Effects of melatonin on severe crush spinal cord injury-induced reactive astrocyte and scar formation

J Neurosci Res. 2016 Dec;94(12):1451-1459. doi: 10.1002/jnr.23930. Epub 2016 Sep 26.


The present work aimed at analyzing the effects of melatonin on scar formation after spinal cord injury (SCI). Upregulation of reactive astrocyte under SCI pathological conditions has been presented in several studies. It has been proved that the crucial factor in triggering this upregulation is proinflammatory cytokines. Moreover, scar formation is an important barrier to axonal regeneration through the lesion area. Melatonin plays an important role in reducing inflammation, but its effects on scar formation in the injured spinal cord remain unknown. Hence, we used the model of severe crush injury in mice to investigate the effects of melatonin on scar formation. Mice were randomly separated into four groups; SCI, SCI+Melatonin 1 (single dose), SCI+Melatonin 14 (14 daily doses), and control. Melatonin was administered by intraperitoneal injection (10 mg/kg) after injury. Immunohistochemical analysis, Western blot, and behavioral evaluation were used to explore the effects of melatonin after SCI for 14 days. The melatonin-treated mice presented higher expression of neuronal markers (P < 0.001). Remarkably, the inflammatory response appeared to be greatly reduced in the SCI+Melatonin 14 group (P < 0.001), which also displayed less scar formation (P < 0.05). These findings suggest that melatonin inhibits scar formation by acting on inflammatory cytokines after SCI. Overall, our results suggest that melatonin is a promising treatment strategy after SCI that deserves further investigation. © 2016 Wiley Periodicals, Inc.

Keywords: astrocytes; axonal regeneration; glial scar; inflammation; melatonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Behavior, Animal / drug effects
  • Cicatrix / metabolism*
  • Female
  • Locomotion
  • Melatonin / pharmacology*
  • Mice
  • Nerve Crush*
  • Neuroprotective Agents / pharmacology*
  • Recovery of Function
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / psychology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Neuroprotective Agents
  • Melatonin