Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, People's Republic of China.
Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, 200032, People's Republic of China.
Cell Mol Neurobiol. 2018 Mar;38(2):467-477. doi: 10.1007/s10571-017-0490-4. Epub 2017 May 8.
Our study aims to investigate the effects of the SDF-1/CXCR4 axis on the repair of traumatic brain injury (TBI) in rats by mediating bone marrow derived from mesenchymal stem cells (BMSCs). Healthy male SD rats were collected, their tibiofibulars were removed, cultured, and BMSCs were collected. The expression of cell-surface molecular proteins was examined using flow cytometry. The mRNA and protein expression of CXCR4 in cells were tested using qRT-PCR and western blotting analysis. An electronic brain injury instrument was utilized to build TBI rat models and each rat was assigned into the experiment, positive control and control groups (10 rats in each group). The morris water maze was used to calculate the escape latency and number of times rats in each group crossed the platform. Neurological severity scores (NSS) was calculated to evaluate the recovery of neurological functioning. The distribution of neuronal nuclear antigens was detected using double-labeling immunohistochemistry. The morphological changes in the hippocampal neuronal and the number of BrdU-positive cells were observed through Nissl's staining and high magnification. The mRNA and protein expressions of CXCR4 were gradually increased as SDF-1 concentration increased. NGF and BDNF positive cells were expressed in each group. The distribution of neuronal nuclear antigens in the experiment group was elevated compared to the control and positive control groups. Among the three groups, the experimental group had the shortest escape latency and the highest number platform crossings. The difference in NSS among the three groups was significant. The experimental group had better cell morphology and a higher number of BrdU-positive cells than the other groups. The present study demonstrates that transplanting BMSCs with SDF-1-induced CXCR4 expression can promote the repair of TBI. This is expected to become a new treatment regimen for TBI.
我们的研究旨在探讨 SDF-1/CXCR4 轴通过介导骨髓间充质干细胞（BMSCs）对创伤性脑损伤（TBI）大鼠的修复作用。收集健康雄性 SD 大鼠，切除其胫腓骨，培养并收集 BMSCs。采用流式细胞术检测细胞表面分子蛋白的表达。采用 qRT-PCR 和 Western blot 分析检测细胞中 CXCR4 的 mRNA 和蛋白表达。使用电子脑损伤仪器构建 TBI 大鼠模型，将每只大鼠分配到实验组、阳性对照组和对照组（每组 10 只）。采用 Morris 水迷宫计算各组大鼠的逃避潜伏期和穿越平台次数。计算神经功能严重程度评分（NSS）评估神经功能恢复情况。采用双标免疫组化检测神经元核抗原的分布。通过尼氏染色和高倍镜观察海马神经元的形态变化和 BrdU 阳性细胞的数量。随着 SDF-1 浓度的增加，CXCR4 的 mRNA 和蛋白表达逐渐增加。各组均有 NGF 和 BDNF 阳性细胞表达。实验组神经元核抗原的分布高于对照组和阳性对照组。三组中，实验组的逃避潜伏期最短，穿越平台次数最多。三组间 NSS 的差异有统计学意义。实验组的细胞形态较好，BrdU 阳性细胞数量较多。本研究表明，移植 SDF-1 诱导表达 CXCR4 的 BMSCs 可促进 TBI 的修复，有望成为 TBI 的一种新的治疗方案。
