'Extreme' Research Unearths Significant Findings

by Guy McKhann, M.D.

September 14, 2007

It is possible to break brain functions into large categories. Input systems bring information to the brain about the body’s sensations, such as vision, hearing, touch, smell, taste and balance. Output systems control actions such as walking, reaching, touching, speaking or looking. There also are “higher functions,” which include think­ing, processing information, consciousness and creating.

There is a fourth system that we don’t spend as much time considering: the autonomic nervous system. This is the brain system that controls basic body functions including blood pressure, heart rate, appetite, temperature, and sleep and our body clocks.

Much of this regulation involves the hypothalamus, a cluster of nerve cells deep within the brain. Some of the best work in studying the specific nerve cells involved in the control of these autonomic functions is being done by Cliff Saper and his colleagues at the Beth Israel Deaconess Medical Center in Boston (see “Research Identifies Brain Site of Fever” in The New York Times).

For control of autonomic functions, the hypothalamus responds to internal signals. In response to infection or inflammation, the signals are hormones called prostaglandins. These hormones enter the brain and are recognized by nerve cells in the hypothalamus, which have specific receptors for prostaglan­dins. The resulting response is fever, a temporary resetting of the body’s tem­perature to a few degrees higher than normal.

The Boston group did a slick experiment to determine exactly which nerve cells do this. They used genetic techniques to delete the receptors from only small groups of nerve cells. Eventually, they found a group which, when altered, resulted in no fever response occurring. What these investigators have done is determine not only which nerve cells produce fever, but also how they do it.

A similar strategy is being used to understand other autonomic functions, such as appetite. There is hope for us dieters yet.

How to treat an irregular heart

Older people often develop irregular heart rhythms, usually caused by atrial fibrillation. In atrial fibrillation the coordination between the chambers of the heart is abnormal, and the heart becomes inefficient and may not empty com­pletely.

Within the heart, blood clots may form, be carried in the general circulation and lodge in the brain, causing strokes. The preferred treatment has been to “thin” the blood, thus preventing the formation of the clots. There have been two treatment approaches: aspirin, which works by keeping one of the blood components, platelets, from forming clumps, and warfarin, which works by interfering with the coagulation mechanisms.

Warfarin is the stronger drug, and more effective in preventing strokes. But the risks are higher, with possibly more chances for bleeding, because the blood won’t clot. So what to do?

A research group in Birmingham, England, collected 973 elderly people with atrial fibrillation and divided the group so one-half got aspirin and one-half warfarin (see “Warfarin Trumps Aspirin in Preventing Stroke in Elderly” in HealthDay News). The two groups were followed for almost three years.

The warfarin group did much better, with 21 strokes, compared with 44 in the aspirin group. Most important, there was no increase in bleeding episodes in the warfarin group.

This study probably took a year to organize, and five to six years to complete. This is a slow, expensive way to get an answer, but there is no other way to get this type of reliable data. In this situation, important guidance about how to treat a common problem has been learned.

These two articles represent extreme types of research in brain science. The first defines the cell biology of a common clinical response, fever; the second uses population-based research to aid decisions about treatment to prevent strokes. Both are clearly needed.