NMR OF FBP PROTECTION IN HYPOXIC RAT BRAIN SLICES
NMR OF FBP PROTECTION IN HYPOXIC RAT BRAIN SLICES
批准号:
6627142
负责人:
Lawrence Litt
金额:
$32.31万
依托单位国家:
美国
项目类别:
财政年份:
1985
资助国家:
美国
项目状态:
已结题
起止时间:
1985-07-01 至 2004-05-31
关键词:
Krebs' cycle NMDA receptors adenosine triphosphate bioimaging /biomedical imaging brain injury brain metabolism cellular respiration cerebral ischemia /hypoxia enzyme activity enzyme inhibitors fructose phosphate gene expression glucose metabolism heat shock proteins immunocytochemistry laboratory rat messenger RNA neuroprotectants neurotoxins nitric oxide synthase nuclear magnetic resonance spectroscopy pentose phosphate pentosyltransferase protooncogene tissue /cell culture
中文摘要
多年来,人们已经知道,在治疗前后,
1,6-二磷酸果糖(FBP)可显著改善缺氧/缺血
在脑、肌肉和肠道组织中的体内耐受性,表明
高危分娩的潜在好处,有重大危险的手术
血液流动中断或全循环停止,以及器官移植。
FBP保护的主要机制影响细胞内代谢,即
由于高分辨率核磁的进步,现在更容易进行探索
共振(核磁共振)光谱。14.1特斯拉在体外和体内的具体目标
新生大鼠脑片体外多核核磁共振波谱研究
确定:1)[1-13C]果糖-1,6-二磷酸是否进入含氧和/或
低氧细胞,如果是这样,它的代谢命运和影响。2)如果FBP诱导
细胞内葡萄糖代谢的代谢变化,特别是
在缺氧期间。[U-13C]葡萄糖将用于区分胶质细胞
由神经元的TCA循环活动引起。[2-13C]葡萄糖将探测酶的活性
磷酸戊糖途径(PPP)。将使用[1-13C]葡萄糖来确定总
葡萄糖利用率。3)如果FBP对ATP的保存次于其
防止谷氨酸毒性和/或其对PARs的损伤
(多聚腺苷5‘-二磷酸核糖合成酶,也称为PARP。)在.期间
低氧FBP通过PPP增加葡萄糖代谢,PPP是核糖的来源。
低氧研究将在无毒谷氨酸受体阻滞剂和
无毒抑制谷氨酸的释放,并与PARS的抑制剂一起使用。4)如果
低氧诱导的ATP变化与伴随的细胞内
脑片水的表观扩散系数,ADCw,通常是
用于临床;增加脑片水分;细胞的组织学测量
肿胀;细胞和线粒体损伤的免疫组织学测量。这个
经检验的假设是:1)FBP在缺氧和缺氧时更容易进入细胞
作为代谢调节剂和底物;2)由于PARS,ATP
FBP在低氧状态下的维持需要增加葡萄糖代谢
PPP;3)表观胞内扩散系数可以准确地
估计细胞肿胀和细胞内代谢的完整性;以及4)
当FBP在缺氧期间维持ATP水平时,线粒体的存活率也
反对有效。
英文摘要
It has been known for years that pre- and post-treatment with
fructose-1,6-bisphosphate (FBP) can dramatically improve hypoxic/ ischemic
tolerance in vivo in brain, muscle, and intestinal tissues, suggesting huge
potential benefits in high risk childbirth, surgeries where there is major
blood flow interruption or total circulatory arrest, and organ transplantation.
Primary mechanisms of FBP protection affect intracellular metabolism, which is
now easier to explore because of advances in high resolution nuclear magnetic
resonance (NMR) spectroscopy. The Specific Aims of 14.1 Tesla ex vivo and in
vitro multinuclear NMR spectroscopy studies of neonatal rat brain slices are to
determine: 1) if [1-13C]fructose-1,6-bisphosphate enters oxygenated and/or
hypoxic cells, and if so, its metabolic fate and influence. 2) if FBP-induces
metabolic changes in the intracellular metabolism of glucose, particularly
during oxygen deprivation. [U-13C]glucose will be used to distinguish glial
from neuronal TCA cycle activity. [2-13C]glucose will probe the activity of the
pentose phosphate pathway (PPP). [1-13C]glucose will be used to determine total
glucose utilization. 3) if FBP preservation of ATP is secondary to its
prevention of glutamate toxicity and/or its prevention of damage from PARS
(polyadenosine 5'-diphosphoribose synthetase, also know as PARP.) During
hypoxia FBP increases glucose metabolism by the PPP, a source of ribose.
Hypoxia studies will be performed with nontoxic glutamate receptor blockade and
nontoxic inhibition of glutamata release, and with inhibitors of PARS. 4) if
hypoxia-induced changes in ATP are associated with concomitant changes in the
apparent diffusion coefficient of brain slice water, ADCw, which is commonly
used clinically; increases in brain slice water; histological measures of cell
swelling; and immunohistological measures of cell and mitochondrial injury. The
hypotheses tested are that: 1) FBP enters cells more readily during hypoxia and
serves as a metabolic modulator and substrate; 2) Because of PARS, ATP
maintenance by FBP during hypoxia requires increased glucose metabolism by the
PPP; 3) apparent intracellular diffusion coefficients can be used to accurately
estimate cell swelling and the integrity of intracellular metabolism; and 4)
when FBP sustains ATP levels during hypoxia, mitochondrial viability is also
sustained.
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BASIC SCIENCE ANESTHESIA TRAINING PROGRAM
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批准号:2654853
-
项目类别:
-
资助金额:$12.13万
-
财政年份:1995
-
负责人:Lawrence Litt
-
依托单位:
BASIC SCIENCE ANESTHESIA TRAINING PROGRAM
-
批准号:6150892
-
项目类别:
-
资助金额:$14.42万
-
财政年份:1995
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负责人:Lawrence Litt
-
依托单位:
BASIC SCIENCE ANESTHESIA TRAINING PROGRAM
-
批准号:2168200
-
项目类别:
-
资助金额:$8.04万
-
财政年份:1995
-
负责人:Lawrence Litt
-
依托单位:
BASIC SCIENCE ANESTHESIA TRAINING PROGRAM
-
批准号:2872565
-
项目类别:
-
资助金额:$15.47万
-
财政年份:1995
-
负责人:Lawrence Litt
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依托单位:
BASIC SCIENCE ANESTHESIA TRAINING PROGRAM
-
批准号:2720971
-
项目类别:
-
资助金额:$3.74万
-
财政年份:1995
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负责人:Lawrence Litt
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依托单位:
BASIC SCIENCE ANESTHESIA TRAINING PROGRAM
-
批准号:2331874
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项目类别:
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资助金额:$8.65万
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财政年份:1995
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负责人:Lawrence Litt
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EXCITOTOXIC NMR ENERGY FAILURE IN ISCHEMIC BRAIN SLICES
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批准号:2177564
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项目类别:
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资助金额:$29.61万
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财政年份:1985
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负责人:Lawrence Litt
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依托单位:
BRAIN METABOLISM DURING ANESTHESIA, LOW PH1, AND HYPOXIA
-
批准号:3286306
-
项目类别:
-
资助金额:$18.9万
-
财政年份:1985
-
负责人:Lawrence Litt
-
依托单位:
BRAIN METABOLISM DURING ANESTHESIA, LOW PH1, AND HYPOXIA
-
批准号:3286309
-
项目类别:
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资助金额:$21.77万
-
财政年份:1985
-
负责人:Lawrence Litt
-
依托单位:
NMR OF FBP PROTECTION IN HYPOXIC RAT BRAIN SLICES
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批准号:6489996
-
项目类别:
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资助金额:$31.62万
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财政年份:1985
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负责人:Lawrence Litt
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依托单位:
NMR OF FBP PROTECTION IN HYPOXIC RAT BRAIN SLICES
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批准号:6045536
-
项目类别:
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资助金额:$33.07万
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财政年份:1985
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负责人:Lawrence Litt
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依托单位:
2D NMR of Energy Rescue from PARP in Brain Slice Hypoxia
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批准号:7071046
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项目类别:
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资助金额:$33.16万
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财政年份:1985
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负责人:Lawrence Litt
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依托单位:
Hypothermia, anesthesia and NMR metabolomics in ischemic neonatal brain slices
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批准号:7797431
-
项目类别:
-
资助金额:$35.84万
-
财政年份:1985
-
负责人:Lawrence Litt
-
依托单位:
Hypothermia, anesthesia and NMR metabolomics in ischemic neonatal brain slices
-
批准号:8019123
-
项目类别:
-
资助金额:$35.47万
-
财政年份:1985
-
负责人:Lawrence Litt
-
依托单位:
BRAIN METABOLISM DURING ANESTHESIA, LOW PH1, AND HYPOXIA
-
批准号:3286307
-
项目类别:
-
资助金额:$19.74万
-
财政年份:1985
-
负责人:Lawrence Litt
-
依托单位:
EXCITOTOXIC NMR ENERGY FAILURE IN ISCHEMIC BRAIN SLICES
-
批准号:2391969
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项目类别:
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资助金额:$28.3万
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财政年份:1985
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负责人:Lawrence Litt
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依托单位:
EXCITOTOXIC NMR ENERGY FAILURE IN ISCHEMIC BRAIN SLICES
-
批准号:2177563
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项目类别:
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资助金额:$29.79万
-
财政年份:1985
-
负责人:Lawrence Litt
-
依托单位:
Hypothermia, anesthesia and NMR metabolomics in ischemic neonatal brain slices
-
批准号:8212446
-
项目类别:
-
资助金额:$35.46万
-
财政年份:1985
-
负责人:Lawrence Litt
-
依托单位:
BRAIN METABOLISM DURING ANESTHESIA, LOW PH1, AND HYPOXIA
-
批准号:3286308
-
项目类别:
-
资助金额:$20.9万
-
财政年份:1985
-
负责人:Lawrence Litt
-
依托单位:
2D NMR of Energy Rescue from PARP in Brain Slice Hypoxia
-
批准号:7238726
-
项目类别:
-
资助金额:$32.2万
-
财政年份:1985
-
负责人:Lawrence Litt
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依托单位:
海外基金