The Brain's Tireless Sentries

On patrol. For 20 minutes, this microglial cell extended (green) and retracted (red) arms in many directions.

Rest assured, the cells that guard your brain are no slackers. New movies of brain cells called microglia reveal that these sentries constantly extend and retract tiny arms to probe the fluid spaces between brain cells for signs of injury or infection. The findings present a radically new view of how these cells protect the brain.

Microglia are the immune system's foot soldiers in the brain. They spring into action when damage occurs, creating a protective barrier around the injury and cleaning up dead cells and other debris. What the microglia do between crises has been unclear, largely because getting the cells under a microscope has required excising a chunk of brain tissue--thereby causing damage that sends the cells into emergency response mode.

The new study gets around that obstacle by using genetically engineered mice whose microglia produce a fluorescent green protein. The research team, led by Axel Nimmerjahn at the Max Planck Institute for Medical Research in Heidelberg, Germany, created a window on the brain of 12 such mice by shaving away a small patch of skull until only a transparent sliver of bone remained. Using a noninvasive technique called two-photon microscopy, the team snapped pictures of glowing microglia near the surface of the brain for several hours and compiled the images into time-lapse movies.

In the movies, the fat bodies of the microglia remain more or less stationary, but their thin, armlike extensions are abuzz. Based on the rate of this activity, the team estimates that microglia survey the entire volume of the brain every few hours. When the researchers made tiny lesions in the brain with a laser, nearby microglia immediately extended new arms to create a barrier around the injury and began retracting arms on the opposite side, the team reports online 14 April in Science. Nearly everyone had assumed that microglia don't move much until something bad happens to the brain, says Michael Dailey, who studies the cells at the University of Iowa in Iowa City. "The picture that emerges here is that they're much more proactive, that they've actively looking at the environment," he says. "This fundamentally changes how we think of microglia," agrees Gary Landreth of Case Western Reserve University in Cleveland, Ohio. "This tells us so much that it's really revolutionary."

Related sites
The Science paper
Movies of microglia in action
Movies of microglia and other brain cells on Dailey's lab site
Basic information about microglia

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