We used lentivirus (LV) to deliver cxcl12 gene into human umbilical cord blood EPCs to generate the engineered CXCL12-EPCs, which were then delivered into the perifocal region at 1 week after permanent middle cerebral artery occlusion to investigate the effects of CXCL12-EPCs on the functional recovery and angiogenesis, neurogenesis, and remyelination in ischemic stroke mice.
SDF-1-positive cell number was increased in the core and penumbra area, which was expressed in macrophage/microglia and transplanted B10 cells at 3 days after MCAO.
Treatment with NGF promoted angiogenesis in the peri-infarct region, increased the serum levels of VEGF and SDF-1 protein, and elevated the number of circulating endothelial progenitor cells (EPCs) on day 4 after MCAO.
LRRC4 was a target gene of miR-381.Compared with the results in the CLB + MCAO group, mNSS, infarction volume, apoptosis rate and TNF-α, IL-1β, IL-6 and Nogo-A contents as well as LRRC4 expression in the CLB + MCAO + miR-381 inhibitor and CLB + MCAO + AMD3100 groups were increased (those in the CLB + MCAO + AMD3100 group > those in the CLB + MCAO + miR-381 mimic + AMD3100 group), while BrdU-positive cell number, contents of NGF and IL-10, and expression of SDF-1, CXCR4, pERK, Slit2 and VEGF in brain tissues were decreased (those in the CLB + MCAO + AMD3100 group < those in the CLB + MCAO + miR-381 mimic + AMD3100 group).
Downregulating the PDGFR signaling pathway with crenolanib from day 1 to day 3 after MCAO significantly decreased the migration of neuroblasts from the SVZ to the peri-infarct region, decreased angiogenesis, and lowered expression of vascular endothelial growth factor, stromal cell-derived factor-1, and monocyte chemotactic protein-1.
A rat model of middle cerebral artery occlusion (MCAO) was established; either Ad- VEGF<sub>165</sub>-SDF-1 or control adenovirus Ad- LacZ was stereotactically microinjected into the lateral ventricle of 80 rats 24 hours after MCAO.