Huntington Medical Research Institutes, Pasadena, CA, USA.
PLoS One. 2012;7(11):e49272. doi: 10.1371/journal.pone.0049272. Epub 2012 Nov 16.
Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART).
Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART.
After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months.
We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury.
单质子磁共振波谱(MRS)可用于监测与 HIV 感染及其治疗相关的脑炎症和神经元完整性的变化。我们使用 MRS 来测量 HIV 感染后最初几周内以及在抗逆转录病毒治疗(ART)期间的大脑变化。
在曼谷,泰国,我们测量了急性 HIV 受试者(n = 31)、慢性 HIV+个体(n = 26)和 HIV 阴性对照受试者(n = 10)的脑内 N-乙酰天冬氨酸(NAA)、胆碱(tCHO)、肌酸(CR)、肌醇(MI)、谷氨酸和谷氨酰胺(GLX)的脑代谢物水平。在额状灰质(FGM)、额状白质(FWM)、枕状灰质(OGM)和基底神经节(BG)中测量了代谢物。在开始 ART 后 1、3 和 6 个月,对 17 名急性患者进行了重复测量。
在调整年龄后,我们发现急性 HIV 病例在基线时(感染 HIV 后 14 天中位数)的 BG tCHO/CR 升高,与对照组(p = 0.0014)和慢性组(p = 0.0023)相比。OGM 也观察到类似的 tCHO/CR 升高;急性组与对照组之间未观察到其他代谢物异常。混合纵向模型显示,ART 后 BG tCHO/CR 升高得到缓解(p = 0.022),6 个月时 tCHO/CR 与对照组相似。
我们在 HIV 感染后的第一个月内检测到细胞炎症,而在急性给予 ART 后,炎症得到了缓解。我们的研究结果表明,早期 ART 可能通过减轻导致中枢神经系统损伤的过程,对 HIV 感染具有神经保护作用。