YJW), 81873317 (to XJC), the National Key R&D Program of China, No. 2018YFC1704300 (to YJW), the Natural Science Foundation of Shanghai, No. 20ZR1459000 (to MY).

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Abstract: Chronic spinal cord compression (CSCC) is induced by disc herniation and other reasons, leading to movement and sensation dysfunction, with a serious impact on quality of life. Spontaneous disc herniation rarely occurs in rodents, and therefore establishing a chronic spinal cord compression (CSCC) animal model is of crucial importance to explore the pathogenesis and treatment of CSCC. The absence of secreted protein, acidic, and rich in cysteine (SPARC) leads to spontaneous intervertebral disc degeneration in mice, which resembles human disc degeneration. In this study, we evaluated whether SPARC-null mice may serve as an animal model for CSCC. We performed rod rotation test, pain threshold test, gait analysis, and Basso Mouse Scale score. Our results showed that the motor function of SPARC-null mice was weakened, and magnetic resonance images revealed compression at different spinal cord levels, particularly in the lumbar segments. Immunofluorescence staining and western blot assay showed that the absence of SPARC induced apoptosis of neurons and oligodendrocytes, activation of microglia/macrophages with M1/M2 phenotype and astrocytes with A1/A2 phenotype; it also activated the expression of the NOD-like receptor protein 3 inflammasome and inhibited brain-derived neurotrophic factor/tyrosine kinase B signaling pathway. Notably, these findings are characteristics of CSCC. Therefore, we propose that SPARC-null mice may be an animal model for studying CSCC caused by disc herniation.

Key words: apoptosis, astrocytes, chronic spinal cord compression, disc degeneration, disc herniation, macrophages, microglia, neuroinflammation, neurons, NOD-like receptor protein 3 inflammasomes, secreted protein, acidic, and rich in cysteine