Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain
Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain
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DOI：
10.1148/radiol.2352040003
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发表时间：
2005-05-01
期刊：
影响因子：
19.7
通讯作者：
González, RG
中科院分区：
文献类型：
--
作者：
Lentz, MR;Kim, JP;González, RG
目得：通过使用猴免疫缺陷病毒（SIV）感染的获得性免疫缺陷综合征神经学表现的猕猴模型，阐明灵长类动物脑中N-乙酰天冬氨酸（NAA）与肌酸（Cr）比值的短暂变化的神经病理学基础。这项研究得到了马萨诸塞州综合医院小组委员会的批准，和哈佛大学的机构动物护理和使用委员会。在感染SIV的第1个月期间评价感染SIV的恒河猴。共研究了11只动物，包括4只对照动物、3只感染后12天处死的动物、3只感染后14天处死的动物和1只感染后28天处死的动物。所有动物进行了体内质子（H-1）磁共振（MR）光谱，和死后额叶组织进行了研究，通过使用高光谱分辨率H-1磁共振波谱的脑提取物。此外，进行定量神经病理学分析，体视学分析，以确定神经元计数，和免疫组化分析，进行分析三个神经元标记物：突触素，微管相关蛋白2（MAP 2），和钙结合蛋白。方差分析（ANOVA）用于确定神经病理学和MR光谱标记物的实质性变化。斯皮尔曼等级相关性计算血浆病毒载量和神经病理学和光谱学markers.Results：在急性感染期间，与SIV，猕猴脑NAA/Cr（P <0.02，方差分析）和突触素（P <0.013，方差分析）表现出显着的变化。Cr浓度无明显变化。在神经元计数或其他免疫组织化学神经元标记物中未发现显著变化。用斯皮尔曼秩和检验，检测到突触素和离体NAA/Cr之间的显著直接相关（r（s）= 0.72，P <0.013）。未发现NAA/Cr与神经元计数、钙结合蛋白或MAP 2相关。结论：NAA/Cr是神经元损伤（不一定是神经元丢失）的敏感标志物，并且与突触素（突触树突功能障碍的标志物）相关性最好。(C)RSNA，2005年。
PURPOSE: To elucidate the neuropathologic basis of transient changes in the ratio of N-acetylaspartate (NAA) to creatine (Cr) in the primate brain by using a simian immunodeficiency virus (SIV)-infected macaque model of the neurologic manifestation of acquired immune deficiency syndrome.MATERIALS AND METHODS: This study was approved by the Massachusetts General Hospital Subcommittee,on Research and Animal Care and the Institutional Animal Care and Use Committee of Harvard University. Rhesus macaques infected with SIV were evaluated during the 1st month of infection. A total of 11 animals were studied, including four control animals, three animals sacrificed 12 days after infection, three animals sacrificed 14 days after infection, and one animal sacrificed 28 days after infection. All animals underwent in vivo proton (H-1) magnetic resonance (MR) spectroscopy, and postmortem frontal lobe tissue was investigated by using high-spectral-resolution H-1 MR spectroscopy of brain extracts. In addition, quantitative neuropathologic analyses were performed, Stereologic analysis was performed to determine neuronal counts, and immunohistochemical analysis-was performed to analyze three neuronal markers: synaptophysin, microtubule-associated protein 2 (MAP2), and calbindin. Analysis of variance (ANOVA) was used to determine substantial changes in neuropathologic and MR spectroscopic, markers. Spearman rank correlations were calculated between plasma viral load and neuropathologic and spectroscopic markers.RESULTS: During acute infection,with SIV, the macaque brain exhibited significant changes in NAA/Cr (P < .02, ANOVA) and synaptophysin (P < .013, ANOVA). There was no significant change in the concentration of Cr. No significant changes were found in neuronal counts or other immunohistochemical neuronal markers. With the Spearman rank test, a significant direct correlation was detected between synaptophysin and ex vivo NAA/Cr (r(s) = 0.72, P < .013). No correlation between NAA/Cr and neuronal counts, calbindin, or MAP2 was found.CONCLUSION: NAA/Cr is a sensitive marker of neuronal injury, not necessarily neuronal loss, and best correlates with synaptophysin, a marker of synaptodendritic dysfunction. (C) RSNA, 2005.