Study that stretched and strained neural connections could yield insights into traumatic injury
Broken axonSudden forces cause microtubules running inside axons to break (arrow), leading to axon swelling and damage, a new study shows. The work may have implications for understanding traumatic brain injury.D. Smith SAN DIEGO — Rigid pathways in brain cell connections buckle and break when stretched, scientists report, a finding that could aid in the understanding of exactly what happens when traumatic brain injuries occur.
Up to 20 percent of combat soldiers and an estimated 1.4 million U.S. civilians sustain traumatic brain injuries each year. But the mechanics behind these injuries have remained mysterious.
New research, described February 19 at the annual meeting of the American Association for the Advancement of Science, suggests exactly how a blow to the brain disrupts this complex organ.
The brain “is not like the heart. If you lose a certain percentage of your heart muscle, then you’ll have a certain cardiac output,” says Geoffrey Manley, a neurologist at the University of California, San Francisco. Rather, the brain is an organ of connections. Car crashes, bomb blasts and falls can damage these intricate links, and even destroying a small number of them can cause devastating damage.
“You can have very small lesions in very discrete pathways which can have phenomenal impact,” says Manley, who did not participate in the study. One of the challenges brain injury researchers face, he says, is that “we’re not really embracing this idea of functional connectivity.
Recently, researchers have found that sudden blows can cause damage to the long fibers that extend from brain cells called axons, sometimes breaking the links between brain cells. But researchers didn’t know exactly what inside the axon snapped. The new research, conducted by Douglas Smith of the University of Pennsylvania and colleagues, finds that tiny tracks called microtubules are damaged inside axons by forces similar to those that cause traumatic brain injury.
Microtubules extend down the length of axons and serve as “superhighways of protein transfer,” says Smith. Brain cells rely on microtubules to move important cellular material out to the end of the axons. When Smith and colleagues quickly stretched brain cells growing on a silicone membrane, the microtubules inside the axons immediately buckled and broke, spilling their contents. “This disconnection at various discrete points spells disaster, and things are just dumped out at that site,” Smith says. “Microtubules are the stiffest component in axons, and they can’t tolerate that rapid, dynamic stretch.”
Smith points out that the duration of the stress applied is crucial to how well the axons — and microtubules — withstand damage. Like Silly Putty pulled apart slowly, axons can adjust to gradual stretching, Smith says. But sudden forces, like those that happen in blasts and car crashes, would cause the Silly Putty to snap.
In their lab dish experiments with brain cells on silicone, the researchers were able to minimize microtubule damage with a drug called Taxol, commonly used to treat cancer. But it’s too early to say whether the drug would work in people with traumatic brain injuries.
Figuring out exactly what happens in traumatic brain injuries could lead to new ways to help patients, Manley says. Currently, traumatic brain injury research is in “the abyss between bench and bedside,” he says.
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