MRI PROBES OF BBB INTEGRITY IN HIV DEMENTIA

在最常见的和衰弱的神经系统并发症 艾滋病相关痴呆（HAD）或艾滋病痴呆综合征（AIDS dementia complex） （ADC）。这种疾病的确切发病机制仍然是一个谜，但 HIV感染的外周巨噬细胞穿过血脑的运输 血脑屏障（BBB）似乎是艾滋病毒进入的重要途径， 这种情况的发生可能是HAD发作和/或进展的决定因素。BBB 已知分解会增加巨噬细胞进入CNS的速率， 有证据表明微血管异常，包括局部 血容量（RCBV）和血脑屏障破坏的HIV血清阳性，特别是在 有病人。事实上，初步结果表明，这些严重性 微血管改变与HAD的严重程度相关。齐多夫 单药治疗和最近的高效抗逆转录病毒治疗（HAART） 可以降低HAD的发病率。此外，齐多夫定或HAART可阻止或抑制 甚至扭转痴呆的过程，至少暂时，在许多但不是全部， 患者HAART可能减缓HAD进展的方法是 不清楚，但可能包括减少感染和/或激活的 由于血清病毒载量降低， 也可以逆转血脑屏障的损伤。在这项研究中， 通过临床检查仔细研究不同严重程度的HAD， 神经心理学成套测试和对比增强磁共振 成像（MRI），我们建议测试过度假设，破坏 脑微血管完整性的丧失是进展为HAD的关键事件， HAD的严重程度与微血管破坏的程度相关）， 逆转这些微血管缺陷的疗法可以改善 RAD.

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.