Systemic inflammatory response reactivates immune-mediated lesions in rat brain.
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 us...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2009
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| _version_ | 1797080982207070208 |
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| author | Serres, S Anthony, D Jiang, Y Broom, K Campbell, S Tyler, D van Kasteren, S Davis, B Sibson, N |
| author_facet | Serres, S Anthony, D Jiang, Y Broom, K Campbell, S Tyler, D van Kasteren, S Davis, B Sibson, N |
| author_sort | Serres, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T01:08:02Z |
| format | Journal article |
| id | oxford-uuid:8c04ac63-ed09-41d4-bb93-2d3381391258 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:08:02Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:8c04ac63-ed09-41d4-bb93-2d33813912582022-03-26T22:41:58ZSystemic inflammatory response reactivates immune-mediated lesions in rat brain.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8c04ac63-ed09-41d4-bb93-2d3381391258EnglishSymplectic Elements at Oxford2009Serres, SAnthony, DJiang, YBroom, KCampbell, STyler, Dvan Kasteren, SDavis, BSibson, NThe 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. |
| spellingShingle | Serres, S Anthony, D Jiang, Y Broom, K Campbell, S Tyler, D van Kasteren, S Davis, B Sibson, N Systemic inflammatory response reactivates immune-mediated lesions in rat brain. |
| title | Systemic inflammatory response reactivates immune-mediated lesions in rat brain. |
| title_full | Systemic inflammatory response reactivates immune-mediated lesions in rat brain. |
| title_fullStr | Systemic inflammatory response reactivates immune-mediated lesions in rat brain. |
| title_full_unstemmed | Systemic inflammatory response reactivates immune-mediated lesions in rat brain. |
| title_short | Systemic inflammatory response reactivates immune-mediated lesions in rat brain. |
| title_sort | systemic inflammatory response reactivates immune mediated lesions in rat brain |
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