Excitatory Amino Acids and Multiple Sclerosis: Evidence From Cerebrospinal Fluid

Abstract

Background Recent evidence suggests an altered glutamate homeostasis in the brain of patients with multiple sclerosis (MS), as seen in experimental models of MS. Objective To test whether the excitotoxic insult contributes to the pathological process in MS by measuring glutamate and aspartate levels in the cerebrospinal fluid of MS patients and control individuals. Participants Twenty-five patients with the relapsing-remitting form of MS during a stable clinical phase, 30 patients with relapsing-remitting MS during relapse, and 25 patients with the secondary progressive form of MS were included in the study. Data were compared with those of 20 age-matched control subjects without diseases of the central and peripheral nervous systems. Methods Glutamate and aspartate levels in the cerebrospinal fluid were measured by high-performance liquid chromatography. Results Cerebrospinal fluid glutamate levels were significantly higher in patients assessed during relapse compared with those of the patients with relapsing-remitting MS examined during the stable clinical phase and the controls (P Conclusions Neurotoxic events occur in MS patients, and they can be responsible for oligodendrocyte and neuronal cell death in patients with this demyelinating disease. The manipulation of glutamate-altered homeostasis or antagonizing glutamate receptor-mediated excitotoxicity may have therapeutic implications in MS patients.