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 (ONDs), while glutamate showed a non-significant trend toward higher concentrations. Glycine concentrations were significantly higher in MS and RR-MS than in the non-neurological control group (CG), whereas GABA showed no significant group differences. Correlation analyses revealed a positive association between glutamate and 8-iso-PGF₂α in MS and RR-MS, whereas the correlation between aspartate and 8-iso-PGF₂α was observed only in ONDs and was based on a small number of observations (n = 6). Glycine showed a significant negative association with neuron-specific enolase in MS and RR-MS, while a positive association with total antioxidant status was observed in CG. These associations should be considered exploratory and do not establish causal or mechanistic relationships. The SP-MS subgroup showed the highest median concentrations of 8-iso-PGF₂α and MDA, while TAS was lower than in RR-MS; however, these findings were based on limited numbers of observations and should therefore be considered exploratory. These biochemical changes were observed in the absence of marked abnormalities in the measured CSF indicators of intrathecal IgG synthesis or blood-CSF barrier function. Together, these findings indicate associations between CSF amino acid homeostasis, oxidative stress and neuronal injury in MS. CSF amino acid profiling may provide complementary information on metabolic and neurotransmission-related alterations in MS and warrants further evaluation alongside established biomarkers in larger, independently characterized cohorts.