A groundbreaking study, published by the NIH and reported on by the Military Medical Research Journal in August 2025, has shed new light on how our brains respond to injury, focusing on a protein called IL-33 that acts as the body’s internal alarm system.

When brain cells are damaged—whether from a traumatic injury, stroke, or repeated mild impacts like those seen in contact sports—they release IL-33 as a distress signal. This protein, known as an “alarmin,” alerts the immune system that something is wrong.

The August 2025 research, conducted in both mice and humans, revealed that IL-33 plays a crucial protective role after brain injury. The study found that when IL-33 levels drop following repetitive mild brain trauma, cognitive problems—like memory loss and difficulty thinking clearly—become significantly worse.

Here’s how it works: IL-33 helps special immune cells called microglia (the brain’s cleanup crew) remove harmful debris and damaged proteins that accumulate after injury. When IL-33 is functioning properly, these cleanup cells work efficiently to clear away toxic buildup, particularly a problematic protein called amyloid-beta.

The researchers discovered that supplementing IL-33 levels through nasal administration dramatically improved brain function and cognitive recovery in injured animals. This finding offers hope for developing new treatments for people suffering from brain injuries, potentially helping millions recover more effectively from trauma-related cognitive decline.

Decreased IL-33 in the brain following repetitive mild traumatic brain injury contributes to cognitive impairment by inhibiting microglial phagocytosis: https://pubmed.ncbi.nlm.nih.gov/40764944/