ALTERATION OF INTRACELLULAR METABOLITE DIFFUSION IN RAT-BRAIN IN-VIVODURING ISCHEMIA AND REPERFUSION

Background and Purpose Diffusion-weighted MRI can demonstrate decrease s of the apparent diffusion coefficient (ADC) of brain tissue water sh ortly after the onset of ischemia. To further elucidate underlying mec hanisms, this study extended diffusion assessment to intracellular met abolites in rat brain in vivo before, during, and after ischemia. Meth ods Changes in molecular mobility were studied in a rat model of globa l forebrain ischemia (n = 8, 20-minute occlusion, 120-minute reperfusi on) with the use of diffusion-weighted localized proton MR spectroscop y. During ischemia and early reperfusion the time course of ADC change s was monitored by strongly diffusion-weighted spectra. ADC values of N-acetylaspartate. creatines, cholines, and myo-inositol were evaluate d from series of differently diffusion-weighted spectra before ischemi a, 90 minutes after reperfusion, and 60 minutes postmortem. Results Pa rallel to a rise in diffusion-weighted water signal (133 +/- 20%), per tinent intensities of all brain metabolites increased during ischemia. Changes were most pronounced for myo-inositol (46 +/- 9%) and smalles t for N-acetylaspartate (12 +/- 4%). During reperfusion water ADC valu es returned to basal values, whereas metabolite ADC values were decrea sed by 22% (after 40 minutes). Postmortem ADC values (after 60 minutes ) were reduced by 46% for water and 38% for metabolites. Conclusions T he present findings indicate that water ADC changes during. ischemic s troke are accompanied by significant alterations in intracellular mobi lity in both neuronal and glial cell populations as reflected by N-ace tylaspartate and myoinositol, respectively. Altered metabolite ADC val ues during reperfusion are consistent with irreversible tissue damage in this model and offer new means to assess circulatory and metabolic compromise.