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Damage to Neurons and Oligodendrocytes in the Hippocampal CA1 Sector after Transient Focal Ischemia in Rats

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Abstract

Focal brain lesions such as transient focal cerebral ischemia can lead to neuronal damage in remote areas, including the ipsilateral substantia nigra and hippocampus, as well as in the ischemic core. In this study, we investigated acute changes in the ipsilateral hippocampus from 1 up to 7 days after 90 min of transient focal cerebral ischemia in rats, using anti-NeuN (neuronal nuclei), anti-Cu/Zn-superoxide dismutase (Cu/Zn-SOD), anti-Mn-SOD, anti-neuronal nitric oxide synthase (nNOS), anti-inducible NOS (iNOS), anti-glial fibrillary acidic protein (GFAP), anti-ionized calcium-binding adaptor molecule 1(Iba 1) and anti-2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) antibodies. In our western blot and histochemical analyses, present results show that transient focal cerebral ischemia in rats can cause a severe and acute damage of neurons and oligodendrocytes in the ipsilateral hippocampal CA1 sector. The present findings also demonstrate that the expression of iNOS produced by Iba 1-immunopositive microglia precedes the damage of neurons and oligodendrocytes in the ipsilateral hippocampal CA1 sector after transient focal cerebral ischemia. In contrast, our results suggest that increased reactive oxygen species (ROS) production during reperfusion cannot lead to damage of neurons and oligodendrocytes in the ipsilateral hippocampal CA1 sector after transient focal cerebral ischemia, because of an insufficient expression of Cu/Zn-SOD and Mn-SOD. Our double-labeled immunohistochemical study demonstrates that the overexpression of iNOS produced by Iba 1-immunopositive microglia may play a pivotal role in the damage of neurons and oligodendrocytes in the ipsilateral hippocampal CA1 sector at an acute stage after transient focal cerebral ischemia.

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Acknowledgements

This study was supported in part by a Grant-in-Aid for Scientific Research (21790376 and 22590935) from the Ministry of Science and Education in Japan.

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Authors and Affiliations

  1. Department of Neurobiology and Therapeutics, Institute of Health Biosciences, The University of Tokushima Graduate School, 1-78 Sho-machi, Tokushima, 770-8505, Japan

    Hiroto Uchida, Yuki Fujita, Misato Matsueda, Masahiro Umeda, Shunsuke Matsuda, Jiro Kasahara & Tsutomu Araki

  2. Department of Neurology, Organized Center of Clinical Medicine, International University of Health and Welfare, Tochigi, Japan

    Hiroyuki Kato

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  1. Hiroto Uchida
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  2. Yuki Fujita
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  3. Misato Matsueda
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Correspondence to Tsutomu Araki.

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Uchida, H., Fujita, Y., Matsueda, M. et al. Damage to Neurons and Oligodendrocytes in the Hippocampal CA1 Sector after Transient Focal Ischemia in Rats. Cell Mol Neurobiol 30, 1125–1134 (2010). https://doi.org/10.1007/s10571-010-9545-5

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  • DOI: https://doi.org/10.1007/s10571-010-9545-5

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