Neuron specific metabolic adaptations following multi-day exposures to oxygen glucose deprivation.
Neuron specific metabolic adaptations following multi-day exposures to oxygen glucose deprivation.
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DOI：
10.1016/j.bbadis.2010.07.013
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发表时间：
2010-11
影响因子：
6.2
通讯作者：
McLaughlin, BethAnn
中科院分区：
文献类型：
--
作者：
Zeiger, Stephanie L. H.;McKenzie, Jennifer R.;Stankowski, Jeannette N.;Martin, Jacob A.;Cliffel, David E.;McLaughlin, BethAnn
关键词：
预先暴露于亚毒性损伤可以诱导一个强大的内源性神经保护程序称为缺血预处理。目前的模型通常依赖于一个单一的应激事件来诱导神经保护，而临床现实是，患者可能会经历多次短暂性脑缺血发作（TIA）之前遭受中风。我们试图开发一个神经元富集预处理模型，使用多个氧葡萄糖剥夺（OGD）事件，以评估内源性保护机制的神经元在代谢和细胞水平的应激适应。我们发现，暴露于葡萄糖剥夺五分钟的神经元恢复氧利用和乳酸生产使用新的微生理技术。使用无毒和能量有利的五分钟暴露，我们开发了一种预处理范例，其中神经元连续三天暴露于这种短暂的OGD。这些细胞经历了45%以上的生存，否则致命的事件，并表现出更持久的保护窗口相比，我们以前在体外预处理模型使用单一的压力。在其他模型中，预处理的细胞表现出轻微的半胱天冬酶激活，氧化蛋白的增加和活性氧的神经保护的要求。热休克蛋白70在预处理过程中上调，但这种蛋白质的大部分被释放到细胞外。我们相信，耦合这种神经元丰富的多日模型与微生理学将使我们能够评估神经元特异性的实时代谢适应必要的预处理。
Prior exposure to sub toxic insults can induce a powerful endogenous neuroprotective program known as ischemic preconditioning. Current models typically rely on a single stress episode to induce neuroprotection whereas the clinical reality is that patients may experience multiple transient ischemic attacks (TIAs) prior to suffering a stroke. We sought to develop a neuron enriched preconditioning model using multiple oxygen glucose deprivation (OGD) episodes to assess the endogenous protective mechanisms neurons implement at the metabolic and cellular level for stress adaptations. We found that neurons exposed to a five minute period of glucose deprivation recovered oxygen utilization and lactate production using novel microphysiometry techniques. Using the non-toxic and energetically favorable five minute exposure, we developed a preconditioning paradigm where neurons are exposed to this brief OGD for three consecutive days. These cells experienced 45% greater survival following an otherwise lethal event and exhibited a longer lasting window of protection in comparison to our previous in vitro preconditioning model using a single stress. As in other models, preconditioned cells exhibited mild caspase activation, an increase in oxidized proteins and a requirement for reactive oxygen species for neuroprotection. Heat shock protein 70 was upregulated during preconditioning, yet the majority of this protein was released extracellularly. We believe coupling this neuron enriched multiday model with microphysiometry will allow us to assess neuronal specific real-time metabolic adaptations necessary for preconditioning.
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影响因子：
4.5
作者：
Eklund, SE;Snider, RM;Cliffel, DE
通讯作者：
Cliffel, DE
影响因子：
--
作者：
DAHL, NA;BALFOUR, WM
通讯作者：
BALFOUR, WM
DOI：
10.1196/annals.1391.032
发表时间：
2007-01-01
期刊：
STRESS RESPONSES IN BIOLOGY AND MEDICINE
影响因子：
--
作者：
Brown, Ian R.
通讯作者：
Brown, Ian R.
影响因子：
4.7
作者：
Dhodda, VK;Sailor, KA;Vemuganti, R
通讯作者：
Vemuganti, R
影响因子：
2.5
作者：
AOKI, M;ABE, K;KOGURE, K
通讯作者：
KOGURE, K