Shock Waves May Create Dangerous Bubbles in the Brain

Lab experiments show how people who survive explosions may still carry cellular damage that can cause psychological problems

A bomb blast engulfs a mountainside near the town of Barg-e Matal in Afghanistan. David Bathgate/Corbis

Advances in body armor and helmet design mean that more soldiers will survive being close to a blast from a roadside bomb or enemy fire. But many people come back from the battlefield with brain injuries that aren't immediately visible and are hard to detect even with advanced scans. The trouble is that it's unclear just what a blast wave does to the brain.

Christian Franck, an assistant professor of engineering at Brown University, is trying to change that by imaging small groups of brain cells in 3D and taking movies of neurons exposed to tiny shocks. The idea is to see exactly how individual brain cells change shape and react in the hours after trauma.

Some 25,000 servicemen and women suffered traumatic brain injuries in 2014, according to the U.S. Department of Defense. Only 303 of the injuries were "penetrating," or the kind that leave visible wounds. The rest were from various forms of concussion caused by events such as explosives, falls and vehicle accidents.

Most of those injuries—about 21,000—were considered mild, which means that the person was confused, disoriented or suffered memory loss for less than 24 hours or was unconscious for 30 minutes or less. Such patients don't usually get brain scans, and if they do, the images generally look normal.

That's a problem, Franck says, because psychological problems arising from concussive head injuries can come from cell-level damage, since the brain "rewires" as it tries to heal.

"The rewiring takes place after the insult, so you don't notice," Franck says. "We want to see at the cellular scale how fast these cells are being deformed. With blunt trauma we have a much bigger database. With explosions, it's mostly people in the armed services, and they're having a hard time because they'd like to access treatment and get help, but they don't know what to screen for."

Past experiments with rats have shown brain damage from explosive blasts, especially to the hippocampus, but did not look at the cellular level. And while previous studies in humans have examined brain cells in head injury cases, the tissue has only come from patients who were already dead.

Since we can't peer inside a live human brain as it is being concussed, Franck grew cells from rat brains on biological scaffolding inside a gel-like substance. The setup allows the cells to grow in clusters similar to how they would bunch up in a brain.

The cells aren't as densely packed and are not doing all the things that brain cells would usually do, but they do provide a rough analogue. Franck can then expose these brain-like bundles to shock waves to see what happens.

A blast wave is different from, say, getting hit in the head with a brick, because the time scale is much shorter, Franck says. A typical smack in the head happens over the course of a few thousandths of a second, whereas a blast wave lasts for just millionths of a second. In addition, the effects of a blast wave don't have a single, focused point of origin, as with a physical strike.

Franck is working with a hypothesis that shock waves from explosions cause a phenomenon in the human brain called cavitation—the same process that makes bubbles in the water near a boat propeller. The theory of cavitation in brains isn't new, and there is pretty solid evidence that cavitation happens, but we don't have the right observations yet to clinch it as the cause of cell damage.

According to the theory, as a blast happens near a soldier, shock waves move through the skull and create small regions of low pressure in the liquids that surround and permeate the brain. When the pressure in some regions gets low enough, a small space or cavity opens up. A tiny fraction of a second later, the low-density region collapses.

Since the cavities aren't perfectly spherical, they collapse along their long axes, and any cells nearby either get crushed inside the cavity or get hit with a blast of high-density fluid shooting from the ends. It seems obvious that such an event would damage and kill cells, but it's far from clear what that damage looks like. 

That's why Franck made movies of his lab-grown brain cells and presented his findings this week at the 68th annual meeting of the American Physical Society's Division of Fluid Dynamics in Boston. To simulate cavitation from an explosion, he fired laser beams at the cellular clumps. The brief laser shots heated up bits of the gel holding together the cell matrix, creating cavities.

He used a white LED coupled to a microscope and a diffraction grating, which generates images from two different perspectives to scan the laser-blasted cells repeatedly. Each snapshot makes a 3D picture of the cells using the two images to generate a kind of 3D movie. Franck then watched the cells for a day to see what they did and if they died.

The experiment showed clear indication of cell damage due to cavitation. But it's just a first step: The inside of a brain is not uniform, which makes calculating the actual impact of cavitation difficult. In addition, modeling the effects of a blast wave is hard, because the fluid involved is fairly complex, says Jacques Goeller, an engineer at Advanced Technology and Research Corporation who is now semi-retired. He experimented with putting the heads of corpses in the paths of shock waves, which provided indirect evidence for cavitation during a blast.

But another complicating factor is that skulls vibrate at certain frequencies, which can affect how much they deform and trigger cavitation. "As the skull is vibrating, it can cause another series of bubbles," Goeller says.

On the bright side, in Franck's experiment it's possible to control the size of the bubbles and their position, as well as the properties of the gel. That means future research can use the same setup to test multiple possible scenarios.

The injuries these lab cells suffer can then be compared to real brains from concussion victims to get a better picture of what's happening. That should make it easier to develop treatments and diagnoses.

Franck agrees, though, that there's still some way to go before researchers know for sure how blasts affect the brain. "It's a lot of work in progress still," he said. "We're about half way through this." 

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