Bone marrow-derived mesenchymal stromal cells (MSCs) used as "MSC therapy" after traumatic brain injury act as remote "bioreactors" via stimulation of lung macrophages and augmention of T regulatory cell production by the spleen, leading to systemic increases in circulating anti-inflammatory cytokines and alteration of the locoregional milieu of the central nervous system. The altered intracerebral microenvironment leads to modulation of the resident microglia population, thereby stimulating an increase in the ratio of M2 (anti-inflammatory) macrophage to M1 (proinflammatory) macrophage, and it is this effect that accounts for the observed neuroprotection.