Increased production of tumor necrosis factor-α induces apoptosis after traumatic spinal cord injury in rats

Tae Y. Yune, Mi J. Chang, Sun J. Kim, Young B. Lee, Song W. Shin, Hyewhon Rhim, Young C. Kim, Moon L. Shin, Young J. Oh, Ching T. Han, George J. Markelonis, Tae H. Oh

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Abstract

We showed previously that, after spinal cord injury (SCI), tumor necrosis factor-α (TNF-α) may serve as an external signal, initiating apoptosis in neurons and oligodendrocytes. To further characterize the apoptotic cascade initiated by TNF-α A after SCI, we examined the expression of TNF-α, inducible nitric oxide (NO) synthase (iNOS), and the level of NO after SCI. Western blots and reverse transcription polymerase chain reactions showed an early upregulation of TNF-α A after injury. A peak TNF-α expression was observed within 1 h of injury. By 4 h after injury, the expression of iNOS and the level of NO were markedly increased in the injured spinal cord. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL)-positive cells were also first observed in the lesioned area 4 h after SCI. The largest number of TUNEL-positive cells was observed between 24-48 h after SCI. Injecting a neutralizing antibody against TNF-α into the lesion site after injury significantly reduced the expression of iNOS, the level of NO and the number of TUNEL-positive cells in the injured spinal cord. Injecting the NOS inhibitors, NG-monomethyl-L-arginine monoacetate and S-methylisothiourea sulfate, or an NO scavenger, carboxy-PTIO, into the lesion site also significantly reduced the level of NO and the degree of DNA laddering in the injured spinal cord. These data suggest that after SCI, apoptosis induced by TNF-α may be mediated in part by NO via upregulation of iNOS, induced in response to TNF-α.

Original languageEnglish
Pages (from-to)207-219
Number of pages13
JournalJournal of Neurotrauma
Volume20
Issue number2
DOIs
Publication statusPublished - 2003 Feb 1

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

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    Yune, T. Y., Chang, M. J., Kim, S. J., Lee, Y. B., Shin, S. W., Rhim, H., Kim, Y. C., Shin, M. L., Oh, Y. J., Han, C. T., Markelonis, G. J., & Oh, T. H. (2003). Increased production of tumor necrosis factor-α induces apoptosis after traumatic spinal cord injury in rats. Journal of Neurotrauma, 20(2), 207-219. https://doi.org/10.1089/08977150360547116