Domenico Tupone, PhD: Researching Therapeutic Hypothermia for Better Stroke Treatment

Dr. Domenico Tupone, PhD, Department of Neurological Surgery at OHSU

Dr. Domenico Tupone, PhD, Department of Neurological Surgery at OHSU

When I first met Domenico Tupone at a reception for the Italian Film Festival in Portland, I would not have guessed he is an Instructor and Researcher in the Department of Neurological Surgery at Oregon Health and Sciences University. Charming and friendly with a quick sense of humor, Domenico is an easy fellow to get to know. He is not pretentious about his work; he is genuinely excited about his research and his fascination is contagious.

Recently, I interviewed him in his office at OHSU where he started our time by brewing us both an espresso.

Domenico grew up in the little town of Lanciano in the hills of Abruzzo, located about 14 kilometers inland from the Adriatic. From a young age, he was a gregarious boy with an insatiable curiosity to learn the mechanics of everything.

Dr. Domenico Tupone, PhD, Department of Neurological Surgery at OHSUDr. Domenico Tupone, PhD, Department of Neurological Surgery at OHSU

“My father would give me radios and things and the only interest for me was in taking them apart to find out how they worked,” he laughs. His father was an ironworker and mechanic; his mother was head nurse in a neonatal unit.

Domenico obtained his PhD in Neurophysiology in 2010 from the Alma Mater Studiorum-University of Bologna. His studies fueled his fascination with the human brain and the intricate way in which it functions. While he was at university in Bologna, the Italian Sleep Research Society (SIRS) presented him with the annual “Igino Fagioli” award for the best doctoral thesis in basic sleep research, for his neurophysiological studies on the relationship between REM sleep and central regulation of metabolism.

Domenico’s research at OHSU now focuses on the central neural regulation of body temperature. He is looking for a way to turn off the body’s internal heat regulators, and recreate a state similar to hibernation that could allow better induction of hypothermia for treatment of stroke patients.

A stroke is a sudden interruption in the blood supply of the brain. Because stroke occurs rapidly and requires immediate treatment, it is essential that victims receive effective medical care immediately. “The long term side effects of a stroke are depending on which part of the brain is injured, and how severely it is injured,” Domenico explains.

The statistics for the impact of stroke are daunting. In the United States alone, approximately 795,000 people have a stroke every year. Stroke is the fifth leading cause of death in the US, killing nearly 129,000 people a year; in fact, stroke causes 1 of every 20 deaths in this country.

“During stroke the brain is still active and working; it is still trying to reestablish a normal situation within the brain and in the body by controlling your body physiology.”

Fever is another side effect of stroke and is often resistant to common drug therapies. Fever during stroke is harmful because the increased temperature accelerates brain metabolism and increases the extent of the injuries. “During the ischemic stroke or brain hemorrhage, areas of the brain and then neurons are in lack of oxygen and nutrient which are normally transported by the blood. An active brain under this condition is more prone to injuries. In this circumstance, body hypothermia and then reduction of brain temperature could help by reducing brain metabolism to reduce the extent of the injuries.”

In other words, by reducing temperature, you reduce metabolism; by reducing the temperature of the brain, you slow down the chemical reaction and you slow down the time for damage. Unfortunately, the brain and body fight against being cold, and “the more we try to cool the body, the harder the brain and body work to stay warm, leading to more damage for the patient.”

“The body uses several involuntary processes to regulate against cold; when we are cold, our muscles shiver, our circulatory system restricts blood flow to our extremities to keep our organs warmer, and we activate function of an organ called brown adipose tissue (BAT) which generates heat.” Despite best efforts and use of medications, these involuntary processes continue.

“There are several treatments used to bring down the body’s temperature. Several types of cooling devices and drugs,” says Domenico. “But their effectiveness in stroke treatment is not completely proved yet. It can take a very long time to cool the body only a few degrees. We need some new and more effective approaches. Replicate hibernation can help to not only reduce the temperature but also reduce drastically brain activity. “

An animal in hibernation is not asleep but in a state of inactivity, characterized by low body temperature, slow breathing and heart rate, and low metabolic rate. Yet, the brain is constantly working, maintaining its connections and memory.

Domenico is experimenting with the hypothesis that a hibernation-like state can be duplicated in non-hibernating mammals, and eventually in humans. However, finding a way to induce the characteristics of the hibernation state all at once is key to its success. In 2013, Domenico successfully accomplished an important first step in this process – he created a hibernation-like state in a rat, a non-hibernating mammal.

“If we can find a way to activate the hibernation function in the human, we can reduce body temperature. If you have stroke we can reduce your fever; we can shift down your metabolism, slow down your respiration, slow down your heart rate, your brain function - everything at once - and still maintain everything in a physiological balance suitable for life.”

Within this balanced state, treatment of stroke would become more effective, and recovery more complete.

The skills he learned at his father’s side and the mechanical engineering he studied in school have been vital to his research. Not many people know that researchers must often build the very equipment they utilize in their research, and any researcher will tell you that one of the hardest parts of their job is writing grants to fund their work. “The research is the passion. Writing grants, looking for your salary is the work.”

Domenico is an accomplished chef. At the age of eight, he discovered his mother’s collection of cooking encyclopedias and asked her to teach him to cook. By the age of ten, he was cooking complete meals for the family. “My mother loved it but she would complain ‘you are making me fat’ because all my cooking at the time was with butter.”

He still enjoys cooking, often preparing elaborate meals with friends. “I like to have people over to my place and we cook together,” Domenico says. Not long ago, he led a cooking demonstration for the Portland-Bologna Sister City Association, teaching the group how to make piadina. He jokes that if he ever stops working in research, he will just cook pizza.

As a member of the Associazione Culturale Italiana di Portland, Domenico helps organize and staff the Portland Italian Film Festival USA. This year’s festival featured ten Italian films and was a great success.

To Domenico, one of the most rewarding aspects of his research is the recognition for what he has accomplished. “It is a thing no one else has done, it is you. The work is unique.”

“The main thing is I like to break things into pieces and see how they work,” he says. “The brain fascinates me; I always ask questions.”

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