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Scientists ID Brain Pathway That Stops Seizures

Mouse study finds gene affects acids that regulate severity of convulsions

SUNDAY, June 8 (HealthDay News) -- A brain pathway that stops seizures has been found by Iowa researchers.

Applying modern genetics and molecular biology to clinical observations made more than 80 years ago, a team from the University of Iowa and the Veterans Affairs Iowa City Health Care System found that increased acid (pH) activates an ion channel in the brain that shuts down seizure activity. The findings were expected to be published online June 8 in Nature Neuroscience.

"Although this work provides insight into how seizures normally stop and might help us learn more about how to terminate those seizures that don't stop, it will take more work to turn the finding into a new therapeutic approach," senior study author Dr. John Wemmie, an assistant professor of psychiatry in the University of Iowa's Roy J. and Lucille A. Carver College of Medicine, said in a prepared statement. "We will be working with colleagues in neurology and neurosurgery to try and translate the findings to treatments."

Clinical experiments from the first half of the 20th century show breathing carbon dioxide, which creates more acid in brain tissue, helps stop epileptic seizures while the seizures themselves lower brain pH. The modern discovery of an acid-activated ion channel (ASIC1a) in the brain helped the team piece the puzzle together.

"We found that ASIC1a does not seem to play a role in how a seizure starts, but as the seizure continues, and the pH is reduced, ASIC1a appears to play a role in stopping additional seizure activity," study co-lead author Adam Ziemann, a student in the Medical Scientist Training Program at the university, said in a prepared statement.

Researchers found that seizures are more severe and longer in mice lacking the ASIC1a gene than those with the gene. Also, chemically blocking ASIC1a causes the seizures to be longer and more severe in mice with the gene, while increasing ASIC1a in mice protects them from severe seizures.

"One of the most exciting aspects of the work is that it highlights the potent anti-epileptic effects of acid in the brain -- effects that have been recognized for nearly 100 years but until recently have been poorly understood -- and it identifies ASIC1a as a key player in mediating the anti-epileptic effect of low pH," Ziemann said.

Seizures occur when brain neurons work out of synch, causing physical spasms or convulsions and even disrupting vital functions, such as breathing. Most seizures stop by themselves, but if they don't, a life-threatening condition called status epilepticus that claims a mortality rate of up to 20 percent could occur.

It is thought that 2 percent to 4 percent of people will have a seizure at some time. People who have epilepsy experience repeated seizure activity.

More information

The U.S. National Library of Medicine has more about seizures.

-- Kevin McKeever

SOURCE: University of Iowa, news release, June 8, 2008

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