aDepartment of Radiology, New York University School of Medicine, New York, New York bMassachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging and Neuroradiology Division, Charlestown, Massachusetts, USA.
AIDS. 2013 Oct 23;27(16):2519-28. doi: 10.1097/01.aids.0000433244.32105.96.
As ~40% of persons with HIV also suffer neurocognitive decline, we sought to assess metabolic dysfunction in the brains of simian immunodeficiency virus (SIV)-infected rhesus macaques, an advanced animal model, in structures involved in cognitive function. We test the hypothesis that SIV-infection produces proton-magnetic resonance spectroscopic imaging (H-MRSI)-observed decline in the neuronal marker, N-acetylaspartate (NAA), and elevations in the glial marker, myo-inositol (mI), and associated creatine (Cr) and choline (Cho) in these structures.
Pre- and 4-6 weeks post-SIV infection (with CD8 T-lymphocyte depletion) was monitored with T2-weighted quantitative MRI and 16×16×4 multivoxel H-MRSI (TE/TR = 33/1400 ms) in the brains of five rhesus macaques.
Exploiting the high-resolution H-MRSI grid, we obtained absolute, cerebrospinal fluid partial volume-corrected NAA, Cr, Cho and mI concentrations from centrum semiovale, caudate nucleus, putamen, thalamus and hippocampus regions.
Pre- to post-infection mean Cr increased in the thalamus: 7.2±0.4 to 8.0±0.8 mmol/l (+11%, P<0.05); mI increased in the centrum semiovale: 5.1±0.8 to 6.6±0.8 mmol/l, caudate: 5.7±0.7 to 7.3±0.5 mmol/l, thalamus: 6.8±0.8 to 8.5±0.8 mmol/l and hippocampus: 7.7±1.2 to 9.9±0.4 mmol/l (+29%, +27%, +24% and +29%, all P<0.05). NAA and Cho changes were not significant.
SIV-infection appears to cause brain injury indirectly, through glial activation, while the deep gray matter structures' neuronal cell bodies are relatively spared. Treatment regimens to reduce gliosis may, therefore, prevent neuronal damage and its associated neurocognitive impairment.
由于约 40%的艾滋病毒感染者也存在神经认知能力下降，我们试图评估感染猴免疫缺陷病毒（SIV）的恒河猴（一种先进的动物模型）大脑中的代谢功能障碍，这些大脑结构与认知功能有关。我们检验了以下假设，即 SIV 感染会导致质子磁共振波谱成像（H-MRSI）观察到神经元标志物 N-乙酰天门冬氨酸（NAA）下降，以及神经胶质标志物肌醇（mI）、相关肌酸（Cr）和胆碱（Cho）升高。
在五只恒河猴的大脑中，通过 T2 加权定量 MRI 和 16×16×4 多体素 H-MRSI（TE/TR = 33/1400 ms），在 SIV 感染前和感染后 4-6 周进行监测，同时伴随着 CD8 T 淋巴细胞耗竭。
利用高分辨率 H-MRSI 网格，我们从半卵圆中心、尾状核、壳核、丘脑和海马区获得绝对的、脑脊液部分容积校正的 NAA、Cr、Cho 和 mI 浓度。
感染前到感染后，丘脑的 Cr 平均增加：7.2±0.4 至 8.0±0.8 mmol/l（增加 11%，P<0.05）；半卵圆中心的 mI 增加：5.1±0.8 至 6.6±0.8 mmol/l，尾状核：5.7±0.7 至 7.3±0.5 mmol/l，丘脑：6.8±0.8 至 8.5±0.8 mmol/l，海马：7.7±1.2 至 9.9±0.4 mmol/l（增加 29%、27%、24%和 29%，均 P<0.05）。NAA 和 Cho 的变化不显著。
SIV 感染似乎通过神经胶质激活间接导致脑损伤，而深部灰质结构的神经元细胞体相对未受影响。因此，减少神经胶质增生的治疗方案可能预防神经元损伤及其相关的神经认知障碍。
