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Histopathological reports of multiple sclerosis and its animal models have sh own evidence of a link between axonal injury in active lesions and impaired glut amate metabolism. Mature oligodendrocytes play a role in glutamate uptake to mai ntain glutamate homeostasis but in multiple sclerosis white matter the loss of e xpression of glutamate transporters in the lesion vicinity results in ineffectiv e glutamate removal. Using a magnetic resonance spectroscopy technique that isol ates the glutamate resonance at 3 T, we compared glutamate levels between normal subjects and multiple sclerosis patients in different brain areas. Metabolite c oncentrations (glutamate, glutamine, N- acetyl- aspartate, myo- inositol, cho line, creatine) were derived from LC model and corrected for T1 relaxation time. Glutamate concentrations were found to be elevated in acute lesions (P=0.02) an d normal- appearing white matter (P=0.03), with no significant elevation in chr onic lesions (P=0.77). The N- acetyl- aspartate level in chronic lesions was s ignificantly lower (P < 0.001) than in acute lesions and normal- appearing whit e matter. The choline level in acute lesions was significantly higher (P < 0.001 ) than in chronic lesions. Evidence was also found for increased glial activity in multiple sclerosis, with significantly higher (P < 0.001) myo- inositol leve ls in acute lesions compared with control white matter. These in vivo results su pport the hypothesis that altered glutamate metabolism is present in brains of m ultiple sclerosis patients.
Histopathological reports of multiple sclerosis and its animal models have sh own evidence of a link between axonal injury in active lesions and impaired glut amate metabolism. Mature oligodendrocytes play a role in glutamate uptake to mai ntain glutamate homeostasis but in multiple sclerosis white matter the loss of e xpression of glutamate transporters in the lesion vicinity results in ineffectiv e glutamate removal. Using a magnetic resonance spectroscopy technique that isol ates the glutamate resonance at 3 T, we compared glutamate levels between normal subjects and multiple sclerosis patients in different brain areas. Metabolite c oncentrations (glutamate, glutamine, N-acetyl-aspartate, myo-inositol, cho line, creatine) were derived from LC model and corrected for T1 relaxation time. Glutamate concentrations were found to be elevated in acute lesions (P = 0.02) normal-appearing white matter (P = 0.03) with no significant elevation in chr onic lesions (P = 0.77). The N- acetyl- aspartate level in chronic lesions was ignificantly lower (P <0.001) than in acute lesions and normal- appearing whit e matter. The choline level in acute lesions was significantly higher (P <0.001) than in chronic lesions. Evidence was also found for Increased glial activity in multiple sclerosis, with significantly higher (P <0.001) myo- inositol leve ls in acute lesions than with control white matter. These in vivo results su pport the hypothesis that altered glutamate metabolism is present in brains of m ultiple sclerosis patients .