The experiments described above demonstrate the crucial dynamics between M1 and M2 polarization during injury state. One piece of information that comes out of this research is the critical role the environment plays in controlling the shift from classical to alternative activation. With spinal cord injury and traumatic brain injury, the domination of M1 microglia is mainly due to the high levels of proinflammatory cytokines present [60,68]. Importantly, polarized microglia are not locked in a particular state; both microglia and macrophages are plastic cell types that can be altered if the cytokine environment changes [84]. However, in many acute injuries, the continued production of cytokines like IFNγ and TNFα maintains an M1 activation state. One would therefore hypothesize that altering the environment could be used to treat injuries. To that end, in models of the injuries described previously, investigators have begun to utilize techniques to inject M2 cells directly or cause polarization indirectly. In spinal cord injury, the transplantation of mesenchymal stem cells has been shown to increase IL-4/13 and decrease TNFα levels [85]. These cytokine changes were associated with
