Leading Advances in the Science of Strokes

Despite advances in research and treatment, stroke continues to be a dangerous and worrisome health issue. Stroke ranks as the 4th leading cause of death in the U.S., and approximately 800,000 people in this country have a stroke each year. Only heart disease, cancer and chronic lower respiratory diseases are more deadly. There are three main types of stroke; ischemic strokes, hemorrhagic strokes and transient ischemic attacks (TIAs), also referred to as mini-strokes. Ischemic strokes are caused by a narrowing or blocking of arteries to the brain. Hemorrhagic strokes are caused by blood vessels in and around the brain bursting or leaking.

Stroke research and knowledge during the past quarter century has flourished thanks to Dr. John Hallenbeck, ’64

Solving mysteries related to that affliction known as the “silent killer” has defined the work of Dr. John Hallenbeck. Hallenbeck, a 1964 graduate of the University of South Dakota School of Medicine (two-year program), occupies a prominent and critical place in the evolution of stroke research and science.

Under his direction, and resulting from his research, significant advances have been made in the understanding of strokes, particularly the mechanisms involved in the pathobiology of ischemic stroke damage. This work has helped guide efforts that resulted in improved treatment of strokes.

Dr. Hallenbeck’s interest in research began when he was a student at the University of South Dakota School of Medicine. “I was offered a chance to do some work in a laboratory, and I found out that I really enjoyed it,” Hallenbeck recalled. During a subsequent residency in neurology at the University of Michigan Hallenbeck was able to once again work on research projects. That experience confirmed for him that research was an enjoyable, rewarding aspect of health care and medicine. And the topic – translational neuroscience – portended a theme that would dominate his working career. “The experience at Michigan,” he explained, “set things up for the rest of my life.”

It was the era of the Vietnam War, and Hallenbeck, a native of Rochester, Minn., and the son and grandson of physicians, signed up for the Berry Plan with the U.S. Navy, which permitted completion of his neurology residency. “The Navy noticed my background in neurological research,” he explained, “and they assigned me to study decompression problems and spinal cord injuries incurred by Navy divers.”

By 1976 his neurological emphasis had shifted to strokes, and in 1983 he was named chief of neurology in the Neurology Department at the National Naval Medical Center in Bethesda. M.D. He was also named vice-chair and then chair for research at the Uniformed Services Hospital of the Health Sciences, also in Bethesda. In that dual capacity he saw patients, helped train naval physicians, and continued his involvement in research. When he retired from

the Navy in 1991, after a busy 20 years of service, he literally walked across the street and began working full time as a senior investigator for the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health.

“NINDS was very appealing,” Hallenbeck explained, “because they offered me the opportunity to conduct important research projects related to stroke in areas that could be characterized as high risk – high reward research.”

Hallenbeck was indeed offered a golden opportunity – he would be able to establish and direct a new research team focused on stroke. And so, in 1991, he organized a clinical investigations section and began a series of complex analyses related to states of natural and induced tolerance to brain ischemia. Later, a stroke diagnostics and therapeutics section was combined with the clinical investigation section and an NIH Stroke Branch was formed with Hallenbeck as branch chief. Early on the focus was basic stroke research, but soon the goal became translational stroke research. Hallenbeck has been at the helm of the Stroke Branch since the outset.

It’s been a fruitful 23 years.

“When we began our research at NINDS,” recalled Dr. Hallenbeck, “it was generally held by the medical and scientific community that single factors caused strokes and stroke damage.”

Early on, Hallenbeck led research that revealed that inflammatory and immune system responses were involved in strokes.

Hallenbeck and his group of researchers recognized that there isn’t a single, dominant cause of physical damage during stroke. “We know now, for example, that the process by which the brain is damaged during a stroke doesn’t have a single determinant factor, but is instead multi-modal. We concluded that there are multiple mechanisms and many processes working in a network-like fashion during a stroke.”

This new insight – as pioneered by the Hallenbeck team and other investigators – guided further research, and helped the medical community better understand strokes.

“I was a very early voice supporting the ‘systems biology’ idea, even when there were high levels of skepticism,” said Hallenbeck. “The scientific community has since come around to strongly support this idea.”

One of the central benefits of acknowledging the “systems biology,” multi-modal analysis, is reflected, according to Hallenbeck, in the rising interest in targeting network dynamics in therapies pursued by medical science to treat stroke victims. “We raised awareness that drug therapies aimed at a single protection of brain cells during stroke might have failed because they targeted only single factors, rather than considering the whole biological system.”

New drugs and new protocols aimed at rapidly restoring brain perfusion are now limiting stroke damage, and helping patients recover from the severe effects of stroke. “We still need a lot more work to understand how to make brain cells more resistant to the stress of brain ischemia,” said Hallenbeck.

In recent years the Stroke Branch has been working to determine how to suppress stokes. Hallenbeck is a leader in efforts to study immune and inflammatory mechanisms as they relate to the initiation and progression of stroke, and also in the area of novel approaches to stroke prevention. His work uncovering the pathobiology of strokes and the mechanisms of strokes is considered seminal in the field.

“It has been exciting and rewarding work,” said Hallenbeck. “What drives everything is the hope that we can one day prevent strokes or secondary strokes. It is especially meaningful that my work has helped open paths toward minimizing disease, suffering and death.”

This story originally appeared in the Fall/Winter 2014 issue of South Dakotan M.D. magazine. Read the full issue.