A multicenter study led by scientists at the University of Pittsburgh School of Medicine shows that mild traumatic brain injury after blast exposure produces inflammation, oxidative stress and gene activation patterns akin to disorders of memory processing such as Alzheimer's disease. Their findings were recently reported in the online version of the Journal of Neurotrauma.
Blast-induced traumatic brain injury (TBI) has become an important issue in combat casualty care, said senior investigator Patrick Kochanek, M.D., professor and vice chair of critical care medicine and director of the Safar Center for Resuscitation Research at Pitt. In many cases of mild TBI, MRI scans and other conventional imaging technology do not show overt damage to the brain.
"Our research reveals that despite the lack of a lot of obvious neuronal death, there is a lot of molecular madness going on in the brain after a blast exposure," Dr. Kochanek said. "Even subtle injuries resulted in significant alterations of brain chemistry."
The research team developed a rat model to examine whether mild blast exposure in a device called a shock tube caused any changes in the brain even if there was no indication of direct cell death, such as bleeding. Brain tissues of rats exposed to blast and to a sham procedure were tested two and 24 hours after the injury.
Gene activity patterns, which shifted over time, resembled patterns seen in neurodegenerative diseases, particularly Alzheimer's, Dr. Kochanek noted. Markers of inflammation and oxidative stress, which reflects disruptions of cell signaling, were elevated, but there was no indication of energy failure that would be seen with poor tissue oxygenation.
"It appears that although the neurons don't die after a mild injury, they do sustain damage," he said. "It remains to be seen what multiple exposures, meaning repeat concussions, do to the brain over the long term."
Co-authors include researchers from the Safar Center for Resuscitation Research and the University of Pittsburgh School of Medicine; University of
California, San Diego; ORA Inc., of Fredericksburg, Va.; Walter Reed Army Institute of ResearchDyn-FX Consulting Ltd, Amherstburg, ON; Uniformed Services University of the Health Sciences, Bethesda, MD; and Integrated Services Group, Inc., Potomac, MD.
The project was funded by the Defense Advanced Research Projects Agency.
About the University of Pittsburgh School of Medicine
As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.
Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see http://www.