Therapy for Strokes

COLUMBUS: Researchers here have developed a new model for testing the effectiveness of therapies for stroke patients.

Reported on August 25, 2008 in the Proceedings of the National Academy of Sciences, the method may be useful in protecting many of the thousands of people each year who suffer debilitating strokes. 

Stroke is currently the leading cause of serious long-term disability and the third leading cause of death in the United States, with 780,000 Americans afflicted by a new or recurring stroke each year, according to the American Heart Association Statistics Committee and Stroke Statistics Subcommittee.

Researchers at The Ohio State University Medical Center’s Dorothy M. Davis Heart and Lung Research Institute are the first to report a minimally invasive technique to re-enact the occurrence of stroke.

“We have been successful in creating a very powerful and robust preclinical model of stroke to help us get a clearer picture of what causes this condition, thus improving the efficacy of our treatment,” says Dr. Chandan Sen, director of research for the Center for Minimally Invasive Surgery at Ohio State’s Medical Center and principal investigator of the study.

“The new model has the ability to screen drugs for their effectiveness in treating stroke patients and bridges the translational gap between laboratory and clinical research,” added Sen.

Strokes occur when the blood flow to the brain is obstructed. Quick treatment is critical to reduce the risk of irreversible complications, which include cerebral swelling and hemorrhaging, paralysis, and death.

“Minimizing injury to the brain in a stroke-affected patient is the key. Improved preclinical models help us understand the biology of strokes and guide us in developing effective therapeutics,” said Sen, who authored the study.

Sen and colleagues, using large animal models, threaded a small platinum coil through the femoral artery in the leg and used a fluoroscope to watch as they guided the coil into the middle cerebral artery of the brain, the blood vessel affected in 70 percent of all human strokes.

The coil blocked blood supply to the area for one hour, after which it was removed, allowing blood to again flow. This “re-enactment” of a stroke mimics what would occur in a patient if the clot was medically dissolved or if blood pressure suddenly rose after the stroke event.

After 24 hours, magnetic resonance images were taken and a three-dimensional reconstruction of the brain was generated using advanced software.  The detailed images enable dissecting the brain digitally to understand the nature of injury on a three-dimensional basis.

“We developed a highly sophisticated experimental system, including a novel surgical approach and state-of-the-art post-image processing, that lends itself to identifying the cause of stroke, as well as investigating the effectiveness of pharmacological therapies,” Sen says. 

The vast majority of previous stroke trials using cell cultures and small animal models have failed to show the effectiveness of potential therapeutic agents. As of 2000, 75 different therapeutic strategies, originating from small animal studies, have been tested in severe-stroke clinical trials and only two of them proved beneficial.

Sen said the brain size and structure of large animals allows for the minimally invasive approach to potentially lifesaving surgical treatment while providing a way to retrieve a real-time look at the blockage.

“We are hopeful that this new approach to study stroke biology and intervention in a preclinical model will prove to be an effective tool to address stroke as a major cardiovascular disease in humans,” Sen said.

Along with Sen, other Ohio State researchers involved in the study were Cameron Rink, Greg Christoforidis, Amir Abduljalil, Marinos Kontzialis, Valerie Bergdall, Sashwati Roy, Savita Khanna, Andrew Slivka and Michael Knopp.

Grants from the National Institutes of Health and the American Heart Association supported this research.