Li Y, Mao W W, Zhang C G, Wan L, Jing C H, Hua X M, Li S T, Cheng J
Department of Neurosurgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China.
Laboratory of Microbiology and Biochemical Pharmaceutics, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Behav Brain Res. 2016 Mar 15;301:287-92. doi: 10.1016/j.bbr.2015.07.048. Epub 2015 Jul 26.
Our previous findings showed bone marrow mononuclear cells (BMMNCs) from 5- fluorouracil (5-FU) pre-treated rats (named BMRMNCs) had a better therapeutic efficacy in ischemia/reperfusion rats as compared to BMMNCs from untreated rats. This study was undertaken to explore the potential mechanisms underlying the neuroprotective effects of BMRMNCs in middle cerebral artery occlusion (MCAO) rat model. Rats were intravenously pre-treated with 5-FU and BMRMNCs were collected at different time points. The contents of growth factors in the supernatant and CXCR4 expression were detected by ELISA and flow cytometry, respectively. MCAO was introduced to rats, and BMMNCs and BMRMNCs collected at 7 days after 5-FU pre-treatment were independently transplanted via the tail vein 24h later. The neurological function was evaluated before cell transplantation and at 24h, 7d and 14d after cell transplantation. Rats were sacrificed at 14d after cell transplantation, the brains were collected for TTC staining, infarct volume detection, NISSL staining, counting of viable cells in the CA1 region, and observation of transplanted cells. BMRMNCs had elevated expressions of growth factors as well as CXCR4 expression. Our results confirmed the better therapeutic effects of BMRMNCs in MCAO rats, demonstrated by reduction in infarct volume, improvement of neurological function and more viable cells in the hippocampus. In addition, more transplanted cells were found after BMRMNCs transplantation at 7 days and 14 days although there was no marked difference at 14 days. These findings indicate that BMRMNCs transplantation may protect ischemic stroke, at least partially, via increasing the secretion of growth factors and migration to the injured site.
我们之前的研究结果表明，与未处理大鼠的骨髓单个核细胞（BMMNCs）相比，来自5-氟尿嘧啶（5-FU）预处理大鼠的骨髓单个核细胞（命名为BMRMNCs）对缺血/再灌注大鼠具有更好的治疗效果。本研究旨在探讨BMRMNCs在大脑中动脉闭塞（MCAO）大鼠模型中神经保护作用的潜在机制。大鼠经静脉注射5-FU进行预处理，并在不同时间点收集BMRMNCs。分别采用酶联免疫吸附测定（ELISA）和流式细胞术检测上清液中生长因子的含量和CXCR4的表达。对大鼠进行MCAO手术，并在5-FU预处理7天后收集的BMMNCs和BMRMNCs于24小时后分别经尾静脉移植。在细胞移植前以及细胞移植后24小时、7天和14天评估神经功能。细胞移植14天后处死大鼠，取脑进行TTC染色、梗死体积检测、尼氏染色、CA1区活细胞计数以及移植细胞观察。BMRMNCs的生长因子表达以及CXCR4表达均升高。我们的结果证实了BMRMNCs对MCAO大鼠具有更好的治疗效果，表现为梗死体积减小、神经功能改善以及海马区有更多的活细胞。此外，尽管在14天时差异不显著，但在7天和14天时BMRMNCs移植后发现更多的移植细胞。这些发现表明，BMRMNCs移植可能至少部分地通过增加生长因子的分泌并迁移至损伤部位来保护缺血性中风。
