Finally, of the most clinical relevance, this study is also important in identifying a novel, rational therapeutic strategy for treating tumor-related epilepsy. The decrease in seizure activity following administration of the xc− glutamate-cysteine transporter inhibitor, sulfasalazine, in the mouse model raises the possibility of inhibiting glutamatergic systems as a treatment for tumor-related epilepsy in people. However, the effects were short-lived, being most prominent for the first 2 hours following treatment, which likely reflects the short half-life of sulfasalazine. This rapidly reversible effect of sulfasalazine suggests that the mechanism involves direct reduction in neuronal excitability by inhibition of glutamate release, but sulfasalazine could also have other actions, such as anti-inflammatory effects. Alternative therapeutic approaches that would also decrease glutamate stimulation, but have longer lasting effects, might include upregulation of astrocyte glutamate transporters or direct antagonism of glutamate receptors. Future mechanistic studies may lead to the development of a variety of unique therapeutic approaches specifically targeting tumor-related epilepsy.
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