Angiopoietin-1 Protects Spinal Cord Ischemia and Reperfusion Injury by Inhibiting Autophagy in Rats

Neurochem Res. 2019 Dec;44(12):2746-2754. doi: 10.1007/s11064-019-02893-3. Epub 2019 Oct 19.

Abstract

Spinal cord ischemia and reperfusion (SCIR) injury can induce autophagy, which is involved in the survival of neurons. However, whether autophagy plays a neuroprotective or a detrimental role in SCIR injury remains controversial. Angiopoietin-1 (Ang-1), an endothelial growth factor, has been shown to have neuroprotective effects. The present study aimed to explore the neuroprotective mechanisms of Ang-1 in neuronal cells in a rat model of SCIR injury in vivo. Ang-1 protein and rapamycin were injected intrathecally. Basso Beattie Bresnahan (BBB) scoring and hematoxylin and eosin staining were used to assess the degree of SCIR injury. Proteins that reflected the level of autophagy expression, such as Beclin-1 and LC3, were evaluated by western blotting. The results indicated that SCIR injury resulted in loss in lower limb motor function. Ang-1 protein inhibited the expression of Beclin-1 and LC3, which improved the BBB score and alleviated spinal cord injury. In contrast, rapamycin, an autophagy activator, caused the opposite effect. This study provides evidence that Ang-1 plays a neuroprotective role by inhibiting of autophagy expression in SCIR injury. Overall, findings could be useful for the treatment of SCIR injury.

Keywords: Angiopoietin-1; Autophagy; Ischemia; Reperfusion; Spinal cord.

MeSH terms

  • Angiopoietin-1 / therapeutic use*
  • Animals
  • Autophagy / drug effects*
  • Male
  • Neurons / drug effects
  • Neuroprotective Agents / therapeutic use*
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / physiopathology
  • Sirolimus / pharmacology
  • Spinal Cord / drug effects
  • Spinal Cord / pathology
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Ischemia / drug therapy*
  • Spinal Cord Ischemia / physiopathology

Substances

  • Angiopoietin-1
  • Neuroprotective Agents
  • Sirolimus