Yune, TY Chang, MJ Kim, SJ Lee, YB Shin, SW Rhim, HW Kim, YC Shin, ML Oh, YJ Han, CT Markelonis, GJ Oh, TH 2024-01-21T09:32:18Z 2024-01-21T09:32:18Z 2021-09-01 2003-02 0897-7151 https://pubs.kist.re.kr/handle/201004/138885 We showed previously that, after spinal cord injury (SCI), tumor necrosis factor-alpha (TNF-alpha) may serve as an external signal, initiating apoptosis in neurons and oligodendrocytes. To further characterize the apoptotic cascade initiated by TNF-alpha after SCI, we examined the expression of TNF-alpha, 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-a after injury. A peak TNF-alpha expression was observed within 1 h of injury. By 4 h after injury, the expression of MOS 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-alpha into the lesion site after injury significantly reduced the expression of MOS, the level of NO and the number of TUNEL-positive cells in the injured spinal cord. Injecting the NOS inhibitors, N-G-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-alpha may be mediated in part by NO via upregulation of MOS, induced in response to TNF-alpha. English MARY ANN LIEBERT, INC NITRIC-OXIDE SYNTHASE CENTRAL-NERVOUS-SYSTEM CELL-DEATH TNF-ALPHA BRAIN-INJURY FUNCTIONAL RECOVERY NEURONAL APOPTOSIS GLIAL APOPTOSIS GENE-EXPRESSION TRANSGENIC MICE Increased production of tumor necrosis factor-alpha induces apoptosis after traumatic spinal cord injury in rats Article 10.1089/08977150360547116 1 JOURNAL OF NEUROTRAUMA, v.20, no.2, pp.207 - 219 JOURNAL OF NEUROTRAUMA 20 2 207 219 scie scopus 000181406900007 2-s2.0-0037294824 Critical Care Medicine Clinical Neurology Neurosciences General & Internal Medicine Neurosciences & Neurology Article NITRIC-OXIDE SYNTHASE CENTRAL-NERVOUS-SYSTEM CELL-DEATH TNF-ALPHA BRAIN-INJURY FUNCTIONAL RECOVERY NEURONAL APOPTOSIS GLIAL APOPTOSIS GENE-EXPRESSION TRANSGENIC MICE apoptosis iNOS NO NOS inhibitors spinal cord injury TNF-alpha TUNEL