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在神经艾滋病猕猴模型急性SIV感染期间脑损伤与修复的体内1H磁共振波谱分析

In vivo 1H MRS of brain injury and repair during acute SIV infection in the macaque model of neuroAIDS.

作者信息

Greco Jane B, Westmoreland Susan V, Ratai Eva M, Lentz Margaret R, Sakaie Ken, He Julian, Sehgal Prabhat K, Masliah Eliezer, Lackner Andrew A, González R Gilberto

机构信息

Massachusetts General Hospital NMR Center and Neuroradiology Division, Charlestown, Massachusetts, USA.

出版信息

Magn Reson Med. 2004 Jun;51(6):1108-14. doi: 10.1002/mrm.20073.

Abstract

The metabolic response of the rhesus macaque brain during acute simian immunodeficiency virus (SIV) infection was investigated with in vivo (1)H MR spectroscopy. Fifteen rhesus macaques were studied before inoculation, and once or twice after infection. In all, 13/15 macaques had elevations of Cho/NAA at 11-13 days postinoculation (dpi); all 10 macaques measured after 13 dpi had subsequent reduction of this ratio (ANOVA, P < 10(-6)). There were significant increases in Cho/Cr (20%, P = 0.04) and MI/Cr (14%, P = 0.003) at 11 dpi. At 13 dpi a 7.7% decrease (P = 0.02) in NAA/Cr was observed, while Cho/Cr was no longer significantly different from baseline. At 27 dpi Cho/Cr was decreased to 18% (P = 0.004) below preinoculation values, while NAA/Cr and MI/Cr were at baseline values. Absolute concentrations of Cho, MI, and NAA showed a similar time course, with no observed changes in Cr. There was a strong correlation between Cho/Cr change and plasma viral load (r(s) = 0.79, P < 0.01). Acute SIV produces extensive metabolic abnormalities in the brain, which may reflect inflammation and neuronal injury, which are reversed with immunological control of the virus. Similar events are likely to occur in acutely HIV-infected people, and may explain the neurobehavioral symptoms associated with acute HIV infection.

摘要

采用体内¹H磁共振波谱技术研究了恒河猴在急性感染猿猴免疫缺陷病毒(SIV)期间大脑的代谢反应。对15只恒河猴在接种前、感染后一次或两次进行了研究。总共13/15只猕猴在接种后11 - 13天(dpi)时胆碱/ N - 乙酰天门冬氨酸(Cho/NAA)升高;在13 dpi后测量的所有10只猕猴该比值随后下降(方差分析,P < 10⁻⁶)。在11 dpi时,胆碱/肌酸(Cho/Cr)显著增加20%(P = 0.04),肌醇/肌酸(MI/Cr)增加14%(P = 0.003)。在13 dpi时,观察到NAA/Cr下降7.7%(P = 0.02),而Cho/Cr与基线不再有显著差异。在27 dpi时,Cho/Cr降至低于接种前值18%(P = 0.004),而NAA/Cr和MI/Cr处于基线值。Cho、MI和NAA的绝对浓度显示出相似的时间进程,未观察到肌酸(Cr)的变化。Cho/Cr变化与血浆病毒载量之间存在强相关性(斯皮尔曼相关系数r(s) = 0.79,P < 0.01)。急性SIV感染会在大脑中产生广泛的代谢异常,这可能反映了炎症和神经元损伤,随着病毒的免疫控制这些异常会逆转。类似的情况可能发生在急性HIV感染的人群中,并且可能解释与急性HIV感染相关的神经行为症状。

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