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Thrombin-Induced Cerebral Hemorrhage: Role of Protease-Activated Receptor-1

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Abstract

Thrombin causes blood–brain barrier disruption, and this study examined whether thrombin can cause brain hemorrhage through protease-activated receptor-1 (PAR-1). Male wild type and PAR-1 knockout mice had an intracerebral injection of thrombin or saline. Mice then underwent serial T2 magnetic resonance imaging and were euthanized for brain hemoglobin, iron, and interleukin-1β measurements. Thrombin caused massive T2 lesions and brain hemorrhage in wild type mice. These effects were markedly reduced in PAR-1 knockout mice. Thrombin also increased brain interleukin-1β, and this was absent in PAR-1 knockout mice. In conclusion, thrombin increases interleukin-1β levels and induces intracerebral hemorrhage through PAR-1 activation.

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Acknowledgments

This study was supported by grants NS-057539, NS-073595, NS-079157, and NS-084049 from the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Conflict of Interest

Yingying Cheng, Guohua Xi, Hang Jin, Richard F. Keep, Jiachun Feng, and Ya Hua declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA

    Yingying Cheng, Guohua Xi, Hang Jin, Richard F. Keep & Ya Hua

  2. Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin, China

    Yingying Cheng, Hang Jin & Jiachun Feng

Authors
  1. Yingying Cheng
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  2. Guohua Xi
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  3. Hang Jin
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  4. Richard F. Keep
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  5. Jiachun Feng
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  6. Ya Hua
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Correspondence to Ya Hua.

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Cheng, Y., Xi, G., Jin, H. et al. Thrombin-Induced Cerebral Hemorrhage: Role of Protease-Activated Receptor-1. Transl. Stroke Res. 5, 472–475 (2014). https://doi.org/10.1007/s12975-013-0288-8

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  • DOI: https://doi.org/10.1007/s12975-013-0288-8

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