| Objective:Neurosurgery doctor and researchers have more and more concern about mild traumatic brain injury (TBI) recently. Because these kind of patients always have no regular treatment or early biomarkers used for prognostic judgment. We have already proven in prophase research that endothelial progenitor cells (EPCs) could participate in angiogenesis and tissue repair after TBI. We also have discovered SDF-1α/CXCR4 axis could chemo attract CD34+cells to injury area and enhanced angiogenesis after TBI in our recent study. In this study, we test TBI patients’SDF-la level in serum and CXCR4 expression in blood and tissue samples to find biomarkers which could relate with prognostic conditions through statistic analysis.Methods:1) We totally choose 63 clinic TBI patients in our research:mild TBI 53 cases, moderate TBI 10 cases. Collect blood samples at dayl,4,7,14 and 21 post-injury, then use BD FACS ArisTM flow cytometry to test cells number and CXCR4+express percentage in EPCs (CD34+/CD133+), CD34+ and CD133+cells. By ELISA kit, we could test TBI patients’SDF-la level in serum. Proteins was extracted from contusive brain tissue which had been resected from operation followed by Western-blot test. Also the parts of the brain was formalin fixed, paraffin embedded and tissue sliced for immunofluorescence staining to observe local SDF-1α release and CXCR4 protein expression after trauma.2) Patients prognosis were evaluated by Extended Glasgow Outcome Scale (GOS-E), Activity of Daily Living Scale (ADLS) at 3th and 6th month post-injury. Also use HAMA and HAMD evaluated psychology state of TBI patients. Correlation analysis was conducted between test results mentioned above and TBI patients’ prognosis. Finally find out biomarkers which could reflect prognostic conditions by receiver operating characteristic curve (ROC) and relative risk (RR) analysis.Results:1) Circulating EPCs number of mild TBI patients was depressed at early time and then rised quickly, also more then the control group at 7,14 day (p<0.05). CD34+ and CD133+ cells were at high level at first time point, then gradually decreased in later days, there were no statistic different between mild TBI group and moderate TBI group (p>0.05). We also observed high level expressed CXCR4 percentage or MFI on EPCs, CD34+ and CD133+ cells at the beginning of TBI. Moderate TBI patients have higher CXCR4 percentage of EPCs then mild TBI group at 4,7,14,21 day (p<0.05).2) SDF-1α/CXCR4 was highly expressed in contusive brain tissue after TBI. SDF-la was obveresly increased in serum, moderate TBI group was then mild group at 1,4day(p<0.05).3) Through the results of GOS-E, ADLS, HAMA and HAMD, there was correlationship between CXCR4 percentage of EPCs and mild TBI patients prognosis (R2=0.183, P=0.021). Value of AUC on ROC was 0.78, CXCR4 percentage on EPCs at 7 day more than 42.35% indicate bad recovery. RR of mild TBI patients’ bad recovery was 2.455.Conclusion:1) EPCs could be mobilized effectively in mild TBI patients which depressed at first and then rised quickly.2)7 day could be an key point in time of angiogenesis and tissue repairment, when circulating CD34+, CD133+ cells or EPCs began to decrease in peripheral blood.3) CXCR4 percentage on different cells group was a sensitive biomarker to effectively evaluate the prognosis of mild TBI patients which could reflect the severity of brain injury in mild and moderat TBI patients. If CXCR4 percentage on EPCs at 7 day more than 42.35%, it means bad recovery.4) SDF-1α/CXCR4 could be an important way to induce CD34+, CD133+ cells and EPCs to the injury site in the early phase. |
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