Research

What the Research Shows About Timing

Medically reviewed by Dr. Matt DeGaetano

A common misunderstanding about brain injury blood testing is that it is only informative in the first day or two after injury. The published record says otherwise, and it is worth walking through carefully.

Where the short windows come from

The FDA's cleared indications for GFAP and UCH-L1 testing specify testing within 12 hours of injury in the original 2018 authorization and 2021 and 2023 clearances [, , ], and within 24 hours in the 2024 bedside clearance []. Those windows exist because the cleared purpose of those tests is narrow: helping an emergency physician decide whether a head CT is needed. For that specific decision, the earliest hours are what matter.

The window is a property of that regulatory use, not a biological expiration date. The FDA itself extended it from 12 to 24 hours as evidence accumulated [].

What peer-reviewed research shows beyond the acute window

Months.

In a National Institutes of Health cohort published in Neurology, serum NfL remained significantly elevated compared with controls throughout five years of follow-up after TBI, and GFAP showed a biphasic pattern, declining over the first months and rising again at later visits [].

Years.

In a Cambridge-led cohort published in Brain, GFAP showed secondary, temporally distinct elevations up to and beyond five years after injury, and NfL levels measured around eight months predicted the rate of white-matter volume loss years later [].

Decades.

In a Monash University cohort published in Brain, patients a mean of 22 years after a single moderate to severe TBI had UCH-L1 levels 67 percent higher and phosphorylated tau 181 levels 27 percent higher than matched controls, and those levels correlated with white-matter microstructure and verbal memory performance [].

The field's synthesis.

A 2025 systematic review in the Journal of Neurotrauma examined 30 studies of blood protein biomarkers measured a year or more after injury and found reproducible differences between TBI patients and controls in the chronic phase, while noting that the overall strength of evidence is still developing [].

The National Academies' 2022 report recommends that TBI classification be updated as the person's condition evolves [], and its 2023 biomarker workshop identified longitudinal biomarker measurement, understanding injury progression and late complications, as a research priority [].

What we do and do not claim

We do not claim that any blood test taken weeks or months after an injury is FDA-cleared for that use. No such clearance exists. Testing outside the acute window is laboratory-developed testing performed in certified clinical laboratories, ordered by a physician, and interpreted alongside examination findings, history, and imaging.

What the published record supports is narrower and still significant: measurable, objective biomarker abnormalities persist in many patients from the subacute period through the chronic phase, in some cohorts more than a decade after injury [, , , ]. A physician evaluating a patient months after a crash is not operating outside the science by ordering objective testing. The science is exactly where that evaluation now lives [, , ].