Inflammation generated by stroke and ischemic reperfusion injury is regarded as a major factor contributing to tissue damage [60] and, like spinal cord injury, the damaged tissue environment favors an M1 phenotype [78]. In addition to neutrophils, it is these M1 microglia, and, to a lesser degree, macrophages, that contribute to the inflammatory cascade and further propagate cell death beyond the initial ischemic region [79,80]. Even though the proinflammatory response is dominant, there does appear to be an anti-inflammatory signal that attempts to regulate the inflammation [78]. Consistent with the idea that an M2 response is needed to properly downregulate inflammation and initiate repair, mice that lack appropriate signals for M2 induction have worse outcomes after experimental cerebral ischemia. For example, mice lacking either IL-4 or IL-10 show increased infarct volume and worse cognitive performance following cerebral ischemia [81,82]. Additionally, deletion of galectin-3, a protein required for microglial activation, leads to a reduction in M2-associated cytokines, such as IGF-1, which results in worse pathology after stroke [83]. This highlights the importance of M2 cells in mitigating and repairing damage.
