Immunological Demyelination Triggers Macrophage/Microglial Cells Activation without Inducing Astrogliosis

The glial scar formed by reactive astrocytes and axon growth inhibitors associated with myelin play important roles in the failure of axonal regeneration following central nervous system (CNS) injury. Our laboratory has previously demonstrated that immunological demyelination of the CNS facilitates...

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Main Authors: Frank Cloutier, Ilse Sears-Kraxberger, Krista Keachie, Hans S. Keirstead
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2013/812456
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author Frank Cloutier
Ilse Sears-Kraxberger
Krista Keachie
Hans S. Keirstead
author_facet Frank Cloutier
Ilse Sears-Kraxberger
Krista Keachie
Hans S. Keirstead
author_sort Frank Cloutier
collection DOAJ
description The glial scar formed by reactive astrocytes and axon growth inhibitors associated with myelin play important roles in the failure of axonal regeneration following central nervous system (CNS) injury. Our laboratory has previously demonstrated that immunological demyelination of the CNS facilitates regeneration of severed axons following spinal cord injury. In the present study, we evaluate whether immunological demyelination is accompanied with astrogliosis. We compared the astrogliosis and macrophage/microglial cell responses 7 days after either immunological demyelination or a stab injury to the dorsal funiculus. Both lesions induced a strong activated macrophage/microglial cells response which was significantly higher within regions of immunological demyelination. However, immunological demyelination regions were not accompanied by astrogliosis compared to stab injury that induced astrogliosis which extended several millimeters above and below the lesions, evidenced by astroglial hypertrophy, formation of a glial scar, and upregulation of intermediate filaments glial fibrillary acidic protein (GFAP). Moreover, a stab or a hemisection lesion directly within immunological demyelination regions did not induced astrogliosis within the immunological demyelination region. These results suggest that immunological demyelination creates a unique environment in which astrocytes do not form a glial scar and provides a unique model to understand the putative interaction between astrocytes and activated macrophage/microglial cells.
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spelling doaj-art-4a432660010d4431a4841bac4d9151af2025-08-20T02:38:02ZengWileyClinical and Developmental Immunology1740-25221740-25302013-01-01201310.1155/2013/812456812456Immunological Demyelination Triggers Macrophage/Microglial Cells Activation without Inducing AstrogliosisFrank Cloutier0Ilse Sears-Kraxberger1Krista Keachie2Hans S. Keirstead3Reeve-Irvine Research Center, Sue and Bill Gross Stem Cell Research Center, School of Medicine, University of California at Irvine, 845 Health Sciences Road, Irvine, CA 92697, USAReeve-Irvine Research Center, Sue and Bill Gross Stem Cell Research Center, School of Medicine, University of California at Irvine, 845 Health Sciences Road, Irvine, CA 92697, USAReeve-Irvine Research Center, Sue and Bill Gross Stem Cell Research Center, School of Medicine, University of California at Irvine, 845 Health Sciences Road, Irvine, CA 92697, USAReeve-Irvine Research Center, Sue and Bill Gross Stem Cell Research Center, School of Medicine, University of California at Irvine, 845 Health Sciences Road, Irvine, CA 92697, USAThe glial scar formed by reactive astrocytes and axon growth inhibitors associated with myelin play important roles in the failure of axonal regeneration following central nervous system (CNS) injury. Our laboratory has previously demonstrated that immunological demyelination of the CNS facilitates regeneration of severed axons following spinal cord injury. In the present study, we evaluate whether immunological demyelination is accompanied with astrogliosis. We compared the astrogliosis and macrophage/microglial cell responses 7 days after either immunological demyelination or a stab injury to the dorsal funiculus. Both lesions induced a strong activated macrophage/microglial cells response which was significantly higher within regions of immunological demyelination. However, immunological demyelination regions were not accompanied by astrogliosis compared to stab injury that induced astrogliosis which extended several millimeters above and below the lesions, evidenced by astroglial hypertrophy, formation of a glial scar, and upregulation of intermediate filaments glial fibrillary acidic protein (GFAP). Moreover, a stab or a hemisection lesion directly within immunological demyelination regions did not induced astrogliosis within the immunological demyelination region. These results suggest that immunological demyelination creates a unique environment in which astrocytes do not form a glial scar and provides a unique model to understand the putative interaction between astrocytes and activated macrophage/microglial cells.http://dx.doi.org/10.1155/2013/812456
spellingShingle Frank Cloutier
Ilse Sears-Kraxberger
Krista Keachie
Hans S. Keirstead
Immunological Demyelination Triggers Macrophage/Microglial Cells Activation without Inducing Astrogliosis
Clinical and Developmental Immunology
title Immunological Demyelination Triggers Macrophage/Microglial Cells Activation without Inducing Astrogliosis
title_full Immunological Demyelination Triggers Macrophage/Microglial Cells Activation without Inducing Astrogliosis
title_fullStr Immunological Demyelination Triggers Macrophage/Microglial Cells Activation without Inducing Astrogliosis
title_full_unstemmed Immunological Demyelination Triggers Macrophage/Microglial Cells Activation without Inducing Astrogliosis
title_short Immunological Demyelination Triggers Macrophage/Microglial Cells Activation without Inducing Astrogliosis
title_sort immunological demyelination triggers macrophage microglial cells activation without inducing astrogliosis
url http://dx.doi.org/10.1155/2013/812456
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AT hansskeirstead immunologicaldemyelinationtriggersmacrophagemicroglialcellsactivationwithoutinducingastrogliosis