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New Insights Into Brain's Repair System Point to Improved Stroke Therapies

Dr. Walter Koroshetz, deputy director of the National Institute of Neurological Disorders and Stroke, discusses brain-computer interfaces and stroke recovery. [AAAS/Carla Schaffer]
New research is revealing how the stroke-damaged brain can respond to treatment, even after the crucial first six months when most recovery typically occurs, a leading stroke expert said at a briefing arranged by AAAS with support from the Dana Foundation.

Dr. Walter Koroshetz, deputy director of the National Institute of Neurological Disorders and Stroke, said research on the brain's plasticity as well as some striking developments in robotics and brain-machine interfaces are giving new hope for stroke patients.

He called the science of stroke recovery "the brightest and most exciting area in stroke research." But in remarks at the 22 May Capitol Hill briefing — hosted by AAAS in conjunction with Rep. Chaka Fattah (D- Pa.) — Koroshetz offered some sobering statistics on the prevalence, impact and cost of stroke.

A Preventable but Growing Problem

Strokes occur when blood flow to a part of the brain is blocked by a clot or when blood vessels break and bleeding into brain tissue occurs. There are almost 800,000 new strokes each year in the United States, and it remains the fourth leading cause of death. The average lifetime cost of a clot-caused (or ischemic) stroke is $140,048, Koroshetz said. Such strokes account for about 87 percent of cases, according to the American Stroke Association. Globally, the picture is no better. Stroke incidence is growing at its fastest rate in the developing world, Koroshetz said, due largely to the spread of the Western diet of red meat, sugary desserts and high-fat and processed foods. Stroke is now the leading cause of death in China and, globally, it is the 3rd leading cause of death.

Stroke is not itself a disease, Koroshetz noted, but rather the consequence of diseases of the blood vessels such as hypertensive vascular disease (due to high blood pressure) and deposits of cholesterol in arteries (atherosclerosis). Those diseases worsen for decades before they trigger a stroke. The good news is that up to 70 percent of strokes are considered preventable by fairly simple measures such as blood pressure control, improved diet and exercise.

In fact, attention to such treatable risk factors has brought a steady decline in the annual risk of stroke for individuals, Koroshetz said. But because stroke risk rises sharply after age 60, the aging of the large "baby boomer" population means the United States is still on course for a 21.9 percent increase in stroke prevalence by 2030.

"The key thing is that a lot of stroke is preventable," echoed Rep. Fattah, the ranking Democrat on the House Appropriations Subcommittee on Commerce, Justice, Science, and Related Agencies. "We all need to be working together on some of these issues. We need to communicate better to people about diet and lifestyle" as factors in stroke prevention.

The impact of strokes can range from minor, asymptomatic lesions visible on brain scans, to major damage that can cause death or severe disability such as paralysis, imbalance, seizures, inability to speak or understand language, disturbances of vision or feeling, and memory loss. Stroke symptoms usually occur suddenly, Koroshetz said, and it is important to know them because time is of the essence for the initial treatment of stroke. For instance, administration of a clot-busting protein called tissue plasminogen activator (tPA) can dramatically improve the outcome for those with strokes caused by clots. However the drug works only if the person is treated within three hours from onset of symptoms. Similarly, the lightning-like onset of an extremely painful headache can be the sign of bleeding around the brain from a damaged blood vessel. Fixing the vessel before it bleeds again can be lifesaving.

Still, despite improved prevention and acute treatment of strokes, Koroshetz said, millions of Americans need highly effective recovery strategies to regain brain functions lost at the time of crippling strokes. Standard rehabilitation treatments allow the majority of patients to recover substantial function, he said. But there is much room for improvement, and scientists are using functional magnetic resonance imaging (fMRI) and other methods to better understand what goes on in the brain to make recovery possible.

Projected Global Mortality Trends for Major Diseases

The World Health Organization (WHO) projects that deaths due to cardiovascular disease, including those caused by stroke, will continue to rise if appropriate measures are not taken. [A Global Brief on Hypertension, WHO; Graph: Janel Kiley]

Harnessing the Brain's Natural Plasticity

Unfortunately, brain tissue damaged by stroke cannot grow back, Koroshetz said. Instead, research has shown that when one part of the brain dies in a stroke, another part of the brain "learns" to take over its function. Often, this early functional recovery is associated with engagement of neural circuits on the opposite side of the brain from where the stroke occurred. Investigators have learned that the best recovery occurs when function later switches back to undamaged regions on the side of the brain where the stroke occurred.

Much of what scientists are learning about this dynamic rewiring of the brain, called neuroplasticity, comes from studying brain development in childhood, Koroshetz said. During childhood, wiring connections between brain cells are being formed, strengthened or pruned at an astounding rate as directed by the child's interaction with the environment. That allows the young brain to adapt to circumstances. Koroshetz noted the example of a common condition, termed "lazy eye," in which the eyes are not perfectly aligned and the child preferentially focuses with one eye. The other, so-called "lazy eye" will become blind over time. The eye itself is perfectly normal, Koroshetz said, but the brain circuits that should serve that eye deteriorate due to lack of neural activity. The most common treatment is simply to force the brain to start using the "bad" eye by putting a patch over the "good" eye.

[MedicalRF/Science Source]

"The stimulus the brain is getting has a lot to do with the rewiring," Koroshetz said, and that same principle applies in the treatment of stroke, where neural development patterns that have been suppressed since childhood can start working again and be enhanced and molded by intensive rehabilitation therapy. He noted an Emory University-led study with stroke patients who had a disabled arm. Researchers immobilized the good arm, thereby forcing the patient to use the weaker arm. Patients gained dexterity in the affected arm, including some who started the treatment regime as long as 21 months after their strokes.

At the cellular level, the brain's plasticity can be seen in individual neurons, including growth of new axons, long fibers that can connect new regions of the brain after stroke. When mice with stroke-like symptoms recover in an enriched environment with lots of opportunity for physical activity and sensory stimulation, their neurons also show new growth of branch-like extensions (called dendrites) that are crucial for receiving communication from the axons of other neurons. "In animal models, you can actually see the rewiring occurring," Koroshetz said.

New Approaches Offer Hope

As scientists learn more about these intrinsic repair processes, they are finding more potential targets for therapies. But most relevant for patients right now, Koroshetz said, are the efforts to improve standard rehabilitation care. Studies suggest that intense physical therapy — even after the crucial six month window after the stroke — can produce results.

Koroshetz noted a clinical trial of stroke patients from five hospitals in Florida and California which showed that intensive rehabilitation, either with in-home exercises or on a specially outfitted treadmill, led to improved walking ability as compared to "standard of care" rehabilitation. Most surprising, Koroshetz said, was the finding that even six months after their strokes, patients who had received only standard care could still make substantial improvement in walking by undergoing intensive treadmill training.

"This tells us that our standard of physical and rehabilitation therapy after a stroke is not optimal," Koroshetz. Patients often can benefit from more intensive therapy regimes, he said, and clinicians, patients and health care systems need to recognize that.

For those whose strokes have left them beyond the reach of available rehabilitation methods, researchers are exploring more dramatic options. Koroshetz noted work with brain-machine interfaces using implanted electrodes that can record neuronal signals in the motor cortex of the brain. In a study reported last year, a woman paralyzed by a stroke learned to use her thoughts to generate neuronal signals to steer a robot arm to grab a bottle of coffee and lift it to her lips. Such studies also provide unique data from neural circuits as they "learn," he said.

Robotic systems also can enhance more traditional rehabilitation methods. Researchers have developed "therapeutic exoskeletons," motor-powered mechanical braces wrapped around legs or arms that do much of the work of walking or lifting. The devices can help patients carry out the intensive activity they need to perhaps trigger some of the brain's intrinsic repair mechanisms.

New recording technologies, such as optical probes that can detect tiny flashes of light by thousands of firing nerve cells, offer new possibilities for listening in on the electrochemical "language of the brain," Koroshetz said. The BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies), announced by President Barack Obama at the White House on 2 April, should greatly expand the amount of information scientists can glean from new technologies for recording the activity in brain circuits, Koroshetz said, offering insights on the process occurring as a brain rewires itself after a stroke.

Author

Earl Lane