An existing drug already approved by the FDA may protect newborns from brain injury and long-term neurologic problems caused by excitotoxicity, or over-activation of neurons, report two NIH-funded studies from Children's Hospital Boston. The drug, topiramate, is currently approved to control seizures in adults and in children over age 3, but the findings may provide the basis for a protective therapy that could be given to babies immediately after traumatic birth events that compromise the brain's blood and oxygen supply. Such events can cause long-term neurologic abnormalities that underlie serious conditions like cerebral palsy and epilepsy. Premature infants, who are surviving in greater numbers, are especially vulnerable to excitotoxicity.

When the brain's blood and oxygen supply are compromised, a condition known as hypoxia-ischemia, the chemical glutamate accumulates in brain tissues. Glutamate binds to receptors on neurons and over-activates them, causing the brain cells to die. The Children's Hospital researchers, led by Dr. Frances Jensen, have found that the neurons of premature infants and other newborns have more glutamate receptors than the adult brain, making them very vulnerable to excitotoxic brain injury from hypoxia-ischemia. In two studies, they investigated whether compounds that block a certain type of glutamate receptor, known as AMPA, can dampen the harmful effects of excitotoxicity in the immature brain.

The first study, published in the May 5 issue of The Journal of Neuroscience, examined a type of brain damage called periventricular leukomalacia (PVL) that underlies cerebral palsy. PVL is most common in the preterm infant and is thought to be caused by excitotoxic damage to oligodendrocytes, cells that produce a substance called myelin. Myelin insulates neurons and enhances signal transmission; without it, neurons cannot communicate efficiently and neuromotor problems result.

In the study, Jensen, Dr. Pa
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Contact: Aaron Patnode
aaron.patnode@childrens.harvard.edu
617-355-5337
Children's Hospital Boston
14-Jun-2004

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