In contrast, mice that received hMSC treatment showed decreased lesion size, which is associated with decreased astrocyte and microglia activation. In agreement with these results, we described in a recent paper that MSC treatment resolves the glial scar as Iba1 and GFAP Bortezomib Proteasome inhibitor positive fluorescence significantly decreases over time, returning to sham level at 18 days following treatment. Reactive astrocytes contribute to a process called glial scar formation, which forms a physical and chemical barrier that prevents inflammation from spreading through the tissue, thus restricting the progression of the injury. However, a downside of scar formation is that it also inhibits growth cone motility, thereby impairing axon regeneration. This may be one of the reasons underlying impaired neurogenesis following a HI insult in the neonatal brain. Hence, our data suggest that hMSCinduced reduction in astrocyte activation is crucial for repair of the lesion after HI brain damage. The decrease in astrocyte and microglia activity may be mediated by anti-inflammatory cytokines secreted by the hMSCs. We and others have previously shown that MSCs secrete IL-10, which is known to suppress the pro-inflammatory phenotype of both microglia and astrocytes. Interestingly, the effect of MSCs on GFAP positive cells is apparently restricted to reactive astrocytes involved in astrogliosis, as GFAP expression can still be observed in the hippocampus following repair and the staining strongly resembles the hippocampus of sham-operated animals. Future studies should focus on the mechanisms underlying MSC-mediated reduction of astrocytic scar in brain lesions, which may be crucial in promoting a proneurogenic microenvironment that supports tissue repair. Besides showing the potential of hMSCs to repair the HI injured brain, we also provide new insight into factors that may be involved in MSC migration from the nose to the injury site. Our results show that expression of the integrin beta 2 protein is upregulated at 10 days after HI. Itgb-2 together with the Intercellular Adhesion Molecule 1 mediates the migration of leukocytes along endothelial cells and may be involved in the migration of MSCs through blood vessels and regulate transmigration into the brain tissue. The results from the PCR array show that CXCL10 is the chemotactic factor with the highest fold change at 10 days following HI. Interestingly, at 17 days after HI, the expression level of this chemokine has returned to sham level. We also show that the expression of the CXCL10 receptor, CXCR3, increases following co-culture of hMSCs with brain extract from 10 days after HI. Together these results suggest that CXCL10 may play an important role in regulating homing of MSCs to the lesion site. We also found that Ccl5 significantly decreases at 17 days following HI, which also suggests a role for this chemokine in MSC homing to lesion.