Auch! Repeated head trauma changes brain chemistry in former football players

Auch! Repeated head trauma changes brain chemistry in former football players
Photo by John Torcasio

What happens in the brain after years of football tackles? Spoiler: it’s not just about concussions.

Even without knockouts or dramatic injuries, decades after having left college, the brain may be quietly keeping score.

A new study sampled cerebrospinal fluid of former American football players, looking for changes in chemical messengers from the brain, like dopamine and norepinephrine.

Turns out, repeated head impacts may disrupt these systems in ways that echo long after the helmet’s off. Not all changes were bad, not all players were affected the same, but the patterns were hard to ignore.

Surprisingly, some former college players with higher chemical levels also had worse symptoms. Confused? So were we—but fortunately, the scientist offers an explanation for us.

Brain chemistry after repeated blows
A growing body of research has raised concerns about the long-term effects of repeated head impacts in contact sports. American football, with its frequent collisions and tackles, is one of the most studied.

While traumatic brain injuries such as concussions are a known risk, many players are also exposed to hundreds or thousands of sub-concussive blows throughout their careers.

These injuries often leave no immediate symptoms but may add up over time.

Researchers now believe they could silently alter the brain’s chemistry and, much later in life, increase the risk for mood changes, cognitive problems, and degenerative brain conditions such as chronic traumatic encephalopathy.

In this large study, researchers examined the levels of key brain chemicals, called catecholamines, in the cerebrospinal fluid (CSF) of former football players.

By comparing former professional and college-level players to men with no history of head trauma, the team uncovered distinct patterns that suggest long-term changes in brain function after years of impact exposure.

What are catecholamines?

Catecholamines are chemical messengers made in specific regions of the brain and the adrenal glands. They help brain cells communicate by carrying signals from one cell to another, playing a key role in how the brain functions.

The two key catecholamines in the brain are dopamine and norepinephrine. Dopamine helps signal motivation, movement, thinking, and feeling rewarded when something good happens. It's also a major player in conditions like Parkinson’s, schizophrenia, and ADHD.

Norepinephrine is more like the brain’s alert system. It keeps you focused, manages mood, and helps you respond to stress. Norepinephrine levels are off in conditions like depression, anxiety, and even Alzheimer’s dementia.

These chemicals do not float freely in the bloodstream. Instead, they are released from neurons in the brain and enter the cerebrospinal fluid, the clear fluid in which the brain and spinal cord float.

By measuring catecholamine levels in CSF, researchers can get a snapshot of what is happening deep in the brain.

This approach is especially useful for studying areas where these chemicals are produced (nerd alert: like the locus coeruleus and substantia nigra). Damage to these brain regions areas, or the nerve pathways that carry their signals can lead to significant changes in the level of chemical messengers.

In this study, scientists focused on not just dopamine and norepinephrine themselves, but also their precursors (a precursor is a building block the body uses to make another substance) and breakdown products: l-DOPA and DOPAC for dopamine, and DHPG for norepinephrine.

Measuring these related substances shows how the brain produces, uses, and recycles its chemical messengers.

Lower catecholamines in former players

The researchers examined CSF samples from 120 former football players and 38 men with no history of head trauma.

Players were further divided into two groups based on exposure: former professionals, who had the longest and most intense football careers, and former college players.

CSF was collected and analyzed to measure levels of norepinephrine, dopamine, l-DOPA, DOPAC, and DHPG.

The results revealed lower levels of norepinephrine, l-DOPA, and DOPAC in the football players compared to the unexposed group.

Most pronounced differences were seen in former professionals, suggesting a dose-response relationship between head trauma exposure and chemical changes. In contrast, dopamine and DHPG levels did not differ significantly.

This supports the idea that repeated head impacts can impair the brain’s ability to regulate these critical systems.

The lack of change in dopamine itself may reflect compensatory mechanisms that preserve short-term dopamine signaling despite damage to its pathways.

These findings line up with earlier research in conditions like Parkinson’s and Alzheimer’s, where the brain cells that make catecholamines are damaged or lost. That’s a pretty unsettling thought.

One of the key questions was whether these changes in brain chemistry are reflected in real-life problems.

Surprisingly, the researchers did not find clear connections between catecholamine levels and symptoms across the full group of former players.

In other words, the lowest norepinephrine levels in the CSF were not significantly related to the worst cognitive test results, depression, anxiety, or symptoms like impulsivity or emotional instability.

There were also no differences in these brain chemical levels based on whether players were diagnosed with traumatic encephalopathy syndrome or showed signs of Parkinsonism.

However, a closer look at subgroups offered some insight. Among the former college players, higher levels of norepinephrine, l-DOPA, and DOPAC were linked to worse executive function, more impulsive behavior, emotional dysregulation, and higher anxiety.

This was not seen in the former professional group, which showed lower overall catecholamine levels. How do you explain that?

One interpretation is that in the early or moderate stages of exposure to brain trauma, like in college players, the catecholamine systems become overactive or dysregulated, as a possible way to compensate for injury.

Over time, with continued exposure, these systems may burn out or break down, leading to lower levels. The professional players, having sustained more years of high-intensity impacts, may have crossed that threshold.

This hypothesis, while preliminary, could explain the differing patterns seen between the two groups.

Brain damage and chemical imbalance

The locus coeruleus and substantia nigra, key producers of norepinephrine and dopamin, are located deep within the brainstem.

Unfortunately, these areas are especially vulnerable to the effects of repetitive head trauma. Previous postmortem studies of athletes have shown abnormal protein deposits and cell loss in these regions.

These structural changes may disrupt catecholamine production and release.

Even without overt structural damage, the long axonal (nerve fiber) pathways that carry norepinephrine and dopamine signals can be sheared by rotational forces during head impacts. That's called axonal damage and can sometimes be seen on MRI brain scans as tiny scattered micro-bleeds in the white matter.

Inflammation, chronic immune system activation, and damage to upstream regions like the prefrontal cortex may also interfere with basic brain regulation.

Altogether, these processes create a complex picture of injury and compensation, where the chemical signatures (here messengers in the cerebrospinal fluid) may vary depending on the stage of brain damage.

Cerebrospinal fluid as a window to monitor brain health

The use of cerebrospinal fluid to measure brain chemistry is a powerful tool in neuroscience.

Unlike blood, which reflects the entire body, CSF is in direct contact with the brain and spinal cord. Samples of CSF are, therefore, considered a more direct measure of brain function than blood tests. It captures changes in neurotransmitter production, turnover, and metabolism.

The CSF findings in this study offer early evidence that repeated head trauma affects core neurochemical systems.

In the future, CSF markers might help identify people at risk for cognitive or emotional problems before symptoms become obvious.

They could also serve as targets for treatments that aim to restore chemical balance in the brain.

Whatever you do, take care of your amazing brain. Be smart, stay safe during sports, and wear a helmet when you need one (yes, you can look pretty cool with a helmet on!).

About the paper that inspired:

First Author: Suzan van Amerongen, The Netherlands
Published: Neurology, June 2025
Link to paper: https://www.neurology.org/doi/10.1212/WNL.0000000000213584?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

Pssst - remember to subscribe to our free newsletter!