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.
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.
Authors: Agnieszka Smolinska; Joram M Posma; Lionel Blanchet; Kirsten A M Ampt; Amos Attali; Tinka Tuinstra; Theo Luider; Marek Doskocz; Paul J Michiels; Frederic C Girard; Lutgarde M C Buydens; Sybren S Wijmenga Journal: Anal Bioanal Chem Date: 2012-03-07 Impact factor: 4.142
Authors: Marek J Noga; Adrie Dane; Shanna Shi; Amos Attali; Hans van Aken; Ernst Suidgeest; Tinka Tuinstra; Bas Muilwijk; Leon Coulier; Theo Luider; Theo H Reijmers; Rob J Vreeken; Thomas Hankemeier Journal: Metabolomics Date: 2011-04-16 Impact factor: 4.290
Authors: M P Kurnellas; H Li; M R Jain; S N Giraud; A B Nicot; A Ratnayake; R F Heary; S Elkabes Journal: Cell Death Differ Date: 2010-05-21 Impact factor: 15.828
Authors: Robert Nisticò; Francesco Mori; Marco Feligioni; Ferdinando Nicoletti; Diego Centonze Journal: Philos Trans R Soc Lond B Biol Sci Date: 2013-12-02 Impact factor: 6.237