CORE--FUNCTIONAL ASSESSMENT

神经艾滋病是艾滋病毒感染的一个重要方面， 病毒引起的病理和毒性变化影响中枢神经系统 系统结构和功能。 HIV相关的认知和运动复合体 可能影响高达30%的免疫抑制早期患者 和高达50%的有症状的患者，而约10-20%的有症状的患者， 艾滋病发展成痴呆症。 随着最近治疗引起的 艾滋病患者的生存时间，大量和越来越多的幸存者 艾滋病患者可能经历神经艾滋病迫使我们了解和 处理这个复杂的基础。 神经艾滋病的动物模型已经 它模拟了免疫缺陷的整体发病机制， 感染（FIV，SIV）或专注于选定的潜在候选病毒- 与HIV神经发病机制有关的宿主衍生因子 （转基因小鼠）。 动物模型的实用性得到增强， 证明这些模型中明显的神经系统疾病是 足以产生CNS功能变化， 与人类艾滋病病毒感染有关。 功能的目标 评估核心是记录CNS功能的改变， 在各种小鼠、猫和猴的神经艾滋病模型中， 如果这种功能改变可以通过治疗逆转或阻止， 手段 该核心分为两个方面：电生理和 行为评估 电生理评估将直接 测量神经元功能，如电兴奋性和对 突触输入或神经递质，之前和之后病毒感染或 细胞因子表达，使用四种体内和体外测定：1） 细胞外记录的诱发场电位和单个单位活动 (in体内和体外;电路功能的区域测定）; 2） 体外单个神经元细胞内记录的膜特性 (i.e.,神经元功能的细胞测定）; 3）细胞内-或 对突触输入、递质、细胞因子的通路钳记录反应 和病毒片段（即，受体/分子测定）; 4）红外 神经元兴奋性的整体变化的视频显微镜评价 大脑区（体外）;神经行为评估将 从出生到成年，为了研究结果， 转基因蛋白的产生对神经行为成熟和行为的影响 在成年人中。 有针对性的行为包括那些已知受损的行为， 神经艾滋病患者和与大脑区域相关的行为， 在艾滋病患者中受到影响，并在小鼠模型中重现。 成人 小鼠，将探讨转基因表达的神经行为后遗症 在与运动能力、对压力源的反应以及 新奇/探索和认知。 因此，功能评估核心 将有助于整合中心的总体目标， 通过电生理学和 行为手段，病毒学，形态学和免疫病理学 调查结果。

NeuroAIDS is a significant aspect of HIV infection in which the pathological and toxic changes induced by the virus affect central nervous system structure and function. HIV-Associated Cognitive and Motor Complex may affect up to 30% of patients in the early stages of immune suppression and up to 50% of symptomatic patients, while about 10-20% of those with AIDS develop frank dementia. With recent treatment-induced increases in survival time for AIDS patients, the large and growing numbers of surviving AIDS patients likely to experience NeuroAIDS obliges us to understand and treat the bases of this complex. Animal models of NeuroAIDS have been developed which mimic the overall pathogenesis of immunodeficiency infection (FIV,SIV) or focus on selected potential candidates for virus- derived or host-derived factors involved in HIV neuropathogenesis (transgenic mice). The utility of the animal models is augmented by demonstration that the neurologic disease evident in these models is sufficient to produce CNS functional changes reminiscent of those associated with HIV infection in humans. The goal of the Functional Assessment Core is to document alterations of CNS functions that develop in the various mouse, cat and monkey models of NeuroAIDS, and to determine if such functional alterations can be reversed or arrested by therapeutic means. This Core is divided into 2 aspects: electrophysiological and behavioral assessment. Electrophysiological assessment will directly measure neuronal function as electrical excitability and responsivity to synaptic input or neurotransmitters, before and after viral infection or cytokine expression, using four in vivo and in vitro assays: 1) Extracellularly recorded evoked field potentials and single unit activity (in vivo and in vitro; a regional assay of circuit functionality); 2) Intracellularly recorded membrane properties of single neurons in vitro (i.e., a cellular assay of neuronal function); 3) Intracellularly- or path-clamp-recorded responses to synaptic input, transmitters, cytokines and viral fragments (i.e., a receptor/molecular assay); 4) Infrared videomicroscopic evaluation of global changes in neuronal excitability in large brain regions (in vitro); Neurobehavioral assessment will be conducted from birth through adulthood, in order to study the consequences of transgene protein production on neurobehavioral maturation and behavior in adults. Targeted behaviors include those known to be impaired in patients with NeuroAIDS and behaviors associated with brain regions, affected in AIDS patients and recapitulated in the mouse models. In adult mice, the neurobehavioral sequelae of transgenic expression will be probed in tasks related to motor ability, reactivity to stressors and novelty/exploration, and cognition. Thus, the Functional Assessment Core will help to integrate the overall purpose of the Center by correlating disruptions in brain function, measured by electrophysiological and behavioral means, with virological, morphological, and immunopathological findings.