Functional recovery after embolic stroke in rodents by activated protein C.
A serine protease activated protein C has been shown to be a powerful neuroprotectant in stressed neurons and in hypoxic brain endothelium. In a clinically relevant model of embolic stroke in rodents, we now show that administration of activated protein C alone or in combination with tissue plasminogen activator, or both, 4 hours after embolic stroke improves the functional outcome and reduces brain infarction within 7 days of stroke. In contrast, tissue plasminogen activator alone was not protective. Thus, activated protein C may be useful as a new stand-alone therapy for clinical stroke and to extend the time window of thrombolytic therapy.
Zlokovic
Berislav V
BV
Department of Neurosurgery and Division of Neurovascular Biology, Frank P. Smith Laboratory for Neuroscience and Neurosurgical Research, University of Rochester Medical Center, Rochester, NY 14642, USA. berislav_zlokovic@urmc.rochester.edu
Zhang
Chunling
C
Liu
Dong
D
Fernandez
Jose
J
Griffin
John H
JH
Chopp
Michael
M
D000818:Animals; D001522:Behavior, Animal; D001929:Brain Edema / Q000473:pathology / Q000517:prevention & control; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use; D011486:Protein C / Q000378:metabolism* / Q000627:therapeutic use; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D020521:Stroke / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D018696:Neuroprotective Agents; D011486:Protein C; D010959:Tissue Plasminogen Activator