Administration of CR2 ligands including C3d reduces the proliferation of wild-type primary mouse neural progenitor cells in vitro. They follow with in vivo experiments utilizing direct injection of C3d into the dentate gyrus of wild-type mice to demonstrate a decrease in proliferating neuroblasts Vorinostat molecular weight relative to saline-injected animals. Based on the available literature, the influence of complement on neurogenesis is complex, and demands careful analysis of each complement component across varying time-points in a specific a disease model. In the present study, low-dose C3aRA administration limited to the acute post-stroke period increases the proliferation of migrating neuroblasts in the SVZ. The differences observed between our study and that of Rahpeymai et al. are likely explained in part by variations in experimental protocols. First, Rahpeymai et al. employ models of permanent stroke, which are known to induce a substantially different pathological response than that of reperfused stroke. Furthermore, the dose of C3aRA utilized by Rahpeymai et al. in their work was forty times greater than the low-dose utilized in our study and in previous studies demonstrating a neuroprotective benefit in stroke. In fact, we demonstrate that a high-dose regimen of C3aRA suppresses both BrdU+ and DCx/BrdU++ cells in the SVZ relative to the low-dose regimen, suggesting a dose-dependent effect of C3aRA administration on neural progenitor proliferation. It is important to note that we did not observe a corresponding increase in newly-formed mature neurons either in the SVZ or in the peri-infarct region. This likely relates to our use of a 7-day sacrifice time-point, as the process of neuroblast migration from the SVZ to the ischemic territory and subsequent maturation is not complete by this time. Additionally, we did not observe a significant difference between the number of DCx/ BrdU++ cells in the ischemic and non-ischemic hemispheres in any of the treatment cohorts. Given that the absolute value of the DCx/BrdU cell count in the ipsilateral hemisphere of each cohort is larger than that of the contralateral hemisphere, the lack of significance between these comparisons might simply reflect a lack of statistical power. Alternatively, while an increase in DCX+BrdU+ cells in the hemisphere ipsilateral to an ischemic insult has been described, increased neurogenesis contralateral to an ischemic lesion has also been previously reported. This increase in contralateral neurogenesis may mask an anticipated difference between hemispheres, and may go unnoticed in studies that only examine cell counts in the ipsilateral hemisphere. Finally, the proliferation of cells in the ischemic SVZ has been reported as maximal later than 7 days post-ischemia, and thus a significant inter-hemispheric difference may ultimately be noted at a later time-point. Future experiments are planned examining the functional and histologic effects of C3aRA administration at later time-points.