Effect of stromal ceil-derived factor-1α on angiogenesis in focal infarct in the cerebral cortex in adult rats / 国际脑血管病杂志

ABSTRACT

Objective To investigate the effect of exogenous stromal cell-derived factor-1 α (SDF-1 α) on angiogenesis peri-infarct region in cerebral cortex in adult rats and its possible mechanisms.Methods Twenty-four adult male Sprague-Dawley rats were randomly divided into four groupssham operation,solvent control,SDF-1α treatment,and SDF-1α + CXCR4 antagonist (n =6 in each group).A model of focal infarct in the cerebral cortex was induced by permanent ligation of the cortical branch of the right middle cerebral artery with temporary clip occlusion of both common carotid arteries.At 1 h after cortical branch occlusion of the right middle cerebral artery,SDF-1 α (1 μg/d) or equal volume of normal saline were injected via the lateral ventricle in the SDF-1α treatment group and solvent control group,and continued for 6 days.CXCR4 antagonist AMD3100 (1 mg/d) was injected subcutaneously before injecting SDF-1 α in the SDF-1 α + CXCR4 antagonists group,and continued for 6 days.Before all the rats were sacrificed,5-bromo-2-deoxyuridine (BrdU) was injected intraperitoneally and their newly proliferated cells were labeled.At day 7 after modeling,the rats were sacrificed after neurological scores.Immunofluorescence staining was used to detect the vascular density,the numbers of neovasculature endothelial cells and the CXCR4 + cells in the peri-infarct regions or sham operation regions.Results At 7 d after modeling,the neurological function of the SDF-1α treatment group was improved significantly compared with those of the solvent control group and the SDF-1α + CXCR4 antagonist group (all P＜ 0.01).The vascular densities in the peri-infarct or sham operation regions in the groups of sham operation,solvent control,SDF-1α treatment,and SDF-1α+ CXCR4 antagonist were 2.1±0.3％,7.0±0.3％,10.0 ±0.9％ and 7.1 ±0.3％,respectively (F=232.469,P＜0.001),and that in the sham operation was significantly lower than that in the SDF-1α group (P ＜0.001),SDF-1 α group significantly higher than both groups of solvent control (P =0.002) and SDF-1oα + CXCR4 antagonist (P =0.001).The numbers of BrdU+/laminin+ cells in the peri-infarct regions in the groups of sham operation,solvent control,SDF-1α treatment,and SDF-1α + CXCR4 antagonist were 21.7 ± 3.1,79.7 ± 6.0,176.0 ± 12.5 and 90.3 ± 6.9,respectively (F=391.550,P＜0.001),and that in the sham operation was significantly less than that in the SDF-1 α group (P ＜ 0.001),SDF-1 α group was significantly more than both groups of solvent control and SDF-1 oα + CXCR4 antagonist (all P ＜0.001).The numbers of CXCR4 + cells in the peri-infarct regions in the groups of solvent control,SDF-1α treatment,and SDF-1α+ CXCR4 antagonist were 59.3± 4.5,120.3 ± 13.9 and 62.9 ± 5.9,respectively (F =85.052,P ＜ 0.001),and that in SDF-1α group was significantly more than those in the both groups of solvent control and SDF-1 α + CXCR4 antagonist (all P ＜ 0.001).Conclusions SDF-1α treatment may improve the neurological function after focal infarction in the cerebral cortex in adult rats and promote angiogenesis in peri-infarct region.The SDF-1/CXCR4 signal pathway may play an important regulatory role in the process of angiogenesis after cerebral infarction.