Complement C6 deficiency exacerbates pathophysiology after spinal cord injury.

Complement C6 deficiency exacerbates pathophysiology after spinal cord injury.
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DOI:
10.1038/s41598-020-76441-3
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发表时间:
2020-11-11
期刊:
影响因子:
4.6
通讯作者:
Anderson AJ
Anderson AJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Su D;Hooshmand MJ;Galvan MD;Nishi RA;Cummings BJ;Anderson AJ

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从历史上看,由补体组分C5b-9组成的膜攻击复合物与溶解性细胞死亡有关,并与中枢神经系统损伤后的继发性损伤有关。然而,迄今为止的研究使用的要么是非同窝对照大鼠模型,要么是缺乏显著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,我们制造了PVG C6野生型和缺陷大鼠,并使用Infinite Horizon impact测试中度挫伤后的功能和组织学恢复情况。我们比较了两种情况下C6缺乏对PVG大鼠运动功能恢复和组织学损伤参数的影响:(1)单独维持C6 WT和C6- d纯合菌落的动物;(2)建立杂合菌落,产生C6 WT和C6- d窝伴对照。结果表明,维持单独的纯合子菌落不足以测试C6缺乏对脊髓损伤后运动和组织恢复的影响,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。
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.
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