Preventive effects of intrathecal methylprednisolone administration on spinal cord ischemia in rats: The role of excitatory amino acid metabolizing systems

G. J. Wu, W. F. Chen, C. S. Sung, Y. H. Jean, C. M. Shih, C. Y. Shyu, Z. H. Wen

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Spinal cord ischemic injury usually results in paraplegia, which is a major cause of morbidity after thoracic aorta operations. Ample evidence indicates that massive release of excitatory amino acids (EAAs; glutamate) plays an important role in the development of neuronal ischemic injuries. However, there is a lack of direct evidence to indicate the involvement of EAAs in the glutamate metabolizing system (including the glutamate transporter isoforms, i.e. the Glu-Asp transporter (GLAST), Glu transporter-1 (GLT-1), and excitatory amino acid carrier one (EAAC1); glutamine synthetase (GS); and glutamate dehydrogenase (GDH)) in spinal cord ischemia. In the present results, we found that methylprednisolone (MP; intrathecal (i.t.) injection, 200 μg twice daily administered for 3 days before ischemia), a synthetic glucocorticoid, is the therapeutic agent for the treatment of spinal injuries in humans, can significantly reduce the ischemia-induced motor function defect and down-regulate the glutamate metabolizing system (including GLAST, GLT-1, GS, and GDH) in male Wistar rats. The spinal cord ischemia-induced down-regulation of EAAC1 protein expression in the ventral portion of the lumbar spinal cord was partly inhibited by pretreatment with i.t. MP. However, MP did not affect the down-regulation of EAAC1 in the dorsal portion of the lumbar spinal cord after spinal cord ischemia. The i.t. injection of MP alone did not change the neurological functions and the expression of proteins of the glutamate metabolizing system in the spinal cord. Our results indicate that spinal cord ischemia-induced neurological deficits accompany the decrease in the expression of proteins of the glutamate metabolizing system in the lumbar portion of the spinal cord. The i.t. MP pretreatment significantly prevented these symptoms. These results support the observation that MP delivery through an i.t. injection, is beneficial for the treatment of spinal cord ischemic injuries.

Original languageEnglish
Pages (from-to)294-303
Number of pages10
JournalNeuroscience
Volume147
Issue number2
DOIs
Publication statusPublished - Jun 29 2007

Fingerprint

Spinal Cord Ischemia
Excitatory Amino Acids
Methylprednisolone
Spinal Cord
Glutamic Acid
Spinal Injections
Glutamate Dehydrogenase
Glutamate-Ammonia Ligase
Down-Regulation
Spinal Cord Injuries
Excitatory Amino Acid Transporter 1
Ischemia
Amino Acid Transport System X-AG
Spinal Injuries
Proteins
Paraplegia
Thoracic Aorta
Glucocorticoids
Wistar Rats
Protein Isoforms

Keywords

  • glutamate metabolizing systems
  • intrathecal
  • methylprednisolone
  • spinal cord ischemia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Preventive effects of intrathecal methylprednisolone administration on spinal cord ischemia in rats : The role of excitatory amino acid metabolizing systems. / Wu, G. J.; Chen, W. F.; Sung, C. S.; Jean, Y. H.; Shih, C. M.; Shyu, C. Y.; Wen, Z. H.

In: Neuroscience, Vol. 147, No. 2, 29.06.2007, p. 294-303.

Research output: Contribution to journalArticle

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