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Inhibition of post-ischemic brain injury by clusterin overexpression

Nature Medicine volume 7, pages 977–978 (2001)Cite this article

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At 7 days post-ischemia, a 30–50% increase in clusterin mRNA levels was reproducibly observed in the ischemic as compared with the control hemisphere of wild-type mouse brains, and localized by in situ hybridization to the peri-infarct penumbral area of tissue that separates necrotic from normal brain tissue (data not shown). This area sustains the inflammation and contains cells that retain the potential for salvage. Morphometric analysis of the ischemic hemisphere revealed that the size of the penumbra (identified by the presence of a layer of glial and inflammatory cells4) was significantly thinner in CLU-overexpressing mice (27815 ± 1010 pixels) as compared with wild-type mice (50904 ± 2309 pixels), and significantly thicker in Clu−/− mice (71938 ± 3210 pixels) (Fisher's test, P < 0.01) (Fig. 1c–h and l). At 14 days post-ischemia, wild-type mice still displayed a much higher number of inflammatory cells and a worse structural recovery in the peri-infarct region than CLU-overexpressing mice. Overall, Clu−/− mice showed the worst morphological resolution at this late time point. Thus in two distinct molecular models, an inverse correlation between clusterin expression and ischemic brain damage was observed, clearly showing that clusterin protects against ischemic brain damage (Fig. 1c–h and l).

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Figure 1: Analysis of brain injury following MCAO in function of clusterin expression.

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Authors and Affiliations

  1. Department of Dermatology, Geneva University Medical School, Geneva, Switzerland

    Philippe Wehrli, Isabelle Viard-Leveugle & Lars E. French

  2. Division of Neuropsychiatry, Department of Psychiatry University of Geneva School of Medicine, Geneva, Switzerland

    Yves Charnay, Philippe Vallet & Constantin Bouras

  3. Department of Psychiatry University of Geneva School of Medicine, Clinic of Geriatric Psychiatry, Geneva, Switzerland

    Panteleimon Giannakopoulos

  4. Division of Molecular Developmental Biology Children's Hospital Research Foundation Cincinnati, Ohio, USA

    Guang Zhu, Judith Harmony & Bruce Aronow

  5. Institute of Biochemistry, Lausanne University, Lausanne, Switzerland

    Jürg Tschopp

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Wehrli, P., Charnay, Y., Vallet, P. et al. Inhibition of post-ischemic brain injury by clusterin overexpression. Nat Med 7, 977–978 (2001). https://doi.org/10.1038/nm0901-977

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