Open AccessResponse of Glia, Mast Cells and the Blood Brain Barrier, in Transgenic Mice Expressing Interleukin‐3 in Astrocytes, an Experimental Model for CNS Demyelination
Author(s) -
Powell Henry C.,
Garrett Robert S.,
Brett Francesca M.,
Chiang ChiShuin,
Chen Emily,
Masliah Eliezer,
Campbell Iain L.
Publication year - 1999
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.1999.tb00220.x
Subject(s) - astrocytosis , microglia , pathology , biology , genetically modified mouse , neuroinflammation , parenchyma , infiltration (hvac) , central nervous system , astrocyte , neuroglia , inflammation , immunology , neuroscience , medicine , transgene , biochemistry , physics , thermodynamics , gene
Transgenic mice overexpressing cytokines facilitate analysis of the effects of these immunomodulators on indigenous cells of the central nervous system. This study examines morphological aspects of demyelination and permeability changes, in a recently described transgenic model (termed GFAP‐IL3). GFAP‐IL3 mice develop progressive motor disease at approximately 5 months. Lesions identified after disease onset, showed activation of microglia, astroglial proliferation with phagocytosis of lipids, and immigration of macrophages and mast cells into neural parenchyma. Lymphocytes failed to appear until the later stages of the disease. Later, cerebellar and brain stem white matter contained focal demyelinating lesions with intense macrophage infiltration and a proliferative astrocytosis. Dystrophic axonal changes were noted, in addition to demyelination in heavily infiltrated lesions. Mast cells, variably present in the thalamus and meninges of wild type mice, were greatly increased at these sites in GFAP‐IL3 mice. Blood‐brain barrier (BBB) defects were documented with leakage of intravenously injected horseradish peroxidase. Mast cell infiltration into the CNS and their degranulation at the site of injury, may represent initial events in a spontaneous process of macrophage mediated demyelination in which glial cells and macrophages are both involved in the phagocytic process.