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Mystery brain particles may link head injuries to dementia

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    Mystery brain particles may link head injuries to dementia

    Tiny particles secreted in response to head injury in the brains of mice could help explain how inflammation spreads and ultimately boosts the risk of developing dementia.

    Head injuries are increasingly being linked to cognitive problems and degenerative brain disease in later life. Mysterious particles a micrometre in diameter have previously been found in the spinal fluid of people with traumatic brain injury, but their function has remained unknown.

    Now Alan Faden at the University of Maryland School of Medicine in Baltimore and his colleagues have discovered that activated immune cells called microglia secrete such microparticles in response to brain injury, and they seem to spread inflammation well beyond the injury site itself. They can even cause brain inflammation when injected into uninjured animals.

    The particles have receptors that latch onto cells, and are packed with chemicals such as interleukins, which trigger inflammation, and fragments of RNA capable of switching whole suites of genes on or off.

    When Faden injured the brains of sedated mice, the microparticles spread well beyond the site of damage. Further experiments on cultured microglial cells revealed that the microparticles activate resting microglia, making them capable of triggering further inflammation themselves.

    Indeed, when Faden injected microparticles from injured animals into the brains of uninjured animals, they propagated inflammation. This didn’t happen when microparticles from uninjured mice were injected.

    “The effect of these particles in driving inflammation even in animals without traumatic brain injury is convincing,” says Marie-Ève Tremblay of Laval University in Québec, Canada, who last year discovered unusual microglia that could be linked with dementia.

    She thinks microglia might secrete other particles too. “I wonder if they might be counterbalanced by anti-inflammatory and pro-repair effects of other microparticle subsets,” she says.

    One of Faden’s co-authors, Stephen Thom, has already developed an agent that might work against these microparticles.

    Called PEG-TB, it neutralizes the capacity of microparticles to trigger inflammation by causing them to fall apart. Experiments in pigs have shown that PEG-TB reduces the degree of inflammation resulting from traumatic brain injuries “It shows that in principle, the concept of neutralizing them could be effective,” says Faden.

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