The Future of Concussion Testing: Can Blood Biomarkers Tell Us What's Happening in the Brain?

One of the most frustrating experiences after concussion is being told, “Your scan is normal.” A normal CT scan or conventional MRI can be reassuring because it helps rule out certain serious structural injuries. But it does not necessarily explain why you are still struggling with headaches, brain fog, fatigue, dizziness, memory problems, or difficulty functioning months after an injury.

For decades, this has been one of the fundamental problems in concussion medicine: how do we objectively measure an injury that often does not appear on conventional imaging? That question is driving an exciting area of neuroscience research involving blood biomarkers, proteins released from injured neurons, inflammatory signals, exosomes, microRNAs, eye movements, and machine learning.

I recently explored this research with neurologist and neuroscientist Dr. Ioannis Mavroudis, whose work sits at the intersection of clinical neurology, neuropathology, traumatic brain injury, and neurodegeneration. His research offers a fascinating glimpse into where concussion medicine may be headed.

What Is a Brain Biomarker?

A biomarker is simply something measurable that gives us information about what is happening biologically. Blood glucose, cholesterol, and troponin are familiar examples. Researchers have long wanted something similarly useful for the brain.

After a brain injury, changes can occur in proteins and signaling molecules associated with neurons, axons, glial cells, inflammation, and other biological processes. Some substances may eventually be detected in blood—and potentially even saliva. The challenge is figuring out what those measurements actually mean. As Dr. Mavroudis emphasized in our conversation, there will probably not be one magical “concussion biomarker.” The future may lie in patterns of multiple biomarkers interpreted alongside symptoms, history, neurological examination, and other testing.

Some Biomarkers Are Already Moving Into Concussion Medicine

This is not entirely futuristic. Biomarkers associated with brain injury are already studied and used in some acute-care contexts, particularly to help determine whether someone with a mild head injury may need a CT scan. But acute diagnosis and recovery prognosis are two different problems.

One test might help determine whether something happened to the brain. A much more sophisticated test would help answer a different question: What is happening now, and where is this person's recovery trajectory headed?

Neurofilament Light: A Clue About Axonal Injury

One biomarker researchers have studied extensively is neurofilament light chain, or NfL. Neurofilaments are structural components of neurons, particularly their axons—the long extensions neurons use to communicate across the nervous system. When axons are injured, neurofilament proteins can be released and eventually become measurable in biofluids.

That makes NfL potentially useful as a signal of neuroaxonal injury. But an elevated NfL does not simply announce, “This person has a concussion.” Levels can be influenced by other neurological conditions and biological factors. Other candidate TBI biomarkers have similar specificity problems, which is why one biomarker is unlikely to equal one diagnosis.

Neurogranin: Are the Synapses Telling Us Something?

Dr. Mavroudis' more recent work has investigated neurogranin, a protein concentrated in neurons and closely involved with synaptic function and plasticity. Synapses are the tiny communication points where neurons exchange information, and neuroplasticity—the brain's ability to modify and reorganize its connections—is fundamental to recovery after brain injury.

A 2025 systematic review led by Mavroudis examined neurogranin as a potential biomarker in mild traumatic brain injury. The findings make it a promising research candidate, while also underscoring the need for larger, standardized, longitudinal studies before it becomes a routine clinical tool.

It is an intriguing possibility: rather than looking only for evidence that a cell or axon was damaged, could we eventually measure something about how well synapses themselves are functioning? That is much closer to the difficulties people with persistent symptoms often describe—brain fog, slowed processing, memory difficulty, mental fatigue, and trouble multitasking. We are not yet at the point where a neurogranin blood test can explain those symptoms for an individual patient, but that is exactly why the research is exciting.

Microglia, Exosomes and the Injured Brain

Another major area of research involves microglia, the resident immune cells of the central nervous system. After injury, they participate in the brain's immune and repair responses. That response is necessary, but inflammatory signaling that becomes dysregulated or prolonged may contribute to secondary injury and persistent neurological dysfunction.

Dr. Mavroudis and colleagues have investigated microglial exosomes after traumatic brain injury. You can think of an exosome as a microscopic biological package released by a cell. These tiny extracellular vesicles can contain proteins, lipids, and genetic regulatory material such as microRNAs, forming one part of how cells communicate.

What makes them particularly interesting is the possibility that some of this biological information could ultimately become detectable outside the brain. Researchers may someday examine patterns within circulating extracellular vesicles to learn more about processes occurring inside the nervous system.

Could a Saliva Test Someday Tell Us About the Brain?

Potentially—and this was one of the more futuristic parts of our conversation. Many biomarkers currently require blood or cerebrospinal fluid. Dr. Mavroudis believes that exosomes and microRNAs could eventually contribute to less-invasive testing, potentially including saliva-based approaches.

We are not there yet, but that is the direction researchers are exploring.

Can We Predict Who Will Have a Difficult Recovery?

This may ultimately be one of the most important applications. Immediately after a concussion, two people can look remarkably similar: both have headaches, dizziness, brain fog, and fatigue. Three months later, one may feel almost completely recovered while the other remains significantly impaired. Why?

Dr. Mavroudis has published on risk factors and predictors associated with prolonged recovery after mild traumatic brain injury. The research points toward recovery as a multifactorial process, rather than one determined by a single injury variable. Biomarkers could eventually become one additional layer of prediction, helping clinicians identify higher-risk patients earlier and intervene more strategically.

Why Eye Movements May Become Part of This Picture Too

Blood is not the only place researchers are looking for objective information. Dr. Mavroudis also uses computerized cognitive testing and virtual-reality-based eye tracking in his clinical work. Eye movements offer a unique window into brain function because even a seemingly simple eye movement requires coordinated activity across multiple neurological systems.

During our conversation, he discussed saccades and antisaccades. A saccade requires you to rapidly move your eyes toward a target. An antisaccade adds another layer: when a stimulus appears, you must inhibit the automatic response to look toward it and instead look in the opposite direction. That introduces attention, inhibitory control, and executive function into an eye-movement task.

Repeating standardized testing over time allows clinicians to examine change, rather than relying exclusively on how someone feels on a particular day. It is another glimpse of where concussion assessment may be heading: not one test, but multiple objective windows into the nervous system.

Post-Traumatic Headaches May Need More Personalized Treatment

Dr. Mavroudis has also published extensively on post-traumatic headache, one of the most common persistent symptoms after concussion. An important takeaway from our conversation is that post-traumatic headache is not necessarily synonymous with migraine. A person may have migraine-like features, tension-type features, cervical contributions, neuralgic pain, or a combination.

He is particularly interested in CGRP—calcitonin gene-related peptide, a signaling molecule already well established in migraine biology—as a potential biomarker related to post-traumatic headache. The long-term goal is not simply to say, “You have headaches after your concussion,” but to better identify an individual's clinical and biological headache phenotype and tailor care accordingly.

What Does Any of This Mean for Someone With a Concussion Today?

Most technologies discussed here are not yet routine tests you can walk into a doctor's office and request. A commercially available test is not automatically a clinically validated concussion test. For now, the practical lesson is different: persistent symptoms after a normal CT or MRI do not mean researchers believe nothing is happening in the brain.

Researchers are actively investigating inflammation, axonal integrity, synaptic function, neuroplasticity, eye movements, cognitive performance, and other physiological systems after mild TBI. While we wait for better testing, we do not have to wait for better care.

From “Your Scan Is Normal” to Personalized Concussion Medicine

Perhaps the most important message from this conversation is that diagnosis is rarely deterministic. It is probabilistic. No single biomarker, MRI, eye movement, symptom questionnaire, or cognitive test is likely to explain an entire human being. The power comes from putting the pieces together.

Imagine combining symptoms, neurological examination, cognitive testing, eye tracking, biomarkers, imaging, and individual medical history to understand not merely whether someone had a concussion, but what may be preventing this particular brain from recovering. Dr. Mavroudis and his team are working toward approaches that combine multiple biomarkers with machine learning to better understand concussion diagnosis and prognosis. That is still research—not clinical reality—but it is a future worth watching.

This article is educational and is not a substitute for individualized medical advice. If you have persistent, worsening, or safety-affecting symptoms, seek evaluation from an appropriately qualified healthcare professional.