CHANGES IN N-ACETYL-ASPARTATE CONTENT DURING FOCAL AND GLOBAL BRAIN ISCHEMIA OF THE RAT

N-Acetyl-aspartate (NAA) is almost exclusively localized in neurons in the mature brain and might be used as a neuronal marker. It has been reported that the NAA content in human brain is decreased in neurodege nerative diseases and in stroke. Since the NAA content can be determin ed by nuclear magnetic resonance techniques, it has potential as a dia gnostic and prognostic marker. The objective of this study was to exam ine the change of NAA content and related substances following cerebra l ischemia and compare the results to the damage of the tissue. We use d rats to study the changes of NAA, N-acetyl-aspartyl-glutamate (NAAG) , glutamate, and aspartate contents over a time course of 24 h in brai n regions affected by either permanent middle cerebral artery occlusio n (focal ischemia) or decapitation (global ischemia). The decreases of NAA and NAAG contents following global brain ischemia were linear ove r time but significant only after 4 and 2 h, respectively. After 24 h, the levels of NAA and NAAG were 24 and 44% of control values, respect ively. The concentration of glutamate did not change, whereas the aspa rtate content increased at a rate comparable with the rate of decrease of NAA content. This is consistent with NAA being preferentially degr aded by the enzyme amidohydrolase II in global ischemia. In focal isch emia, there was a rapid decline of NAA within the first 8 h of ischemi a followed by a slower rate of reduction. The reductions of NAA and NA AG contents in focal ischemia were significant after 4 and 24 h, respe ctively. After 24 h, the NAA and NAAG contents were 33 and 64% of cont rol values, respectively. Also, the glutamate and aspartate contents e xhibited significant decreases in focal ischemic tissue. Our studies s how that NAA decreases during brain ischemia, the initial rate being f aster in focal ischemia than in global ischemia. In rat transient foca l ischemia, others have shown that a middle cerebral artery occlusion of 2- to 3-h duration is sufficient to produce an infarct that is simi lar in size to that following permanent occlusion for 24 h. The fact t hat we observed only a 10% decrease of NAA content 2 h after occlusion demonstrates that the NAA content of the tissue does not reflect neur onal viability. Thus, the incompetence with which ischemic/infarcted t issue removes NAA will lead to overestimation of the number of viable neurons in acute situations. Only when steady state prevails may [NAA] be used as a marker of viable nerve cells.