Astrocyte scar formation aids central nervous system axon regeneration

Nature. 2016 Apr 14;532(7598):195-200. doi: 10.1038/nature17623. Epub 2016 Mar 30.

Abstract

Transected axons fail to regrow in the mature central nervous system. Astrocytic scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocytic scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules. Our findings show that contrary to the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / pathology*
  • Axons / physiology*
  • Central Nervous System / cytology
  • Central Nervous System / pathology*
  • Central Nervous System / physiology*
  • Chondroitin Sulfate Proteoglycans / biosynthesis
  • Cicatrix / pathology*
  • Cicatrix / prevention & control
  • Female
  • Genomics
  • Mice
  • Models, Biological*
  • Nerve Regeneration*
  • Reproducibility of Results
  • Spinal Cord Injuries / genetics
  • Spinal Cord Injuries / pathology

Substances

  • Chondroitin Sulfate Proteoglycans

Associated data

  • GEO/GSE76097