Li Mingfeng, Liu Xinlong, Yue Haiyan, Xiong Weiming, Gu Jianfeng, Xu Mao
455 Hospital of PLA, Shanghai, China.
Cell Physiol Biochem. 2013;32(6):1776-89. doi: 10.1159/000356611. Epub 2013 Dec 13.
BACKGROUND/AIMS: Neural stem cells (NSCs) hold considerable potential as a therapeutic tool for repair of the damaged nervous system. In the current study, we examined whether transplanted N-acetyl aspartyl-glutamate synthetase (NAAGS)-activated NSCs (NAAGS/NSCs) further improve neurological recovery following traumatic brain injury (TBI) in Sprague-Dawley rats.
Animals received TBI and stereotactic injection of NSCs, NAAGS/NSCs or phosphate buffered saline without cells (control) into the injured cortex. NAAGS protein expression was detected through western blot analysis. Dialysate NAAG levels were analyzed with radioimmunoassay. Cell apoptosis was detected via TUNEL staining. The expression levels of specific pro-inflammatory cytokines were detected with enzyme-linked immunosorbent assay.
Groups with transplanted NSCs and NAAGS/NSCs displayed significant recovery of the motor behavior, compared to the control group. At 14 and 21 days post-transplantation, the motor behavior in NAAGS/NSC group was significantly improved than that in NSC group (p<0.05). Additionally, transplanted NAAGS/NSCs inhibited cell apoptosis and the expression levels of specific pro-inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α.
Our results collectively demonstrate that NAAGS/NSCs provide a more powerful autoplastic therapy for the injured nervous system.
背景/目的:神经干细胞(NSCs)作为修复受损神经系统的治疗工具具有巨大潜力。在本研究中,我们检测了移植的N-乙酰天门冬氨酰谷氨酸合成酶(NAAGS)激活的神经干细胞(NAAGS/NSCs)是否能进一步改善Sprague-Dawley大鼠创伤性脑损伤(TBI)后的神经功能恢复。
动物接受TBI,并将神经干细胞、NAAGS/NSCs或无细胞的磷酸盐缓冲盐水(对照)立体定向注射到损伤的皮质中。通过蛋白质印迹分析检测NAAGS蛋白表达。用放射免疫分析法分析透析液中NAAG水平。通过TUNEL染色检测细胞凋亡。用酶联免疫吸附测定法检测特定促炎细胞因子的表达水平。
与对照组相比,移植神经干细胞和NAAGS/NSCs的组运动行为有显著恢复。在移植后14天和21天,NAAGS/NSC组的运动行为比神经干细胞组显著改善(p<0.05)。此外,移植的NAAGS/NSCs抑制细胞凋亡以及特定促炎细胞因子的表达水平,包括白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α。
我们的结果共同表明,NAAGS/NSCs为受损神经系统提供了一种更有效的自身修复疗法。