Cerebrospinal fluid amino acid alterations are associated with oxidative stress and neuronal injury markers in multiple sclerosis

Altered glutamatergic neurotransmission and oxidative stress are implicated in the pathophysiology of multiple sclerosis (MS), yet their interplay remains incompletely understood. This study investigated cerebrospinal fluid (CSF) levels of neuroactive amino acids (aspartate, glutamate, glycine, γ-aminobutyric acid) in relation to markers of lipid peroxidation, antioxidant capacity, and neuronal injury. Amino acids were quantified using a validated high-performance liquid chromatography method with fluorescence detection. Aspartate levels were significantly elevated in MS compared with other neurological diseases, with a consistent trend across relapsing–remitting (RR) and secondary-progressive (SP) subtypes. Glycine concentrations were increased in RR-MS, whereas glutamate and γ-aminobutyric acid levels remained unchanged. Correlation analyses revealed positive associations between aspartate and glutamate with lipid peroxidation markers, supporting a link between excitatory metabolism and oxidative damage. In contrast, glycine showed a negative association with neuron-specific enolase, suggesting a modulatory or neuroprotective role. Markers of oxidative stress were increased, particularly in SP-MS, accompanied by reduced total antioxidant status. These changes occurred in the absence of significant intrathecal immune activation or blood–brain barrier dysfunction. Together, these findings indicate that altered amino acid homeostasis is coupled to oxidative stress and neuronal injury in MS. A composite CSF profile integrating excitatory amino acids with oxidative and neurodegenerative markers may complement established biomarkers such as neurofilament light chain by capturing metabolic and excitotoxic components of disease activity.