From gut bacteria to the brain, a chemical, sodium butyrate traveled through the bloodstream after traumatic injury, where 4 months of treatment helped scientists reduce inflammation, protect brain cells and made seizures less frequent

Post-traumatic epilepsy treatment: A traumatic brain injury may look like it is healing on the outside while the brain continues to change underneath. Inflammation can persist, injured brain circuits can rewire in harmful ways, and weeks, months, or even years after the original injury, post-traumatic epilepsy (PTE) can develop, as per a report.

Researchers at Texas A&M University are studying whether the period between the initial injury and the first seizure could offer a chance to intervene.

Their focus is sodium butyrate, a chemical naturally produced by bacteria in the gut. Once released into the bloodstream, it can travel through the body and reach the brain.


In a study published in Experimental Neurology, a team led by Texas A&M distinguished professor of neuroscience and experimental therapeutics Dr. Samba Reddy found that four months of sodium butyrate treatment was associated with less inflammation, greater survival of existing brain cells, healthier growth of new brain cells, and fewer, less intense seizures following traumatic brain injury, as per an EurekAlert report.

The research was supported by the U.S. Department of War.

The damage can continue after the injury appears to heal

A severe traumatic brain injury can happen after a battlefield explosion, car crash, violent fall or other major impact. While visible injuries may eventually heal, biological changes can continue inside the brain.

Reddy's team is focused on epileptogenesis, the process through which changes in an injured brain can eventually lead to post-traumatic epilepsy.

For decades, TBI-related epilepsy has largely been addressed after seizures begin. Reddy's research takes a different approach by targeting the period when the brain is undergoing changes that could eventually lead to epilepsy.

Reddy said, "Epileptogenesis identifies the earliest biological markers associated with TBI, intervening at the earliest stages, to prevent PTE from manifesting in the first place," as quoted by EurekAlert.

The researcher explained that, “Seizures, memory loss, depression, anxiety and cognitive decline can emerge long after the initial impact has healed,” adding, “If we can intervene during the critical window after the initial injury, we have the potential to not only treat seizures, but to preserve overall brain function,” as quoted by EurekAlert.

The treatment starts with a chemical made in the gut

Sodium butyrate is produced naturally when bacteria in the gut break down foods rich in fiber and other nutrients.

The chemical can enter the bloodstream and cross the blood-brain barrier, giving it a route to influence cells inside the brain.

That connection between the gut and brain is central to the researchers' approach.

Reddy said, “Microbes inside the gut don’t just digest food, they manufacture chemicals that influence inflammation, immune activity, metabolism and even certain brain cells,” adding, “Sodium butyrate is unique because it’s already produced naturally in the body, making it a universal and non-invasive dietary treatment,” as quoted by EurekAlert.

Sodium butyrate may help turn down harmful inflammation

The researchers focused on sodium butyrate's ability to block enzymes known as histone deacetylases, or HDACs.

According to Reddy, HDACs act as molecular switches for immune pathways. Sodium butyrate acts on these switches by turning them off and suppressing harmful inflammatory pathways.

That matters after a brain injury because inflammation is one of the processes linked to the continuing changes inside the injured brain.

In the study, treatment was associated with reduced inflammation and greater survival of existing brain cells. The researchers also observed healthier growth of new brain cells.

After four months, treated animals showed fewer seizures

To test the approach, Reddy and his team used a laboratory technique called controlled cortical impact, or CCI, to recreate conditions associated with severe traumatic brain injury.

The researchers then followed the animals for months, monitoring inflammation, brain changes and seizure development.

After four months, the groups treated with sodium butyrate showed significantly less inflammation and less harmful rewiring of the brain.

They also experienced significantly fewer seizures. When seizures did occur, they were less intense, according to Reddy.

The treatment was also associated with better performance in behavioral tests.

Treated groups showed improvements in recognizing new objects and navigating spatial tests, reflecting stronger learning, memory and adaptability.

The researchers saw more than fewer seizures

The findings suggested that sodium butyrate's effects went beyond reducing seizure activity.

Reddy said the researchers observed greater survival of existing brain cells and healthier growth of new ones.

He said, “It was so exciting, seeing the brain repair itself from the inside out,” adding, “But this is just the beginning, and sodium butyrate is giving us the platform to pursue a new option in the treatment against epilepsy,” as quoted by EurekAlert.

The results point toward an approach that targets the biological changes occurring after TBI rather than waiting until epilepsy has already developed.

The treatment is still experimental

Despite the results, sodium butyrate is not currently FDA-approved for therapeutic use.

The researchers point to previous studies involving sodium butyrate and related butyrate derivatives, as well as the existence of FDA-approved HDAC inhibitors, as reasons the approach could have potential for future clinical research.

Reddy said, “The successful clinical use of related butyrate derivatives in other diseases supports its strong translational potential for conditions like PTE, stroke and cancer,” adding, “Also, because FDA-approved HDAC inhibitors already exist, this epigenetic therapy for epilepsy prevention has potential for rapid translation into clinical trials for patients with TBI,” as quoted by EurekAlert.

Further research is still needed before the approach could be evaluated in clinical trials involving patients with traumatic brain injury.

A decade-long effort to prevent epilepsy before it starts

For Reddy, the research grew from a question he began pursuing more than a decade ago: whether seizures and epilepsy could be prevented or cured instead of simply managed.

His work has focused in part on people who suffer combat-related traumatic brain injuries and later face the possibility of post-traumatic epilepsy and cognitive decline.

He pointed out that, “I’m a clinical pharmacist, too, and in my 25 years of practice, I’ve seen the pain of patients living with TBI and epilepsy, and how little control they feel they have. I want to give them back that control, in a way that promotes their well-being,” as quoted by EurekAlert.

The latest findings do not establish sodium butyrate as a cure for PTE. But they give researchers another way to study what happens between a traumatic brain injury and the development of epilepsy.

For now, the research suggests that a chemical made by gut bacteria may offer a potential way to intervene earlier, traveling through the bloodstream to the brain and targeting inflammation and other changes that follow traumatic injury.