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Characterization of nestin expression and vessel association in the ischemic core following focal cerebral ischemia in rats

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Abstract

The present study aimed to provide a detailed characterization of the cellular phenotypes of nestin-positive cells in a rat model of ischemic stroke. Nestin-positive cells included reactive astrocytes in the peri-infarct region. In the ischemic core, in which astrocytes had virtually disappeared, nestin expression was exclusively associated with the vasculature, including the microvasculature and larger caliber vessels. Induction of nestin expression in the ischemic core occurred by 3 days post-ischemia. Nestin expression continued through at least 28 days post-ischemia but the cellular profiles of nestin-positive cells changed over this period. In the ischemic core at day 3, nestin-positive cells frequently had long processes that ran parallel along the longitudinal axis of the vasculature. These cells were highly proliferative and expressed the transcription factor for neural/glial progenitors, Sox9. Based on their morphological characteristics and on a double-labeling study, most nestin-positive cells were clearly distinguishable from vasculature-associated cells including endothelial cells, smooth muscle cells and microglia/macrophages. Immunoelectron microscopic findings demonstrated that most nestin-positive cells lay in the perivascular space and had macrophage-like features, indicating morphological similarity to perivascular macrophages. Nestin expression was still associated with the vasculature 14 days after ischemia but appeared in fibroblast-like cells. Thus, our data indicated that, in the ischemic core, nestin expression was not limited to a progenitor/stem cell population but was induced in the vasculature-associated cells. These cell types included perivascular macrophages and fibroblast-like cells that appeared to undergo dynamic structural changes. These results suggest that nestin facilitates cellular structural remodeling in response to ischemic injury.

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Authors and Affiliations

  1. Department of Anatomy, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, South Korea

    Yoo-Jin Shin, Jang-Mi Park, Jeong Min Cho & Mun-Yong Lee

  2. Integrative Research Support Center, Laboratory of Electron Microscope, College of Medicine, The Catholic University of Korea, 137-701, Seoul, South Korea

    Hong Lim Kim

  3. Department of Pharmacology, College of Medicine, The Catholic University of Korea, 137-701, Seoul, South Korea

    Seong Yun Kim

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  1. Yoo-Jin Shin
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  2. Hong Lim Kim
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  3. Jang-Mi Park
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  4. Jeong Min Cho
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Correspondence to Mun-Yong Lee.

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This study was supported by the Mid-career Researcher Program through a National Research Foundation of Korea (NRF) grant funded by the MEST (2011–0028319).

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Shin, YJ., Kim, H.L., Park, JM. et al. Characterization of nestin expression and vessel association in the ischemic core following focal cerebral ischemia in rats. Cell Tissue Res 351, 383–395 (2013). https://doi.org/10.1007/s00441-012-1538-x

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