Role of Microglia and Macrophages in Secondary Injury of the Traumatized Spinal Cord: Troublemakers or Scapegoats?

  • Phillip G. Popovich


Spinal cord injury (SCI) initiates a cascade of cellular and biochemical reactions that propagate tissue damage beyond the original site of trauma. In theory, circumventing this destructive secondary pathology will lead to increased preservation of neurons and glia, and presumably to functional recovery. However, the actual onset, duration and mechanisms of secondary neuronal injury are poorly understood. To date, numerous mechanisms of secondary injury have been proposed including the possibility that microglia and macrophages play a role in lesion expansion. In 1985, Blight saw in a cat model of SCI that axons surviving the initial mechanical trauma did not undergo significant demyelination until at least two days post-injury. Because delayed demyelination correlated with the timing of significant macrophage influx, and large lipid-filled macrophages were closely apposed to denuded axons, Blight postulated a role for macrophages in secondary injury (Blight (1985); Blight (1992)). Later independent studies in guinea pig, rabbit and rodent models of SCI supported this notion that inflammation in general, and macrophages in particular, contribute to delayed secondary injury (Giulian and Robertson (1990); Blight (1994); Blight et al. (1995); Popovich et al. (1999)) (Guth et al. (1994a); Guth et al. (1994b); Zhang et al. (1997)) . Owing to their ability to release prodigious amounts of noxious chemicals and enzymes involved in host defense, it is reasonable to assume a role for macrophages in acute neuronal injury, microvascular damage and delayed demyelination.


Spinal Cord Injury Microglial Activation Quinolinic Acid Secondary Injury Brain Macrophage 
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  • Phillip G. Popovich

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