S100BETA, A POSSIBLE SURROGATE MARKER FOR SIV ENCEPHALITIS
S100BETA, A POSSIBLE SURROGATE MARKER FOR SIV ENCEPHALITIS
批准号:
7716298
负责人:
ANDREW G MACLEAN
金额:
$6.46万
依托单位国家:
美国
项目类别:
财政年份:
2008
资助国家:
美国
项目状态:
已结题
起止时间:
2008-07-21 至 2009-04-30
关键词:
AIDS Dementia ComplexAIDS neuropathyAcquired Immunodeficiency SyndromeAnimalsBrainCellsCessation of lifeComputer Retrieval of Information on Scientific Projects DatabaseDevelopmentDiseaseEncephalitisFundingGiant CellsGrantHIVHighly Active Antiretroviral TherapyIncidenceIndividualInflammatoryInstitutionKnowledgeLesionMacaca mulattaModelingNervous system structureNeurologicPathogenesisPathway interactionsPatientsPrevalenceResearchResearch PersonnelResourcesSerumSourceStagingSurrogate MarkersThinkingUnited States National Institutes of HealthUrticariaViral Load resultimprovednervous system disorderneurotrophic protein S100beta
中文摘要
这个子项目是许多研究子项目中的一个
由NIH/NCRR资助的中心赠款提供的资源。子项目和
研究者(PI)可能从另一个NIH来源获得了主要资金,
因此可以在其他CRISP条目中表示。所列机构为
研究中心,而研究中心不一定是研究者所在的机构。
尽管在接受高效抗逆转录病毒治疗(HAART)的患者中艾滋病毒痴呆的发病率降低,但生存率的提高导致艾滋病神经系统并发症的累积患病率增加。在与艾滋病毒相关神经系统疾病的发展有关的机制和途径的知识方面仍然存在根本性的差距。与脑炎相关的病变包括显著的星形胶质细胞和小胶质细胞活化,伴有频繁的多核巨细胞、高病毒载量和由遍及脑的炎性细胞的多个播散灶组成的病变。病变的发病机制尚不清楚,但认为与BBB的改变有关。因此,在尸检之前无法确定一个人是否患有脑炎。通过确定血清中胶质蛋白S100 b的水平,我们表明,这不仅是可能的,以确定相关的死后,但也可以预测哪些人将有脑炎死亡前。这可能对使用恒河猴模型阐明neuroAIDS的发病机制产生深远的影响,该模型允许在神经系统疾病的最早阶段对动物实施安乐死,或者预测感染HIV的患者的HIVE,从而进行定制治疗。
英文摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
Despite a reduced incidence of HIV dementia in patients on highly active antiretroviral therapy (HAART), the improved survival has resulted in increased cumulative prevalence of nervous system complications of AIDS. Fundamental gaps remain in knowledge relating to mechanisms and pathways involved in the development of HIV-associated neurologic disease. Lesions associated with encephalitis include marked astrocytic and microglial activation with frequent multinucleated giant cells, high viral load and lesions consisting of multiple disseminated foci of inflammatory cells throughout the brain. The pathogenesis of the lesions is unknown, but it is thought to be associated with alterations in the BBB. Heretofore, it has not been possible to determine if an individual has encephalitis before post mortem examination. By determining levels of the glial protein S100b in serum, we show that it is possible not only to determine correlates post mortem, but also to predict which individuals will have encephalitis before death. This could have profound impact on elucidating the pathogenesis of neuroAIDS using the rhesus macaque model allowing one to euthanize an animal during the earliest stages of neurological disease or to predict HIVE in patients infected with HIV and thus, tailor treatment administered.
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