The biology of regeneration failure and success after spinal cord injury

Amanda Phuong Tran, Philippa Mary Warren, Jerry Silver

Research output: Contribution to journalReview article

  • 7 Citations

Abstract

Since no approved therapies to restore mobility and sensation following spinal cord injury (SCI) currently exist, a better understanding of the cellular and molecular mechanisms following SCI that compromise regeneration or neuroplasticity is needed to develop new strategies to promote axonal regrowth and restore function. Physical trauma to the spinal cord results in vascular disruption that, in turn, causes blood-spinal cord barrier rupture leading to hemorrhage and ischemia, followed by rampant local cell death. As subsequent edema and inflammation occur, neuronal and glial necrosis and apoptosis spread well beyond the initial site of impact, ultimately resolving into a cavity surrounded by glial/fibrotic scarring. The glial scar, which stabilizes the spread of secondary injury, also acts as a chronic, physical, and chemo-entrapping barrier that prevents axonal regeneration. Understanding the formative events in glial scarring helps guide strategies towards the development of potential therapies to enhance axon regeneration and functional recovery at both acute and chronic stages following SCI. This review will also discuss the perineuronal net and how chondroitin sulfate proteoglycans (CSPGs) deposited in both the glial scar and net impede axonal outgrowth at the level of the growth cone. We will end the review with a summary of current CSPG-targeting strategies that help to foster axonal regeneration, neuroplasticity/sprouting, and functional recovery following SCI.

LanguageEnglish (US)
Pages881-917
Number of pages37
JournalPhysiological Reviews
Volume98
Issue number2
DOIs
StatePublished - Apr 1 2018

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Spinal Cord Injuries
Neuroglia
Regeneration
Cicatrix
Chondroitin Sulfate Proteoglycans
Neuronal Plasticity
Growth Cones
Blood Vessels
Axons
Rupture
Edema
Spinal Cord
Cell Death
Necrosis
Ischemia
Apoptosis
Hemorrhage
Inflammation
Wounds and Injuries
Therapeutics

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Physiology (medical)

Cite this

The biology of regeneration failure and success after spinal cord injury. / Tran, Amanda Phuong; Warren, Philippa Mary; Silver, Jerry.

In: Physiological Reviews, Vol. 98, No. 2, 01.04.2018, p. 881-917.

Research output: Contribution to journalReview article

Tran, Amanda Phuong ; Warren, Philippa Mary ; Silver, Jerry. / The biology of regeneration failure and success after spinal cord injury. In: Physiological Reviews. 2018 ; Vol. 98, No. 2. pp. 881-917.
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