Activation of complement pathways after contusion-induced spinal cord injury
Activation of complement pathways after contusion-induced spinal cord injury
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DOI：
10.1089/neu.2004.21.1831
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发表时间：
2004-12-01
影响因子：
4.2
通讯作者：
Cotman, CW
中科院分区：
文献类型：
--
作者：
Anderson, AJ;Robert, S;Cotman, CW
先前的研究表明，实验性脊髓损伤（SCI）后，细胞炎症反应启动，并合成炎性细胞因子。在本研究中，我们测试的假设，补体级联反应，先天性和适应性免疫反应的主要组成部分，也被激活后，实验性SCI。我们使用纽约大学（NYU）的重物下落撞击器研究了急性挫伤诱导的SCI后大鼠脊髓中补体激活的途径、细胞定位、时程和程度。在损伤后1、7和42天的时间点评价轻度和重度损伤（12.5和50 mm跌落高度）。经典（C1 q和C4），替代（因子B）和终端（C5 B-9）补体途径在SCI后1天内被强烈激活。补体蛋白免疫反应性主要见于易变性的细胞类型、神经元和少突胶质细胞，而在炎性细胞或星形胶质细胞中通常未观察到。令人惊讶的是，补体蛋白的免疫反应性在损伤后6周也是明显的，并且观察到补体激活远至损伤部位的嘴侧20 mm。还观察到C1 q和因子B的轴突染色，表明补体级联在脱髓鞘或轴突变性中的潜在作用。这些数据支持补体激活在SCI中起作用的假设。
Previous studies have shown that a cellular inflammatory response is initiated, and inflammatory cytokines are synthesized, following experimental spinal cord injury (SCI). In the present study, we tested the hypothesis that the complement cascade, a major component of both the innate and adaptive immune response, is also activated following experimental SCI. We investigated the pathways, cellular localization, timecourse, and degree of complement activation in rat spinal cord following acute contusion-induced SCI using the New York University (NYU) weight drop impactor. Mild and severe injuries (12.5 and 50 mm drop heights) at 1, 7, and 42 days post injury time points were evaluated. Classical (C1q and C4), alternative (Factor B) and terminal (C5b-9) complement pathways were strongly activated within 1 day of SCI. Complement protein immunoreactivity was predominantly found in cell types vulnerable to degeneration, neurons and oligodendrocytes, and was not generally observed in inflammatory or astroglial cells. Surprisingly, immunoreactivity for complement proteins was also evident 6 weeks after injury, and complement activation was observed as far as 20 mm rostral to the site of injury. Axonal staining by C1q and Factor B was also observed, suggesting a potential role for the complement cascade in demyelination or axonal degeneration. These data support the hypothesis that complement activation plays a role in SCI.