Pros and Cons: Autophagy in Acute Spinal Cord Injury

  • Zheng Li
  • Tianshi Chen
  • Yuanwu Cao
  • Xiaoxing Jiang
  • Haodong LinEmail author
  • Jian ZhangEmail author
  • Zixian ChenEmail author

Autophagy plays an important role in the development and pathogenesis of various diseases. It can be induced by a variety of events such as hypoxia, nutrient-starvation, and mechanical damage. Many neurological disorders such Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, cerebral ischemia, and acute spinal cord injury (ASCI), are closely related to autophagy. However, therapeutic strategies to manipulate autophagy have not yet been fully deciphered due to the limited knowledge of the molecular mechanisms underlying autophagy in these disorders.

ASCI is a severe condition characterized by major disability and poor prognosis. Due to the fact that pathological processes of secondary injury in ASCI usually last for several days or even months, the study and treatment of this disease have mainly focused on reducing the progression. Animal studies have shown that rat models with different degrees of contusion in the lower thoracic spinal cord...



This insight was supported by the National Natural Science Foundation of China (81301047).


  1. 1.
    Ganz J, Shor E, Guo S, Sheinin A, Arie I, Michaelevski I et al. Implantation of 3D constructs embedded with oral mucosa-derived cells induces functional recovery in rats with complete spinal cord transection. Front Neurosci 2017, 11:589.CrossRefGoogle Scholar
  2. 2.
    Cheriyan T, Ryan DJ, Weinreb JH, Cheriyan J, Paul JC, Lafage V et al. Spinal cord injury models: a review. Spinal Cord 2014, 52: 588–595.CrossRefGoogle Scholar
  3. 3.
    Liu S, Sarkar C, Dinizo M, Faden AI, Koh EY, Lipinski MM et al. Disrupted autophagy after spinal cord injury is associated with ER stress and neuronal cell death. Cell Death Dis 2015, 6: e1582.CrossRefGoogle Scholar
  4. 4.
    Zhou KL, Chen DH, Jin HM, Wu K, Wang XY, Xu HZ et al. Effects of calcitriol on experimental spinal cord injury in rats. Spinal Cord 2016, 54: 510.CrossRefGoogle Scholar
  5. 5.
    Li Z, Liu F, Zhang L, Cao Y, Shao Y, Wang X, Jiang X et al. Neuroserpin restores autophagy and promotes functional recovery after acute spinal cord injury in rats. Mol Med Rep 2018, 17: 2957–2963.Google Scholar
  6. 6.
    Wu D, Hao Z, Ren H, Wang G. Loss of VAPB Regulates Autophagy in a Beclin 1-Dependent Manner. Neurosci Bull 2018, 34: 1037–1046.CrossRefGoogle Scholar
  7. 7.
    Kanno H, Ozawa H, Sekiguchi A, Yamaya S, Itoi E. Induction of autophagy and autophagic cell death in damaged neural tissue after acute spinal cord injury in mice. Spine 2011, 36: E1427.CrossRefGoogle Scholar
  8. 8.
    Tang P, Hou H, Zhang L, Lan X, Mao Z, Liu D et al. Autophagy reduces neuronal damage and promotes locomotor recovery via inhibition of apoptosis after spinal cord injury in rats. Mol Neurobiol 2014, 49: 276–287.CrossRefGoogle Scholar
  9. 9.
    Goldshmit Y, Kanner S, Zacs M, Frisca F, Pinto AR, Currie PD et al. Rapamycin increases neuronal survival, reduces inflammation and astrocyte proliferation after spinal cord injury. Mol Cell Neurosci 2015, 68: 82–91.CrossRefGoogle Scholar
  10. 10.
    Saghazadeh A, Rezaei N. The role of timing in the treatment of spinal cord injury. Biomed Pharmacother 2017, 92: 128–139.CrossRefGoogle Scholar
  11. 11.
    Li HT, Zhao XZ, Zhang XR, Li G, Jia ZQ, Sun P et al. Exendin-4 enhances motor function recovery via promotion of autophagy and inhibition of neuronal apoptosis after spinal cord injury in rats. Mol Neurobiol 2016, 53: 4073–4082.CrossRefGoogle Scholar
  12. 12.
    Hachem LD, Ahuja CS, Fehlings MG. Assessment and management of acute spinal cord injury: From point of injury to rehabilitation. J Spinal Cord Med 2017, 40(6): 665–675.CrossRefGoogle Scholar
  13. 13.
    Zhang HY, Wang ZG, Wu FZ, Kong XX, Yang J, Lin BB et al. Regulation of autophagy and ubiquitinated protein accumulation by bFGF promotes functional recovery and neural protection in a rat model of spinal cord injury. Mol Neurobiol 2013, 48: 452–464.CrossRefGoogle Scholar
  14. 14.
    Zhang D, Xuan J, Zheng BB, Zhou YL, Lin Y, Wu YS et al.. Metformin Improves Functional Recovery After Spinal Cord Injury via Autophagy Flux Stimulation. Mol Neurobiol 2017, 54: 1–15.CrossRefGoogle Scholar
  15. 15.
    Zhao H, Chen S, Gao K, Zhou Z, Wang C, Shen Z et al. Resveratrol Protects Against Spinal Cord Injury by Activating Autophagy and Inhibiting Apoptosis Mediated by the SIRT1/AMPK Signaling Pathway. Neuroscience 2017, 348: 241–251.CrossRefGoogle Scholar
  16. 16.
    Guo Y, Liu S, Zhang X, Wang L, Gao J, Han A et al. G-CSF promotes autophagy and reduces neural tissue damage after spinal cord injury in mice. Lab Invest 2015, 95: 1439.CrossRefGoogle Scholar
  17. 17.
    Xia Y, Xia H, Chen D, Liao Z, Yan Y. Mechanisms of autophagy and apoptosis mediated by JAK2 signaling pathway after spinal cord injury of rats. Exp Thera Med 2017, 14: 1589–1593.CrossRefGoogle Scholar
  18. 18.
    Zhang YB, Li SX, Chen XP, Yang L, Zhang YG, Liu R et al. Autophagy is activated and might protect neurons from degeneration after traumatic brain injury. Neurosci Bull 2008, 24: 143–149.CrossRefGoogle Scholar
  19. 19.
    Wang ZY, Liu WG, Muharram A, Wu ZY, Lin JH. Neuroprotective effects of autophagy induced by rapamycin in rat acute spinal cord injury model. Neuroimmunomodulat 2014, 21: 257–267.CrossRefGoogle Scholar
  20. 20.
    Bai L, Mei X, Shen Z, Bi Y, Yuan Y, Guo Z et al. Netrin-1 improves functional recovery through autophagy regulation by activating the AMPK/mTOR signaling pathway in rats with spinal cord injury. Sci Rep 2017, 7: 42288.CrossRefGoogle Scholar

Copyright information

© Shanghai Institutes for Biological Sciences, CAS 2019

Authors and Affiliations

  1. 1.Department of Orthopedics, Zhongshan HospitalFudan UniversityShanghaiChina
  2. 2.Department of OrthopedicsPeople’s Hospital of Boluo CountyHuizhouChina
  3. 3.Department of Orthopedic Surgery, Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghaiChina

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