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 excitotoxic 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.

Original languageEnglish
Pages (from-to)1390-1400
Number of pages11
JournalGLIA
Volume56
Issue number13
DOIs
Publication statusPublished - Oct 2008

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Chondroitin Sulfate Proteoglycans
Glial Fibrillary Acidic Protein
Methylprednisolone
Astrocytes
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Neurocan
Glucocorticoid Receptors
Spinal Cord Injuries
Class 5 Receptor-Like Protein Tyrosine Phosphatases
Down-Regulation
Isoxazoles
Gliosis
Propionates
Spinal Ganglia
Conditioned Culture Medium
Neuroglia
Small Interfering RNA
Glucocorticoids
Regeneration
Anti-Inflammatory Agents

Keywords

  • Central nervous system
  • Chondroitin sulfate proteoglycans
  • Gliosis
  • Glucocorticoid
  • Spinal cord injury

ASJC Scopus subject areas

  • Immunology

Cite this

Methylprednisolone inhibits the expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycans in reactivated astrocytes. / Liu, Wei Lin; Lee, Yi-Hsuan; Tsai, Shih-Ying; Hsu, Chung-Yi; Sun, Yu Yo; Yang, Liang Yo; Tsai, Shing Han; Yang, Wei Chung Vivian.

In: GLIA, Vol. 56, No. 13, 10.2008, p. 1390-1400.

Research output: Contribution to journalArticle

Liu, Wei Lin ; Lee, Yi-Hsuan ; Tsai, Shih-Ying ; Hsu, Chung-Yi ; Sun, Yu Yo ; Yang, Liang Yo ; Tsai, Shing Han ; Yang, Wei Chung Vivian. / Methylprednisolone inhibits the expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycans in reactivated astrocytes. In: GLIA. 2008 ; Vol. 56, No. 13. pp. 1390-1400.
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