Role of tumor necrosis factor-α in neuronal and glial apoptosis after spinal cord injury
Role of tumor necrosis factor-α in neuronal and glial apoptosis after spinal cord injury
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DOI：
10.1006/exnr.2000.7494
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发表时间：
2000-11-01
影响因子：
5.3
通讯作者：
Oh, TH
中科院分区：
文献类型：
--
作者：
Lee, YB;Yune, TY;Oh, TH
我们研究了肿瘤坏死因子-α在大鼠创伤性脊髓挤压伤后神经细胞和神经胶质细胞凋亡发生中的作用。损伤后4h损伤区内及周围可见少量TUNEL阳性细胞，以伤后24~48h最多。用细胞类型特异性标记物对细胞进行双重标记，结果显示TUNEL阳性细胞可能是神经元，也可能是少突胶质细胞。损伤后1h，损伤区神经元和神经胶质细胞内可见较强的肿瘤坏死因子-α免疫反应，但在距损伤区吻侧和尾侧数mm处的细胞中也可见强烈的肿瘤坏死因子-α免疫反应。脊髓损伤后4h，脊髓组织中一氧化氮(NO)水平明显升高。损伤后几分钟向损伤部位注射抗肿瘤坏死因子-α的中和抗体可显著降低损伤后4小时的NO水平和24小时后观察到的细胞凋亡数。一氧化氮合酶抑制剂N-G-单甲基-L-精氨酸乙酸酯(L-精氨酸乙酯)也能减少凋亡细胞的数量。这种凋亡细胞的减少与琼脂糖凝胶电泳法上DNA梯状条带的减少有关。这些结果提示：(1)在脊髓损伤后，肿瘤坏死因子-α可能是启动神经元和少突胶质细胞凋亡的外部信号；(2)肿瘤坏死因子-α启动的细胞凋亡可能部分是由响应肿瘤坏死因子-α而表达的一氧化氮合酶产生的一氧化氮所介导的。(C)2000年学术出版社。
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.