Revolutionary nasal spray transforms traumatic brain injury treatment

Traumatic brain injury (TBI) remains a major cause of death and long-term disability. Beyond the immediate damage, TBI triggers ongoing neuroinflammation, leading to cognitive decline, motor deficits, and even neurodegenerative diseases.

Despite its severe impact, no approved treatment effectively prevents the long-term effects of TBI. Scientists are now exploring an innovative approach: a nasal spray designed to modulate the immune response and reduce brain inflammation.

When the brain experiences trauma, it undergoes a two-phase injury process. The primary injury occurs at the moment of impact, causing direct damage to brain tissue. However, the secondary injury—driven by a complex biochemical response—often leads to further neurological damage.

A critical component of this secondary phase is chronic neuroinflammation. Activated microglia and infiltrating immune cells release cytokines, creating an inflammatory environment that can persist for months or even years. This prolonged immune response contributes to ongoing cognitive and motor impairment.

Studies show that regulatory T cells (Treg cells) play a crucial role in controlling immune responses. These cells help maintain immune balance and prevent excessive inflammation. In animal models, depleting Treg cells worsens TBI outcomes, while boosting their levels leads to neurological improvement. Given these findings, researchers have sought ways to enhance Treg cell function as a potential treatment for TBI.

Researchers at Mass General Brigham have developed a nasal spray using an anti-CD3 monoclonal antibody (aCD3 mAb) to stimulate Treg cells. Previous studies show this method successfully reduces inflammation in multiple sclerosis and Alzheimer’s disease models. Now, the team has tested its effects in a mouse model of TBI.

Dr. Saef Izzy, a neurologist leading the Immunology of Brain Injury Program at Brigham and Women’s Hospital, emphasized the significance of this research. “Traumatic brain injury is a leading cause of death and disability—including cognitive decline—and chronic inflammation is one of the key reasons,” Izzy said. “Currently, there is no treatment to prevent the long-term effects of traumatic brain injury.”

The team tested the nasal treatment in mice with moderate-to-severe TBI. Results showed a significant reduction in brain inflammation, improved motor function, and decreased anxiety-like behavior.

The nasal spray appeared to alter immune signaling between Treg cells and microglia, shifting the immune response from harmful inflammation to tissue repair.

Dr. Howard Weiner, co-director of the Ann Romney Center for Neurologic Diseases, highlighted the broader implications of these findings. “This opens up a whole new area of research and treatment in traumatic brain injury, something that’s almost impossible to treat,” he said. “It also means this could work in intracerebral hemorrhage and other stroke patients with brain injury.”

Beyond the preclinical results, the study provides a deeper understanding of immune responses in TBI. Researchers tracked how immune cells behaved over time, identifying key pathways that could serve as therapeutic targets. The next challenge is translating these findings into human trials.

“Our patients with traumatic brain injury still don’t have an effective therapeutic to improve their outcomes,” Izzy said. “This is a very promising and exciting time to move forward with something that’s backed up with solid science and get it to patients’ bedsides.”

If successful in human trials, this nasal spray could be a game-changer for TBI patients, including athletes with repeated head injuries. Weiner envisions a future where this treatment could be administered immediately after injury. “We imagine giving a nasal spray right there on the sidelines,” he said. “It isn’t something we can do yet, but we see the potential.”

Traumatic brain injury has long been a medical challenge with no clear treatment options for reducing long-term effects. By targeting the immune response with a simple nasal spray, researchers may have unlocked a new path for intervention.

While clinical trials are needed, this approach could revolutionize how TBI is managed, offering hope to millions affected by brain injuries each year.

Study findings are published in the journal Nature Neuroscience.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

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