Biomarker Test May Give Early Warning Of Brain Woes

UF scientists have discovered they can use an approach similar toone commonly used in HIV or pregnancy testing to find bits of axons -nerve fibers that help brain cells communicate - in the blood andspinal fluid of laboratory rats modeling human spinal cord or traumaticbrain injuries.

The discovery could lead to tests for the clinic or battlefield todiagnose ailments with just a few drops of blood, bypassing cumbersomeand expensive CT or MRI brain scanning equipment. The researchersreport their findings in the current online edition of Biochemical andBiophysical Research Communications.

The cellular debris, derived from a protein called NF-H, was not foundin the blood or other fluids of healthy animals and humans. That leadsresearchers to believe it is a biomarker, a substance in blood thatsignals the presence of disease or injury.

"We could easily see that this particular protein is detectable verysoon after a disease starts or an injury occurs," said Gerry Shaw,Ph.D., a professor of neuroscience in the College of Medicine. "A lotmore of it is then released in the two or three days following a brainor spinal cord injury, which is interesting because it signals a kindof brain cell death that you could potentially do something abouttherapeutically."

The test would be helpful in emergency rooms or in combatsituations if it could be developed into a simple handheld device thatcould confirm brain or spinal injury.

"Shaken-soldier syndrome is a traumatic brain injury that shows inveterans who have survived roadside blasts," said Douglas Anderson,Ph.D., chairman of neuroscience at the McKnight Brain Institute whoparticipated in the research. "In patients who are unconscious but withno penetrating head wounds, it would be extremely helpful for emergencymedical technicians to test for a marker to see how severe the injuriesare. Then perhaps something can be done early on."

Shaw, who, along with UF, has interest in a company to market thebiotechnology, said studies already under way will seek to determinewhether the protein is detectable in people who have had strokes or whosuffer from amyotrophic lateral sclerosis, a debilitating disorderfrequently referred to as ALS or Lou Gehrig's disease. Further studieswill evaluate patients suffering from Alzheimer's disease and otherserious damage and disease states of the nervous system.

Drug researchers can already use the technique to monitor theeffectiveness of experimental medicines in animal models of stroke andtraumatic brain injury.

"This may become an important clinical marker, but it's also importantin terms of experimental work for basic scientists," said Dena Howland,Ph.D., an assistant professor of neuroscience at UF who investigatestherapies for spinal cord repair and another of the paper's authors."It's a way for us to assess whether our interventions are working."

Investigators detect the NF-H protein with a widely usedscreening method called an ELISA, short for enzyme-linked immunosorbentassay. Versions of it are used to test women for pregnancy and screenpatients for HIV. It uses components of the immune system calledantibodies, which have a natural affinity to latch onto certaincompounds.

In this case, Shaw developed antibodies that react positively to thepresence of NF-H. The structure of the molecule lends itself to easydetection, because it contains protein sequences that are repeateddozens of times, each of which can be bound by a detection antibody,increasing the sensitivity of the test. Other potential biomarkers maybe identifiable by only one short, non-repeating sequence, making thetask more difficult.

"NF-H is a very stable protein; one that does not degrade easily," saidJean-Pierre Julien, Canada research chair in the mechanisms ofneurodegeneration at theUniversitéLaval in Quebec, who was not connected with the UF study. "It makessense that when there is damage to axons this protein would be releasedand would be detectable."

The next step is for researchers to determine whether the release ofNF-H is a universal characteristic of all brain injury and disease.

If so, scientists hope the test will give early warning of disorderssuch as ALS, Parkinson's disease and Alzheimer's disease, which do muchdamage before actual symptoms appear in patients.