Furthermore, a few injected NPCs, which were identified as GFP-positive cells, expressed GFAP in the peri-infarcted areas (Fig. 8B), although most injected NPCs were still positive for the NPC marker musashi-1 on day 28 after the embolism (not shown). Figure 8 Histological analysis of neural progenitor cell (NPC)-injected brain after the embolism. Effect of injection of NPCs on the expression of angiopoietin-1 (Ang-1) and glial fibrillary acidic protein (GFAP) after

cerebral embolism. Ang-1 protein is expressed … Discussion In this study, we showed an increase in the number of BrdU-positive vascular endothelial cells in the peri-selleck chemical infarct region on day 7 after cerebral embolism. Although the number of these cells Inhibitors,research,lifescience,medical tended to be increased compared with that for the sham-operated rats on day 28, the ability of the endothelial cells to proliferate was

attenuated compared with that at day 7. Taken together, our data indicate that long-term and severe cerebral embolism enhanced endogenous angiogenesis transiently and then suppressed Inhibitors,research,lifescience,medical it at later stages. In this study, the intravenous injection of NPCs promoted angiogenesis in the peri-infarct area even on day 28 after Inhibitors,research,lifescience,medical the embolism, which increase was accompanied by the alteration of angiogenic factors and their receptors. Although angiogenesis was required for protection of infarct area in the ischemic brain (Richardson et al. Inhibitors,research,lifescience,medical 2001), our previous results demonstrated that the injection of NPCs does not repair the injured tissue after an embolism (Moriyama et al. 2011). Therefore, NPC-induced angiogenesis at the later stage may contribute to improvement of ischemia-induced brain dysfunction rather than have a restorative effect on the infarcted areas. As VEGF and Ang play a pivotal Inhibitors,research,lifescience,medical role in the angiogenesis, we further investigated changes in the level of these angiogenic factors and their receptors. In this study, the levels of VEGF and VEGFR2 were increased on day 7 after the embolism.

It has been suggested that angiogenesis in ischemic tissues is promoted by VEGF, the expression of which is upregulated by hypoxia-inducible factor 1α (HIFα), via VEGFR2 signaling (Marti et al. 2000). In this sense, the expression of HIFα might have been increased in our vehicle-injected ME rats, as ME is reported to induce a sustained decrease in the cerebral blood flow in the ipsilateral hemisphere (Miyake et al. 1993). Therefore, microsphere embolism-induced angiogenesis on day 7 might Rolziracetam have been due to the increased level of VEGF proteins in response to the ischemic condition, although the underlying mechanism for the increased level of VEGFR2 on day 7 remains to be determined. We also demonstrated that the injection of NPCs further increased the level of VEGF compared with that of vehicle-injected ME rats on day 28. In addition, the level of VEGFR2 was maintained at that of the age-matched sham-operated rats by injection of NPCs.