Acute spinal cord injury: a cascade of pathological events

Initial mechanical injury to the spinal cord begins a cascade of response that leads to further damage to the neural tissue, known as secondary injury. Unchecked, this response can lead to progressive cyst formation and glial scarring. Interrupting this cascade and attempting to reduce the loss of white matter is one strategy for limiting damage and restoring function.

Pathophysiology of Acute SCIInitial Injury1

  • Primary mechanical injury directly disrupts axons, blood vessels, and cell membranes.
  • The most common forms of acute SCI are compressive-contusive-type injuries, in which displaced components of the vertebral column exert force on the cord.

Vascular injury and increased spinal cord tissue pressure contribute to secondary injury, including ischemic destruction of gray matter and demyelination1-6

  • Initial injury results in vessel shearing and hemorrhage, particularly into the gray matter. Vasospasm and thrombosis formation may also contribute to ischemia at the site of injury.
  • Increased spinal cord tissue pressure also contributes to secondary injury, including ischemia.

After 24 hours: Irreversible destruction of gray matter, but some white matter is spared7

White and Gray Matter

  • Most gray matter loss occurs within hours of injury and is complete by 24 hours.
  • Destruction of myelin-producing oligodendrocytes occurs soon after injury, and loss of the myelin sheath interrupts neuronal signaling and exposes axons to further damage from free radicals and inflammatory cytokines.
  • Progressive loss of white matter occurs more slowly over the course of 1 week. Loss of neurologic function below the level of an SCI is due predominantly to loss of white matter in and around the injury site.

1. Rowland JW, et al. Neurosurg Focus. 2008;25:E2.
2. Ng MT, et al. Transl Stroke Res. 2011;2:474-491.
3. Werndle MC, et al. Crit Care Med. 2014;42:646-655.
4. Ducker TB, et al. Surg Neurol. 1978;10:60-63.
5. Ek CJ, et al. PLoS One. 2010;5:e12021.
6. Oyinbo CA. Acta Neurobiol Exp. 2011;71:281-299.
7. InVivo Therapeutics Data on File.