TY  - JOUR
A1  - Förch, Christian
A1  - Rosidi, Nathanael L.
A1  - Schlunk, Frieder
A1  - Lauer, Arne
A1  - Cianchetti, Flor A.
A1  - Mandeville, Emiri
A1  - Arai, Ken
A1  - Yigitkanli, Kazim
A1  - Fan, Xiang
A1  - Wang, Xiaoying
A1  - Leyen, Klaus van
A1  - Steinmetz, Helmuth
A1  - Schaffer, Chris B.
A1  - Lo, Eng H.
T1  - Intravenous tPA therapy does not worsen acute intracerebral hemorrhage in mice
T2  - PLoS One
N2  - 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.
Y1  - 2013
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/28889
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-288894
SN  - 1932-6203
N1  - 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.
VL  - 8
IS  - (2): e54203
PB  - PLoS
CY  - Lawrence, Kan.
ER  -