MRI PROBES OF BBB INTEGRITY IN HIV DEMENTIA

最常见和最令人衰弱的神经系统并发症 HIV感染的主要原因是HIV相关性痴呆(HAD)或艾滋病痴呆综合征 (ADC)。这种疾病的确切发病机制仍然是一个谜，但 感染艾滋病毒的外周巨噬细胞在血脑中的运输 屏障(BBB)似乎是艾滋病毒进入的重要途径，而在 这种情况的发生可能是HAD发病和/或进展的决定因素。BBB 已知崩溃会增加巨噬细胞向中枢神经系统的转运速度，并且 有证据表明有微血管异常，包括局部增加 HIV血清阳性患者的血容量(RCBV)和血脑屏障紊乱 有病人。事实上，初步结果表明，这些问题的严重性 微血管改变与HAD的严重程度相关。齐多夫定 单一疗法和最近的高效抗逆转录病毒疗法(HAART) 可能会降低HAD的发生率。此外，齐多夫定或HAART可能会阻止或 甚至逆转了精神错乱的过程，至少是暂时的，在许多但不是所有的情况下 病人。HAART可能减缓HAD进展的方法是 不清楚，但可能包括减少受感染和/或激活的贩运 巨噬细胞进入中枢神经系统，这是血清病毒负荷减少的结果，以及 也是通过扭转对BBB的损害。在这项研究中，雇用了患有 HAD的严重程度各不相同，通过临床检查仔细研究， 神经心理测试组件和对比增强磁共振 成像(MRI)，我们建议测试破坏的最重要的假设 脑微血管完整性是HAD进展过程中的关键事件(与 HAD的严重程度与微血管破坏的程度相关)和 逆转这些微血管缺陷的治疗方法可以改善 拉德。

Among the most common and debilitating neurological complications of HIV infection is HIV associated dementia (HAD) or AIDS dementia complex (ADC). The exact pathogenesis of this disorder remains a conundrum, but trafficking of HIV-infected peripheral macrophages across the blood-brain barrier (BBB) appears to be an important route of entry of HIV, and the rate at which this occurs may be a determinant of HAD onset and/or progression. BBB breakdown is known to increase the rate of macrophage trafficking into CNS, and there is evidence for microvascular abnormalities, including increased regional blood volume (RCBV) and BBB disruption in HIV seropositive and particularly in HAD patients. Indeed preliminary results suggest that the severity of these microvascular changes is correlated with the severity of HAD. Zidovudine monotherapy and, more recently, highly active anti-retroviral therapy (HAART) may reduce the incidence of HAD. Furthermore, zidovudine or HAART may arrest or even reverse the dementing process, at least temporarily, in many but not all patients. The means by which HAART might slow the progression of HAD is unclear, but may include reduced trafficking of infected and/or activated macrophage into the CNS both as a result of a reduced serum viral load, and also by reversing the damage to the BBB. In this study employing patients with HAD of varying severity, carefully studied by clinical examination, neuropsychological test battery, and contrast-enhanced magnetic resonance imaging (MRI), we propose to test the over-arching hypothesis that disruption of cerebral microvascular integrity is a key event in progression to HAD, (with the severity of HAD correlated with the degree of microvascular disruption) and that therapies which reverse these microvascular defects lead to improvement in RAD.