The reduction of the apparent diffusion coefficient (ADC) of brain tissue water in acute
cerebral ischemia, as measured by diffusion-weighted magnetic resonance imaging, is generally associated with the development of cytotoxic
edema. However, the underlying mechanism is still unknown. Our aim was to elucidate diffusion changes in the intracellular environment in cytotoxic edematous tissue. The ADC of intracellular metabolites was measured by use of diffusion-weighted 1H-magnetic resonance spectroscopy after (1) unilateral
N-methyl-D-aspartate (
NMDA) injection and (2)
cardiac arrest-induced global
ischemia in neonatal rat brain. The distinct water ADC drop early after 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 excitotoxic injury, the ADC of water and the metabolites
taurine and
N-acetylaspartate dropped significantly (P < 0.05, n = 8). At 24 and 72 hours after
NMDA injection brain metabolite levels were diminished and metabolite ADC approached 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 hours later and, water and metabolite ADC had normal values (n = 8). The contribution of brain temperature changes (calculated from the chemical shift between the water and
N-acetylaspartate signals) and tissue deoxygenation to
ischemia-induced intracellular ADC changes was minor. These data lend support to previous suggestions that the
ischemia-induced brain water ADC drop may partly be caused by reduced diffusional displacement of intracellular water, possibly involving early alterations in intracellular tortuosity, cytoplasmic streaming, or intracellular molecular interactions.