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Activation of vascular endothelial cells and perivascular cells by systemic inflammation—an immunohistochemical study of postmortem human brain tissues

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Abstract

We investigated postmortem human brain tissues to determine whether systemic inflammation causes activation of vascular endothelial cells and perivascular cells. In some cases, we used serum concentrations of an acute-phase reactant, C-reactive protein (CRP), as an index of systemic inflammation. Since the serum concentration of CRP at the agonal stage was available only in a limited number of patients, we estimated the degree of systemic inflammation by the intensity of immunohistochemical staining of the residual blood in brain tissue for CRP. Expressions of intercellular adhesion molecule (ICAM)-1, CD40 and cyclooxygenase (COX)-2 were used as markers for activation of vascular endothelial cells. Activation of perivascular cells was estimated by the occurrence of HLA-DR- and CD68-positive perivascular cells. In cases without brain lesions, activation of vascular endothelial cells and perivascular cells was related to the degree of systemic inflammation. In cases with brain lesions, these cells are often activated even in the absence of systemic inflammation. We suggest that inflammatory stimuli derived from the peripheral blood and the brain parenchyma adjunctly activate vascular cells. Under such circumstances, low-grade inflammation in the pre-existing brain lesions might enhance inflammatory signaling to the brain parenchyma from the periphery. The results of this study could explain the vulnerability of neurological patients to delirium caused by systemic inflammatory conditions.

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Acknowledgement

We thank Dr. Makoto Honda (Tokyo Institute of Psychiatry) for providing the monoclonal antibody to macrophage scavenger receptor (clone MH1).

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Authors and Affiliations

  1. Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, 156-8585, Tokyo, Japan

    Hirotake Uchikado, Haruhiko Akiyama, Hiromi Kondo & Kenji Ikeda

  2. Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan

    Kuniaki Tsuchiya

  3. Soga Hospital, Odawara, Japan

    Masanori Kato

  4. National Shimofusa Sanatorium, Chiba, Japan

    Tatsuro Oda

  5. Department of Psychiatry, Yokohama City University, Yokohama, Japan

    Hirotake Uchikado, Takashi Togo, Eizo Iseki & Kenji Kosaka

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  1. Hirotake Uchikado
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  2. Haruhiko Akiyama
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  3. Hiromi Kondo
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  4. Kenji Ikeda
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  5. Kuniaki Tsuchiya
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  6. Masanori Kato
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  7. Tatsuro Oda
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  8. Takashi Togo
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  9. Eizo Iseki
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  10. Kenji Kosaka
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Correspondence to Haruhiko Akiyama.

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Uchikado, H., Akiyama, H., Kondo, H. et al. Activation of vascular endothelial cells and perivascular cells by systemic inflammation—an immunohistochemical study of postmortem human brain tissues. Acta Neuropathol 107, 341–351 (2004). https://doi.org/10.1007/s00401-003-0815-x

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  • DOI: https://doi.org/10.1007/s00401-003-0815-x

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