Pilot results of in vivo brain glutathione measurements in stroke patients

Abstract

Measurement of glutathione concentration for the study of redox status in subjects with neurological disease has been limited to peripheral markers. We recruited 19 subjects with large strokes. Using magnetic resonance spectroscopy we measured brain glutathione concentration in the stroke region and in healthy tissue to calculate a glutathione-ratio. Elevated glutathione-ratio was observed in subacute (<72 hours) subjects without hemorrhagic transformation (mean=1.19, P=0.03, n=6). No trend was seen when all subjects were considered (n=19, 3 to 754 hours, range=0.45 to 1.41). This technique can detect glutathione changes because of disease, and may be valuable in clinical trials of stroke and other neurological diseases.

Figure 1

Averaged spectra for six subjects without hemorrhagic transformation imaged within the first 3 days after stroke. In this subgroup the γ-ℒ-glutamyl-ℒ-cysteinglycine (GSH)-ratio was significantly elevated in the lesion compared with the contralateral hemisphere. The reduction in lesion NAA did not reach statistical significance (P=0.08, paired t-test). The Upper spectrum illustrates the averaged data from the lesion and the lower spectrum illustrates the data from the contralateral side. Dashed lines correspond to the edited spectrum. Dotted lines correspond to unedited spectrum. Solid lines correspond to the difference spectrum. The latter spectrum unmasks the GSH peak at 2.95 p.p.m. by canceling out larger peaks, which ordinarily obscure the smaller GSH peak.