Deficiency in complement C1q improves histological and functional locomotor outcome after spinal cord injury.
Deficiency in complement C1q improves histological and functional locomotor outcome after spinal cord injury.
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DOI：
10.1523/jneurosci.2823-08.2008
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发表时间：
2008-12-17
期刊：
影响因子：
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通讯作者：
Anderson AJ
中科院分区：
文献类型：
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作者：
Galvan MD;Luchetti S;Burgos AM;Nguyen HX;Hooshmand MJ;Hamers FP;Anderson AJ
虽然研究表明补体系统在脊髓损伤（SCI）的病理生理学中的作用，但该作用仍然不明确。此外，单个补体途径在SCI中的相对作用尚不清楚。我们的初步研究表明，系统性补体激活受遗传背景和性别的强烈影响。因此，为了研究经典补体途径在挫伤诱导的SCI中的作用，在补体充足背景（BUB）上的雄性C1 q敲除（KO）和野生型（WT）小鼠用无限地平线（IH）撞击器接受轻度-中度T9挫伤。与BUB WT小鼠相比，BUB C1 q KO小鼠表现出更大的运动恢复（p < 0.05）。在BUB C1 q KO小鼠中观察到的恢复改善也与使用von Frey细丝测试从轻度刺激中退缩的阈值降低相关。令人惊讶的是，通过FACS分析对小胶质细胞/巨噬细胞（F4/80）的定量显示，与损伤后3天的BUB WT小鼠相比，BUB C1 q KO小鼠在脊髓中表现出显著更大百分比的巨噬细胞（p < 0.05）。然而，这种增加的巨噬细胞反应似乎是短暂的，因为损伤后28天获得的脊髓组织的体视学评估显示组间F4/80阳性细胞无差异。脊髓组织的体视学评估显示，与BUB WT小鼠相比，BUB C1 q KO小鼠具有减少的病变体积和增加的组织保留（p < 0.05）。总之，这些数据表明，经典补体途径通过C1 q的启动是有害的SCI后恢复。
Although studies have suggested a role for the complement system in the pathophysiology of spinal cord injury (SCI), that role remains poorly defined. Additionally, the relative contribution of individual complement pathways in SCI is unknown. Our initial studies revealed that systemic complement activation was strongly influenced by genetic background and gender. Thus, to investigate the role of the classical complement pathway in contusion-induced SCI, male C1q knockout (KO) and wildtype (WT) mice on a complement sufficient background (BUB) received a mild-moderate T9 contusion injury with the Infinite Horizon (IH) impactor. BUB C1q KO mice exhibited greater locomotor recovery in comparison to BUB WT mice (p < 0.05). Improved recovery observed in BUB C1q KO mice was also associated with decreased threshold for withdrawal from a mild stimulus using von Frey filament testing. Surprisingly, quantification of microglia/macrophages (F4/80) by FACS analysis showed that BUB C1q KO mice exhibited a significantly greater percentage of macrophages in the spinal cord compared to BUB WT mice 3 days post injury (p < 0.05). However, this increased macrophage response appeared to be transient as stereological assessment of spinal cord tissue obtained 28 days post injury revealed no difference in F4/80 positive cells between groups. Stereological assessment of spinal cord tissue showed that BUB C1q KO mice had reduced lesion volume and an increase in tissue sparing in comparison to BUB WT mice (p < 0.05). Taken together, these data suggest that initiation of the classical complement pathway via C1q is detrimental to recovery after SCI.