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 neurodegenerative diseases and in stroke. Since the NAA content can be determined by nuclear magnetic resonance techniques, it has potential as a diagnostic and prognostic marker. The objective of this study was to examine the change of NAA content and related substances following cerebral ischemia and compare the results to the damage of the tissue. We used rats to study the changes of NAA, N-acetyl-aspartyl-glutamate (NAAG), glutamate, and aspartate contents over a time course of 24 h in brain regions affected by either permanent middle cerebral artery occlusion (focal ischemia) or decapitation (global ischemia). The decreases of NAA and NAAG contents following global brain ischemia were linear over 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, respectively. The concentration of glutamate did not change, whereas the aspartate content increased at a rate comparable with the rate of decrease of NAA content. This is consistent with NAA being preferentially degraded by the enzyme amidohydrolase II in global ischemia. In focal ischemia, there was a rapid decline of NAA within the first 8 h of ischemia followed by a slower rate of reduction. The reductions of NAA and NAAG contents in focal ischemia were significant after 4 and 24 h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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Pharmaceuticals Division, Novo Nordisk A/S, Måløv, Denmark.
Laursen
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Hansen
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D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004355:Drug Stability; D018698:Glutamic Acid / Q000134:cerebrospinal fluid / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000378:metabolism; D011180:Postmortem Changes; D051381:Rats; D017208:Rats, Wistar
D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate