Laquinimod reduces neuroaxonal injury through inhibiting microglial activation
Article first published online: 26 MAY 2014
© 2014 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
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Annals of Clinical and Translational Neurology
Volume 1, Issue 6, pages 409–422, June 2014
How to Cite
Mishra, M. K., Wang, J., Keough, M. B., Fan, Y., Silva, C., Sloka, S., Hayardeny, L., Brück, W. and Yong, V. W. (2014), Laquinimod reduces neuroaxonal injury through inhibiting microglial activation. Annals of Clinical and Translational Neurology, 1: 409–422. doi: 10.1002/acn3.67
- Issue published online: 19 JUN 2014
- Article first published online: 26 MAY 2014
- Manuscript Accepted: 22 APR 2014
- Manuscript Revised: 19 APR 2014
- Manuscript Received: 27 MAR 2014
- Teva Pharmaceuticals, Israel
- Canadian Institutes of Health Research
- Alberta Innovates – Health Solutions
- MS Society of Canada
|acn367-sup-0001-FigS1.tif||image/tif||245K||Figure S1. Treatment of mice from 30 days of EAE with laquinimod reduced clinical severity, demyelination, and activated microglia/macrophage density in lesions. Mice were immunized for EAE with MOG35-55 peptide. At day 30, with mice having impairment of tail, fore- and hind limbs (EAE is on a five-point scale), daily oral laquinimod treatment was initiated. Clinical scores declined in the laquinimod but not the control vehicle group (A). The extent of demyelination was tabulated by previously described methods. In contrast to the progression of demyelination in the control group from day 30 to 60 of EAE, this was prevented by laquinimod (C); mean ± SEM, n of 15 each. Density of activated S100A9-positive microglia/macrophages was also reduced by laquinimod treatment at day 60 compared to day 30 controls.|
|acn367-sup-0002-FigS2.tif||image/tif||185K||Figure S2. Laquinimod did not protect human neurons against insults that kill neurons directly. Ferrous ion (Fe) and hydrogen peroxide (H2O2) are two stressors that kill neurons in neuron-enriched (data herein) or neuron-microglia cocultures (not shown). MAP-2 staining for neurons 24 h after exposure shows prominent loss of neurons in H2O2 or iron-exposed cultures that were not reduced by the presence of laquinimod (LQ) (A). This was confirmed by quantitation using ImageXpress (B). Mean ± SEM, n of four cultures. ***P < 0.001 compared to neurons only, or neurons + iLPS (interferon-γ and LPS). The above also demonstrates that iLPS added to neuron-enriched cultures without microglia did not result in neuronal loss. Thus, the protection against microglia-induced neuronal loss by laquinimod reported in this article occurred through affecting the microglia intermediary and not by a direct action on neurons.|
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