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Tissue plasminogen activator neurovascular toxicity is controlled by activated protein C

Article Abstract:

The tissue plasminogen activator (tPA) potentiates apoptosis in ischemic human brain endothelium and in mouse cortical neurons treated with N-methyl-D-aspartate (NMDA), which directly activates caspase-9 to caspase-3 without amplification through the Bid-mediated mitochondrial pathway is reported. Activated protein (APC) blocks tPA's neurovascular toxicity and may add substantially to the effectiveness of tPA therapy for stroke.

Author: Griffin, John H., Fernandez, Jose A., Zlokovic, Berislav, Dong Liu, Tong Cheng, Huang Guo, Xiaomei Song
Publisher: Nature America, Inc.
Publication Name: Nature Medicine
Subject: Health
ISSN: 1078-8956
Year: 2004

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Activate protein C inhibits tissue plasminogen activator-induced brain hemorrhage

Article Abstract:

An activated protein C (APC), a plasma serine protease with systemic anticoagulant, anti-inflammatory and antiapoptotic activities and direct vasculoprotective activities blocks tissue plasminogen activator (tPA)-mediated brain hemorrhage after transient brain ischemia and embolic stroke in rodents. It is shown that APC, by reducing tPA-mediated hemorrhage, may improve thrombolytic therapy for strokes.

Author: Griffin, John H., Cheng, Tong, Fernandez, Jose A., Zlokovic, Berislav V., Deane, Rashid, Zhang Li, Dong Liu, Zhenhua Wu, Petraglia, Anthony L., Thiyagarajan, Meenakshisundaram, Zhihui Zhong, Maggirwar, Sanjay B., LaRue, Barbara, Chopp, Michael
Publisher: Nature America, Inc.
Publication Name: Nature Medicine
Subject: Health
ISSN: 1078-8956
Year: 2006
Brain, Brain hemorrhage

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Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective

Article Abstract:

Research shows that the activated protein C protects the brain from ischemic injury by direct prevention of apoptosis in hypoxic human brain endothelium through tumor suppressor protein 53, normalization of the pro-apoptotic Bax/Bcl-2 ratio and by decreasing the caspace-3 signaling. Furthermore, low-dose activated protein C possesses neuroprotective effects in vivo.

Author: Liu, Dong, Griffin, John H., Cheng, Tong, Fernandez, Jose A., Castellino, Francis, Rosen, Elliot D., Fukudome, Kenji, Zlokovic, Berislav V.
Publisher: Nature America, Inc.
Publication Name: Nature Medicine
Subject: Health
ISSN: 1078-8956
Year: 2003
Japan, Prevention, Tumor suppressor genes, Cerebral ischemia, Apoptosis, Tumour suppressor genes

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Subjects list: Research, United States, Endothelium, Tissue plasminogen activator, Protein C, Physiological aspects
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