Glioma, glutamate (SLC7A11) and seizures—a commentary
Glioma, a common type of adult primary brain tumor and also the most dreaded, often presents to the clinic with seizures. These seizures are usually difficult to control with the standard anti-epileptics. Some of the patients presenting with medically refractory epilepsy due to a low grade glioma, achieve seizure control by surgical resection but some remain symptomatic despite surgery. Excitability in the human CNS is predominantly mediated by glutamate and recent compelling evidence points to the role of glutamate in excitotoxic damage resulting in seizures as well as maintenance and invasion of malignant glioma (1). Furthermore, recent studies have shown that excitotoxicity favours glioma preservation, progression and invasion in cases of malignant glioma (2-4). For instance, necrosis in glioblastoma was reported to result due to glutamate excitotoxicity through inhibition of system XC- (SXC), which normally exchanges intracellular glutamate with extracellular cystine, causing deficient intracellular cystine or through change in calcium homeostasis eventually leading to cell death resulting from reactive oxygen species damage (5). Thus, targeting excitotoxicity in glioma patients not only helps in symptomatic management of the seizures but may, possibly, play a role in altering the underlying tumor pathogenesis.