Adapted focal experimental autoimmune encephalomyelitis to allow MRI exploration of multiple sclerosis features.
Experimental Neurology. 2011-08-01; 230(2): 248-257
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1. Exp Neurol. 2011 Aug;230(2):248-57. doi: 10.1016/j.expneurol.2011.04.023. Epub
2011 May 6.
Adapted focal experimental autoimmune encephalomyelitis to allow MRI exploration
of multiple sclerosis features.
Tourdias T(1), Hiba B, Raffard G, Biran M, Nishiguchi T, Aussudre J, Franconi JM,
Brochet B, Petry KG, Dousset V.
(1)INSERM U.1049 Neuroinflammation, imagerie et thérapie de sclérose en plaques,
F-33076 Bordeaux, France.
We aimed to determine an optimal protocol for inducing a focal inflammatory
lesion within the rat brain that could be large enough for an easier MRI
monitoring while still relevant as a multiple sclerosis (MS) like lesion. We
adapted a two-hit model based on pre-sensitization of the Lewis rat with myelin
oligodendrocyte protein (MOG) followed by stereotaxic injection of
pro-inflammatory cytokines (TNFα+IFNγ) within the internal capsule. We compared
the following two strategies to increase focal lesion development for an easier
MR translation: (1) a higher sensitization step (MOG50) or (2) a higher cytokine
step with lower sensitization (MOG25). Control animals were administered only
cytokines without MOG pre-sensitization. Animals were followed with T2, diffusion
and T1 post gadolinium weighted images at 1, 3 and 7days following cytokine
injection. Immunostaining was performed at the same time points for macrophages
(ED1), myelin (MBP and Luxol Fast Blue) and blood brain barrier integrity (IgG).
At day 1, the focal lesions depicted with T2-weighted images were very similar
among groups and related to vasogenic edema (high apparent diffusion coefficient
(ADC), gadolinium enhancement and IgG extravasation) induced by cytokines
irrespective of the pre-sensitization step. Then, at day 3, MOG50 rats developed
statistically larger T2 lesions than MOG25 and control rats that were correlated
with inflammatory cell accumulation. At day 7, MOG50 rats also showed larger T2
lesions than MOG25 and control rats, together with loss of anisotropy that were
correlated with demyelination. In contrast, MOG25 and control rats developed
similar MR lesions decreasing over time and almost undetectable at day 7. We
conclude that with a high pre-sensitization step, the focal lesion can be
monitored by MRI whose signal reflects some features of a MS-like lesion, i.e.
edema, inflammatory cell accumulation and later demyelination.
Copyright © 2011 Elsevier Inc. All rights reserved.
PMID: 21575634 [Indexed for MEDLINE]