Christian Förch, Nathanael L. Rosidi, Frieder Schlunk, Arne Lauer, Flor A. Cianchetti, Emiri Mandeville, Ken Arai, Kazim Yigitkanli, Xiang Fan, Xiaoying Wang, Klaus van Leyen, Helmuth Steinmetz, Chris B. Schaffer, Eng H. Lo
- Tissue plasminogen activator (tPA) is the only FDA-approved treatment for reperfusing ischemic strokes. But widespread use of tPA is still limited by fears of inadvertently administering tPA in patients with intracerebral hemorrhage (ICH). Surprisingly, however, the assumption that tPA will worsen ICH has never been biologically tested. Here, we assessed the effects of tPA in two models of ICH. In a mouse model of collagenase-induced ICH, hemorrhage volumes and neurological deficits after 24 hrs were similar in saline controls and tPA-treated mice, whereas heparin-treated mice had 3-fold larger hematomas. In a model of laser-induced vessel rupture, tPA also did not worsen hemorrhage volumes, while heparin did. tPA is known to worsen neurovascular injury by amplifying matrix metalloproteinases during cerebral ischemia. In contrast, tPA did not upregulate matrix metalloproteinases in our mouse ICH models. In summary, our experimental data do not support the assumption that intravenous tPA has a deleterious effect in acute ICH. However, due to potential species differences and the inability of models to fully capture the dynamics of human ICH, caution is warranted when considering the implications of these findings for human therapy.
MetadatenAuthor: | Christian FörchORCiDGND, Nathanael L. Rosidi, Frieder Schlunk, Arne LauerGND, Flor A. Cianchetti, Emiri Mandeville, Ken Arai, Kazim Yigitkanli, Xiang Fan, Xiaoying Wang, Klaus van LeyenORCiD, Helmuth SteinmetzORCiDGND, Chris B. Schaffer, Eng H. Lo |
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URN: | urn:nbn:de:hebis:30:3-288894 |
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DOI: | https://doi.org/10.1371/journal.pone.0054203 |
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ISSN: | 1932-6203 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/23408937 |
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Parent Title (English): | PLoS One |
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Publisher: | PLoS |
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Place of publication: | Lawrence, Kan. |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2013/02/08 |
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Date of first Publication: | 2013/02/08 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2013/02/13 |
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Volume: | 8 |
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Issue: | (2): e54203 |
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Page Number: | 9 |
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Note: | Copyright: © 2013 Foerch et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
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HeBIS-PPN: | 331551934 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 3.0 |
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