Sager T N, Laursen H, Hansen A J
Pharmaceuticals Division, Novo Nordisk A/S, Måløv, Denmark.
J Cereb Blood Flow Metab. 1995 Jul;15(4):639-46. doi: 10.1038/jcbfm.1995.79.
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)
N-乙酰天门冬氨酸(NAA)几乎仅存在于成熟大脑的神经元中,可作为神经元标志物。据报道,在神经退行性疾病和中风中,人脑的NAA含量会降低。由于NAA含量可通过核磁共振技术测定,它具有作为诊断和预后标志物的潜力。本研究的目的是检测脑缺血后NAA含量及相关物质的变化,并将结果与组织损伤情况进行比较。我们用大鼠研究了在永久性大脑中动脉闭塞(局灶性缺血)或断头(全脑缺血)影响的脑区中,NAA、N-乙酰天门冬氨酰谷氨酸(NAAG)、谷氨酸和天门冬氨酸含量在24小时时间进程中的变化。全脑缺血后NAA和NAAG含量的降低随时间呈线性,但分别仅在4小时和2小时后才显著。24小时后,NAA和NAAG的水平分别为对照值的24%和44%。谷氨酸浓度未改变,而天门冬氨酸含量的增加速率与NAA含量的降低速率相当。这与在全脑缺血中NAA优先被酰胺水解酶II降解一致。在局灶性缺血中,缺血后最初8小时内NAA迅速下降,随后下降速度较慢。局灶性缺血中NAA和NAAG含量的降低分别在4小时和24小时后显著。(摘要截短于250字)