A prospective longitudinal in vivo 1H MR spectroscopy study of the SIV/macaque model of neuroAIDS.
A prospective longitudinal in vivo 1H MR spectroscopy study of the SIV/macaque model of neuroAIDS.
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DOI：
10.1186/1471-2202-5-10
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发表时间：
2004-03-05
期刊：
影响因子：
2.4
通讯作者：
González RG
中科院分区：
文献类型：
--
作者：
Fuller RA;Westmoreland SV;Ratai E;Greco JB;Kim JP;Lentz MR;He J;Sehgal PK;Masliah E;Halpern E;Lackner AA;González RG
艾滋病毒感染的神经系统并发症仍然知之甚少。在临床上，即使MRI正常，体内1H磁共振波谱（MRS）也能显示HIV感染引起的脑损伤。我们的目标是通过对SIV/猕猴神经艾滋病模型进行纵向体内1H MRS研究来了解脑损伤的动力学。8只恒河猴感染SIVmac251后，连续进行MRI和1H MRS成像，直至艾滋病晚期或2年终点。急性感染期间，出现典型的脑MRS改变，主要表现为额叶皮质Cho/Cr比值显著升高。随后，不同动物的大脑代谢模式出现了分化。2只SIV脑炎动物接种后4周基底神经节Cho/Cr升高（p = 0.022）。在接种后2周的任何时间点，所有8只动物的平均代谢物比率与基线没有显著差异。然而，对8只动物的线性回归分析显示，额叶Cho/Cr变化与血浆病毒载量呈正相关（P < 0.001, R = 0.80），基底节区NAA/Cr变化与血浆病毒载量呈负相关（P < 0.02, R = -0.73）。未见MRI异常。猕猴感染SIV后，脑代谢发生复杂变化，受脑区、宿主因素和病毒载量的影响。SIV感染后4周基底神经节Cho/Cr升高可能是发生SIV脑炎倾向的标志。Cho/Cr的升高通常在中枢神经系统炎症中观察到，与急性和慢性感染期间血浆病毒载量的增加有关。慢性感染期基底神经节神经元损伤与血浆病毒载量增加有关。这些观察结果支持使用能够控制病毒复制和病毒进入中枢神经系统的药物，并可能有助于解释在HAART时代，尽管大多数药物无法有效进入中枢神经系统，但艾滋病毒相关痴呆的发病率降低。
The neurological complications of HIV infection remain poorly understood. Clinically, in vivo 1H magnetic resonance spectroscopy (MRS) demonstrates brain injury caused by HIV infection even when the MRI is normal. Our goal was to undertsand the dynamics of cerebral injury by performing a longitudinal in vivo 1H MRS study of the SIV/macaque model of neuroAIDS. Eight rhesus macaques were infected with SIVmac251 and serially imaged with MRI and 1H MRS to terminal AIDS or the endpoint of 2 years. During acute infection, there were stereotypical brain MRS changes, dominated by a significant elevation of the Cho/Cr ratio in the frontal cortex. Subsequently, brain metabolic patterns diverged between animals. There was an elevation of basal ganglia Cho/Cr four weeks post-inoculation in 2 animals that developed SIV encephalitis (p = 0.022). Metabolite ratios averaged across all 8 animals were not significantly different from baseline at any time point after 2 weeks post inoculation. However, linear regression analysis on all 8 animals revealed a positive correlation between a change in frontal lobe Cho/Cr and plasma viral load (P < 0.001, R = 0.80), and a negative correlation between NAA/Cr in the basal ganglia and the plasma viral load (P < 0.02, R = -0.73). No MRI abnormalities were detected at any time. After infection with SIV, macaque brain metabolism changes in a complex manner that is dependent on brain region, host factors and viral load. An elevation of basal ganglia Cho/Cr 4 weeks after SIV infection may be marker of a propensity to develop SIV encephalitis. Elevations of Cho/Cr, often observed in CNS inflammation, were associated with increased plasma viral load during acute and chronic infection. Evidence of neuronal injury in the basal ganglia was associated with increased plasma viral load in the chronic stage of infection. These observations support the use of drugs capable of controlling the viral replication and trafficking of virus into the CNS, and may help explain the reduction in incidence of HIV-associated dementia in the era of HAART despite the inability of most of those drugs to effectively enter the CNS.
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影响因子：
3.8
作者：
González, RG;Cheng, LL;Lackner, AA
通讯作者：
Lackner, AA
影响因子：
56.9
作者：
COFFIN, JM
通讯作者：
COFFIN, JM
影响因子：
0.7
作者：
Greco, JB;Sakaie, KE;Gonzalez, RG
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影响因子：
5.4
作者：
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Lackner, AA
影响因子：
1.3
作者：
MENON, DK;AINSWORTH, JG;HARRIS, JRW
通讯作者：
HARRIS, JRW