Another important element that critically determines the destructive or neuroprotective role of microglia is the timing of their activation. Because large and very complicated communications pathways exist between immunocompetent cells and cytokines in the CNS, the timing of microglial activation leads to diverse trends and outcomes related to the entire inflammation event. In a model of optic nerve crush injury, Shaked et al. found that an earlier onset of phagocytic activity and antigen presentation by microglia results in a resistance to injury and neurons survived [133] ; the early, moderate, transient and well-controlled activation of local microglia caused them to function as APCs, leading to the communication with Treg cells that subsequently proves to be neuroprotective through the modulation of microglial activation states [133] . In a multiple sclerosis (MS) Luo and Chen Translational Neurodegeneration 2012, 1:9