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 Wood

Research output: Contribution to journalArticle

107 Citations (Scopus)

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
Externally publishedYes

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Microglia
Insulin-Like Growth Factor I
Macrophages
Brain
Insulin-Like Growth Factor Binding Protein 2
Glial Fibrillary Acidic Protein
Messenger RNA
Insulin-Like Growth Factor Binding Protein 5
Brain Hypoxia-Ischemia
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor Binding Protein 3
Protein S
Proliferating Cell Nuclear Antigen
Thalamus
Inbred C57BL Mouse
Mitogens
Lectins
Astrocytes
Thymidine
Brain Injuries

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

O'Donnell, S. L., Frederick, T. J., Krady, J. K., Vannucci, S. J., & Wood, T. (2002). IGF-I and microglia/macrophage proliferation in the ischemic mouse brain. Glia, 39(1), 85-97. https://doi.org/10.1002/glia.10081
O'Donnell, Steven L. ; Frederick, Terra J. ; Krady, J. Kyle ; Vannucci, Susan J. ; Wood, Teresa. / IGF-I and microglia/macrophage proliferation in the ischemic mouse brain. In: Glia. 2002 ; Vol. 39, No. 1. pp. 85-97.
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O'Donnell, SL, Frederick, TJ, Krady, JK, Vannucci, SJ & Wood, T 2002, 'IGF-I and microglia/macrophage proliferation in the ischemic mouse brain', Glia, vol. 39, no. 1, pp. 85-97. https://doi.org/10.1002/glia.10081

IGF-I and microglia/macrophage proliferation in the ischemic mouse brain. / O'Donnell, Steven L.; Frederick, Terra J.; Krady, J. Kyle; Vannucci, Susan J.; Wood, Teresa.

In: Glia, Vol. 39, No. 1, 01.07.2002, p. 85-97.

Research output: Contribution to journalArticle

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O'Donnell SL, Frederick TJ, Krady JK, Vannucci SJ, Wood T. IGF-I and microglia/macrophage proliferation in the ischemic mouse brain. Glia. 2002 Jul 1;39(1):85-97. https://doi.org/10.1002/glia.10081