Changes in the diffusion of water and intracellular metabolites after excitotoxic injury and global ischemia in neonatal rat brain

The reduction of the apparent diffusion coefficient (ADC) of brain tissue w ater in acute cerebral ischemia, as measured by diffusion-weighted magnetic resonance imaging, is generally associated with the development of cytotox ic edema. However, the underlying mechanism is still unknown. Our aim was t o elucidate diffusion changes in the intracellular environment in cytotoxic edematous tissue. The ADC of intracellular metabolites was measured by use of diffusion-weighted H-1-magnetic resonance spectroscopy after (1) unilat eral N-methyl-D-aspartate (NMDA) injection and (2) cardiac arrest-induced g lobal ischemia in neonatal rat brain. The distinct water ADC drop early aft er global ischemia was accompanied by a significant reduction of the ADC of all measured metabolites (P < 0.01, n = 8). In the first hours after excit otoxic injury, the ADC of water and the metabolites taurine and N-acetylasp artate dropped significantly (P < 0.05, n = 8). At 24 and 72 hours after NM DA injection brain metabolite levels were diminished and metabolite ADC app roached contralateral values. Administration of the NMDA-antagonist MK-801 1.5 hours after NMDA injection completely normalized the water ADC but not the metabolite ADC after 1 to 2 hours (n = 8). No damage was detected 72 ho urs later and, water and metabolite ADC had normal values (n = 8). The cont ribution of brain temperature changes (calculated from the chemical shift b etween the water and N-acetylaspartate signals) and tissue deoxygenation to ischemia-induced intracellular ADC changes was minor. These data lend supp ort to previous suggestions that the ischemia-induced brain water ADC drop may partly be caused by reduced diffusional displacement of intracellular w ater, possibly involving early alterations in intracellular tortuosity, cyt oplasmic streaming, or intracellular molecular interactions.