Lentz M R, Kim W K, Lee V, Bazner S, Halpern E F, Venna N, Williams K, Rosenberg E S, González R G
Harvard Medical School/Massachusetts General Hospital, Building 149, 13th Street, Rm 2301, Charlestown, MA 02129, USA.
Neurology. 2009 Apr 28;72(17):1465-72. doi: 10.1212/WNL.0b013e3181a2e90a.
To determine if changes in brain metabolites are observed during early HIV infection and correlate these changes with immunologic alterations.
Eight subjects with early HIV infection, 9 HIV-seronegative controls, and 10 chronically HIV-infected subjects without neurologic impairment underwent 1H magnetic resonance spectroscopy. Subjects with early stage infection were identified near the time of HIV seroconversion and imaged within 60 days of an evolving Western blot, while still having detectable plasma virus. Subjects had blood drawn for viral RNA and T cell quantification.
Both N-acetylaspartate (NAA) and Glx (glutamate + glutamine) were decreased in the frontal cortical gray matter of seropositive subjects. NAA levels were found to be decreased in the centrum semiovale white matter of chronically HIV-infected subjects, but not in those with early infection. Both HIV-infected cohorts demonstrated a lower number of CD4+ T lymphocytes and a higher number of CD8+ T lymphocytes in their blood. Lower NAA levels in the frontal cortex of subjects with early infection were associated with an expansion of CD8+ T cells, especially effector CD8+ T cells.
These results verify metabolism changes occurring in the brain early during HIV infection. Lower NAA and Glx levels in the cortical gray matter suggests that HIV causes neuronal dysfunction soon after infection, which correlates to the expansion of CD8+ T cells, specifically to an activated phenotype. Utilizing magnetic resonance spectroscopy to track NAA levels may provide important information on brain metabolic health while allowing better understanding of the virus-host interactions involved in CNS functional deficits.
确定在早期HIV感染期间是否能观察到脑代谢物的变化,并将这些变化与免疫改变相关联。
8名早期HIV感染患者、9名HIV血清阴性对照者以及10名无神经功能损害的慢性HIV感染患者接受了氢质子磁共振波谱检查。早期感染患者在HIV血清转换时被确诊,并在免疫印迹结果出现变化后的60天内进行成像,此时血浆病毒仍可检测到。所有受试者均采集血液用于检测病毒RNA和T细胞定量。
血清阳性受试者额叶皮质灰质中的N-乙酰天门冬氨酸(NAA)和Glx(谷氨酸+谷氨酰胺)均降低。发现慢性HIV感染患者半卵圆中心白质中的NAA水平降低,但早期感染患者未出现这种情况。两个HIV感染队列的血液中CD4+T淋巴细胞数量均较低,CD8+T淋巴细胞数量均较高。早期感染患者额叶皮质中较低的NAA水平与CD8+T细胞的扩增有关,尤其是效应性CD8+T细胞。
这些结果证实了HIV感染早期大脑中发生的代谢变化。皮质灰质中较低的NAA和Glx水平表明,HIV在感染后不久就会导致神经元功能障碍,这与CD8+T细胞的扩增相关,特别是与活化表型相关。利用磁共振波谱追踪NAA水平可能会提供有关脑代谢健康的重要信息,同时有助于更好地理解中枢神经系统功能缺陷中涉及的病毒-宿主相互作用。