Lee, YB Yune, TY Baik, SY Shin, YH Du, S Rhim, H Lee, EB Kim, YC Shin, ML Markelonis, GJ Oh, TH 2024-01-21T13:14:09Z 2024-01-21T13:14:09Z 2021-09-04 2000-11 0014-4886 https://pubs.kist.re.kr/handle/201004/140997 We investigated the role of tumor necrosis factor (TNF)-alpha 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-alpha 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-alpha 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), N-G-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-alpha may function as an external signal initiating apoptosis in neurons and oligodendrocytes after spinal cord injury; and (ii) TNF-alpha -initiated apoptosis may be mediated in part by NO as produced by a NOS expressed in response to TNF-alpha. (C) 2000 Academic Press. English ACADEMIC PRESS INC OLIGODENDROCYTE APOPTOSIS MULTIPLE-SCLEROSIS ACTIVATION EXPRESSION RATS DEMYELINATION GLIOSIS Role of tumor necrosis factor-alpha in neuronal and glial apoptosis after spinal cord injury Article 10.1006/exnr.2000.7494 1 EXPERIMENTAL NEUROLOGY, v.166, no.1, pp.190 - 195 EXPERIMENTAL NEUROLOGY 166 1 190 195 scie scopus 000165119800017 2-s2.0-0033767832 Neurosciences Neurosciences & Neurology Article OLIGODENDROCYTE APOPTOSIS MULTIPLE-SCLEROSIS ACTIVATION EXPRESSION RATS DEMYELINATION GLIOSIS TNF-alpha neutralizing antibody TUNEL NO NOS L-NMMA DNA laddering