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Researchers in the making:
Seizures and the developing brain

McLeod Scholarship winner Michael Galic studies the effect of inflammation on the developing brain.

Story by Janet Harvey/Photos by Trudie Lee, Dustin Delfs, and Martin Dee

The first few years of a child's life are an important time—a time of tremendous opportunity for growth as well as tremendous vulnerability to harm. Exposure to inflammation during this time can affect various aspects of physiology and behavior. Now Dr. Michael Galic, one of three winners of this year's Dr. Lionel E. McLeod Health Research Scholarship, has demonstrated that inflammation may also influence the brain's excitability later in life.

The excitability of the brain affects its ability to perceive its environment, perceive information, and control bodily functions. Brain excitability varies; generally speaking the brain will adopt the best level of functioning for everyday cognitive performance. "If we were to explain brain excitability as existing along a spectrum, a coma would occupy the low end and a seizure would be at the high end," explains Galic.

To learn more about the high end of this spectrum, Galic administers mild inflammatory compounds (comparable to minor cold or flu symptoms) to rats during their second week of life—roughly equivalent to humans aged between one and two years. When the rats have grown to adulthood, Galic gives them seizure-inducing drugs to measure the excitability of their brains. He has shown that brief periods of inflammation during critical periods of development—when the brain is susceptible—can make the animals more prone to seizures when they are given these seizure-inducing drugs as adults.

Important chemical messengers called cytokines are at work here. The release of cytokines during inflammation seems to reorganize or reprogram the brain, making it more excitable. In some cases this release is also associated with changes in how neurons communicate with each other and may lead to impaired learning and memory.

But don't panic. That cold or flu bug your child is fighting doesn't necessarily mean they will go on to have the recurrent, unprovoked seizures that define epilepsy. The seizures Galic is inducing occur only in the presence of seizure-evoking drugs. The key point is that the presence of inflammation and fever in the newborn may alter the way in which the adult brain subsequently responds to different situations. "All babies have infections from time to time," he confirms. "That doesn't mean they will all grow up to suffer from epilepsy."

In fact, the causes of epilepsy in adults remain quite elusive. Some causes, such as congenital abnormalities, head injuries, stroke, and encephalitis (brain inflammation) are known. The piece Galic's work adds to the puzzle is the discovery that peripheral inflammation (inflammation equivalent in the human body to an upper-respiratory or gastrointestinal infection) appears to change the brain in a way similar to inflammation in the brain itself (such as encephalitis). Both types of inflammation cause the release of cytokines. "So the conclusion is that if we block the cytokines we can prevent this inflammatory process and possibly reduce the predisposition to seizures later in adulthood," he explains.

Compounds that can do this already exist to treat other conditions. A drug for rheumatoid arthritis called Infliximab, and an antibiotic with anti-inflammatory properties called minocycline, both block cytokines. Since minocycline is a very safe and inexpensive drug it could be used, for example, to supplement the current treatment for encephalitis. The result? "What we've learned could help prevent the development of epilepsy," concludes Galic.