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Excitatory amino acids and multiple sclerosis: evidence from cerebrospinal fluid
Paola Sarchielli1, Laura Greco, Ardesio Floridi
1Neuroscience Department, Institute of Clinical and Applied Biochemistry, Policlinico Monteluce, University of Perugia, Via E Dal Pozzo, 06126 Perugia, Italy. neuro.pg@tiscalinet.it
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<.001). The levels of glutamate detected in patients with relapsing-remitting MS during the stable phase who had active lesions were significantly higher than in those without neuroradiological evidence of disease activity (P<.001). Significantly higher levels of glutamate were found in patients with secondary progressive MS with an increase of 1 or more points on the Expanded Disability Status Scale score compared with stable patients with secondary progressive MS and control subjects (P<.001).
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.