Deficiency in complement C1q improves histological and functional locomotor outcome after spinal cord injury.
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 knock-out (KO) and wild-type (WT) mice on a complement sufficient background (BUB) received a mild-moderate T9 contusion injury with the Infinite Horizon impactor. BUB C1q KO mice exhibited greater locomotor recovery compared with 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 with BUB WT mice 3 d post-injury (p<0.05). However, this increased macrophage response appeared to be transient as stereological assessment of spinal cord tissue obtained 28 d 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 compared with BUB WT mice (p<0.05). Together, these data suggest that initiation of the classical complement pathway via C1q is detrimental to recovery after SCI.
Galvan
Manuel D
MD
Departments of Physical Medicine & Rehabilitation, Reeve-Irvine Research Center, University of California, Irvine, Irvine, California 92697-4292, USA.
Luchetti
Sabina
S
Burgos
Adrian M
AM
Nguyen
Hal X
HX
Hooshmand
Mitra J
MJ
Hamers
Frank P T
FP
Anderson
Aileen J
AJ
D000818:Animals; D003167:Complement Activation / Q000235:genetics; D015922:Complement C1q / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism; D005911:Gliosis; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D017628:Microglia / Q000473:pathology; D009043:Motor Activity / Q000235:genetics; D010812:Physical Stimulation; D020127:Recovery of Function / Q000235:genetics; D012684:Sensory Thresholds; D012737:Sex Factors; D013045:Species Specificity; D013119:Spinal Cord Injuries / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*
D005353:Fibronectins; D015922:Complement C1q