J Korean Soc Spine Surg.  2004 Mar;11(1):14-23. 10.4184/jkss.2004.11.1.14.

The Expression and Function of the Tumor Necrosis Factor Receptor I (TNFRI), TNFRII, and X-Linked Inhibitor of Apoptosis Genes after Spinal Cord Injury in Rats

• Yang JY
• Lee JK
• Kim KT
• Lee HH
• Byun BN
• Ahn SH

• KMID: 2003187
• DOI: http://doi.org/10.4184/jkss.2004.11.1.14

Abstract

STUDY DESIGN AND OBJECTIVE: Tumor necrosis factor-alpha(TNF-alpha), a key inflammatory mediator, has been demonstrated in spinal cord injury (SCI). However, the expression of TNF receptors following SCI remains to be identified. To elucidate the expressions of TNF receptor I (TNFRI), TNFRII, XIAP, and their function in SCI, in situ hybridization and RT-PCR were performed in a SCI model. MATERIAL AND METHODS: Sprague-Dawley rats were anesthetized with halothane and laminectomized at the level of the eleventh and twelfth thoracic vertebra. Using a modified New York University Impactor, SCI was induced by dropping a 10 gm weight from a height of 20 mm. The rod of the impactor had a constant circular surface, 3 mm in diameter. After induction of the injury, rats were placed in a temperature and humidity-controlled chamber overnight.
RESULTS
The TNFRI gene was not detected in the control rats, but the TNFRII gene was expressed in the neurons in the control rats. The TNFRI gene expression was maximally increased in the spinal cord 1 day after the SCI; however, that of the TNFRII gene occurred 3 days after the SCI. In the white matter, both the TNFRI and TNFRII genes were increased in the oligodendrocytes 3 days after the SCI. The XIAP gene was increased in neurons of the gray matter 1 and 3 days after the SCI, but was not detected in the white matter after the SCI.
CONCLUSION
Up-regulation of the expression of TNFRII occurs later than that of TNFRI in the spinal cord after a SCI. TNFR may be related to neuronal survival considering its similar expression pattern to that of XIAP. The results from these studies may lead to alternative therapeutic targets of TNF receptors in spinal cord injury, providing the basis for developing agonist and antagonist systems for TNF receptor subtypes and also for encouraging better strategies for the treatment of spinal cord disorders related to trauma.

Keyword

Spinal cord injury; TNFRI; TNFRII; XIAP

MeSH Terms

Animals
Apoptosis*
Gene Expression
Halothane
In Situ Hybridization
Necrosis
Neurons
Oligodendroglia
Rats*
Rats, Sprague-Dawley
Receptors, Tumor Necrosis Factor*
Spinal Cord Diseases
Spinal Cord Injuries*
Spinal Cord*
Spine
Tumor Necrosis Factor-alpha*
Up-Regulation
Halothane
Receptors, Tumor Necrosis Factor
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1. TNFRI gene expression in the spinal cord after SCI, cross sectional view (GM, gray matter; WM, white matter). (A) normal control, × 25. TNFRI gene expression is not detected in the spinal cord. (B) spinal cord 1 day after SCI, × 25. TNFRI gene is expressed in neurons in the gray matter around the contused spinal cord. (C) spinal cord 3 days after SCI, × 25. TNFRI gene is expressed in neurons in the gray matter around the contused spinal cord. (D) spinal cord 7 days after SCI, × 25. A few neurons in the gray matter express TNFRI gene around the contused spinal cord.

• 

  Fig. 2. TNFRII gene expression in the spinal cord after SCI, cross sectional view (GM, gray matter; WM, white matter). (A) normal control, × 25. TNFRII gene expression was detected in many neurons in the gray matter. (B) spinal cord 1 day after SCI, ×25. TNFRII gene expression increases slightly in neurons in the gray matter around the contused spinal cord. (C) spinal cord 3 days after SCI, × 25. TNFRII gene expression increases prominently in the neurons in the gray matter and oligodendrocytes in the white matter around the contused spinal cord. (D) spinal cord 7 days after SCI, × 25. TNFRII gene expression decreas-es to similar level with control group around the contused spinal cord.

• 

  Fig. 3. XIAP gene expression in the spinal cord after SCI, cross sectional view (GM, gray matter; WM, white matter). (A) normal control, × 25. XIAP gene expression is not detected distinctively in the spinal cord. (B) spinal cord 1 day after SCI, × 25. XIAP gene is expressed in neurons in the gray matter around the contused spinal cord. (C) spinal cord 3 days after SCI, × 25. Neurons in gray matter express XIAP gene around the contused spinal cord. (D) spinal cord 7 days after SCI, × 25. XIAP gene expression is not detected distinctively in the spinal cord.

• 

  Fig. 4. TNFRI, TNFRII, and XIAP genes expression in SCI

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