Methylprednisolone Inhibits the Expression of Glial Fibrillary Acidic Protein and Chondroitin Sulfate Proteoglycans in Reactivated Astrocytes |
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| Authors: | WEI-LIN LIU YI-HSUAN LEE SHIH-YING TSAI CHUNG YI HSU YU-YO SUN LIANG-YO YANG SHING-HAN TSAI AND WEI-CHUNG VIVIAN YANG |
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| Affiliation: | [1]Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University, Taipei, Taiwan [2]Graduate Institute of Neuroscience, College of Medicine, Taipei Medical Uni- versity, Taipei, Taiwan [3]Division of Physiology and Neuroscience, Graduate Institute of Medi- cal Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan [4]Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Tai- wan [5]Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei, Taiwan [6]Department of Neurosurgery, Taipei Municipal WanFang Hospital, Taipei, Taiwan |
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| Abstract: | Reactive gliosis caused by post-traumatic injury often results in marked expression of chondroitin sulfate proteoglycan(CSPG),which inhibits neurite outgrowth and regeneration.Methylprednisolone(MP),a synthetic 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 α-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 treatment.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 glucocorticoid receptor(GR) antagonist RU486 and GR siRNA reversed the inhibitory effects of MP on GFAP and neurocan expression.Taken together,these results 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 |
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| Keywords: | central nervous system chondroitin sulfate proteoglycans gliosis glucocorticoid spinal cord injury |
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