After injury, brain may be its own worst enemy

U. COLORADO (US)—After a traumatic injury, the brain’s immune system jumps into action, releasing “curative” chemicals that researchers have discovered actually cause seizures and may do more harm than good.

Acquired epilepsy, one of the most common forms of adult epilepsy, is often found in people who have suffered a brain injury or infection. Daniel Barth, psychology and neuroscience professor at the University of Colorado at Boulder and chief author of a new study, say the new findings could help prevent acquired epilepsy.

For decades researchers have focused on neurons as the culprits in seizures, which can be characterized as debilitating “electrical storms” in the brain. But recent research has shown that micro-glial cells, supportive cells that constitute a major part of the brain’s immune system and cluster within areas of the brain when a severe injury has occurred, may play a major role.

“When there has been serious damage to the brain, such as a head injury or infection, the immune system is activated and tries to counteract the damage and repair it,” Barth says.

The glial cells travel to the damaged area and release chemicals called cytokines, which increase the excitability of nearby neurons. Researchers applied bacteria to the brains of rats that activated the micro-glial cells, which then rapidly clustered around the area where the bacteria were applied.

“In our new study, we showed for the first time that glial cells moving in and secreting these cytokines cause the neurons in the area to become excitable enough to cause seizures,” Barth says.

By directly applying drugs that blocked the activation of the glial cells, all signs of increased brain excitability and seizures were abolished.

The findings are extremely promising, according to Barth, because if the brain’s initial immunity reaction can be temporarily shut down, development of acquired epilepsy can be prevented.

“After a traumatic brain injury, there is often a period of several months where nothing seems to be happening,” Barth explains. “And then suddenly the person may start having seizures, which often develop into chronic epilepsy.”

What the research team believes is happening is that the initial immune response to the brain injury causes the first seizures. Then the adaptive immune system, which works on a longer-term basis, kicks in and makes structural changes in the brain that could perpetuate epilepsy as a lifelong condition, says Barth.

Drugs that suppress the immune system temporarily are already on the market. Even more promising, Barth says, are drugs currently under FDA trial that effectively suppress the glial cells and stops them from reacting.

“The thought is that maybe there is a window of opportunity where we could go in after an injury and administer one of these immune response inhibitors and stop a process that we think is going to lead to epilepsy,” Barth says.

“So instead of giving anti-seizure drugs, which have no effect in preventing or subsequently treating post-traumatic epilepsy, we could give some anti-immune drugs which may actually stop the process of developing epilepsy in the first place.”

Researchers at the University of Adelaide in Australia contributed to the study, which was funded by the National Institutes of Health. Results appear in the July issue of the journal Brain.

University of Colorado at Boulder news: www.colorado.edu/news

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