Portal de Periódicos da CAPES

Role of Tumor Necrosis Factor-α in Neuronal and Glial Apoptosis after Spinal Cord Injury

2000; Elsevier BV; Volume: 166; Issue: 1 Linguagem: Inglês

10.1006/exnr.2000.7494

1090-2430

Young B. Lee, Tae Young Yune, Seoung Y. Baik, Young Hee Shin, Shen Du, Hyewhon Rhim, Eunhee B. Lee, Young C. Kim, Moon L. Shin, George J. Markelonis, Tae Hwan Oh,

Cardiac Arrest and Resuscitation

We investigated the role of tumor necrosis factor (TNF)-α in the onset of neuronal and glial apoptosis after traumatic spinal cord crush injury in rats. A few TUNEL-positive cells were first observed within and surrounding the lesion area 4 h after injury, with the largest number observed 24–48 h after injury. Double-labeling of cells using cell type-specific markers revealed that TUNEL-positive cells were either neurons or oligodendrocytes. One hour after injury, an intense immunoreactivity to TNF-α was observed in neurons and glial cells in the lesion area, but also seen in cells several mm from the lesion site rostrally and caudally. The level of nitric oxide (NO) also significantly increased in the spinal cord 4 h after injury. The injection of a neutralizing antibody against TNF-α into the lesion site several min after injury significantly reduced both the level of NO observed 4 h thereafter as well as the number of apoptotic cells observed 24 h after spinal cord trauma. An inhibitor of nitric oxide synthase (NOS), NG-monomethyl-l-arginine acetate (l-NMMA), also reduced the number of apoptotic cells. This reduction of apoptotic cells was associated with a decrease in DNA laddering on agarose gel electrophoresis. These results suggest that: (i) TNF-α may function as an external signal initiating apoptosis in neurons and oligodendrocytes after spinal cord injury; and (ii) TNF-α-initiated apoptosis may be mediated in part by NO as produced by a NOS expressed in response to TNF-α.