Often on the mind of Gary Fiskum, PhD, are the more than 250,000 people in the U.S. who get resuscitated from cardiac arrest each year, the 6 million living with traumatic brain injuries, and the wounded warriors whose brain whose brains sustain enormous G-forces from roadside bombs in the war zone.
For the past 14 years Fiskum and his research team at the University of Maryland School of Medicine have uncovered vast new understanding of the effects of brain injuries that is helping to improve outcomes of patients with new treatments and protective measures.
For such outstanding work, Fiskum was recently named the University of Maryland 2011 Researcher of the Year. In addition, Jay A. Perman, MD, president of the University of Maryland, says Fiskum is also honored for taking on many junior faculty members into his laboratory, who, in turn, have launched successful research careers. Perman said, "Apart from being Researcher of the Year, he is a great mentor for this year and every year. So we are very proud to have you at the university, Gary. And, I'm very proud to be your colleague." Fiskum is the School's vice chair for research and the Matjasko Professor for Research in Anesthesiology.
Fiskum and his team have described many molecular mechanisms that can damage the brain. Their achievements include describing how different levels of harmful free radicals can be produced from oxygen in the cells, how exposure to certain pesticides can accelerate harmful free radical production, and finding direct evidence for certain brain injury mechanisms after traumatic brain injury. They also found that a chemical called sulforaphane found in broccoli protects the brain against free radical formation following cardiac arrest.
"A human being's metabolic machinery has to be extremely efficient in order to keep producing enough energy to keep bodily systems in order ... And, the brain uses a disproportion of the body's energy," Fiskum told a standing-room-only audience at the Researcher of the Year lecture "Love is Like Oxygen" at the University's founding building, Davidge Hall, on Oct. 27.
The energy-producing bundles in human cells called the mitochondria, fueled by oxygen, have been the root of much of Fiskum's investigations. At Davidge Hall, he summarized current knowledge on the effects of too much or not enough . He and his team are determining the best level of oxygen to give a patient after different forms of acute brain injury. Excess oxygen can actually slow down metabolism, increase neuronal death, and worsen neurological outcomes, according to findings by Fiskum. He said, "We want to know for sure the right amount of oxygen to give a patient following cardiac arrest—normal levels or a super high level, which was the standard of care published by the American Heart Association."
Fiskum's team has identified certain dangers in the use of 100 percent resuscitative oxygen. "The excess of free radicals can cause a variety of molecular modifications to proteins, DNA, lipids, etc. leading in turn to damage to neurons, other brain cells and triggers inflammatory responses, which can promote brain injury." The AHA has changed its guidelines, but Fiskum said despite complete confidence in his preclinical findings, he wished the group would have "at least" waited for clinical trial findings first.
Fiskum and his team also have uncovered evidence of excessive oxidative stress and impaired energy metabolism in certain brain areas following traumatic brain injury. He stresses that the immature brain is particularly vulnerable to oxidative stress and to damage caused by exposure to unnecessarily high levels of oxygen. Traumatic brain injury is the leading cause of death and disability in children and adolescents.
He also emphasized that 1.5 million people sustain traumatic brain injury each year in the U.S. alone.
Another concern, said Fiskum, is that one in four or one in five personnel deployed in a war zone experience some level of traumatic brain injury. His lab is defining the neuropathology caused by exposure to blasts with the goal of developing engineering-based and drug-based approaches to mitigate such injury. There are very few available treatments currently, he said.
The recent Fiskum studies have led to a $3 million dollar grant from the National Institutes of Health and nearly $4 million in funds from the Department of Defense, including a $2.7 million U.S. Air Force grant. However, he insists, "Success should not be measured by grant dollars, but by peer respect for the quality, integrity, and impact of one's research.
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