Neuroprotection in diet-induced ketotic rat brain after focal ischemia.
Neuroprotection in diet-induced ketotic rat brain after focal ischemia.
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DOI：
10.1038/jcbfm.2008.79
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发表时间：
2008-12
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影响因子：
--
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中科院分区：
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酮症的神经保护特性可能与缺氧诱导因子1（HIF-1α）的上调有关，缺氧诱导因子1是与缺氧血管生成相关的主要成分，也是神经保护反应的调节剂。脑对酮的利用导致细胞内琥珀酸升高（一种已知的脯氨酰羟化酶（负责降解HIF-1α的酶）抑制剂）的原理被认为是酮病上调HIF-1α的潜在机制。研究了饮食诱导的酮症（喂养生酮饮食3周）作为预处理对可逆性大脑中动脉闭塞（MCAO）后梗死体积和HIF-1α上调的神经保护作用。在MCAO后，还研究了β-羟基丁酸酯（BHB）作为脑室内输注（卒中前输注4天）的预处理的作用。检测HIF-1α和Bcl-2（抗凋亡蛋白）蛋白水平以及琥珀酸含量。分别在BHB输注或饮食诱导的酮症中观察到梗死体积减少55-70%。HIF-1α和Bcl-2蛋白水平随着饮食诱导的酮症增加3倍; BHB输注导致这些蛋白增加。正如假设的那样，饮食诱导的酮病导致琥珀酸含量增加了55%，BHB输注导致琥珀酸含量增加了4倍。结论：酮中毒与HIF-1α稳定化之间的生化联系是通过琥珀酸水平的升高，HIF-1α稳定化和Bcl-2上调在酮诱导的脑神经保护中发挥作用。
Neuroprotective properties of ketosis may be related to the up-regulation of hypoxia inducible factor 1 (HIF-1α), a primary constituent associated with hypoxic angiogenesis and a regulator of neuroprotective responses. The rationale that the utilization of ketones by brain results in elevation of intracellular succinate, a known inhibitor of prolyl-hydroxylase (the enzyme responsible for the degradation of HIF-1α) was deemed as a potential mechanism of ketosis on the up-regulation of HIF-1α. The neuroprotective effect of diet-induced ketosis (3 weeks of feeding a ketogenic diet), as pretreatment, on infarct volume, following reversible middle cerebral artery occlusion (MCAO) and the up-regulation of HIF-1α was investigated. The effect of beta-hydroxybutyrate (BHB), as a pretreatment via intraventricular infusion (4 days of infusion prior to stroke) was also investigated following MCAO. HIF-1α and Bcl-2 (anti-apoptotic protein) protein levels, and succinate content were measured. A 55–70% reduction in infarct volume was observed with BHB infusion or diet-induced ketosis, respectively. HIF-1α and Bcl-2 protein levels increased 3-fold with diet-induced ketosis; BHB infusions resulted in increases in these proteins. As hypothesized, succinate content increased by 55% with diet-induced ketosis and 4-fold with BHB infusion. We conclude, the biochemical link between ketosis and the stabilization of HIF-1α is through the elevation of succinate, and both HIF-1α stabilization and Bcl-2 up-regulation play a role in ketone induced neuroprotection in brain.
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影响因子：
3
作者：
Freeman, Robert S.;Barone, Maria Cecilia
通讯作者：
Barone, Maria Cecilia
DOI：
10.1196/annals.1320.007
发表时间：
2004-01-01
期刊：
CARNITINE: THE SCIENCE BEHIND A CONDITIONALLY ESSENTIAL NUTRIENT
影响因子：
--
作者：
Ferrari, R;Merli, E;Ceconi, C
通讯作者：
Ceconi, C
影响因子：
11.2
作者：
Parsons, MW;Barber, PA;Davis, SM
通讯作者：
Davis, SM
DOI：
10.1073/pnas.97.10.5440
发表时间：
2000-05-09
影响因子：
11.1
作者：
Kashiwaya, Y;Takeshima, T;Veech, RL
通讯作者：
Veech, RL
影响因子：
5.5
作者：
Agani, FH;Puchowicz, M;LaManna, J
通讯作者：
LaManna, J