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Background: Protection of cerebral endothelial cells (ECs) from hypoxia/reoxygenation (H/R)-induced injury is an important strategy for treating ischemic stroke. In this study, we investigated whether co-culture with endothelial progenitor cells (EPCs) and neural progenitor cells (NPCs) synergistically protects cerebral ECs against H/R injury and the underlying mechanism. Results: EPCs and NPCs were respectively generated from inducible pluripotent stem cells. Human brain ECs were used to produce an in vitro H/R-injury model. Data showed: 1) Co-culture with EPCs and NPCs synergistically inhibited H/R-induced reactive oxygen species (ROS) over-production, apoptosis, and improved the angiogenic and barrier functions (tube formation and permeability) in H/R-injured ECs. 2) Co-culture with NPCs up-regulated the expression of vascular endothelial growth factor receptor 2 (VEGFR2). 3) Co-culture with EPCs and NPCs complementarily increased vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) levels in conditioned medium, and synergistically up-regulated the expression of p-Akt/Akt and p-Flk1/VEGFR2 in H/R-injured ECs. 4) Those effects could be decreased or abolished by inhibition of both VEGFR2 and tyrosine kinase B (TrkB) or phosphatidylinositol-3-kinase (PI3K). Conclusions: Our data demonstrate that EPCs and NPCs synergistically protect cerebral ECs from H/R-injury, via activating the PI3K/Akt pathway which mainly depends on VEGF and BDNF paracrine. [ABSTRACT FROM AUTHOR]

Background Atherosclerosis is the leading etiologic factor of Atherosclerotic Cerebral Infarction (ACI). Previous studies have shown that thrombin activatable fibrinolysis inhibitor (TAFI) may play an important role in the occurrence of acute cerebral infarction, and the levels of TAFI are affected by several single nucleotide polymorphisms (SNPs) located in the regulatory and coding regions of the gene encoding TAFI. The present study aimed to determine whether polymorphisms (TAFI -2345 2G/1G, -1690 A/G, -438 A/G, +1583 A/T) of the TAFI gene were associated with ACI in a Han Chinese population. Methods The variant genotypes were identified by restriction fragment length polymorphism (RFLP) and allele-specific polymerase chain reactions (AS-PCR) in 225 patients with ACI and 184 age-matched healthy individuals. Results There was a significant difference in the genotype and allele frequencies of TAFI -2345 2G/1G and -1690 A/G polymorphisms between the ACI and control subjects. Further stratification analysis by gender revealed that the presence of the -438 AA genotype and the A allele conferred a higher risk of developing ACI in male patients (p < 0.05). Haplotype analysis demonstrated that four haplotypes of TAFI are significantly associated with ACI. Conclusions Our study provides preliminary evidence that the TAFI -2345 2G/1G and -1690 A/G polymorphisms are associated with ACI susceptibility in a Han Chinese population. [ABSTRACT FROM AUTHOR]