In one of the papers, published in today in PLoS One, the researchers attached magnetic beads to integrin complexes that act as a kind of structural anchor in cells, along the axons of neurons. They found that just a small force applied to the beads was necessary to injure axons. Furthermore, the forces on one bead would propagate through the cell’s skeleton down another axon, causing the distant axon to break or be injured. Parker says the propagation of forces through neurons explains why damage to axons can be seen even far from the injury site in human brains.
The other paper, published last week in Proceedings of the National Academy of Sciences, shows that integrins can also mediate a problem called cerebral vasospasm, a narrowing of blood-vessel openings that begins days to months after a blast injury. Parker explains that while vasospasm can occur when blood vessels break and bleed out, sometimes there is no bleeding and another process must be in play. His team engineered arteries from blood-vessel cells and studied the effects of blast-like stretching. “We found that within 24 hours, the blast had induced the flip of a genetic switch,” he says. That creates chemical and physical changes characteristic of cells in cerebral vasospasm.
In both the neurons and the blood-vessel cells, treating cells with a drug that inhibits a protein activated by integrins lessened the injury. Parker believes that targeting this or similar chemical pathways could be a way to treat soldiers directly after blasts, in order to prevent some of the slower biochemical effects that follow from the initial trauma.
Parker, a major in the U.S. Army who served in Afghanistan, normally works on other biophysics problems but got involved in the project after spending time on a battlefield with Colonel Geoffrey Ling, a U.S. Army neurologist specializing in brain trauma; Ling is now a program manager at the Defense Advanced Research Projects Agency (DARPA), where he directs efforts to fund research into the science of TBI. Because it’s very difficult to know what’s happening in the brains of injured soldiers, Parker says, we need another way of studying the problem: “If you don’t build models for IED blasts, then it’s going to be difficult to get people to come into this field.”