Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T
Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T
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DOI：
10.1093/brain/awh467
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发表时间：
2005-05-01
期刊：
影响因子：
14.5
通讯作者：
Pelletier, D
中科院分区：
文献类型：
--
作者：
Srinivasan, R;Sailasuta, N;Pelletier, D
多发性硬化症及其动物模型的组织病理学报告显示，活动性病变中的轴突损伤与谷氨酸代谢受损之间存在联系。成熟的少突胶质细胞在谷氨酸摄取中发挥作用，以维持谷氨酸稳态，但在多发性硬化症白色物质中，损伤附近谷氨酸转运体表达的丧失导致谷氨酸清除无效。使用磁共振波谱技术，分离谷氨酸共振在3 T，我们比较正常人和多发性硬化症患者在不同的大脑区域之间的谷氨酸水平。代谢物浓度（谷氨酸、谷氨酰胺、N-乙酰天冬氨酸、肌醇、胆碱、肌酸）来自LC模型，并针对T1弛豫时间进行校正。谷氨酸浓度在急性病变（P = 0.02）和外观正常的白色物质（P = 0.03）中升高，而在慢性病变中无显著升高（P = 0.77）。慢性病变组的N-乙酰天冬氨酸水平显著低于急性病变组和正常白色物质组（P < 0.001）。急性病变组胆碱水平明显高于慢性病变组（P < 0.001）。在多发性硬化中也发现了胶质细胞活性增加的证据，与对照白色物质相比，急性病变中的肌醇水平显著更高（P < 0.001）。这些体内结果支持了多发性硬化症患者大脑中存在谷氨酸代谢改变的假设。
Histopathological reports of multiple sclerosis and its animal models have shown evidence of a link between axonal injury in active lesions and impaired glutamate metabolism. Mature oligodendrocytes play a role in glutamate uptake to maintain glutamate homeostasis but in multiple sclerosis white matter the loss of expression of glutamate transporters in the lesion vicinity results in ineffective glutamate removal. Using a magnetic resonance spectroscopy technique that isolates the glutamate resonance at 3 T, we compared glutamate levels between normal subjects and multiple sclerosis patients in different brain areas. Metabolite concentrations (glutamate, glutamine, N-acetyl-aspartate, myo-inositol, choline, creatine) were derived from LCmodel and corrected for T1 relaxation time. Glutamate concentrations were found to be elevated in acute lesions (P = 0.02) and normal-appearing white matter (P = 0.03), with no significant elevation in chronic lesions (P = 0.77). The N-acetyl-aspartate level in chronic lesions was significantly lower (P < 0.001) than in acute lesions and normal-appearing white matter. The choline level in acute lesions was significantly higher (P < 0.001) than in chronic lesions. Evidence was also found for increased glial activity in multiple sclerosis, with significantly higher (P < 0.001) myo-inositol levels in acute lesions compared with control white matter. These in vivo results support the hypothesis that altered glutamate metabolism is present in brains of multiple sclerosis patients.