日前,，在線出版的《自然—醫(yī)學(xué)》期刊上發(fā)表的一項(xiàng)研究表明，研究人員發(fā)現(xiàn),，阻止胱氨酸—谷氨酸脂輸送器能減少神經(jīng)膠質(zhì)瘤所誘導(dǎo)的小鼠癲癇發(fā)作,。
因?yàn)槟[瘤細(xì)胞分泌出刺激性的神經(jīng)遞質(zhì)谷氨酸酯，神經(jīng)膠質(zhì)瘤患者常常會發(fā)生癲癇,。神經(jīng)膠質(zhì)瘤的生存需要有氨基酸胱氨酸的存在,，在腫瘤上的胱氨酸—谷氨酸酯輸送器將胱氨酸送往腫瘤細(xì)胞中之時(shí)，腫瘤也在附近的腦組織周圍分泌出大量的谷氨酸酯,，導(dǎo)致腫瘤附近的神經(jīng)細(xì)胞過度活躍,，癲癇發(fā)作。
柳氮磺胺吡啶是食品和藥物管理署（FDA）批準(zhǔn)使用的胱氨酸—谷氨酸酯輸送器抑止劑,，用于治療腸道炎癥患者,。Harald Sontheimer和同事給患腫瘤的小鼠使用柳氮磺胺吡啶，發(fā)現(xiàn)這種藥物能阻止導(dǎo)致腫瘤的大腦谷氨酸酯水平的升高,，也能減少神經(jīng)膠質(zhì)瘤所引發(fā)的小鼠癲癇發(fā)作,。這些新發(fā)現(xiàn)表明,，有望開發(fā)新的治療方法以減少人類因腦腫瘤引發(fā)的癲癇發(fā)作,。（生物谷 Bioon.com）
doi:10.1038/nm.2453
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PMID:
Glutamate release by primary brain tumors induces epileptic activity
Susan C Buckingham, Susan L Campbell, Brian R Haas, Vedrana Montana, Stefanie Robel, Toyin Ogunrinu & Harald Sontheimer
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 xc− 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 xc−. 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.
