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November 28, 2017

Penn study spots evidence for higher concussion vulnerability in women

Sports-related concussions occur about 2 million times a year in the United States and recent findings from the American Academy of Neurology suggest women face a 50 percent greater risk than men.

With a growing body of research into the long-term dangers of concussions, neuroscientists have increasingly looked to find a biological explanation for this risk disparity between men and women.

New findings from the University of Pennsylvania, published in the journal Experimental Neurology, now point to differences in the nerve fibers of the brain's "electric grid" as a possible source of higher concussion prevalence in women.

The research team, led by Dr. Douglas H. Smith of the Penn Center for Brain Injury and Repair, focused on the structure and resilience of axons—the slender, hose-like parts of neurons that transmit messages between cells.

Study results from in vitro rat and human cells, examined using transmission electron microscopy, revealed that women have leaner and more breakable nerve fibers than men. Their axons also possess fewer and more fragile microtubules, the "train tracks" that guide intracellular transport of molecules.

“The paper shows us that there is a fundamental, anatomical difference between male and female axons,” Smith said. “In the male axon, there are a great number of microtubules, which make the entire structure stronger, whereas in female axons, it’s more of a leaner type of architecture, so it’s not as strong.”

Following a traumatic impact to the head, axons are rapidly stretched to the point of rupturing microtubules. The resulting molecular imbalance is believed to produce the dizziness, confusion, headache and loss of consciousness associated with concussions.

Anatomical differences appear to be a key factor in the greater destabilization found in women.

“You can imagine that if something goes wrong with that transport system, the cargos get dumped out and start to pile up and that will create a huge problem,” Smith said.

Twenty-four hours after the test trauma, researchers found that female axons had a greater number of swellings and loss of calcium-signaling function than male axons. A buildup of proteins may be responsible for setting in motion a destructive enzyme function that degrades axons and compromises nerve fibers.

The study carries added significance because women who play the same sports as men often suffer worse concussion outcomes in the short- and long-term.

Future research will aim to explore axonal biomarkers that may help explain the differing responses to concussions in men and women, with an eye toward treatment options specifically designed to restore the brain function of women.

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