Journal
NEUROCHEMISTRY INTERNATIONAL
Volume 63, Issue 7, Pages 696-701Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2013.01.027
Keywords
Glioma; Seizures; Astrocytes; Gliosis; Hyperexcitability; Glutamate
Categories
Funding
- German Research Foundation [RO 4224/1-1]
- Epilepsy Foundation [222427]
- National Institute of Health [5 RO1-NS052634]
- Eunice Kennedy Shriver National Institute of Child Health & Human Development [5P30HD038985]
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Seizures are a serious and debilitating co-morbidity of primary brain tumors that affect most patients, yet their etiology is poorly understood. In many CNS pathologies, including epilepsy and brain injury, high levels of extracellular glutamate have been implicated in seizure generation. It has been shown that gliomas release neurotoxic levels of glutamate through their high expression of system xc-. More recently it was shown that the surrounding peritumoral cortex is spontaneously hyperexcitable. In this review, we discuss how gliomas induce changes in the surrounding environment that may further contribute to elevated extracellular glutamate and tumor-associated seizures. Peritumoral astrocytes become reactive and lose their ability to remove glutamate, while microglia, in response to signals from glioma cells, may release glutamate. In addition, gliomas increase blood brain barrier permeability, allowing seizure-inducing serum components, including glutamate, into the peritumoral region. These factors, working together or alone, may influence the frequency and severity of tumor-associated epilepsy. (C) 2013 Elsevier Ltd. All rights reserved.
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