Blood-brain barrier traversal by African trypanosomes
Blood-brain barrier traversal by African trypanosomes
批准号:
6463413
负责人:
Dennis John Grab
金额:
$36.79万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2002
资助国家:
美国
项目状态:
已结题
起止时间:
2002-05-01 至 2006-04-30
关键词:
Trypanosoma brucei rhodesiense blood brain barrier brain cell fluorescent dye /probe host organism interaction human tissue intracellular parasitism intracellular transport light microscopy membrane permeability organ culture scanning electron microscopy tight junctions transmission electron microscopy vascular endothelium western blottings
中文摘要
描述:(由申请人提供):睡眠的神经症状
由布氏冈比亚锥虫和 T b. 引起的人类疾病。罗德西亚群岛
归因于锥虫侵入中枢神经系统。
然而,非洲锥虫如何穿过血脑屏障(BBB)仍然是一个未知数。
未解决的问题。使用由人脑构建的体外 BBB 系统
我们已经启动了旨在破译微血管细胞(BMEC)的研究
非洲锥虫穿过血脑屏障的机制。初步研究
表明人类传染性 T. b.冈比亚血流形式寄生虫分离物
比动物感染性 T. b. 更有效地穿过体外 BBB 模型。
brucei 427.寄生虫似乎与细胞间的连接结合
BMEC。同样运动的原环形式既不结合也不穿过
障碍。更重要的是,BBB 紧密连接保持完整,这一发现
之前已经在体内描述过。抑制寄生虫 BBI3
蛋白酶抑制剂的交叉表明寄生虫蛋白酶在
血脑屏障渗透。我们的人类血脑屏障体外模型将成为一个重要的工具
了解非洲锥虫如何穿过血脑屏障。总体目标
这项研究将检验非洲锥虫的体外潜力
穿越宿主血脑屏障并解剖底层
机制。我们将描述相互作用的动力学
布氏锥虫的遍历。跨 BBB 体外模型。我们会
识别穿越障碍的方式;例如细胞旁或
跨细胞并检查寄生虫的潜在机制
和 BMEC 相互作用。从拟议的研究中获得的结果将是
我们对非洲锥虫最初事件的理解迈出了重要一步
侵入大脑。有了这些知识,我们将能够更好地
设计阻止寄生虫进入大脑的疗法
预防许多令人痛苦的神经症状,这些症状最终导致
死亡。
英文摘要
DESCRIPTION: (provided by the applicant): The neurological symptoms of sleeping
sickness in man caused by Trypanosoma brucei gambiense and T b. rhodesiense are
attributed to the penetration of the central nervous system by trypanosomes.
Yet, how African trypanosomes cross the blood-brain barrier (BBB) remains an
unresolved issue. Using an in vitro BBB system constructed of human brain
microvascular cells (BMEC) we have initiated studies aimed at deciphering the
mechanisms used by African trypanosomes to cross the BBB. Preliminary studies
show that a human infective T. b. gambiense bloodstream form parasite isolate
crossed the in vitro BBB model more efficiently than animal infective T. b.
brucei 427. The parasites appeared to bind to intercellular junctions between
BMEC. Equally motile procyclic forms do not bind or nor do they cross the
barrier. More importantly, the BBB tight junctions remain intact, a finding
that has been previously described in vivo. Inhibition of parasite BBI3
crossing by protease inhibitors suggests that parasite proteases play a role in
BBB penetration. Our in Vitro model of the human BBB will be an important tool
for understanding how African trypanosomes cross the BBB. The overall aims of
this study will be to examine the in vitro potential of African trypanosomes to
transverse the host blood-brain barrier and to dissect the underlying
mechanism(s). We will characterize the kinetics of the interaction and
traversal of Trypanosoma brucei spp. across an in vitro model of BBB. We will
identify the mode of traversal of the barrier; e.g. paracellular or
transcellular as well as examine the underlying mechanism(s) of the parasite
and BMEC interactions. The results obtained from the proposed study will be a
major step in our understanding of the initial events of African trypanosome
invasion into the brain. Armed with this knowledge we will be better able to
design therapies that will stop the parasites from entering the brain and
prevent many of the agonizing neurological symptoms, which eventually lead to
death.
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Blood-brain barrier traversal by African trypanosomes
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批准号:6623141
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资助金额:$36.79万
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负责人:Dennis John Grab
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Blood-brain barrier traversal by African trypanosomes
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资助金额:$36.79万
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负责人:Dennis John Grab
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依托单位:
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资助金额:$36.79万
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负责人:Dennis John Grab
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LACTOFERRIN BINDING ACTIVITY IN TRITRICHOMONAS FOETUS
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资助金额:$5.88万
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财政年份:1998
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FOAMY VIRUS INFECTION OF PERIPHERAL BLOOD FIBROCYTES: LYME DISEASE
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批准号:6277428
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资助金额:$5.88万
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FIBRONECTIN BINDING ADHESINS IN BORRELIA BURGDORFERI: LYME DISEASE
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资助金额:$5.88万
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财政年份:1998
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依托单位:
KININOGEN ACTIVATES CYSTEINE PROTEASE: TRYPANOSOMA CRUZI: CHAGAS DISEASE
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批准号:6277429
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项目类别:
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资助金额:$5.88万
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财政年份:1998
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INHIBIT MOSQUITO PHENOL OXIDASE ACTIVITY BY NATURALLY OCCURING ENDOGENOUS DOPA
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GOLGI ASSOCIATED PHOSPHOHYDROLASES IN TRYPANOSOMA BRUCEI
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资助金额:$5.43万
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海外基金