Methylprednisolone Inhibits the Expression of Glial Fibrillary Acidic Protein and Chondroi

Methylprednisolone Inhibits the Expression of Glial Fibrillary Acidic Protein and Chondroitin Sulfate

Proteoglycans in Reactivated Astrocytes

WEI-LIN LIU;YI-HSUAN LEE;SHIH-YING TSAI;CHUNG YI HSU;YU-YO SUN;LIANG-YO YANG;SHING-HAN TSAI;WEI-CHUNG VIVIAN YANG

【期刊名称】《神经损伤与功能重建》 【年(卷),期】2008(003)005

【摘要】创伤后的神经胶质增生导致硫酸软骨素蛋白聚糖(CSPG)的显著表达,从而抑制轴突生长和再生.甲基强地松龙(MP),一种合成的糖皮质激素,在急性脊髓损伤(SCI)的治疗中有神经保护作用和抗炎效应.但是,MP对于CSPG在活性胶质细胞中的表达的作用尚不清楚.本文用a-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯(AM-PA)诱导星形胶质细胞再活化,用环噻嗪模拟SCI的兴奋性中毒刺激.AMPA治疗后,星形胶质细胞再活化的标志物-胶质纤维酸性蛋白(GFAP)、CSPG神经聚糖和磷酸盐的表达都显著上调.AMPA治疗星形胶质细胞的条件培养液强烈抑制大鼠背根神经节中神经元的轴突生长,但这种作用能被MP的预处理所逆转.此外,MP下调成年SCI大鼠中GFAP和CSPG的表达,对抗RU486的糖皮质激素受体(GR)和GR siRNA能逆转MP对GFAP和神经聚糖表达的抑制作用.这些结果提示,MP能在兴奋性中毒损伤后通过GR介导的星形胶质细胞再活化下调和GSPG表达抑制来改善神经修复,促进轴突生长.%Reactive gliosis caused by post-traumatic injury often results in marked expression of chondroitin sul-fate proteoglycan(CSPG), which inhibits neurite outgrowth and regeneration. Methylprednisolone (MP), a synthet-ic

glucocorticoid, has been shown to have neuroprotective and anti-inflammatory effects for the treatment of acute spinal cord injury (SCI). However, the effect of MP on CSPG expression in reactive glial cells remains unclear. In our study, we induced astrocyte reactivation using a-amino-3-hydroxy-5-methyl-4-isoxazole

propionate

(AMPA)

and

cyclothiazide to mimic the exciotoxic stimuli of SCI. The expression of glial fibrillary acidic protein (GFAP), a marker of astrocyte reactivation, and CSPG neurocan and phosphacan were significantly elevated by AMPA treat-ment. The conditioned media from AMPA-treated astrocytes strongly inhibited neurite outgrowth of rat dorsal root ganglion neurons, and this effect was reversed by pretreatment with MP. Furthermore, MP downregulated GFAP and CSPG expression in adult rats with SCI. Additionally, both the glueoeorticoid receptor (GR) antagonist RU486 and GR siRNA reversed the inhibitory effects of MP on GFAP and neurocan expression. Taken together, these re-sults suggest that MP may improve neuronal repair and promote neurite outgrowth after excitotoxic insult via GR-mediated downregulation of astrocyte reactivation and inhibition of CSPG expression. V 2008 Wiley-Liss, Inc

【总页数】11页(342-351,356)

【关键词】中枢神经系统;硫酸软骨素蛋白聚糖;神经胶质增生;糖皮质激素;脊髓损伤

【作者】WEI-LIN LIU;YI-HSUAN LEE;SHIH-YING TSAI;CHUNG YI HSU;YU-YO SUN;LIANG-YO YANG;SHING-HAN TSAI;WEI-CHUNG VIVIAN YANG 【作者单位】Graduate Institute of Biomedical Materials and Engineering, Taipei

Medical

University,Taipei,

Taiwan;Graduate

Institute

of

Neuroscience, College of Medicine, Taipei Medical University, Taipei, Taiwan;Graduate Institute of Neuroscience, College of Medicine, Taipei Medical Uni-versity, Taipei, Taiwan;Division of Physiology and Neuroscience, Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan;Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;Division of Physiology and Neuroscience, Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan;Graduate Institute of Neuroscience, College of Medicine, Taipei Medical University, Taipei, Taiwan;Division of Physiology and Neuroscience, Graduate Institute of Medi-cal Sciences, College

of

Medicine,

Taipei

Medical

University,

Taipei,

Taiwan;Department ofrn Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;Graduate Institute of Neuroscience, College of Medicine, Taipei Medical Uni-versity, Taipei, Taiwan;Division of Physiology and Neuroscience, Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan;Department of Physiology, School of Medicine, College of

Medicine, Taipei Medical University, Taipei, Taiwan;Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei, Taiwan;Department of Neurosurgery, Taipei Municipal WanFang Hospital, Taipei, Taiwan;Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University, Taipei, Taiwan 【正文语种】中文

【中图分类】R741;R741.02 【文献来源】

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