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Upregulation of fibroblast growth factor-receptor messenger RNA expression in rat brain following transient forebrain ischemia

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Abstract

Recently, we demonstrated that transient forebrain ischemia in rats leads to an early and strong induction of basic fibroblast growth factor (bFGF) synthesis in astrocytes in the injured brain regions. In this study, in order to clarify the targets of such raised endogenous bFGF levels, the messenger RNA (mRNA) expression of its receptors (flg and bek) at in the hippocampus following transient forebrain ischemia induced by four-vessel occlusion for 20 min was investigated using an in situ hybridization technique. Transient forebrain ischemia induced an increase in the number of flg mRNA-positive cells from an early stage (24 h after ischemia) in the hippocampal CA1 subfield where delayed neuronal death occurred later (48–72 h after ischemia). This increase became more marked with the progression of neuronal death and was still evident in the same area 30 days later. The time course of the appearance and distribution pattern of flg mRNA-positive cells in the CA1 subfield were quite similar to those of bFGF mRNA-positive cells. On the other hand, in situ hybridization for bek mRNA showed only slight and transient (observed 72 h and 5 days after ischemia) increases in the number of mRNA-positive cells in the CA1 subfield following ischemia. The use of in situ hybridization and glial fibrillary acidic protein immunohistochemistry in combination demonstrated that the cells in the CA1 subfield that exhibited ischemia-induced flg or bek mRNA expression were astrocytes. These data indicate that transient forebrain ischemia induces upregulation of fibroblast growth factor-receptor expression, accompanied by increased bFGF expression in astrocytes, and suggest that the increased astrocytic bFGF levels in injured brain regions act on the astrocytes via autocrine systems and are involved in the development and maintenance of astrocytosis.

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Authors and Affiliations

  1. Drug Safety Research Laboratories, Pharmaceutical Development Division, Takeda Chemical Industries Ltd., 6-10-1 Himuro-cho, Takatsuki, 569, Osaka, Japan

    K. Takami, R. Tsukuda & A. Shino

  2. Research Laboratories I, Pharmaceutical Research Division, Takeda Chemical Industries Ltd., 2-17-85 Jusohonmachi, Yodogawa-ku, 532, Osaka, Japan

    Y. Kiyota & M. Miyamoto

  3. Research Laboratories II, Discovery Research Division, Takeda Chemical Industries Ltd., 2-17-85 Jusohonmachi, Yodogawa-ku, 532, Osaka, Japan

    M. Iwane & K. Igarashi

  4. Department of Anatomy and Neuroscience, Osaka University Medical School, 2-2 Yamadaoka, Suita, 565, Osaka, Japan

    A. Wanaka & M. Tohyama

  5. Department of Cellular and Structural Biology, Advanced Institute of Science and Technology, Nara, 8916-5 Takayama-cho, Ikoma, 630-01, Nara, Japan

    S. Shiosaka

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  1. K. Takami
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  2. Y. Kiyota
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  3. M. Iwane
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  4. M. Miyamoto
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  8. A. Wanaka
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Takami, K., Kiyota, Y., Iwane, M. et al. Upregulation of fibroblast growth factor-receptor messenger RNA expression in rat brain following transient forebrain ischemia. Exp Brain Res 97, 185–194 (1993). https://doi.org/10.1007/BF00228688

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