Syracuse University Magazine

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Figure: The number of neurons that express COX-2 in the mouse brain is increased after a strong brief seizure. Green color marks neurons that express COX-2; blue color marks all cells.

Upper panel: The number of cells marked in green is very low in the absence of a seizure.

Lower panel: This number is increased markedly after a seizure. Note that both panels show the same population of neurons from different mouse brains. These data are from the thesis research of Yifan Gong, a Ph.D. student in Professor Hewett's laboratory.

Images courtesy of James Hewett



Research Snapshot

Project: Cyclooxygenase-2: An Endogenous Neuromodulator in Seizures and Epileptogenesis

Investigator: James Hewett

Department: Biology

Sponsor: National Institute of Neurological Disorders and Stroke, National Institutes of Health, U.S. Department of Health and Human Services

Amount Awarded: $444,000 (September 1, 2014–August 31, 2017)

Background: The brain controls a myriad of complex mental and behavioral processes that are made possible by the transmission of electrical signals between neurons. Epilepsy is a chronic debilitating disorder of the brain in which abnormal bursts of electrical activity of neurons predispose affected individuals to recurrent spontaneous seizures. Research in my laboratory in the Department of Biology at Syracuse University focuses on the premise that neurons have ways to suppress abnormal electrical activity, thus reducing the likelihood of seizures. One of these ways appears to be through the release of local hormone-like substances called prostaglandins. Prostaglandin production in the brain is linked to neuronal electrical activity by a protein called cyclooxygenase-2 (COX-2). The level of this enzyme is rapidly increased by epileptic seizures (see figure). Moreover, we have shown that seizures are worsened when the activity of this protein is blocked, but suppressed when neurons are forced to make more of the protein. These observations support the hypothesis that COX-2 is an endogenous antiepileptic pathway in the brain. This notion forms the basis of my research that was recently awarded funding by a grant from the National Institutes of Health. This award will not only permit my laboratory to continue to expand our knowledge about how the brain protects itself against abnormal electrical activity, but it will also allow me to continue to expose undergraduate and graduate students in the Department of Biology to biomedical research.

Impact: It is estimated that epilepsy affects nearly 1 in 100 individuals in the United States. It can be acquired at any time over the life span, although the incidence is highest in children and elderly people. The effects on normal brain development and function can be severe and often render routine daily activities difficult or impossible. Unfortunately, current pharmacotherapies are frequently limited by adverse side effects and are not always effective, resulting in a high incidence of intractable epilepsy. Although advances have been made toward the development of safer antiepileptic drugs, drug resistance remains an important clinical problem. Moreover, no treatments are available to prevent the acquisition of epilepsy, and curative approaches are limited to surgical resection of affected brain areas in a very small percentage of patients. Thus, an important goal of my research is to provide a foundation upon which more effective therapeutic approaches can be developed.



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