Early neuronal expression of tumor necrosis factor-α after experimental brain injury contributes to neurological impairment
Early neuronal expression of tumor necrosis factor-α after experimental brain injury contributes to neurological impairment
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DOI：
10.1016/s0165-5728(98)00273-2
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发表时间：
1999-03-01
影响因子：
3.3
通讯作者：
Faden, AI
中科院分区：
文献类型：
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作者：
Knoblach, SM;Fan, L;Faden, AI
肿瘤坏死因子-α (TNF α) 是一种多效细胞因子，参与与中枢神经系统损伤相关的炎症级联反应。为了研究 TNF α 在创伤性脑损伤 (TBI) 急性病理生理学中的作用，我们研究了其在临床相关的非穿透性头部创伤大鼠模型中的表达、定位和调节。严重侧向液体冲击创伤（2.6-2.7 atm）后第 1 小时和第 4 小时，受损皮质中的 TNF α 水平显着增加，但在 12、14 或 72 小时则没有增加。轻度损伤后 TNF α 未升高。严重 TBI 后 1 小时和 4 小时，免疫细胞化学显示 TNF α 显着增加，位于受损大脑皮层的神经元中。一小群星形胶质细胞、心室细胞和微血管也显示出阳性 TNF α 染色，但这种表达不依赖于损伤。 TBI后4小时，沿外囊、胼胝体和海马出血区存在的巨噬细胞不表达TNFα。在TBI前15分钟和TBI后1小时脑室内注射选择性TNFα拮抗剂-可溶性TNFα受体融合蛋白（sTNFR：Fc）（37.5μg），可改善损伤后一系列标准化运动任务的表现。相比之下：创伤后 15 分钟静脉注射 sTNFR:Fc（0.2、1 或 5 mg/kg）并不能改善运动结果。总的来说，这一证据表明 TBI 后早期神经元 TNF α 表达的增强会导致随后的神经功能障碍。 (C) 1999 Elsevier Science B.V. 保留所有权利。
Tumor necrosis factor-alpha (TNF alpha) is a pleiotropic cytokine involved in inflammatory cascades associated with CNS injury. To examine the role of TNF alpha in the acute pathophysiology of traumatic brain injury (TBI), we studied its expression, localization and modulation in a clinically relevant rat model of non-penetrating head trauma. TNF alpha levels increased significantly in the injured cortex at I and 4, but not at 12, 14 or 72 h after severe lateral fluid-percussion trauma (2.6-2.7 atm). TNF alpha was not elevated after mild injury. At I and 4 h after severe TBI, marked increases of TNF alpha were localized immunocytochemically to neurons of the injured cerebral cortex. A small population of astrocytes, ventricular cells and microvessels, also showed positive TNF alpha staining, but this expression was not injury-dependent. Macrophages that were present in a hemorrhagic zone along the external capsule, corpus callosum and alveus hippocampus at 4 h after TBI did not express TNF alpha. Intracerebroventricular administration of a selective TNF alpha antagonist-soluble TNF alpha receptor fusion protein (sTNFR:Fc) (37.5 mu g)-at 15 min before and 1 h after TBI, improved performance in a series of standardized motor tasks after injury. In contrast: intravenous administration of sTNFR:Fc (0.2, 1 or 5 mg/kg) at 15 min after trauma did not improve motor outcome. Collectively, this evidence suggests that enhanced early neuronal expression of TNF alpha after TBI contributes to subsequent neurological dysfunction. (C) 1999 Elsevier Science B.V. All rights reserved.