'Biochemical Storm' Following Brain Trauma An Important Factor In Treatment, University of Florida Researcher Finds
GAINESVILLE—A forceful blow to the head can trigger a “Pacmanlike” enzyme to begin gobbling up important structural proteins in the brain for up to one month afterward — weeks longer than previously suspected, according to a University of Florida Brain Institute researcher.
The finding, based on studies in rats, suggests that treatment for traumatic brain injury must take into account tissue damage that continues to occur long after an accident. Although a number of studies recently have assessed therapies for traumatic brain injury, currently no effective treatment exists.
“Emergency room medical personnel often talk about a golden hour, that if you don’t get a person into treatment within the first hour or so after an injury, a lot of damage has been done to the patient,” said Ronald L. Hayes, director of UF’s planned Center for Traumatic Brain Injury Studies, a component of the university’s multidisciplinary Brain Institute. “With traumatic brain injury, the thought has been that treatment within the first two days is critical.”
But data from Hayes’ lab suggest this critical period may extend much longer.
“In our studies, we’ve found that a biochemical storm that is initiated with an injury continues for at least a month. The implication is that we may need to treat these patients over a much longer period than anyone had ever imagined,” said Hayes, who is reporting his findings on the action of calpains on Saturday (10/23) at the annual meeting of the National Neurotrauma Society in Miami Beach. Calpains are a type of protein-destroying enzyme found in cells throughout the body.
“This is one of a very few research efforts that opens up a potential window for treatment in which we might be able to suppress the harmful activity of calpains while allowing repair to occur,” said Kevin Wang, a senior research associate at Parke-Davis Pharmaceutical Research who is conducting laboratory experiments seeking to block the action of calpains.
Automobile crashes, gunshot wounds, sporting accidents and other incidents cause an estimated 52,000 brain injury deaths each year in the United States, according to the National Institutes of Health. An additional 70,000 people — with men outnumbering women 2 to 1 — suffer a blow that results in substantial ongoing difficulties with communication tasks, coordination, memory and thinking. An estimated 5.3 million people are permanently disabled.
Because of the lasting consequences of brain damage, lifetime costs for care and rehabilitation for a person with a severe injury range from $600,000 to $1.9 million, according to NIH.
Hayes and Brian Pike, an assistant professor of neuroscience, conducted their experiments with colleagues at the University of Texas Medical School before transferring their efforts to UF this past summer. The experiments showed that calpains switch on when calcium floods cells after traumatic brain injury.
The activation of the calpains is associated with the death of brain cells and could contribute to the extensive atrophy and shrinkage of the brain seen after traumatic injury.
“In the past several years, there have been a large number of clinical trials testing treatments for brain injury that have shown no effect,” said Hayes, a professor of neuroscience in UF’s College of Medicine. “Researchers thought they had an effective therapy, but when they tried it, the people didn’t get better. One reason may be that they didn’t treat the patient long enough because the biochemical storm lasted longer than two days.”
To complicate matters, some level of calpain activity may actually be a necessary part of a “resculpting” effort that can repair damage.
“We may have to completely redefine our approach to therapy, because if you try to get in there too early and for too brief a time with a treatment, you might not block the damage that lies ahead,” Hayes said. “But if you give a treatment for too long, you might block some of the self-repair that will make the patient better. Understanding these relationships is critical, and our research is a necessary first step in this effort.”