Non-Human Primate Model for Stroke
OHSU # 1219
The current technology describes a stroke model in the rhesus macaque. The current transorbital approach to model stroke is one that has been successfully used in macaques, squirrel monkeys and baboons with some unique procedural modifications in the current model. Knowledge of the vascular incongruity in rhesus macaques compared to humans led these researchers to test this new model of arterial occlusion.
Strokes in non-human primate models would mimic the human condition more closely if they were located in the cortex of the brain. The current model involves a substantial portion of the cortex of the ischemic hemisphere. The stroke infarct is located in the cortex with very minimal involvement of the deeper structures of the brain. It is thought that the cortex is the most amenable to therapeutic treatment and therefore this model could be used to screen neuroprotectants prior to testing in human clinical trials.
Strokes also cause a defined response in the blood of human patients characterized by lymphocytopenia and an increase in the number of circulating neutrophils and monocytes. As a means of corroborating that this model causes changes in the periphery representative of human stroke, the investigators found pronounced lymphocytopenia, neutrophilia, and an increase in the number of circulating monocytes, which mirrors the response seen in humans and further validates this new stroke model.
Over 700,000 Americans each year suffer a new or recurrent stroke. Stroke kills more than 150,000 people a year in the United States. In 2004, the number of total events in the major markets of the world exceeded 1.4 million and that number is expected to grow. Stroke is the third leading cause of death in the major markets of the world, behind diseases of the heart and cancer. It is estimated that Americans will pay about $65.5 billion in 2008 for stroke-related medical costs and disability.
A similar stroke model exists in the closely related cynomolgus monkey (Macaca fascicularis) which has been used as a model to assess the efficacy of potential stroke therapeutics. However, in this model the cortical infarct which is typically generated has the volume of 1ml, less than 5% of the total ipsilateral hemisphere. In comparison, the current model induces cortical infarcts which involved ~21-30% of the total ipsilateral hemisphere which allows latitude for infact size to be increased or decreased depending on the negative or positive effect of a drug candidate being tested.
Dr. Stenzel-Poore received her Ph.D. in Immunology from Oregon Health & Science University in 1986. She conducted post-doctoral research at Oregon Health & Science University and The Salk Institute for Biological Studies. Following her post-doctoral fellowships, she returned to Oregon Health & Science University in 1993 and is currently a Professor and Interim Chair in the Department of Molecular Microbiology and Immunology.
Dr. West received his Ph.D. from the University of Virginia in 1984 and his M.D. from the University of Virginia in 1989. He conducted post-graduate training at the University of Washington and the University of London – St. George Medical School. He has held assistant professorships at the University of Texas Health Science Center and the University of Washington Harborview Medical Center. Most recently Dr. West was an Associate Professor at Oregon Health & Science University. He is currently a board certified neurological surgeon at the Colorado Brain and Spine Institute specializing in the broad range of micro-neurosurgery and minimally invasive neurosurgery.
Roger Simon joined Legacy Health System in 1999 as Director and Chair of the Robert S. Dow Neurobiology Laboratories. After completing undergraduate work at Penn State, he received his M.D. from Cornell University, did his clinical training at New York Hospital and UCSF, and was a post-doctoral fellow at The Maudsley Hospital in London. He was the Chief of Neurology at San Francisco General Hospital from 1981 to 1994, during which time he was also a professor of neurology at the University of California at San Francisco. Prior to joining Legacy, Dr. Simon was Professor and Chairman of the Department of Neurology at the University of Pittsburgh School of Medicine.
J Cereb Blood Flow Metab. 2009 Apr 22. [Epub ahead of print] “A new model of cortical stroke in the rhesus macaque”
The model is available for collaborative research and drug testing.
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