Complement C6 deficiency exacerbates pathophysiology after spinal cord injury.

Abstract

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.

• Authors: Diane Su, Mitra J Hooshmand, Manuel D Galvan, Rebecca A Nishi, Brian J Cummings, Aileen J Anderson
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 19500 (11 11 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 33177623 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Complement C6
• Complement Membrane Attack Complex
• Glial Fibrillary Acidic Protein
• Myelin Basic Protein

Topics

• Animals
• Behavior, Animal
• Complement C6 (deficiency, genetics)
• Complement Membrane Attack Complex (genetics, metabolism)
• Disease Models, Animal
• Female
• Genotype
• Glial Fibrillary Acidic Protein (metabolism)
• Gray Matter (cytology, metabolism)
• Hereditary Complement Deficiency Diseases (complications, genetics)
• Heterozygote
• Locomotion
• Male
• Myelin Basic Protein (metabolism)
• Rats, Mutant Strains
• Selective Breeding
• Spinal Cord Injuries (etiology, genetics, metabolism, physiopathology)
• Thoracic Vertebrae (injuries)
• White Matter (cytology, metabolism)