Response of glia, mast cells and the blood brain barrier, in transgenic mice expressing interleukin-3 in astrocytes, an experimental model for CNS demyelination

Transgenic mice overexpressing cytokines facilitate analysis of the effects of these immunomodulators on indigenous cells of the central nervous syste m, This study examines morphological aspects of demyelination and permeabil ity changes, in a recently described transgenic model (termed GFAP-IL3), GF AP-IL3 mice develop progressive motor disease at approximately 5 months, Le sions identified after disease onset, showed activation of microglia, astro glial proliferation with phagocytosis of lipids, and immigration of macroph ages and mast cells into neural parenchyma. Lymphocytes failed to appear un til the later stages of the disease, Later, cerebellar and brain stem white matter contained focal demyelinating lesions with intense macrophage infil tration and a proliferative astrocytosis, Dystrophic axonal changes were no ted, in addition to demyelination in heavily infiltrated lesions, Mast cell s, variably present in the thalamus and meninges of wild type mice, were gr eatly 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 o f macrophage mediated demyelination in which glial cells and macrophages ar e both involved in the phagocytic process.