Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, USA.
Institute for Memory Impairments and Neurological Disorders (iMIND), University of California, Irvine, Irvine, CA, USA.
Sci Rep. 2020 Nov 11;10(1):19500. doi: 10.1038/s41598-020-76441-3.
Historically, the membrane attack complex, composed of complement components C5b-9, has been connected to lytic cell death and implicated in secondary injury after a CNS insult. However, studies to date have utilized either non-littermate control rat models, or mouse models that lack significant C5b-9 activity. To investigate what role C5b-9 plays in spinal cord injury and recovery, we generated littermate PVG C6 wildtype and deficient rats and tested functional and histological recovery after moderate contusion injury using the Infinite Horizon Impactor. We compare the effect of C6 deficiency on recovery of locomotor function and histological injury parameters in PVG rats under two conditions: (1) animals maintained as separate C6 WT and C6-D homozygous colonies; and (2) establishment of a heterozygous colony to generate C6 WT and C6-D littermate controls. The results suggest that maintenance of separate homozygous colonies is inadequate for testing the effect of C6 deficiency on locomotor and histological recovery after SCI, and highlight the importance of using littermate controls in studies involving genetic manipulation of the complement cascade.
从历史上看，补体成分 C5b-9 组成的膜攻击复合物与裂解细胞死亡有关，并与中枢神经系统损伤后的继发性损伤有关。然而，迄今为止的研究要么使用非同窝对照大鼠模型，要么使用缺乏显著 C5b-9 活性的小鼠模型。为了研究 C5b-9 在脊髓损伤和恢复中的作用，我们生成了同窝 PVG C6 野生型和缺陷型大鼠，并使用 Infinite Horizon Impactor 测试了中度挫伤损伤后的功能和组织学恢复。我们比较了 C6 缺陷对两种情况下 PVG 大鼠运动功能和组织学损伤参数恢复的影响：(1) 将动物分别维持在 C6 WT 和 C6-D 纯合子群体中；(2) 建立杂合子群体以生成 C6 WT 和 C6-D 同窝对照。结果表明，单独维持纯合子群体不足以测试 C6 缺陷对 SCI 后运动和组织学恢复的影响，并强调了在涉及补体级联遗传操作的研究中使用同窝对照的重要性。
