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IGF‐I and microglia/macrophage proliferation in the ischemic mouse brain
Author(s) -
O'Donnell Steven L.,
Frederick Terra J.,
Krady J. Kyle,
Vannucci Susan J.,
Wood Teresa L.
Publication year - 2002
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10081
Subject(s) - microglia , biology , glial fibrillary acidic protein , immunostaining , neuroglia , in situ hybridization , astrocyte , proliferating cell nuclear antigen , pathology , growth factor , messenger rna , microbiology and biotechnology , immunohistochemistry , endocrinology , immunology , central nervous system , inflammation , receptor , medicine , biochemistry , gene
We have used a model of hypoxic‐ischemic brain injury in adult male C57BL/6 mice to study insulin‐like growth factor‐I (IGF‐I) and IGF‐binding protein (IGFBP) expression in response to cerebral hypoxia‐ischemia (H/I) in the adult mouse. A period of 20 min of H/I that resulted in histopathology in cortex, striatum, and thalamus was correlated with induction of mRNA for IGF‐I, IGFBP‐2, IGFBP‐3, IGFBP‐5, and glial fibrillary acidic protein (GFAP) by 4 days of recovery. Increased IGF‐I mRNA was located within damaged regions and was surrounded by IGFBP‐2 mRNA expression. The results of combined immunostaining/in situ hybridzation showed that the cells expressing IGFBP‐2 mRNA were also GFAP‐positive and comprised a subset of activated astrocytes immediately surrounding areas of damage. In contrast, staining within damaged regions showed high numbers of cells immunopositive for F4/80 and lectin B 4 indicative of microglia and macrophages but no cells immunopositive for the astrocytic proteins GFAP or S‐100β. Microglia/macrophages within the damaged areas expressed IGF‐I mRNA and were also immunopositive for the proliferating cell nuclear antigen. To determine whether expression of IGF‐I could contribute to proliferation of microglia, we treated purified cultures of adult brain microglia with IGF‐I in the presence of 3 H‐thymidine. IGF‐I stimulated a twofold increase in DNA synthesis in cultures of adult brain microglia. Taken together with previous data demonstrating that IGF‐I promotes proliferation of peripheral macrophages, these data support the hypothesis that IGF‐I is an autocrine/paracrine mitogen for microglia/macrophages after H/I. GLIA 38:85–97, 2002. © 2002 Wiley‐Liss, Inc.