Glutamate release by primary brain tumors induces epileptic activity
People with brain cancers called gliomas often have seizures due to secretion of the excitatory neurotransmitter glutamate from the tumor. Now, Harald Sontheimer and his colleagues report that blockade of a cystine-glutamate transporter in tumor cells by an FDA-approved drug can reduce glioma-induce...
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Published in | Nature medicine Vol. 17; no. 10; pp. 1269 - 1274 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Nature Publishing Group US
01.10.2011
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | People with brain cancers called gliomas often have seizures due to secretion of the excitatory neurotransmitter glutamate from the tumor. Now, Harald Sontheimer and his colleagues report that blockade of a cystine-glutamate transporter in tumor cells by an FDA-approved drug can reduce glioma-induced epilepsy in mice.
Epileptic seizures are a common and poorly understood comorbidity for individuals with primary brain tumors. To investigate peritumoral seizure etiology, we implanted human-derived glioma cells into severe combined immunodeficient mice. Within 14–18 d, glioma-bearing mice developed spontaneous and recurring abnormal electroencephalogram events consistent with progressive epileptic activity. Acute brain slices from these mice showed marked glutamate release from the tumor mediated by the system x
c
−
cystine-glutamate transporter (encoded by
Slc7a11
). Biophysical and optical recordings showed glutamatergic epileptiform hyperexcitability that spread into adjacent brain tissue. We inhibited glutamate release from the tumor and the ensuing hyperexcitability by sulfasalazine (SAS), a US Food and Drug Administration–approved drug that blocks system x
c
−
. We found that acute administration of SAS at concentrations equivalent to those used to treat Crohn's disease in humans reduced epileptic event frequency in tumor-bearing mice compared with untreated controls. SAS should be considered as an adjuvant treatment to ameliorate peritumoral seizures associated with glioma in humans. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 1078-8956 1546-170X |
DOI: | 10.1038/nm.2453 |