Alteration of Intracellular Metabolite Diffusion in Rat Brain In Vivo During Ischemia and Reperfusion

Abstract

Background and Purpose Diffusion-weighted MRI can demonstrate decreases of the apparent diffusion coefficient (ADC) of brain tissue water shortly after the onset of ischemia. To further elucidate underlying mechanisms, this study extended diffusion assessment to intracellular metabolites in rat brain in vivo before, during, and after ischemia. Methods Changes in molecular mobility were studied in a rat model of global forebrain ischemia (n=8, 20-minute occlusion, 120-minute reperfusion) with the use of diffusion-weighted localized proton MR spectroscopy. During ischemia and early reperfusion the time course of ADC changes was monitored by strongly diffusion-weighted spectra. ADC values of N -acetylaspartate, creatines, cholines, and myo -inositol were evaluated from series of differently diffusion-weighted spectra before ischemia, 90 minutes after reperfusion, and 60 minutes postmortem. Results Parallel to a rise in diffusion-weighted water signal (133±20%), pertinent intensities of all brain metabolites increased during ischemia. Changes were most pronounced for myo -inositol (46±9%) and smallest for N -acetylaspartate (12±4%). During reperfusion water ADC values returned to basal values, whereas metabolite ADC values were decreased by 22% (after 40 minutes). Postmortem ADC values (after 60 minutes) were reduced by 46% for water and 38% for metabolites. Conclusions The present findings indicate that water ADC changes during ischemic stroke are accompanied by significant alterations in intracellular mobility in both neuronal and glial cell populations as reflected by N -acetylaspartate and myo -inositol, respectively. Altered metabolite ADC values during reperfusion are consistent with irreversible tissue damage in this model and offer new means to assess circulatory and metabolic compromise.