IVIg attenuates complement and improves spinal cord injury outcomes in mice

Brennan, Faith H., Kurniawan, Nyoman D., Vukovic, Jana, Bartlett, Perry F., Käsermann, Fabian, Arumugam, Thiruman V., Basta, Milan and Ruitenberg, Marc J. (2016) IVIg attenuates complement and improves spinal cord injury outcomes in mice. Annals of Clinical and Translational Neurology, 3 7: 495-511. doi:10.1002/acn3.318


Author Brennan, Faith H.
Kurniawan, Nyoman D.
Vukovic, Jana
Bartlett, Perry F.
Käsermann, Fabian
Arumugam, Thiruman V.
Basta, Milan
Ruitenberg, Marc J.
Title IVIg attenuates complement and improves spinal cord injury outcomes in mice
Journal name Annals of Clinical and Translational Neurology   Check publisher's open access policy
ISSN 2328-9503
Publication date 2016-07
Sub-type Article (original research)
DOI 10.1002/acn3.318
Open Access Status DOI
Volume 3
Issue 7
Start page 495
End page 511
Total pages 17
Place of publication Chichester, West Sussex, United Kingdom
Publisher John Wiley & Sons
Collection year 2017
Language eng
Formatted abstract
Objective: Traumatic spinal cord injury (SCI) elicits immediate neural cell death, axonal damage, and disruption of the blood–spinal cord barrier, allowing circulating immune cells and blood proteins into the spinal parenchyma. The inflammatory response to SCI involves robust complement system activation, which contributes to secondary injury and impairs neurological recovery. This study aimed to determine whether intravenous immunoglobulin (IVIg), an FDA-approved treatment for inflammatory conditions, can scavenge complement activation products and improve recovery from contusive SCI.

Methods: We used functional testing, noninvasive imaging, and detailed postmortem analysis to assess whether IVIg therapy is effective in a mouse model of severe contusive SCI.

Results: IVIg therapy at doses of 0.5–2 g/kg improved the functional and histopathological outcomes from SCI, conferring protection against lesion enlargement, demyelination, central canal dilation, and axonal degeneration. The benefits of IVIg were detectable through noninvasive diffusion tensor imaging (DTI), with IVIg treatment counteracting the progressive SCI-induced increase in radial diffusivity (RD) in white matter. Diffusion indices significantly correlated with the functional performance of individual mice and accurately predicted the degree of myelin preservation. Further experiments revealed that IVIg therapy reduced the presence of complement activation products and phagocytically active macrophages at the lesion site, providing insight as to its mechanisms of action.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Thu, 28 Jul 2016, 11:03:59 EST by Jana Vukovic on behalf of School of Biomedical Sciences