When brain cells are injured, they release specific proteins into the bloodstream. Measuring those proteins gives providers objective information that does not depend on how a patient describes their symptoms.
GFAP (glial fibrillary acidic protein)
is a structural protein found in astrocytes, the support cells of the brain. It rises in blood after astrocyte injury [1, 2].
UCH-L1 (ubiquitin C-terminal hydrolase L1)
is an enzyme concentrated in the cell bodies of neurons. It rises in blood after neuronal injury [1, 2].
S100B
is a calcium-binding protein found mainly in astrocytes. It has been studied for decades, particularly in Europe, as a screening marker after head injury [24, 25].
Neurofilament light (NfL)
is a structural protein of axons, the long fibers that carry signals between neurons. It rises in blood after axonal injury and has become one of the most studied markers of neurodegeneration [9, 10].
The regulatory history
In February 2018, the FDA authorized the first blood test for evaluating mild TBI, measuring GFAP and UCH-L1, through its De Novo pathway [1]. In January 2021, the FDA cleared a rapid plasma version of the test [2]. In March 2023, it cleared a widely available core-laboratory version [3]. In April 2024, it cleared a whole-blood version that runs at the patient's bedside in 15 minutes [4].
Each of these clearances covers a specific use: helping physicians decide, within hours of injury, whether a head CT is needed. In the pivotal multicenter trial behind the 2018 authorization, the test predicted the absence of intracranial injury on CT with high sensitivity and a negative predictive value above 99 percent [1, 2].
What biomarkers add beyond the scan
A normal CT does not mean an uninjured brain. In the multicenter TRACK-TBI study published in The Lancet Neurology, roughly one in four TBI patients with a normal CT had visible injury on MRI, and blood GFAP levels distinguished those patients from patients with normal MRI with an area under the curve of 0.78 [23]. Day-of-injury GFAP and UCH-L1 levels have also been shown to predict six-month functional outcome, meaning the markers carry information about prognosis, not only about the need for a scan [13].
The honest boundaries
Blood biomarkers are a supportive laboratory finding, not a stand-alone diagnosis. The ACRM diagnostic criteria treat them as one contributing element within a clinical evaluation [8]. FDA clearances cover testing within 12 to 24 hours of injury for CT-triage purposes [1, 2, 3, 4]. Testing outside those windows, and testing for markers such as NfL, is performed as laboratory-developed testing in certified clinical laboratories and interpreted by a provider within the full clinical picture. The published research on those longer time windows is summarized on the timing page.