Complement C6 deficiency exacerbates pathophysiology after spinal cord injury

Scientific Reports, 2020 · DOI: 10.1038/s41598-020-76441-3 · Published: November 13, 2020

Simple Explanation

This study investigates the role of complement component C6 in spinal cord injury (SCI) recovery using PVG rats. The researchers compared rats maintained as separate homozygous colonies versus littermate controls to assess locomotor function and histological injury parameters after SCI. The study found that using separate homozygous colonies for C6-deficient and wildtype rats yielded different results compared to using littermate controls, highlighting the importance of littermate controls in studies involving genetic manipulation of the complement cascade. Surprisingly, the research suggests a potential beneficial role for C5b-9 formation after SCI, which contrasts with previous studies in complement-deficient mice. This benefit could be related to complement's role in debris clearance, crucial for CNS regeneration and plasticity.

Study Duration

42 days

Participants

Female PVG rats (H-C6 WT, H-C6-D, F2-WT, F2-C6-D)

Evidence Level

Not specified

Key Findings

1
Rats maintained as separate homozygous colonies showed improved locomotor outcome with C6 deficiency, while littermate controls exhibited impaired locomotor outcome with C6 deficiency.
2
C6 deficiency altered white matter sparing and lesion volume in homozygous strain rats but not in littermate control rats.
3
The study suggests a potential positive role for C5b-9 in recovery after SCI, possibly related to its role in debris clearance.

Research Summary

This study investigated the impact of C6 deficiency on spinal cord injury (SCI) recovery in PVG rats, comparing outcomes between rats from separate homozygous colonies and littermate controls. The findings revealed that the method of maintaining rat colonies (separate homozygous vs. littermate controls) significantly influenced the results, highlighting the necessity of using littermate controls in complement cascade studies. Contrary to previous assumptions, the study suggests that C5b-9 formation might have beneficial functions after SCI, potentially through its role in debris clearance and promotion of CNS regeneration.

Practical Implications

Methodological implications

Using littermate controls is critical when studying the complement cascade in SCI to avoid confounding factors from separate colony maintenance.

Therapeutic implications

C5b-9 formation may have a beneficial role in SCI recovery, suggesting potential therapeutic targets for promoting CNS regeneration.

Research implications

Re-evaluation of previous studies that used separate homozygous colonies for C6-deficient and wildtype rats may be needed, given the potential for divergent functional strain characteristics.

Study Limitations

1
The study only used female rats to facilitate manual bladder expression after SCI.
2
Statistical comparisons between homozygous colony and littermate control cohorts should be approached with caution, because these cohorts were run at different times.
3
The data presented cannot exclude the possibility of potential variabilities in blood or other immune parameters at baseline between colonies.

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