IGF-I and microglia/macrophage proliferation in the ischemic mouse brain

Steven L. O'Donnell, Terra J. Frederick, J. Kyle Krady, Susan J. Vannucci, Teresa L. Wood

Research output: Contribution to journalArticle

111 Scopus citations

Abstract

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 B4 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 3H-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.

Original languageEnglish (US)
Pages (from-to)85-97
Number of pages13
JournalGlia
Volume39
Issue number1
DOIs
StatePublished - Jul 1 2002

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience

Keywords

  • CNS insult
  • Growth factors
  • Hypoxia-ischemia
  • Macrophages
  • Microglia
  • Stroke
  • Trophic factors

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    O'Donnell, S. L., Frederick, T. J., Krady, J. K., Vannucci, S. J., & Wood, T. L. (2002). IGF-I and microglia/macrophage proliferation in the ischemic mouse brain. Glia, 39(1), 85-97. https://doi.org/10.1002/glia.10081