NEURO AIDS CONSORTIUM

在艾滋病毒感染的后期，患者会出现运动和 被称为艾滋病痴呆综合症(ADC)的认知问题。尸检 HIV患者的报告显示弥漫性髓鞘苍白和 星形细胞增多症。这种损伤在某种程度上是独特的，因为神经元和 星形胶质细胞通常不会感染病毒，尽管它们 参与病理。为此，我们已经开始关注 造成这种伤害的间接机制。我们的工作假设是 HIV相关蛋白改变脑内神经胶质细胞的功能 这样就会释放出更多的艾滋病毒蛋白质以及 细胞因子。这些蛋白质和细胞因子随后增加了Na+/H+交换 在星形胶质细胞中，导致细胞内pH(Phi)增加， 外向K+电导，谷氨酸内流减少。这个 胞外K+和谷氨酸的增加会导致 周围神经的兴奋性毒性。在一个健康的个体中， 星形胶质细胞在脑内环境平衡机制中发挥重要作用。 通过调节离子的运输和调节来调节大脑。上一首 在原代大鼠星形胶质细胞中的实验表明， 对HIV包膜糖蛋白gp120的挑战，有一个 阿米洛利敏感的细胞内碱化和 PH敏感的K+通道电导。在人类星形细胞中，我们看到 K+电导的增加和细胞摄取的减少 神经递质谷氨酸。我们建议将这一变化 星形胶质细胞的活动将负责病理生理学 ADC。只有在以下情况下才能充分认识到这项研究的重要性 我们的假设是在一个完整的系统中进行研究的。因此，我们 已经开始研究艾滋病毒患者大脑中的PH值。酸碱度是 决定于无机磷酸盐(PI)的化学位移。 人脑31P核磁共振谱中的磷酸肌酸 在4.1T场强下进行核磁共振波谱成像。我们的预赛 对无症状的HIV+患者的研究表明，9名患者中有一些人 小脑内的PH值略有升高。需要进一步研究 要做的就是对这个微小的pH变化和代谢物进行观察 对这些集中的患者进行严格的统计分析。 我们建议让这些患者接受一系列的 神经心理评估将这些pH的变化与 测量的痴呆症状态。

In the later stages of HIV infection, patients suffer motor and cognitive problems known as the AIDS dementia complex (ADC). Autopsy reports in HIV patients reveal areas of diffuse myelin pallor and astrocytosis. This injury is somewhat unique in that neurons and astrocytes are usually not infected with the virus despite their participation in the pathology. Therefor, we have begun to look at indirect mechanisms for this injuries. Our working hypothesis is that HIV-related proteins alter the function of glial cells in the brain such that there is a release of more HIV proteins as well as cytokines. These proteins and cytokines then increase Na+/H+ exchange in the astrocyte resulting in an increase in intracellular pH (pHi), outward K+ conductance, and a decrease in glutamate influx. The increase in extracellular K+ and glutamate would result in the excitotoxicity of the surrounding neuros. In a healthy individual, astrocytes play a major role in the homeostatic mechanisms of the brain by regulating ion transport and regulation. Previous experiments in the primary rat astrocytes demonstrate that with a challenge of gp120, an envelope glycoprotein of HIV, there is an amiloride-sensitive intracellular alkalinization and an increase in a pH sensitive K+ channel conductance. In the human astrocyte, we see the increase in K+ conductance and a decrease in the uptake of the neurotransmitter glutamate. We would propose that this alteration in astrocyte activity would then be responsible for pathophysiology of ADC. The importance of this study can only be fully appreciated if our hypothesis is investigated in an intact system. Therefore, we have begun to look at pH in the brains of HIV patients. The pH is determined by the chemical shift of inorganic phosphate (Pi) vs. phosphocreatine (PCr) of the 31P NMR spectra acquired in human brains using NMR spectroscopic imaging at the field of 4.1T. Our preliminary studies of asymptomatic HIV+ patients show some of the 9 patients have a slightly increase in pH within the cerebellum. Further studies need to be done on this small pH changes and to look at the metabolite concentration of these patients with stringent statistical analysis. We are proposing to have these patients undergo a series of neuropsychological evaluation to correlate these changes in pH to a measured dementia state.