Traumatic brain injuries (TBIs) are a major health concern, affecting millions of Americans each year. The consequences can be severe and long-lasting, including loss of coordination, depression, impulsivity, difficulty concentrating, and an increased risk of dementia.
Traumatic brain injuries are typically caused by external forces that jolt the brain within the skull, such as falls, car crashes, or explosions. This can damage the blood-brain barrier, allowing blood to leak into the brain.
Researchers at Gladstone Institutes have discovered that a specific blood protein called fibrin plays a crucial role in the neurodegeneration that occurs after TBI. Fibrin is normally involved in blood coagulation, but in the brain, it activates immune cells that release toxins, leading to neuron damage.
Using advanced imaging techniques, the researchers studied mouse brains and human brains from individuals who had experienced a TBI. They found that fibrin was present in areas of blood-brain barrier leakage and was associated with activated immune cells.
To determine the impact of fibrin, the team used genetic tools to create a specific mutation in fibrin that prevented it from activating immune cells. This mutation did not affect fibrin’s ability to clot blood, which is critical for preventing excessive bleeding in TBI patients.
The researchers found that blocking fibrin’s ability to activate immune cells significantly reduced neuronal damage and improved cognitive function in mice. These findings suggest that targeting fibrin could be a potential new strategy for treating TBI and other neurological diseases.
Gladstone Institutes researchers previously developed a therapeutic monoclonal antibody that blocks fibrin’s inflammatory properties without affecting blood coagulation. This fibrin-targeting immunotherapy has shown promise in protecting against multiple sclerosis and Alzheimer’s disease in mice. A humanized version of this immunotherapy is currently in Phase 1 safety clinical trials.
The study’s findings provide new insights into the molecular mechanisms underlying neurodegeneration after TBI and offer hope for the development of effective treatments to improve outcomes for patients.
