UCI researchers identify link between infant seizures

August 19, 2003

Irvine, Calif., Aug. 19, 2003 -- A new UC Irvine College of Medicine study has identified why infants who suffer prolonged fever-induced seizures are more susceptible to further seizures and epilepsy as adults.

According to the study, prolonged fever-induced seizures increase the brain's production of endocannabinoids, a natural marijuana-related substance that helps regulate the transmission of neural signals. When this occurs, the neural receptors linked to endocannabinoids undergo long-term modifications that increase the possibility of adult epilepsy. The study appeared in the Aug. 14 issue of Neuron.

"The significance of these findings is twofold," said Ivan Soltesz, professor of anatomy and neurobiology. "First, they provide a mechanistic explanation as to why febrile, or fever-induced, seizures in childhood lead to an increased susceptibility to seizures that lasts until adulthood. Second, they suggest a new drug that interferes with this occurrence during childhood may significantly decrease the likelihood of future epileptic seizures. The components of these new drugs will likely be man-made chemicals distantly related to marijuana."

Febrile seizures affect 3 to 5 percent of infants and young children, making them the most common form of childhood seizures. Soltesz and colleagues from the Department of Anatomy and Neurobiology found that experimental prolonged febrile seizures in rats enhanced the number of receptors for endocannabinoids in the part of the brain important for memory and damaged by adult epilepsy. They also discovered that a single episode of febrile seizures was enough to cause a permanent increase in the number and activity of receptors that transmit endocannabinoids.

In the normal, healthy brain, endocannabinoids convey specific messages between nerve cells. Endocannabinoids bind to cannabinoid type 1 (CB-1) receptors and decrease the release of a major inhibitory neurotransmitter called GABA. Rats that experience these febrile seizures exhibit a massive increase in the number of CB-1 receptors, which limits the release of GABA. With less GABA to serve as an inhibitor, neurotrasmitters are more prone to the increased hyper-excitability that can trigger seizures.

"These findings show that prolonged seizures in childhood can have highly specific consequences in certain sensitive areas of the brain," said Soltesz, who first discovered the febrile seizure-epilepsy link in 1999. "The good news is that because the seizure-induced alterations to CB-1 receptors are so specific, the endocannabinoid system provides a unique opportunity for therapeutic drug development that targets controlling seizures in epilepsy."
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The study was funded by a grant from the National Institutes of Health. Soltesz' colleagues in the study included Kang Chen, Anna Ratzliff, Lutz Hilgenberg, Martin Smith, Thien Dinh and Daniele Piomelli of UCI, as well as Attila Gulyas and Tamas Freund from the Hungarian Academy of Sciences in Budapest and Ken Mackie from the University of Washington.

A complete archive of media releases is available on the World Wide Web at http://www.today.uci.edu

University of California - Irvine

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