Excessive extracellular concentrations of L-glutamate (L-Glu) can be neurotoxic and contribute to neurodegenerative processes in multiple sclerosis (MS). The association between cerebrospinal fluid (CSF) L-Glu levels, clinical features, and inflammatory biomarkers in patients with MS remains unclear. In 179 MS patients (relapsing remitting, RR, N = 157; secondary progressive/primary progressive, SP/PP, N = 22), CSF levels of L-Glu at diagnosis were determined and compared with those obtained in a group of 40 patients with non-inflammatory/non-degenerative disorders. Disability at the time of diagnosis, and after 1 year follow-up, was assessed using the Expanded Disability Status Scale (EDSS). CSF concentrations of lactate and of a large set of pro-inflammatory and anti-inflammatory molecules were explored. CSF levels of L-Glu were slightly reduced in MS patients compared to controls. In RR-MS patients, L-Glu levels correlated with EDSS after 1 year follow-up. Moreover, in MS patients, significant correlations were found between L-Glu and both CSF levels of lactate and the inflammatory molecules interleukin (IL)-2, IL-6, and IL-1 receptor antagonist. Altered expression of L-Glu is associated with disability progression, oxidative stress, and inflammation. These findings identify CSF L-Glu as a candidate neurochemical marker of inflammatory neurodegeneration in MS.

中文翻译：

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L-谷氨酸的脑脊液水平信号中枢炎性神经变性在多发性硬化症

L-谷氨酸 (L-Glu) 的细胞外浓度过高可能具有神经毒性，并有助于多发性硬化症 (MS) 的神经退行性过程。MS 患者的脑脊液 (CSF) L-Glu 水平、临床特征和炎症生物标志物之间的关联仍不清楚。在 179 名 MS 患者中（复发缓解，RR，N  = 157；继发进展/原发进展，SP/PP，N = 22)，确定诊断时 L-Glu 的 CSF 水平，并与一组 40 名非炎症/非退行性疾病患者中获得的水平进行比较。诊断时的残疾以及 1 年的随访后，使用扩展残疾状态量表 (EDSS) 进行评估。研究了脑脊液中乳酸和大量促炎和抗炎分子的浓度。与对照组相比，MS 患者的脑脊液 L-Glu 水平略有降低。在 RR-MS 患者中，L-Glu 水平在 1 年随访后与 EDSS 相关。此外，在 MS 患者中，发现 L-Glu 与 CSF 的乳酸水平和炎症分子白细胞介素 (IL)-2、IL-6 和 IL-1 受体拮抗剂之间存在显着相关性。L-Glu 的表达改变与残疾进展、氧化应激、和炎症。这些发现将 CSF L-Glu 确定为 MS 中炎症性神经变性的候选神经化学标志物。