Role of Microglia and Macrophages in Secondary Injury of the Traumatized Spinal Cord: Troublemakers or Scapegoats?
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.
KeywordsSpinal Cord Injury Microglial Activation Quinolinic Acid Secondary Injury Brain Macrophage
Unable to display preview. Download preview PDF.
- Berezovskaya O, Maysinger D, Fedoroff S (1995). The hematopoietic cytokine, colonystimulating factor 1, is also a growth factor in the CNS: congenital absence of CSF-1 in mice results in abnormal microglial response and increased neuron vulnerability to injury. Int J Dev Neurosci 13: 285–299.PubMedCrossRefGoogle Scholar
- Blight AR (1985). Delayed demyelination and macrophage invasion: a candidate for secondary cell damage in spinal cord injury. CNS Trauma 2: 299–315.Google Scholar
- Giulian D (1987). Ameboid microglia as effectors of inflammation in the central nervous system. J Neurosci Res 18: 155–71, 132–3.Google Scholar
- Harrison JK, Jiang Y, Chen S, Xia Y, Maciejewski D, McNamara RK, Streit WJ, Salafranca MN, Adhikari S, Thompson DA, Botti P, Bacon KB, Feng L (1998). Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc Natl Acad Sci USA 95: 10896–10901.PubMedCrossRefGoogle Scholar
- Vezzani A, Conti M, De Luigi A, Ravizza T, Moneta D, Marchesi F, De Simoni MG (1999). Interleukin-1 beta immunoreactivity and microglia are enhanced in the rat hippocampus by focal kainate application: functional evidence for enhancement of electrographic seizures. J Neurosci 19: 5054–5065.PubMedGoogle Scholar