To evaluate the true meaning of N-acetyl-aspartate (NAA) measurements in ischemic stroke, the authors followed the temporal changes in brain NAA content in rats subjected to permanent focal ischemia. Ischemia was induced by photothrombotic cortical occlusion. At 1, 3, 8, and 30 d after onset of ischemia, NAA was measured in the infarct by high-performance liquid chromatography coupled to ultraviolet detection and histologic damage was examined. Cerebral content of NAA was markedly reduced in the lesioned tissue, reaching -90% after 3 d, a time at which viable neurons were no longer detected. N-Acetyl-aspartate concentrations after 8 and 30 d were higher than that observed after 3 d. This metabolic change coincided with an important microglial and astroglial activation. The results of this study raise questions regarding the use of NAA as a specific neuronal marker in chronic stage of stroke.