Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation
Thrombosis and inflammation are hallmarks of ischemic stroke still unamenable to therapeutic interventions. High-molecular-weight kininogen (KNG) is a central constituent of the contact-kinin system which represents an interface between thrombotic and inflammatory circuits and is critically involved...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
August 30, 2012
|
| In: |
Blood
Year: 2012, Volume: 120, Issue: 19, Pages: 4082-4092 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2012-06-440057 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1182/blood-2012-06-440057 Verlag, kostenfrei, Volltext: http://www.bloodjournal.org/content/120/19/4082 
|
| Author Notes: | Friederike Langhauser, Eva Göb, Peter Kraft, Christian Geis, Joachim Schmitt, Marc Brede, Kerstin Göbel, Xavier Helluy, Mirko Pham, Martin Bendszus, Peter Jakob, Guido Stoll, Sven G. Meuth, Bernhard Nieswandt, Keith R. McCrae, and Christoph Kleinschnitz |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1581446098 | ||
| 003 | DE-627 | ||
| 005 | 20220815022702.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 181001s2012 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1182/blood-2012-06-440057 |2 doi | |
| 035 | |a (DE-627)1581446098 | ||
| 035 | |a (DE-576)511446098 | ||
| 035 | |a (DE-599)BSZ511446098 | ||
| 035 | |a (OCoLC)1341019511 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Langhauser, Friederike |e VerfasserIn |0 (DE-588)1168172594 |0 (DE-627)1031810927 |0 (DE-576)511446047 |4 aut | |
| 245 | 1 | 0 | |a Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation |c Friederike Langhauser, Eva Göb, Peter Kraft, Christian Geis, Joachim Schmitt, Marc Brede, Kerstin Göbel, Xavier Helluy, Mirko Pham, Martin Bendszus, Peter Jakob, Guido Stoll, Sven G. Meuth, Bernhard Nieswandt, Keith R. McCrae, and Christoph Kleinschnitz |
| 264 | 1 | |c August 30, 2012 | |
| 300 | |a 11 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 01.10.2018 | ||
| 520 | |a Thrombosis and inflammation are hallmarks of ischemic stroke still unamenable to therapeutic interventions. High-molecular-weight kininogen (KNG) is a central constituent of the contact-kinin system which represents an interface between thrombotic and inflammatory circuits and is critically involved in stroke development. Kng−/− mice are protected from thrombosis after artificial vessel wall injury and lack the proinflammatory mediator bradykinin. We investigated the consequences of KNG deficiency in models of ischemic stroke. Kng−/− mice of either sex subjected to transient middle cerebral artery occlusion developed dramatically smaller brain infarctions and less severe neurologic deficits without an increase in infarct-associated hemorrhage. This protective effect was preserved at later stages of infarction as well as in elderly mice. Targeting KNG reduced thrombus formation in ischemic vessels and improved cerebral blood flow, and reconstitution of KNG-deficient mice with human KNG or bradykinin restored clot deposition and infarct susceptibility. Moreover, mice deficient in KNG showed less severe blood-brain barrier damage and edema formation, and the local inflammatory response was reduced compared with controls. Because KNG appears to be instrumental in pathologic thrombus formation and inflammation but dispensable for hemostasis, KNG inhibition may offer a selective and safe strategy for combating stroke and other thromboembolic diseases. | ||
| 700 | 1 | |a Pham, Mirko |d 1978- |e VerfasserIn |0 (DE-588)132435241 |0 (DE-627)522697763 |0 (DE-576)252667034 |4 aut | |
| 700 | 1 | |a Bendszus, Martin |e VerfasserIn |0 (DE-588)1032676426 |0 (DE-627)738634131 |0 (DE-576)175567697 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Blood |d Washington, DC : American Society of Hematology, 1946 |g 120(2012), 19, Seite 4082-4092 |h Online-Ressource |w (DE-627)266886647 |w (DE-600)1468538-3 |w (DE-576)075961938 |x 1528-0020 |7 nnas |a Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation |
| 773 | 1 | 8 | |g volume:120 |g year:2012 |g number:19 |g pages:4082-4092 |g extent:11 |a Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1182/blood-2012-06-440057 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u http://www.bloodjournal.org/content/120/19/4082 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20181001 | ||
| 993 | |a Article | ||
| 994 | |a 2012 | ||
| 998 | |g 1032676426 |a Bendszus, Martin |m 1032676426:Bendszus, Martin |d 910000 |d 911100 |e 910000PB1032676426 |e 911100PB1032676426 |k 0/910000/ |k 1/910000/911100/ |p 10 | ||
| 998 | |g 132435241 |a Pham, Mirko |m 132435241:Pham, Mirko |d 910000 |d 911100 |e 910000PP132435241 |e 911100PP132435241 |k 0/910000/ |k 1/910000/911100/ |p 9 | ||
| 999 | |a KXP-PPN1581446098 |e 3027475746 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"relHost":[{"disp":"Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammationBlood","physDesc":[{"extent":"Online-Ressource"}],"recId":"266886647","note":["Gesehen am 21.04.2023"],"type":{"media":"Online-Ressource","bibl":"periodical"},"language":["eng"],"title":[{"title":"Blood","title_sort":"Blood","subtitle":"journal of the American Society of Hematology"}],"origin":[{"dateIssuedKey":"1946","dateIssuedDisp":"1946-","publisherPlace":"Washington, DC ; Philadelphia, Pa. ; Stanford, Calif.","publisher":"American Society of Hematology ; Saunders ; HighWire Press"}],"part":{"issue":"19","extent":"11","text":"120(2012), 19, Seite 4082-4092","pages":"4082-4092","volume":"120","year":"2012"},"id":{"eki":["266886647"],"issn":["1528-0020"],"zdb":["1468538-3"]},"corporate":[{"role":"isb","display":"American Society of Hematology"}],"titleAlt":[{"title":"Blood online"}],"pubHistory":["1.1946 -"]}],"person":[{"display":"Langhauser, Friederike","given":"Friederike","role":"aut","family":"Langhauser"},{"display":"Pham, Mirko","given":"Mirko","role":"aut","family":"Pham"},{"display":"Bendszus, Martin","given":"Martin","role":"aut","family":"Bendszus"}],"origin":[{"dateIssuedKey":"2012","dateIssuedDisp":"August 30, 2012"}],"note":["Gesehen am 01.10.2018"],"language":["eng"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"title":[{"title":"Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation","title_sort":"Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation"}],"physDesc":[{"extent":"11 S."}],"recId":"1581446098","name":{"displayForm":["Friederike Langhauser, Eva Göb, Peter Kraft, Christian Geis, Joachim Schmitt, Marc Brede, Kerstin Göbel, Xavier Helluy, Mirko Pham, Martin Bendszus, Peter Jakob, Guido Stoll, Sven G. Meuth, Bernhard Nieswandt, Keith R. McCrae, and Christoph Kleinschnitz"]},"id":{"eki":["1581446098"],"doi":["10.1182/blood-2012-06-440057"]}} | ||
| SRT | |a LANGHAUSERKININOGEND3020 | ||