It is wellestablished that post-ischemic neurogenesis is subject to a complex interplay between complement activation, cytokine release, and other inflammatory processes. In addition to modulating neurogenesis directly, complement activation may also serve to inhibit neurogenesis indirectly through upregulation of inflammatory cytokines. For example, recent work demonstrates the detrimental effect of IFN-c and TNF-a on rat neuronal progenitor cell survival and proliferation. Thus, the direct effect of C3a/ C3aR blockade on neurogenesis cannot be dissociated from its powerful anti-inflammatory effect in a stroke model. As it has been established that inflammation is a more prominent characteristic of reperfused stroke than non-reperfused stroke, the known suppressive effect of inflammatory cytokines on neurogenesis may figure prominently in our model. The histologic findings of our study also support an indirect influence of C3a on neural progenitors, and serve to identify a novel mechanism for complement-mediated ischemic injury beyond the acute phase of stroke. Using confocal microscopy, C3aR antigen was observed only on infiltrating inflammatory cells in the ischemic territory. This calls into question a direct effect of C3aR on SVZ neurogenesis. At 24 hours, C3aR expression was restricted to the surface of granulocytes. By 7 days, however, a distinct population of cells bearing the CD3 marker was observed, the majority of which expressed the C3areceptor. Daily administration of C3aRA suppressed the infiltration of both CD3+ and C3aR+ cells. To our knowledge, this represents the first report of the C3aR localized to infiltrating T-lymphocytes in the brain, and suggests that C3a plays a role in modulating post-ischemic T-cell infiltration. As T-cells infiltrate the ischemic region in a delayed fashion relative to granulocytes, this finding raises the possibility of an extended therapeutic window for anti-complement neuroprotective strategies. In fact, when C3aRA administration was delayed until 72 hours post-ischemia and continued to the sacrifice timepoint of 7 days, significant reductions in subcortical injury were also observed. Furthermore, we observed more robust functional neuroprotection and reduction in mortality when acutely administered, low-dose C3aRA administration was continued through the subacute phase. This indicates that deleterious complement-mediated cerebral inflammation persists into the subacute phase, and that targeting these deleterious subacute processes may afford additional neuroprotection. Additionally, it has been reported that activated T-cells may suppress neural progenitor cell proliferation and differentiation. Therefore, a suppressive effect of C3aRA on T-cell infiltration may also indirectly promote neurogenesis through as yet undefined mechanisms. We must acknowledge several limitations of our study. First, conclusions derived from this work cannot be extrapolated to BU 4061T models of permanent ischemia. We believe that reperfused stroke represents a clinically-relevant experimental model as well as the rapid development of endovascular techniques.