Lieutenant-Colonel Dan Drew has seen any number of soldiers blown up by IEDs (improvised explosive devices). He was one of roughly 200 Canadians embedded with an Afghan brigade of 3,000 in Kandahar province for seven months in 2008, a time when “there were a lot of bad guys and not a lot of us.” IEDs were the Taliban’s weapon of choice. Fighters used them to blow up soldiers on foot patrol. They used them to blow up vehicles. They planted them in roads, in fields, along paths and in stone walls.

When Drew, who is a military adviser at Defence Research and Development Canada (DRDC) at CFB Suffield, Alta., speaks about the importance of research into blast-induced brain injury, he has a particular soldier in mind—a warrant officer who “was blown up four times in the first three months we were there. He came back again, brave as a lion…and finished up his tour back fighting again.” But Drew wonders if 20 or 30 years down the road, this soldier’s brain will be affected by his repeated exposure to blasts.

Blast-induced brain injury is a worry Master Corporal Mike Trauner shares. He served in Afghanistan in 2008, and lost his legs when a remotely controlled IED exploded under his feet. After years in rehab, he’s pretty steady on his prosthetic pins now, and the worst of the shrapnel has been dug out or worked its way out of the parts of his body that were unprotected by armour. Still, he wonders what unseen damage was done as the blast wave moved through his brain.

“I’m concerned, for sure, about long-term effects,” says Trauner. He has headaches and problems with short-term memory. Are they signs of things to come? “I have no idea; all they [the doctors] can do is speculate right now and see what happens.”

More than 30,000 troops have been involved so far in Canada’s combat mission to Afghanistan. Many have been exposed to blast, but most were far enough away to feel no physical sensation. How much exposure leads to brain damage? Does a severe blast such as the one Trauner survived cause delayed injuries? Are there accumulated effects from being exposed several times to minor blasts?

DRDC Suffield’s Blast Injury Program is developing and using cutting-edge techniques to help answer these questions. With so many troops exposed to blast, and the potential for long-term damage, research into the effects of blast on the brain is “probably the most important program at DRDC now for our veterans,” says Drew.

“There’s so much we still don’t know,” adds Stephen Bjarnason, head of DRDC’s casualty management section. “We’re finding out nobody really understands how blast wave goes through your head.” Researchers don’t understand how the physics of a blast affect human biology, he says. “To me, that’s fundamental, basic information. So that’s where we’re starting.”

DRDC Suffield has the ideal combination of expertise for this research. Between 35 and 40 specialists at Suffield are involved in the Blast Injury Program, including microbiologists, toxicologists, pharmacologists, neuroscientists, physicists and blast specialists.

Thomas W. Sawyer with flasks containing brain cells for blast studies.

PHOTO: SHARON ADAMS

Although the brain can sustain physical injury from shrapnel or a hard landing after a soldier is thrown by a blast, Suffield researchers will focus on brain injury caused by the primary blast wave (see “Inside the Blast: Part 1,” November–December 2011). Their ultimate aim is to develop ways to prevent and limit blast-induced brain damage, assess how bad that damage is and find effective treatments, says Bjarnason. Right now, the possibilities he raises sound like science fiction: a drug to stimulate defence systems in the brain, so a single dose at the beginning of a tour of duty or patrol will help prevent brain damage; a drug that can stop the chemical cascade that results in brain injury; gene therapy to prevent damage or heal it after the fact; a blood test to tell whether someone’s been exposed to a damaging blast.

As a first step toward that future, DRDC researchers harnessed their considerable brain power to develop an effective way to create, isolate and measure a discrete blast wave instead of turning to computer simulations or physical manipulations to mimic blast forces. Military engineers determined how to modify a blast tube, which physicists have used for decades to study blasts, to meet the conditions required for medical research (see sidebar).

Another key challenge is developing proper diagnostics, “so one can accurately measure passage of the shock through various materials—soft, wet, etc.,” adds DRDC blast specialist John Anderson. Tiny gauges, which can be placed in tissue or cell cultures, have been built to measure effects of blast forces in microseconds.

DRDC medical researchers have now begun to work on an animal model of blast-induced brain injury. The brains of human blast survivors can’t be opened to study the damage, and brain scans do not capture images at the microscopic scale, so DRDC researchers use rat brain tissue. (The Suffield program complies with guidelines of the Canada Council on Animal Care, the independent body that oversees the ethical use of animals in science). Rats are implanted with measurement devices, and baseline readings are taken as the animals go about their daily activities. The rats are anesthetized before being exposed to a blast, and then closely observed for changes in behaviour, physical ability and memory as they negotiate mazes, run on the rat equivalent of a treadmill, and walk a balance beam. Their brains are examined for signs of damage at various points after the blast.

Yushan Wang studies brain cells at the microscopic level.

PHOTO: SHARON ADAMS

Brain injury can be invisible. Although some damage is immediately apparent—loss of consciousness or fuzzy thinking and slow reactions—it’s not apparent how much damage has been done, or whether the damage is permanent. The brain can be injured even when there are no physical symptoms. In fact, symptoms may not appear for months or even years, or may develop very slowly. And brain injury increases the long-term risk of developing such neurodegenerative conditions as Parkinson’s disease and Alzheimer’s.

By exposing various rats to explosions of different intensities and comparing the damage at discrete points in time, scientists obtain data. This can be used to develop tools for diagnosing injury such as a chart that records damage at different blast intensities; that in turn could be used to determine level of treatment. Identifying substances in the body that increase or decrease depending on the magnitude of the blast exposure could yield a biomarker that would indicate whether soldiers have been exposed to damaging blasts, and the intensity of the exposure.

“Blast affects the brain at the cellular level,” says Yushan Wang, a specialist in neuroscience at DRDC. The most vulnerable areas are the hippocampus, which consolidates short-term memory into long-term memory; the frontal cortex, which is involved in planning and motivation; and white matter, the brain’s message and communication system. The brain has two broad classes of cells: neurons and glial cells. Neurons are the brain’s information processing units. They use tiny arm-like structures called axons to transmit chemical messages to other cells across small gaps called synapses. Dendrites—shorter, branch-like structures covered with microscopic receptors—receive chemical messages. The far more numerous glial cells control the chemical composition of the fluid surrounding the neurons and produce myelin, the axons’ protective covering.

These cells are bound together in such a way that a blast disrupts their chemical messaging. The overpressure blast wave and the subsequent underpressure blast wind cause the brain to quickly contract and then expand, damaging cells. Blood vessels also rapidly expand and violently contract, cutting off blood supply to brain tissues. The blood–brain barrier may tear or weaken, allowing destructive substances to penetrate. A cascade of chemicals, some of them toxic, flood the brain in response to trauma. Genes are turned on that initiate a series of negative events. Inflammation sets in. The result is cell death and brain damage.

Wang points to a pattern in greens and blues on a computer screen in his lab, a microscopic close-up of brain cells that have been marked with dye. “You are looking at the hippocampus, the most important single structure in the brain,” he says. “It is responsible for learning and memory. Without a hippocampus, you would not be able to learn, not be able to memorize anything.” At this extreme magnification, Wang can see damage to individual brain cells and patterns of damage in brain structures. A scar, he says “is not a good sign for the brain. Once you form a scar, the neurons will not be able to communicate any more…. This interrupts the communication of normal brain cells.”

Catherine Tenn at one of the blast tubes.

PHOTO: SHARON ADAMS

In experiments, Wang sees no apparent damage to the gross anatomy of the brain three hours, one day, one week and three weeks after rats are exposed to a moderate blast. But the story is different at the molecular level, with damage to axons appearing on the first day after the blast. “At three weeks, definitely, you are able to see cell death.”

Wang is studying receptors for neurotransmitters, particularly glutamate, which is important for brain development, learning and memory. Normally, the brain finely balances the supply of this chemical. “If you get too little, you’ve got loss of learning and memory,” says Wang. “Too much and you’ve got cell death—part of the brain is going to die.” Blast exposure upsets that balance: too much glutamate is released, and glutamate receptors are altered, which interrupts the exchange of information at the synapses. This leads to cell damage and death, which in turn can contribute to such problems as memory loss, difficulty concentrating, and the gamut of other symptoms reported by troops surviving IED blasts.

So far, Wang has learned that damage happens even after low-intensity blasts, and begins to show up within an hour and continues for weeks. Many questions remain about how the damage is done, and how to slow or stop it.

If Wang’s work can be described as producing snapshots of damage at particular points in time, the ground-breaking work by his colleague Thomas W. Sawyer on a special line of brain cell cultures is more like creating a moving picture of cell damage over time.

Sawyer has been able to cultivate three-dimensional conglomerations of all types of brain cells, which he jokingly refers to as “brain balls” because of their shape. Sawyer and his colleagues bathe embryonic rat brain cells in a nourishing solution, put them into flasks and gently stir. The cells start to grow immediately, and within days all brain cell types are represented. Sawyer suspends the brain balls in gelatine encased in a sphere, a set-up that resembles the architecture of the brain and allows for realistic simulation of a blast wave moving though the skull and into the viscous brain matrix.

In early experiments, Sawyer’s team was able to measure the peak shock wave passing through the brain ball and observe damage developed in axons four to seven days later. This is “one of the first examples of a measured cause-effect relationship between single pulse shock wave exposure and brain tissue damage,” Sawyer stated in a recent report on his research to a NATO conference. His team was able to tell how much damage resulted from a wave of a particular size over a period of a week.

Many, many such experiments will lead to development of an animal model that explains what happens to brains exposed to blasts, what processes lead to damage, and how those processes can be mitigated.

“Once an animal model is developed, you can start to test treatments you would give to humans,” says defence scientist Catherine Tenn, who is engaged in developing that model. “We always have to bring it back to humans.” To that end, Tenn went to Afghanistan with Lt.-Col. Drew for three weeks in 2009 to see the types of injuries troops suffer, how they’re treated, what questions doctors in the field want answered, and what avenues they’d like explored for prevention and treatment. “Our research has to be operationally relevant to the military, to the soldiers,” she says, noting that Drew’s presence on site is a daily reminder of this. Members of the Canadian Forces have to be part of our program, Tenn says, “because we need their input to make sure what we’re doing is relevant to them.” In fact, DRDC Suffield chose to study traumatic brain injury, along with hemorrhage and crush injury, because it is a priority of the surgeon general’s office and medics in the field.

Ultimately, this research will produce the hard evidence needed to develop policies on measuring and recording soldiers’ exposure to blast and determining exposure limits, says Drew. (The Canadian Forces is now looking into using blast exposure meters, such as the helmet-mounted biosensors U.S. troops wear.) For their part, veterans could use this evidence to help build their case for receiving support and benefits should they suffer long-term effects from blast exposure while in combat zones.

And, M.Cpl. Trauner and Drew’s lion of a soldier may eventually get some answers about their futures. If researchers find ways to stop or slow effects that result in brain injury, “that would be great,” says Drew, both for soldiers and for medical personnel and commanders concerned about soldiers’ safety on the battlefield and continued health years after they’ve left it.

Shock Waves

The blast tubes at DRDC Suffield are metal cylinders, with compressed air in a driver at one end. At a certain pressure, this air breaks through a diaphragm and travels down the tube creating a supersonic shock wave replicating the physics of IEDs (improvised explosive devices), rocket-propelled grenades and mines.

“Don’t be fooled,” says Defence Research and Development Canada (DRDC) senior scientist Thomas W. Sawyer. “The blast tube looks really simple, but there’s a significant amount of physics and computational modelling involved.” Sawyer is a toxicologist who has spent more than 30 years studying injury to cells, but he has helped to get DRDC Suffield’s Blast Injury Program up and running. Perfect operation of the blast tube is vital to the outcome of blast-related experiments.

Researchers want to study the effects of just the primary blast wave, but secondary waves can be created as the blast travels down a traditional blast tube. As well, a blast wave travelling in one direction is immediately followed by a pressure wave travelling back in the opposite direction. The tubes’ design makes it possible to “recreate the same exposure conditions again and again and again within a very small margin of error,” explains Stephen Bjarnason, head of DRDC’s casualty management section. Military engineers are specially machining Suffield’s two blast tubes to prevent reflection and reverberation that can skew results of experiments. The engineers have also designed a device to eliminate the pressure wave coming back from the end of the tube.

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