Systemic inflammatory response reactivates immune-mediated lesions in rat brain.

Abstract

The potential association between microbial infection and reactivation of a multiple sclerosis (MS) lesion is an important issue that remains unresolved, primarily because of the absence of suitable animal models and imaging techniques. Here, we have evaluated this question in an empirical manner using immunohistochemistry and magnetic resonance imaging (MRI), before and after the induction of a systemic inflammatory response in two distinct models of MS. In a pattern-II-type focal myelin oligodendrocyte glycoprotein-experimental autoimmune encephalomyelitis model, systemic endotoxin injection caused an increase in regional cerebral blood volume (rCBV) around the lesion site after 6 h, together with a reduction in the magnetization transfer ratio of the lesioned corpus callosum. These changes were followed by an increase in the diffusion of tissue water within the lesion 24 h after endotoxin challenge and new leukocyte recruitment as revealed both immunohistochemically and by MRI tracking of ultrasmall superparamagnetic iron oxide-labeled macrophages. Importantly, we detected in vivo expression of E- and P-selectin in quiescent lesions by MRI-detectable glyconanoparticles conjugated to sialyl Lewis(X). This finding may explain, at least in part, the ability of quiescent MS lesions to rapidly reinitiate the cell recruitment processes. In a pattern-I-type delayed-type hypersensitivity response model, a similar effect of endotoxin challenge on rCBV was observed, together with delayed breakdown of the blood-brain barrier, showing that systemic infection can alter the pathogenesis of MS-like lesions regardless of lesion etiology. These findings will have important implications for the management and monitoring of individuals with MS.

• Authors: Sébastien Serres, Daniel C Anthony, Yanyan Jiang, Kerry A Broom, Sandra J Campbell, Damian J Tyler, Sander I van Kasteren, Benjamin G Davis, Nicola R Sibson
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 29 Issue 15 Pg. 4820-8 (Apr 15 2009) ISSN: 1529-2401 [Electronic] United States
• PMID: 19369550 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipopolysaccharides
• Mog protein, rat
• Myelin Proteins
• Myelin-Associated Glycoprotein
• Myelin-Oligodendrocyte Glycoprotein

Topics

• Animals
• Brain (immunology, pathology)
• Encephalomyelitis, Autoimmune, Experimental (immunology, pathology)
• Lipopolysaccharides (toxicity)
• Male
• Multiple Sclerosis (immunology, pathology)
• Myelin Proteins
• Myelin-Associated Glycoprotein (toxicity)
• Myelin-Oligodendrocyte Glycoprotein
• Rats
• Rats, Inbred Lew
• Systemic Inflammatory Response Syndrome (immunology, pathology)