Takano T, Lin J H, Arcuino G, Gao Q, Yang J, Nedergaard M
Department of Cell Biology, Anatomy and Pathology, New York Medical College, Valhalla, New York, USA.
Nat Med. 2001 Sep;7(9):1010-5. doi: 10.1038/nm0901-1010.
Glutamate neurotoxicity has been implicated in stroke, head trauma, multiple sclerosis and neurodegenerative diseases. Although recent data show that cultured glioma cells secrete glutamate, the growth potential of brain tumors has not yet been linked to an excitotoxic mechanism. Using bioluminescence detection of glutamate release from freshly prepared brain slices, we show that implanted glioma cells continue to secrete glutamate. Moreover, gliomas with high glutamate release have a distinct growth advantage in host brain that is not present in vitro. Treatment with the NMDA receptor antagonists MK801 or memantine slowed the growth of glutamate-secreting tumors in situ, suggesting that activation of NMDA receptors facilitates tumor expansion. These findings support a new approach for therapy of brain tumors, based upon antagonizing glutamate secretion or its target receptors.
谷氨酸神经毒性与中风、头部创伤、多发性硬化症和神经退行性疾病有关。尽管最近的数据表明培养的胶质瘤细胞会分泌谷氨酸，但脑肿瘤的生长潜能尚未与兴奋性毒性机制联系起来。通过对新鲜制备的脑切片中谷氨酸释放进行生物发光检测，我们发现植入的胶质瘤细胞会持续分泌谷氨酸。此外，谷氨酸释放量高的胶质瘤在宿主脑中具有明显的生长优势，而在体外则不存在这种优势。用NMDA受体拮抗剂MK801或美金刚治疗可减缓原位分泌谷氨酸的肿瘤的生长，这表明NMDA受体的激活促进了肿瘤的扩张。这些发现支持了一种基于拮抗谷氨酸分泌或其靶受体的脑肿瘤治疗新方法。
