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Microglial activation and brain injury after intracerebral hemorrhage

  • Conference paper
Cerebral Hemorrhage

Part of the book series: Acta Neurochirurgica Supplementum ((NEUROCHIRURGICA,volume 105))

Abstract

Microglial activation and thrombin formation contribute to brain injury after intracerebral hemorrhage (ICH). Tumor necrosis factor-alpha (TNF-a) and interleukin-1 beta (IL-1β) are 2 major proinflammatory cytokines. In this study, we investigated whether thrombin stimulates TNF-a and IL-1β secretion in vitro, and whether microglial inhibition reduces ICH-induced brain injury in vivo.

There were 2 parts to this study. In the first part, cultured rat microglial cells were treated with vehicle, thrombin (5 and 10U/mL), or thrombin plus tuftsin (0.05 mg/mL), an inhibitor of microglia activation. Levels of TNF-a and IL-1β in culture medium were measured by ELISA at 4, 8, and 24 h after thrombin treatment. In the second part of the study, rats received an intracerebral infusion of 100 µL autologous whole blood with or without 25 µg of tuftsin 1-3 fragment. Rats were killed at day 1 or day 3 for immunohistochemistry and brain water content measurement.

We found that thrombin receptors were expressed in cultured microglia cells, and TNF-a and IL-1β levels in the culture medium were increased after thrombin treatment. Tuftsin reduced thrombin-induced upregulation of TNF-a and IL-1β. In vivo, microglia were activated after ICH, and intracerebral injection of tuftsin reduced brain edema in the ipsilateral basal ganglia (81.1 ± 0.7% vs. 82.7 ± 1.3% in vehicle-treated group; p < 0.05) after ICH.

These results suggest a critical role of microglia activation in ICH-related brain injury.

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Author information

Authors and Affiliations

  1. Medical School, Zhejiang University, Hangzhou, China

    J. Wu, S. Yang, S. Song & G. Fu

  2. Department of Neurosurgery, University of Michigan Medical School, 109 Zina Pitcher Place, R5018 Biomedical Science Research Building, Ann Arbor, MI, 48109-2200, USA

    J. Wu, S. Yang, G. Xi, S. Song, R. F. Keep & Y. Hua M.D.

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  1. J. Wu
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  2. S. Yang
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  3. G. Xi
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  5. G. Fu
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  7. Y. Hua M.D.
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Editor information

Editors and Affiliations

  1. Department of Neurosurgery, School of Medicine, Huashan Hospital, Fudan University, Shanghai, China

    Liang-Fu Zhou , Xian-Cheng Chen  & Feng-Ping Huang ,  & 

  2. Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA

    Guohua Xi , Richard F. Keep , Ya Hua  & Karin Muraszko , ,  & 

  3. Department of Neurosurgery, Shanghai Changzheng Hospital, Shanghai, China

    Yi-Cheng Lu

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© 2008 Springer-Verlag

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Wu, J. et al. (2008). Microglial activation and brain injury after intracerebral hemorrhage. In: Zhou, LF., et al. Cerebral Hemorrhage. Acta Neurochirurgica Supplementum, vol 105. Springer, Vienna. https://doi.org/10.1007/978-3-211-09469-3_13

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  • DOI: https://doi.org/10.1007/978-3-211-09469-3_13

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-09468-6

  • Online ISBN: 978-3-211-09469-3

  • eBook Packages: MedicineMedicine (R0)

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