The utility of the S100B test is limited, however. It cannot predict how well a patient will do in the long term. For example, those who have low levels of the protein after trauma may have cellular damage not visible on a CT scan. And some patients who do have brain bleeds will recover with no long-term consequences. “We and others are looking for markers that are more sophisticated, markers that correlate with cellular damage and with problems down the road,” says Bazarian.
The S100B test might actually aid in this quest. New research by Bazarian and his collaborators shows that it can accurately predict whether the blood-brain barrier–a molecular gate between the bloodstream and the nervous system that prevents the exchange of proteins and other compounds–is open or closed. (Previously, the only way to measure the status of the blood-brain barrier was an invasive test that involves threading a catheter through the skull into the brain.)
While the status of the blood-brain barrier itself is not a specific marker of traumatic brain injury–the barrier can open for other reasons, including heavy exercise, seizures, and meningitis–it could aid in the interpretation of other biomarkers in the blood. If the blood-brain barrier is closed, proteins that accompany brain injury might not reach the blood, making it difficult to evaluate the results of other tests. “If you don’t find any markers of brain injury in the blood, it could be because there is no brain injury, or because there is brain injury but the gate is closed,” says Bazarian.
The test may also aid in clinical trials of new drugs for treating brain injury. A number of trials for drugs designed to stop inflammation and other harmful biological processes that flair up soon after brain injury have failed, possibly because the drugs did not make it into the brain. If physicians knew whether a patient’s blood-brain barrier was open, they could reassess these drugs and test new ones only in these patients.
In the long term, scientists would like to develop a blood test that can predict the severity of a patient’s injury, as well as his or her prognosis. Banyan Biomarkers, a startup based inAlachua, FL, may be the farthest along in this endeavor. Researchers there are testing ways to detect a panel of biomarkers linked to mild, moderate, and severe traumatic brain injury in humans. Scientists at the company are now looking for these biomarkers in several hundred patients shortly after they suffer brain trauma, to determine when the biomarkers appear in the blood, how long they last, and how reliably they can predict the magnitude of an injury. Ronald Hayes, one of the company’s founders, says that the scientists expect to complete those studies late this year and early next year, and to start the larger-scale trials required for FDA approval in early 2010.