One of the better-studied areas of M1 and M2 activation in the CNS is after spinal cord injury. Following the initial trauma of spinal cord injury, secondary inflammation has been identified as an important factor that leads to enhanced damage and impaired regeneration. Consistent with this, several M1 microglial secreted factors have been shown to be neurotoxic and inhibit axon extension [63-65]. Kigerl et al.[63] characterized the response of M1 and M2 cells both acutely and several weeks after spinal cord injury. Initially, they observed early upregulation of both M1- and M2-related proteins and mRNA species. However, three days post-injury, the M1 markers continued to rise and M2 markers were downregulated, leading to a skewed M1 profile [63]. Kigerl et al. suggested that the domination of M1 cells might be one of the reasons for continued damage and lack of repair. For example, in the same report, using cultured neurons, IFNγ-polarized M1-conditioned media was neurotoxic and prevented axon elongation after injury, while IL-4 treated, M2-conditioned media encouraged axon growth [63]. The beneficial functions of IL-4 appear to extend to endogenous
