Mild blast injury causes molecular changes in brain akin to Alzheimer, Pitt team says
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.”
Definition of Mild Traumatic Brain Injury (MTBI)
The term mild traumatic brain injury (MTBI) is used interchangeably with the term concussion. An MTBI or concussion is defined as a complex pathophysiologic process affecting the brain, induced by traumatic biomechanical forces secondary to direct or indirect forces to the head. MTBI is caused by a blow or jolt to the head that disrupts the function of the brain. This disturbance of brain function is typically associated with normal structural neuroimaging findings (i.e., CT scan, MRI). MTBI results in a constellation of physical, cognitive, emotional and/or sleep-related symptoms and may or may not involve a loss of consciousness (LOC). Duration of symptoms is highly variable and may last from several minutes to days, weeks, months, or even longer in some cases.
Magnitude of TBI and MTBI
An estimated 75%-90% of the 1.4 million traumatic brain injury (TBI)-related deaths, hospitalizations, and emergency department visits that occur each year are concussions or other forms of MTBI.
Approximately 1.6 – 3.8 million sportsand recreation-related TBIs occur in the United States each year. Most of these are MTBIs that are not treated in a hospital or emergency department.
Blasts are an important cause of MTBI among military personnel in war zones.
Direct medical costs and indirect costs such as lost productivity from MTBI totaled an estimated $12 billion in the United States in 2000.
Individuals with a history of concussion are at an increased risk of sustaining a subsequent concussion.
Duration of symptoms is highly variable and may last from several minutes to days, weeks, months, or even longer in some cases. Research shows that recovery time may be longer for children and adolescents.
Symptoms or deficits that continue beyond three months may be a sign of post-concussion syndrome. (See the list of common signs and symptoms of MTBI.)
With proper diagnosis and management, most patients with MTBI recover fully.
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.
Traumatic brain injury can have wide-ranging physical and psychological effects. Some signs or symptoms may appear immediately after the traumatic event, while others may appear days or weeks later.
Mild traumatic brain injury
The signs and symptoms of mild traumatic brain injury may include:
Loss of consciousness for a few seconds to a few minutes
No loss of consciousness, but a state of being dazed, confused or disoriented
Memory or concentration problems
Dizziness or loss of balance
Nausea or vomiting
Sensory problems, such as blurred vision, ringing in the ears or a bad taste in the mouth
Sensitivity to light or sound
Mood changes or mood swings
Feeling depressed or anxious
Fatigue or drowsiness
Sleeping more than usual
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.
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