Mild Blast Injury Causes Molecular Changes in Brain Akin to Alzheimer’s Disease, Kochanek-Led Team Says

A multicenter study led by scientists in 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 like Alzheimer’s disease. The findings were recently reported in the online version of the Journal of Neurotrauma.

Blast-induced traumatic brain injury has become an important issue in combat casualty care, said senior investigator Patrick Kochanek, professor and vice chair of critical care medicine in the Pitt School of Medicine and director of Pitt’s Safar Center for Resuscitation Research. In many cases of mild traumatic brain injury, 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,” 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, Kochanek noted. Markers of inflammation and oxidative stress, which reflect 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.”

Coauthors include researchers from Pitt’s Safar Center for Resuscitation Research and the Pitt School of Medicine; University of California, San Diego; ORA Inc., Fredericksburg, Va.; Walter Reed Army Institute of Research, Silver Spring, Md.; Dyn-FX Consulting Ltd., Amherstburg, Ontario, Canada; 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.