The investigation was a collaboration between Swedish scientists from the Karolinska Institute and researchers from Mayo Clinic. It consisted of laboratory experiments in rats, and appears online in Experimental Neurology, http://www.sciencedirect.com/science/journal/00144886.
The finding is welcome, according to Allen Brown, M.D., Mayo Clinic physiatrist who led the international research team, because it establishes a solid scientific foundation for emphasizing physical training over amphetamine use in stroke rehabilitation programs. In so doing, it helps clarify a treatment question that has been muddy ever since the first animal studies in the 1980s suggested a possible role for amphetamine use in human stroke rehabilitation.
While they were intrigued by the early findings from animal studies, the Mayo Clinic and Karolinska Institute investigators also felt the data from the early animal studies were not fully relevant to treating human stroke patients. To correct this, they designed an investigation in rats that had brain damage similar to that suffered by human stroke patients.
"We were surprised amphetamine use didn't have more of the effect that was suggested by previous studies,'' says Dr. Brown. He adds, "Instead, we found that physical training consisting of teaching rats to walk along a beam had the most powerful effect on recovery. This raises significant questions about the role of stimulant treatment to enhance motor recovery following stroke."
About Stroke
An estimated 750,000 Americans experience a stroke every year. Stroke is the leading cause of long-term disability in the United States, and the third most common cause of death. There are two kinds of stroke. Ischemic stroke occurs when the blood supply of the brain is interrupted, such as when a blood vessel to the brain is blocked by fatty build up in the blood vessels. The second kind is a hemorrhagic stroke, which occurs when the vessel weakens and then ruptures, sending blood into the surrounding tissues.
Despite decades of research, there's no drug therapy that promotes stroke recovery. The closest thing to such a drug is a clot-dissolving treatment known as thrombolytic therapy. Its usefulness is limited, however, as it must be administered in a hospital setting within three hours of stroke. It therefore does not help patients who cannot get to the hospital within that time frame.
About the Investigation
Over the past 22 years, experimental evidence in animals suggested that treatment with stimulants such as amphetamines can positively affect recovery rate after strokelike brain injury by improving the ability to concentrate on a task or thought. However, applying these findings to humans in previous studies of stroke recovery has produced mixed results. One reason is that it's difficult to study stroke recovery because of the variety of possible brain injuries.
Physicians engaged in stroke rehabilitation have been left to puzzle out mixed data. As a result, stroke rehabilitation methods varied, depending on a given physician's interpretation of unclear data. The current study aims to eliminate the confusion by laying a solid foundation of clear laboratory evidence upon which to base best care practices for stroke rehabilitation.
In their experiments with brain-damaged rats, Dr. Brown's research team evaluated how various treatments enabled rats to recover function. The treatments evaluated included regular, repeated physical training sessions of walking on a beam, medication with amphetamines and no treatment at all. Results showed physical training alone had the most positive effect on recovery from brain damage.
This work is just a first step toward understanding the larger brain healing and recovery systems, according to Dr. Brown. "The fact that we've shown physical training alone changes recovery behavior is very interesting, because it makes the point that the stroke rehabilitation therapists themselves have an extremely potent effect on how the genes work to direct recovery," Dr. Brown says. He adds that the most effective stroke rehabilitation treatment likely consists of a combination of therapy approaches tailored to each person -- and may include amphetamine use. But this must be verified in future experiments. "Right now, the finding that physical training has such powerful therapeutic effects is an important advance," he concludes.
Research Team Members and Support
In addition to Dr. Brown, the research team consisted of Börje Bjelke, M.D., Ph.D. and Kjell Fuxe, M.D., Ph.D., both of the Karolinska Institute, Stockholm, Sweden. Mayo Foundation for Education and Research, the Svenska Lakarsallskapet, the King Gustav V and Queen Victoria's Foundation, and the Medical Research Council supported their work.
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Journal
Experimental Neurology