Abstract
Study design:
Specificity of serum complement component to elicit immunological demyelination.
Objectives:
To assess the role of complement components and pathways in experimental immunological demyelination of the adult rat spinal cord.
Setting:
ICORD, University of British Columbia, Vancouver, Canada.
Subjects:
We used 32 adult male Sprague–Dawley rats, of approximately 220 g weight.
Methods:
Rats received intraspinal infusions of demyelinating reagents, delivered by osmotic minipump, for a 7-day infusion at 0.5 μl/h. Reagents consisted of a polyclonal antibody to galactocerebroside and human serum complement. Complement sera deficient for a single component were used to assess the role of the alternative pathway, the classical pathway, and the membrane attack complex. Demyelination was assessed, at 7 days, ultrastructurally.
Results:
Removal of C3 protein, common to classical and alternative complement pathways, or C4 protein, a classical pathway protein, resulted in no demyelination. However, complement deficient in Factor B, an alternative pathway protein, produced effective demyelination. Upon removal of C5 or C6, membrane attack complex proteins, demyelination was also observed.
Conclusion:
This suggests that the classical pathway is sufficient for the protocol to demyelinate the adult rat spinal cord, and that the membrane attack complex is also not required.
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Acknowledgements
We thank Claire Huguenot for her assistance in many of these experiments. JAB was supported by a BC Neurotrauma Studentship. JKD was supported by a BC Neurotrauma Research Associate award. This research was funded by an Operating Grant from the Canadian Institutes of Health Research to JDS.
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Dyer, J., Bourque, J. & Steeves, J. The role of complement in immunological demyelination of the mammalian spinal cord. Spinal Cord 43, 417–425 (2005). https://doi.org/10.1038/sj.sc.3101737
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DOI: https://doi.org/10.1038/sj.sc.3101737
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