Urine test might detect brain injury from blasts

A form of brain trauma commonly seen in combat veterans is particularly difficult to diagnose because people who have it often display no neurological symptoms, says Riyi Shi. "Many times they don't even realize they've been injured, and this is particularly alarming because these injuries have been linked to severe long-term psychiatric and degenerative neurological dysfunction." (Credit: UK Ministry of Defense/Flickr)

About one in five wounded soldiers suffers from traumatic brain injury, and an estimated 52 percent of those injuries are blast-induced neurotrauma.

Some of those brain injuries are difficult to diagnose because people don’t always display obvious motor impairment or other neurological symptoms.

“Many times they don’t even realize they’ve been injured, and this is particularly alarming because these injuries have been linked to severe long-term psychiatric and degenerative neurological dysfunction,” says Riyi Shi, a professor in the basic medical sciences department and school of biomedical engineering at Purdue University.

“The underlying mechanisms of injury remain poorly understood, impeding development of diagnostic and treatment strategies.”

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The initial injury is caused by the shock wave from explosions. However, secondary damage can take place in the days and weeks that follow the initial injury—and this secondary damage might be treatable.

Scientists have developed a new strategy to establish a clinically relevant “animal model” that recreates typical human symptom profiles. The model can be used to study the effects and pinpoint mechanisms responsible for ongoing damage that occurs following the initial injury, Shi says.

The findings, published in the Journal of Neurosurgery, suggest that a simple urine test could be used to diagnose the injury—and damaging effects might be alleviated through drug therapy that reduces the concentration of a toxic compound produced by traumatized cells.

Long-term consequences

“Early detection and intervention could potentially mitigate or prevent delayed onset development of significant neurological dysfunction,” Shi says.

The research shows evidence of brain inflammation that may indicate ongoing damage, potentially leading to altered brain function and degenerative diseases.

“We detected structural and biochemical brain damage without obvious motor or cognitive deficits,” Shi says. “These findings highlight the difficulty and importance of early detection, indicating missed early diagnosis and subsequent lack of intervention could lead to serious long-term consequences.”

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A neurotoxin called acrolein is produced within the body after nerve cells are damaged and has been shown to lead to continued damage.  However, the concentration of acrolein could be reduced using the drug hydralazine, which has been approved by the US Food and Drug Administration for hypertension.

The drug was shown to be effective in reducing acrolein levels in previous research led by Shi, who is working to develop a low-dose version for that purpose in humans.

New findings indicate elevated levels of acrolein in brain tissue and in urine from research animals lacking neurological signs of damage. Acrolein concentrations were three times the normal level the first day of the experiment and remained elevated five days later.

Urine tests showing elevated acrolein might indicate trauma despite the lack of symptoms following mild blast injury. Treatment at this point could reduce the risk of developing chronic neurological diseases, Shi says.

The Indiana State Department of Health, National Institutes of Health, and an Indiana CTSI Collaboration in Biomedical Translational Research Pilot Program Grant provided support for the research.

Source: Purdue University